Você está na página 1de 102

Volume 32 October/December Number 4

Official Journal of the


Brazilian Society of Coloproctology

FOUNDER
Klaus Rebel - RJ Brazil

EDITOR IN CHIEF
André da Luz Moreira - RJ Brazil

EXECUTIVE EDITOR
Juliana Goncalves dos Reis - RJ Brazil

Coeditors
Claudio Saddy Rodrigues Coy - SP Brazil
Francisco Sergio Pinheiro Regadas - CE Brazil
João de Aguiar Pupo Neto - RJ Brazil
Paulo Gustavo Kotze - PR Brazil
Rodrigo Oliva Perez - SP Brazil

Editorial board

Angelita Habr-Gama - SP José Ribamar Baldez - MA


Armando Geraldo Francsini Melani - SP Juliana Gonçalves dos Reis - RJ
Antonio Lacerda Filho - MG Júlio Cesar M. dos Santos Junior - SP
Boris Barone - SP Julio Garcia-Aguilar - EUA
Caio Sergio Rizkallah Nahas - SP Karen Delacoste Pires Mallmann - RS
Carmen Ruth Manzione Nadal - SP Luca Stocchi - EUA
Chuan-Gang Fu - China Luiz Felipe de Campos Lobato - DF
Eduardo de Paula Vieira - RJ Lucia Camara de Castro Oliveira - RJ
Ezio Ganio - Itália Lusmar Veras Rodrigues - CE
Fang Chia Bin - SP Maria Cristina Sartor - PR
Fernanda Bellotti Formiga - SP Mário Trompetto - Itália
Fernando Zaroni Swaybricker - RJ Marvin Corman - EUA
Feza Remzi - EUA Mauro de Souza Leite Pinho - SC
Fidel Ruiz Healy - México Michael R.B. Keighley - Reino Unido
Flávio Ferreira Diniz - RS Olival de Oliveira Junior - PR
Francisco Lopes Paulo - RJ Paulo Gonçalves de Oliveira - DF
Geraldo Magela Gomes da Cruz - MG Paulo Roberto Arruda Alves - SP
Giulio Santoro - Itália Peter Marcello - EUA
Guillermo Rosato - Argentina Raul Cutait - SP
Hélio Moreira - GO Ravi P. Kiran - EUA
Helio Moreira Junior - GO Renato Araújo Bonardi - PR
Henrique Sarubbi Fillmann - RS Robert William de Azevedo Bringel - CE
João de Aguiar Pupo Neto - RJ Roberto Misici - CE
João Batista de Sousa - DF Rogerio Saad Hossne - SP
João Francisco Xavier Müssnich - RS Rosalvo José Ribeiro - RJ
João Gomes Netinho - SP Rubens Valarini - PR
Joaquim José Ferreira - RJ Saul Sokol - EUA
Joaquim Manuel Costa Pereira - Portugal Sergio Carlos Nahas - SP
José Alfredo dos Reis Junior - SP Sidney Nadal - SP
José Alfredo Reis Neto - SP Sinara Monica de Oliveira Leite - MG
Jose G. Guillem - EUA Sthela Maria Murad Regadas - CE
José Reinan Ramos - RJ Steven D. Wexner - EUA

Editorial Production
Brazilian Society of Coloproctology Zeppelini Editorial
Av. Marechal Câmara, 160 ‑ Conj. 916 / 917 ‑ Edifício Orly Gráfica Prensa
CEP 20020‑080 ‑ Rio de Janeiro ‑ RJ Editorial Office
Fax (21) 2220‑5803 * Telefone: (21) 2240‑8927 Janilene Andrade Afonso - RJ
Homepage: http://www.sbcp.org.br * E-mail: sbcp@sbcp.org.br Sociedade Brasileira de Coloproctologia
E-mail: sbcp@sbcp.org.br
Brazilian Society
of Coloproctology – Board 2012/2013

PRESIDENT Carlos Walter Sobrado Junior (SP)


Elected president Paulo Gonçalves de Oliveira (DF)
Vice-president Ronaldo Coelho Salles (RJ)
General secretary Eduardo de Paula Vieira (RJ)
First secretary Fabio Guilherme Caserta M. Campos (SP)
Second secretary Luiz Alberto Mendonça de Freitas (DF)
First treasurer Andrés Pessôa Pandelo (RJ)
Second treasurer Sidney Roberto Nadal (SP)

Consulting council board certification committee

João de Aguiar Pupo Neto (RJ) Rogério Saad Hossne (SP)


Renato Valmassoni Pinho (PR) Sergio Eduardo Alonso Araújo (SP)
Karen Delacoste Pires Mallmann (RS) Luciano Dias Batista Costa(DF)
Sergio Carlos Nahas (SP) Afonso Henrique B. Moniz de Aragão (RJ)
Francisco Lopes Paulo (RJ) Antonio Lacerda Filho (MG)
Francisco Sergio Pinheiro Regadas (CE) Carlos Augusto Real Martinez (SP)
Luciana Maria Pyramo Costa (MG) Rômulo Medeiros de Almeida (DF)
Mauro de Souza Leite Pinho (SC)
Sthela Maria Murad Regadas (CE)
Maurício Jose de Mattos e Silva (PE)
Scientific committee Antonio Sergio Brenner (PR)
Henrique Sarubbi Fillmann (RS)
Afonso Henrique da Silva e Sousa Jr.(SP) Roberto Misici (CE)
Lusmar Veras Rodrigues (CE) Olival de Oliveira Junior (PR)
Ignácio Osório Mallmann (RS) Joaquim Simões Neto (SP)

teaching and residency committee

Journal committee Carmen Ruth Manzione Nadal (SP) - Relatora


Silvio Augusto Ciquini(SP)
André da Luz Moreira (RJ) Magda Maria Profeta da Luz (MG)
Claudio Saddy Rodrigues Coy (SP) Maria Cristina Sartor (PR)
Paulo Gustavo Kotze (PR) Fabio Lopes de Queiroz (MG)
César de Paiva Barros (RJ)
João Batista de Sousa (DF)
Sarhan Sydney Saad (SP)
Class defense committee Manoel Alvaro de Freitas Lins Neto (AL)
Francisco Luis Altenburg (SC)
Marcelo Rodrigues Borba (SP) Juvenal da Rocha Torres Neto (SE)
Elias Couto de Almeida Filho (DF) Renato Arione Lupinacci (SP)
Fernando Cordeiro(SP) Hélio Moreira Junior (GO)
Marlise Mello Cerato (RS)
João Gomes Netinho (SP)

SBCP delegates at ALACP

Titular

Sergio Carlos Nahas (SP)


Afonso Henrique da Silva e Sousa Junior (SP)

Alternates

Enio chaves de Oliveira (GO)


Roland Amauri Dagnone (SC)
VOLUME Number

32 4
Contents OCTOBER / December 2012

original article Clinical outcomes of Fournier’s gangrene from a


tertiary hospital
Oxidative stress and changes in the content and pattern of Isaac José Felippe Corrêa Neto, Otávio Nunes Sia, Alexander
tissue expression of β-catenin protein in diversion colitis Sá Rolim, Rogério Freitas Lino Souza, Hugo Henriques Watté,
Carlos Augusto Real Martinez, Fabiano Marcelo de Fabris, Camila Laércio Robles��������������������������������������������������������������������������407
Morais Gonçalves da Silva, Murilo Rocha Rodrigues, Daniela
Tiemi Sato, Marcelo Lima Ribeiro, José Aires Pereira�������������343 Transanal endoscopic microsurgery (TEM): initial experience
Carlos Ramon Silveira Mendes, Luciano Santana de Miranda
Role of bowel preparation on colocolonic anastomosis: Ferreira, Ricardo Aguiar Sapucaia, Meyline Andrade Lima,
experimental study in dogs Sergio Eduardo Alonso Araujo, Mauricio Jose de Matos e Silva,
Francisco Sérgio Pinheiro Regadas, Welligton Ribeiro Figueiredo, Jose Figueiroa Filho, Joaquim Herbenildo Costa Carvalho,
Miguel Augusto Arcoverde Nogueira, Carlos Renato Sales Maurilio Toscano de Lucena, Orcina Fernandes Duarte, Raquel
Bezerra, Péricles Cerqueira de Sousa���������������������������������������359 Kelner Silveira, Anna Christina Cordeiro da Silva, Carolina
Araujo Guenes ���������������������������������������������������������������������� 411
Anthropometric assessment of men with colorectal cancer
after dietary supplement with Agaricus sylvaticus fungus CASE report
Renata Costa Fortes,, João Rodrigo de Lavor e Silva, Maria Rita
Carvalho Garbi Novaes�������������������������������������������������������������365 Sacrococcygeal hernia: a challenge for the coloproctologist
Eron Fábio Miranda, Ilario Froehner Junior, Juliana Stradiotto
Doppler-guided hemorrhoidal artery ligation with rectal Steckert, Cristiano Denoni Freitas, Juliana Ferreira Martins,
mucopexy technique): initial evaluation of 42 cases Paulo Gustavo Kotze ����������������������������������������������������������������416
Carlos Mateus Rotta, Fernando Oriolli de Moraes, Araripe
Fernandez Varella Neto, Thereza Cristina Ariza Rotta, João Vitor Bezoar by mesalazine tablets: cause of intestinal obstruction
Antunes Marques Gregório, Alfredo Luiz Jacomo, Carlos Augusto in Crohn’s disease
Real Martinez����������������������������������������������������������������������������372 Idblan Carvalho de Albuquerque, Mariana Andrade Carvalho,
Rodrigo Rocha Batista, Galdino José Sitonio Formiga������������422
Knowledge and practice of physicians regarding colorectal
cancer screening TECHNICAL NOTE
Elziane da Cruz Ribeiro e Souza, Marina Lise, Thalita Pereira dos
Santos, Luciano Pinto de Carvalho�������������������������������������������385 Operative Technique: Intersphincteric Resection
Marcus Valadão, Daniel Cesar, Guilherme Graziosi, Ricardo Ary
Epidemiological profile of 175 patients with Crohn’s disease Leal�������������������������������������������������������������������������������������������426
submitted to biological therapy
Marcelo Rassweiler Hardt, Paulo Gustavo Kotze, Fabio Vieira SELF-ASSESSMENT QUIZ��������������������������������������� 430
Teixeira, Juliano Coelho Ludvig, Everson Fernando Malluta,
Harry Kleinubing Junior, Eron Fábio Miranda, Wanessa Bertrami
Tonini, Márcia Olandoski, Lorete Maria da Silva Kotze, Claudio Answers for self-ASSESSMENT QUIZ������������ 431
Saddy Rodrigues Coy���������������������������������������������������������������395
Services accredited���������������������������������������� 432
Transanal minimally invasive surgery with single-port
(TAMIS) for the management of rectal neoplasms – a pilot Index��������������������������������������������������������������������������� 435
study
Eduardo Fonseca Alves Filho, Paulo Frederico de Oliveira Costa,
João Cláudio Guerra�����������������������������������������������������������������402
Indexed: Literatura Latino-Americano e do Caribe em Ciências da Saúde (LILACS), Scientific Electronic Library Online (SciELO), SCOPUS, Directory of Open Access Journals (DOAJ)

Instructions for authors


Scope and policy the compliance with the Instructions for Authors, and if any noncompliance is
The Journal of Coloproctology (JCOL) publishes articles that contribute to im- detected, it will be not accepted. If approved, it is submitted to the analysis of two
provements and developments of the medical practice, research and training in evaluators, who will examine it based on the Instrument of Analysis and Opinion,
Coloproctology and related specialties. Also published in English version, starting specifically elaborated for such purpose, and will give their opinion regarding the
in vol. 31, issue 3, 2011. methodological rigor of the approach used in the article. If the opinions disagree,
The guidelines are based on the format proposed by the International Committee of the manuscript is submitted to a third evaluator. Anonymity is ensured during all
Medical Journal Editors (ICMJE) and published in the article Uniform requirements the evaluation process. The evaluators’ opinions are analyzed by the Editorial
for manuscripts submitted to biomedical journals, which was updated in April 2010 Board, which, if required, will indicate the alterations to be made. The studies will
and can be accessed at http://www.icmje.org. be published only after the final approval of the evaluators and Editorial Board.
Flowchart for the procedures. (www.jcol.org.br)
Manuscript categories:
Editorial: manuscript about themes of interest to the historical moment, with reper- Manuscripts format and preparation
cussion in Coloproctology and related specialties. The identification page
Original article: research with unprecedented results that add value to Coloproctology. It should contain:
Clinical information: clinical case report, presentation of techniques, methods and a) The article title, in Portuguese and English, which should be concise and infor-
devices. mative; it should express the manuscript content with precision. In addition, the title
Review article: articles from synthesis – systematic review with or without meta- is important for physicians and investigators to find an article in the bibliographical
analysis and integrative review. databases after it is published. Please, be sure the title:
Special article: articles that do not fit the categories above, but of interest to Coloproc- - Is not a question.
tology. They will be produced after an invitation from the Editorial Board. - Does not have colon or any punctuation that separates it in two parts.
- Does not reaffirm the article type. Ex.: Case Report, Review.
Manuscript originality - Does not indicate the type of statistical analysis. Ex.: Multivariate Analysis.
The manuscripts may be in Portuguese and English, and they should be published - Does not include the institution name.
for the first time, submitted exclusively to the Journal of Coloproctology, not to Full name of each author and institutional affiliation.
another journal simultaneously, applicable to their texts, figures or tables, either Name of the department and institution to which the paper should be attributed.
fully or partially, except for preliminary abstracts or reports published in the Annals Name, address, e-mail of the corresponding author in charge.
of Scientific Meetings. Sources of support to study development.
For studies presented in scientific meetings, indicate the meeting name, place, date,
Authorship criteria: type of presentation.
The inclusion of an author in a manuscript submitted for publication is only justified
if he/she has significantly contributed, in an intellectual perspective, to the manus- Abstract
cript elaboration. It is assumed that the author participated in at least one of the The second page should have the abstract, in Portuguese and English, with no
following phases: more than 200 words. For original and review articles, the abstract structure
1) study conception and planning, as well as interpretation of evidences; should highlight the study objectives, methods, main results with significant
2) text elaboration and/or review of preliminary and definitive versions; data and conclusions. For clinical information and special articles, the abstract
3) approval of final version. does not need to be structured as mentioned above, but it should contain
Data collection and indexing are not authorship criteria. Likewise, authors are not important information for the study value recognition, as described in details
technical assistants that perform routine tasks, physicians that refer patients or interpret in the publications:
routine exams and heads of services or departments not directly involved in the study. Haynes RB, Mulrow CD, Huth EJ, Altman DG, Gardiner MJ. More informative abs-
Special acknowledgments can be made to these people. tracts revisited. Ann Intern Med 1990;113:69-76
Ad Hoc Working Group for Critical Appraisal of the Medical Literature. A proposal for
more informative abstracts of clinical articles. Ann Intern Med 1987;106:598-604
Conflict of interest
We request all authors to declare all forms of conflict of interest. Conflict of Interest
Statement (www.jcol.org.br ) Descriptors
The absence of conflict of interest should be declared. The author may refer to: After the abstract, specify three to six terms in Portuguese and English that define
Richard S. Beyond conflict of interest; A common problem; Building a convincing the study theme. These terms should be based on the Health Science Descriptors
case; What should the BMJ be doing? BMJ. 1998;317. (DeCS) published by Bireme and that can be accessed at http://decs.bvs.br, and
the Medical Subject Headings (MeSH) of the National Library of Medicine, at http://
www.nlm.nih.gov/mesh/meshhome.html.
Records of clinical essays
The Journal of Coloproctology supports the guidelines for clinical essay recording
issued by the World Health Organization (WHO) and the International Committee
Manuscript presentation limits according to the type of article
of Medical Journal Editors (ICMJE). Articles on clinical essays will be accepted for Type of article and maxi- Figures
Abstract Main text References
publication only if an ID number has been assigned by one of the Clinical Essay mum number of authors and tables
Records validated according to the criteria established by the WHO and ICMJE, Editorial None 900 5
whose addresses are at http://www.icmje.org. The ID number should be displayed
Original article (8) 200 3000 5 30
at the end of the abstract.
Clinical information (6) 200 1500 3 20
Ethical considerations Review articles (8) 200 5000 8 60
In research involving human beings, the authors should submit a copy of the approval Special articles 200 2000 30
issued by the Research Ethics Committee, recognized by the National Research Ethics
Commission (CONEP), following the guidelines of Resolution CNS 196/96 from the National Editorial: the text should have up to 900 words and 5 references.
Health Council or equivalent agency in the research country.
Researches should indicate whether directly or indirectly involve human beings. Original articles:
The text should have up to 3000 words, not including references and tables.
Manuscript ownership It should have up to 5 tables and/or figures. The number of references should
Manuscripts are under the sole responsibility of authors, who should sign and submit not exceed 30.
the Statement of Authorship and Copyright Transfer. Their structure should contain the following:
Description of procedures Introduction: it should be brief, defining the studied problem and highlighting its
Each article submitted to the Journal of Coloproctology is first analyzed regarding importance and gaps in knowledge.
Method: the methods employed, the population studied, sources of data and selection Figures
criteria should be described in an objective and detailed manner. Insert the protocol The illustrations (pictures, charts, drawings, etc.) should be submitted individually.
number of approval of the Research Ethics Committee and inform that the study They should be consecutively numbered, with Arabic numerals, in the order of their
was conducted according to the ethical standards required. appearance in the text, and they should be clear enough to enable their reproduction.
Results: they should be clearly and objectively presented, describing the obtained Photocopies will not be accepted.
data only, without interpretations or comments, and, for a better understanding, they Statistical analysis
may have tables, charts and figures. The text should complement and not repeat The authors should demonstrate that the statistical procedures used in the study
what is described in the illustrations. were not only appropriate to test the study hypotheses, but also correctly interpre-
Discussion: it should be limited to the obtained data and results, emphasizing the ted. The levels of statistical significance (ex. p<0.05; p<0.01; p<0.001) should be
new and important aspects observed in the study and discussing the agreements mentioned.
and disagreements with previously published studies.
Conclusion: it should correspond to the study objectives or assumptions, based on Abbreviations
the results and discussion, aligned with the title, proposition and method. Abbreviations should be indicated when they first appear in the text. After that, the
full name should not be repeated.
Clinical information
Clinical case reports, presentation of technical notes, methods and devices. They Drug name
should address questions of interest to Coloproctology and related specialties. The generic names of drugs should be used.

Their structure should contain the following Acknowledgements


Introduction: it should be brief and show the theme relevance. They should include collaborations of people, groups or institutions that deserve
Presentation of the clinical case, or technique, or method, or device: it should be recognition, but that are not considered authors, as well as acknowledgements for
described with clarity and objectiveness. It should present significant data for Co- financial and/or technical support, etc.
loproctology and related specialties, and have up to five figures, including tables.
Discussion: it should be based on the literature. References
The text should not exceed 1500 words, not including references and figures. Patients’ They should be consecutively numbered in the order of their appearance in the text
initials and dates should be avoided, showing only relevant laboratorial exams for and identified with Arabic numerals. They should be presented according to the
diagnosis and discussion. The total number of illustrations and/or tables should not “Vancouver Style”. The titles of journals should be abbreviated according to the style
exceed 3 and the limit of references is 20. When the number of presented cases presented by the List of Journal Indexed in Index Medicus, of the National Library of
exceed 3, the manuscript will be classified as a Case Series, and the rules for original Medicine, which can be accessed at http://www.nlm.gov/tsd/serials/lji.html.
articles should be applicable. The authors should be sure that in-text citations of references are included in the list
of references with exact dates and correctly spelled names of authors. The accuracy
Review articles: of references is the authors’ responsibility. Personal notes, unprecedented studies
Systematic review: broad research method, conducted through a rigorous synthesis or studies in progress may be cited when really required, but should not be included
of results from original studies, either quantitative or qualitative, with the purpose in the list of references; only cited in the text or footnotes.
of clearly answering a specific question of relevance to Coloproctology and related Cite up to six authors for each reference.
specialties. It should include the search strategy of original studies, the selection If any reference has more than six authors, cite the six first names, followed by
criteria for studies included in the review and the procedures used in the synthesis of “et al.”.
results obtained from reviewed studies, which may or may not include meta-analysis. We request texts with lean writing style. Shorter texts involve shorter revision and
Integrative review: research method that presents the synthesis of multiple published formatting times, and have higher chances of quick publication.
studies and enables general conclusions regarding a specific area of study, contri-
buting to enhanced knowledge of the investigated theme. It should follow standards Checklist (www.jcol.org.br)
of methodological rigor, clarity of result presentation, enabling the reader to identify For improved process and enhanced publication quality, we offer a checklist for
the real characteristics of studies included in the review. Integrative review phases: your self-evaluation.
elaboration of a guiding question, search strategy, data collection, critical analysis of
included studies, integrative review presentation and result discussion. Submission
The text should not exceed 5000 words, not including references and tables. The total Articles may be submitted using one of the three submission forms below:
number of illustrations and tables should not exceed 8. The number of references
should be limited to 60. Online submission
The article should be sent directly via website http://submission.scielo.br/index.
Special articles php/jcol/index
They should have up to 2000 words and 30 references.
In all categories, in-text citation of authors should be numerical and sequential, using 2 - Submission via E-mail
superscript Arabic numerals in parentheses, avoiding the indication of authors’ names. The article should be sent with the following:
In-text citations and references mentioned in legends of tables and figures should - Checklist
be consecutively numbered in the order of their appearance in the text, with Arabic - Statement of Authorship and Copyright Transfer
numerals (index numbers). Only the reference number should be included, without - The Research Ethics Committee’s approval
further information. - Conflict of Interest statement
To: jcoloproctol@sbcp.org.br
Tables
Each table should be submitted in a separate sheet. The tables should be consecu-
tively numbered, with Arabic numerals, in the order of their appearance in the text, Via Email to:
with a proper title. They should be cited in the text, without duplication of information. SBCP
Tables, with their titles and footnotes, should be self-explanatory. Tables from other Av. Marechal Câmara, 160 - sala 916 - Ed Orly
sources should bring the original references in footnotes. 20020-080 - Rio de Janeiro - RJ – Brasil
Original Article

Oxidative stress and changes in the content and pattern of tissue


expression of β-catenin protein in diversion colitis
Carlos Augusto Real Martinez1, Fabiano Marcelo de Fabris2, Camila Morais Gonçalves da Silva3,
Murilo Rocha Rodrigues4, Daniela Tiemi Sato4, Marcelo Lima Ribeiro5, José Aires Pereira6

Adjunct Professor of the Postgraduate Program of Health Sciences at Universidade São Francisco (USF) – Bragança
1

Paulista (SP), Brazil. 2Master’s Postgraduate Program of Health Sciences at USF – Bragança Paulista (SP), Brazil.
3
Master’s degree in Health Sciences in the Postgraduate Program of Health Sciences at USF – Bragança Paulista (SP),
Brazil. 4Medical student at USF – Bragança Paulista (SP), Brazil. 5Doctor in Pharmacology at Universidade Estadual de
Campinas (UNICAMP); Assistant Professor of the Postgraduate Program of Health Sciences at USF – Bragança Paulista
(SP), Brazil. 6Master’s degree in Pharmacology at USF; Assistant Professor of Pathology at the Medical School of USF –
Bragança Paulista (SP), Brazil.

Martinez CAR, Fabris FM, Silva CMG, Rodrigues MR, Sato DT, Ribeiro ML, Pereira JA. Oxidative stress and changes in the content and
pattern of tissue expression of β-catenin protein in diversion colitis. J Coloproctol, 2012;32(4): 343-358.
ABSTRACT: Objective: The aim of this study is to verify if oxidative stress is related to changes in content and pattern of β-catenin protein
expression in an experimental model of diversion colitis. Methods: Sixty Wistar rats were submitted to intestinal bypass. The animals were di-
vided into three groups according to the sacrifice to take place in six, 12 and 18 weeks. For each group, five animals only underwent laparotomy
(control). The presence of colitis was diagnosed by histological study, and its severity, by inflammation grading scale. Cellular oxidative stress
was measured by comet assay. Tissue expression of β-catenin protein was analyzed by the immunohistochemistry and quantification of its
tissue content by computerized morphometry. Statistical analysis was performed with the Student’s t-test, median, Mann-Whitney, ANOVA
and Kruskal-Wallis, adopting a significance level of 5% (p <0.05). Results: Colon segments without fecal stream developed colitis, which
worsened with time of exclusion. Segments without fecal stream suffer higher levels of oxidative stress when compared to those with stream,
and it worsens with time of exclusion. The levels of cellular oxidative stress are directly related to the degree of inflammation. The total con-
tent of β-catenin in segments without fecal stream reduces after six weeks, and does not vary thereafter. The content of β-catenin in the apical
portion of the colon crypts decreases with time, whereas in the basal region, it increases. The total content of β-catenin is inversely related
to the degree of inflammation and levels of tissue oxidative stress levels. Conclusion: There are changes in tissue content of E-cadherin and
increased expression of β-catenin in proliferative regions of colonic crypts, related with oxidative tissue stress.
Keywords: colon; colitis; oxidative stress; adherens junctions; cell adhesion molecules; catenins; comet assay; immunohistochemistry;
fatty acids, volatile; rats.

Resumo: Objetivo: O objetivo do presente estudo é avaliar a relação entre estresse oxidativo e conteúdo tecidual de β-catenina em
modelo experimental de colite de exclusão. Métodos: Sessenta ratos Wistar foram submetidos à derivação intestinal e divididos em
três grupos experimentais segundo o sacrifício ser realizado em 6, 12 e 18 semanas. Para cada grupo, cinco animais foram submetidos
apenas a laparotomia (controle). A colite foi diagnosticada por estudo histológico, enquanto sua intensidade por escala de graduação
inflamatória. Os níveis de estresse oxidativo foram mensurados pelo ensaio cometa, enquanto a expressão e o conteúdo tecidual de
β-catenina por imunoistoquímica e morfometria computadorizada, respectivamente. Os resultados foram analisados pelos testes t de
Student, Mann Whitney, ANOVA e Kruskal-Wallis, estabelecendo-se nível de significância de 5% (p<0,05). Resultados: Nos segmen-
tos sem trânsito fecal ocorre desenvolvimento de colite que piora com o tempo de exclusão. Segmentos sem trânsito sofrem maiores

Study carried out at the Postgraduate Program of Health Sciences at Universidade São Francisco – Bragança Paulista (SP), Brazil.
Financing source: São Paulo Research Foundation (FAPESP) – Project number: 2010/12492-7
Conflict of interest: nothing to declare.

Submitted on: 03/07/2012


Approved on: 12/11/2012

343
J Coloproctol Oxidative stress and changes in the content and pattern of tissue expression of β-catenin Vol. 32
October/December, 2012 protein in diversion colitis Nº 4
Carlos Augusto Real Martinez et al.

níveis de estresse oxidativo quando comparados àqueles com trânsito, piorando com o tempo de exclusão. Os níveis de estresse oxida-
tivo encontram-se diretamente relacionados a piora da inflamação. O conteúdo total de β-catenina no cólon sem trânsito reduz após seis
semanas de exclusão. O conteúdo de β-catenina no ápice das criptas cólicas diminui com o tempo, enquanto na região basal, aumenta.
O conteúdo total da β-catenina encontra-se inversamente relacionado ao grau de inflamação e aos níveis de estresse oxidativo.
Conclusão: Existe redução no conteúdo de β-catenina, principalmente no ápice das glândulas cólicas e aumento nas regiões basais,
relacionadas à piora do estresse oxidativo.
Palavras-chave: colo; colite; estresse oxidativo; junções aderentes; moléculas de adesão celular; cateninas; ensaio cometa; imunoistoquímica;
ácidos graxos voláteis; ratos.

INTRODUCTION matory response1. Among the ICJs, AJs are the most
compromised ones in patients with inflammatory
The colonic mucosa is one of the most perfect bowel diseases (IBD)16. Important changes in con-
functional barriers of the human body1. It is formed tent and chemical structure of proteins that form JA
by a single cell layer, separating the intestinal content, were described in patients with ulcerative rectoco-
which is rich in bacteria, from the internal sterile intes- litis (URC)5,8,17,18.
tinal wall. The maintenance of this efficient function- Studies demonstrated that the tissue content and lo-
al barrier is determined by a series of defense mecha- cation of the proteins that constitute AJs are modified in
nisms. When they act together, they protect the internal the tissue that is chronically inflammed in IBD, URC,
intestinal wall from bacterial invasion1. The main com- colorectal cancer (CRC), CRC associated with URC, and
ponents of this defense system are represented by the in models of experimental colitis13,14,19-23. A strong rela-
mucus that covers the mucosal surface, the colonocyte tion was found between the reduced tissue expression of
apical and basolateral membranes, the adhesion sys- β-catenin protein and the worsening of URC24. The im-
tems formed by intercellular junctions, desmosomes, portance of β-catenin protein in the early stages of the
hemidesmosomes and, finally, the basal membrane1,2. development of colitis is more evident when it is dem-
From the defense systems, the intercellular junc- onstrated that knockout mice (Min-/-), for the genes that
tions (ICJ) represent one of the most efficient mecha- translate the AJ proteins, develop severe forms of colitis
nisms1,3. They are formed by three types of junctions: at early stages25. These findings present the existing
occluding (OJ), adherens (AJ) and communication relation between β-catenin protein tissue changes and
(CJ). The OJs are located in the apical portion of the the worsened colitis24,26,27. However, the molecular
intercellular space and seal the space between neigh- mechanisms that determine the ruptured ICJs in pa-
boring cells, thus preventing the migration of small tients with URC are not yet enlightened. Among the
molecules3-6. The AJs, located right below the OJs, possibilities, it has been recently shown that oxygen
connect the cytoskeleton of a cell to its neighbor, and free radicals (OFR) can be the molecules responsible
they also play a relevant role in the mechanisms of for the initial damage to the mucosal barrier1. Since
cellular signalling7. They are formed by a transmem- they are toxic radicals, its excessive production is able
brane protein called E-cadherin and by cytoplasmatic to damage the ICJs, allowing the migration of bacteria
proteins of the catenin family (α, β, γ)8. Finally, the through the intercellular space1. Experimental studies
CJs control the transmission of electrical and chemical confirmed the harmful role of OFR by demonstrating
signals from one cell to the other, making a complex that the exposure of colonic mucosa to hydrogen per-
cell communication network9-11. oxide (H2O2), which is a strong OFR producer, enables
For the development of colitis, it is necessary that the appearance of colitis28,29. When demonstrated that
epithelial barrier mechanisms be compromised12-15. OFR can cause damage to the epithelial barrier, it is
However, the rupture of these defense systems should reasonable to suppose that they can also damage the
be the first stage, which comes before the bacterial in- AJs in the early stages of colitis1,30,31. However, most
vasion of the submucosa and the subsequent inflam- experimental models of colitis do not allow the analy-

344
J Coloproctol Oxidative stress and changes in the content and pattern of tissue expression of β-catenin Vol. 32
October/December, 2012 protein in diversion colitis Nº 4
Carlos Augusto Real Martinez et al.

sis of this possibility, since it causes damage to the Brasileiro de Experimentação Animal (COBEA). This
colonic barrier due to the exposure of the mucosa to project was approved by the Animal Research Ethics
harmful substances, such as trinitrobenzene sulfonic Committee of Universidade São Francisco, Bragança
acid (TNBS), acetic acid or dextran sulfate sodium Paulista (SP).
(DSS)26,30,32. Actually, these models do not reproduce
the initial molecular mechanisms that cause the muco- Animals used for experimentation and
sal barrier to rupture in the different forms of colitis. experimental groups
However, they confirm that the integrity of defense Sixty SPC male Wistar rats, whose weight var-
mechanisms is indispensable to stop bacterial infil- ied from 300 to 350 g and with mean age of 4 months
tration, thus keeping the local immune response at a were used. Three experimental groups with 20 ani-
quiescent state33. Therefore, the ideal experimental mals were randomly constituted and divided accord-
model to confirm the initial stages of colitis should ing to the sacrifice to take place in 6, 12 and 18 weeks
cause damage in the defense systems, and among after surgical intervention. Each group was then di-
them, in ICJs, just with changes in the metabolism vided into two subgroups called experiment and con-
of epithelial cells, without damaging the functional trol. In the experiment group, with 15 animals, bowel
barrier artificially32. stream was bypassed in the left colon, while in the
Glotzer et al.34, in 1981, described the develop- control group, composed of five rats, there was only
ment of an inflammation in the colonic mucosa with- laparotomy, without stream bypass. Animals were
out fecal stream, similar to what happens with URC, kept in individual cages during the experiment, in a
and this condition is called diversion colitis (DC). DC climatized environment, with temperature, light, hu-
appears due to the interruption in the supply of short- midity and noise control. For surgery, they were anes-
chain fatty acids (SCFA), main energetic substrate for thetized with 2% xylazine hydrochloride (Anasedan®)
the oxidative metabolism of epithelial cells in the co- and ketamine chloride (Dopalen®), 0.1 mL/100 g, ad-
lonic mucosa32,35,36. It has been demonstrated that cells ministered via intramuscular in the left back paw.
from the colonic epithelium without fecal stream pro-
duce increasing amounts of OFR with time of exclu- Surgical technique
sion, and that the resulting oxidative stress is related After the anesthesia, a trichotomy of the anterior
to the epithelial lesion31-33,37-40. It is possible that the abdominal region was performed, followed by a medi-
lesion in the colonic mucosa, which triggers DC, is al longitudinal 3 cm long incision and posterior open-
related to the ruptured ICJs, and especially AJs, which ing of the abdominal wall by layers. The left colon
is a result of the increased production of OFR by the was identified and cut 4cm above the Peyer’s patch,
changes in the oxidative cellular metabolism. and the proximal segment was exteriorized as termi-
Although it has been demonstrated, in models nal colostomy in the left hypocondrium, fixated to
of chemically induced colitis, that there are changes the skin with separate stitches made with absorbable
in the expression of β-catenin protein in the sore mu- monofilament thread. The caudal segment of the large
cosa, the evaluation of content and changes in the pat- intestine was catheterized and irrigated with 40 mL of
tern of the protein expression has not been studied in 0.9% physiological solution at 37ºC, until the effluent
experimental models of DC. Thus, the objective of drained by the anus did not present with stool. After
this study is to check if there is a relation between the the irrigation, the distal colon was exteriorized, like a
oxidative stress and the changes in content and pat- distal mucus fistula in the left iliac fossa. Afterwards,
tern of β-catenin protein expression in an experimen- the abdominal wall was closed with two suture lay-
tal model of DC. ers (aponeurosis and skin). After the surgery, the rats
were kept warm in an incubator, and after anesthesia
METHOD recovery, they were placed in individual cages previ-
ously identified with the number of the animal and the
This study obeys the Federal Law 11,794, experimental group to which they belonged. The in-
from October 8, 2008, and the guidelines of Colégio take of standardized water and rat food was allowed

345
J Coloproctol Oxidative stress and changes in the content and pattern of tissue expression of β-catenin Vol. 32
October/December, 2012 protein in diversion colitis Nº 4
Carlos Augusto Real Martinez et al.

after they regained consciousness. They remained in they were included in paraffin blocks and submitted
individual cages until the day of sacrifice, and no addi- to two longitudinal cuts, 5 μ thick, for the histologi-
tional care was taken in relation to the surgical wound cal and immunohistochemical studies. The slides des-
and stomas. No antibiotics or analgesic were adminis- tined to diagnose colitis and to grade the inflammation
tered, and during postoperative follow-up it was nec- score were stained with hematoxylin-eosin (HE). For
essary to sacrifice one animal, which was replaced, the evaluation of colitis severity, the grading system
due to bowel obstruction caused by internal hernia. for inflammation was used, being previously proposed
and validated, which considers the presence of ero-
Material collection sions and ulcers on the colonic mucosal surface and
The day before the date scheduled for material the intensity of the inflammatory cell infiltrate41.
collection, the animals were fasting for 24 hours, ex-
cept for water. For the removal of colonic fragments to Immunohistochemical technique
be analyzed, they were under anesthesia with the same For the research of tissue β-catenin protein ex-
technique previously described. After the cavity was pression, histological cuts obtained from all the sam-
reopened, the whole colon with stream was removed, ples were analyzed (colons with and without stream
including colostomy, and the caudal segment, with- and left colon of the control group) in the three peri-
out fecal stream, involving the anus. In the animals ods of exclusion proposed. After being deparaffinized,
of the control subgroup, the whole large intestine, the cuts were rehydrated in alcohol at decreasing con-
including the anus, was resected. Immediately after centrations and washed in distilled water. Afterwards,
removal, the colonic segments were opened longitu- they were submersed in PBS (0.05 M, pH 7.2) for
dinally by the anti mesocolic border and washed care- 10 minutes and the dry slides at ambient temperature.
fully with warm physiological serum to remove fecal The endogenous peroxidase activity was blocked with
residue. Two fragments were taken from each colonic 3% H2O2 at ambient temperature for 10 minutes, fol-
segment, and each of them were 20 mm long, being lowed by another wash with PBS for more 10 minutes.
one of them sent to histological and immunohisto- Afterwards, the antigen recovery with 10 mM sodi-
chemical analysis, and the other one to determine the um citrate was performed (pH 6.0) in bath water at
tissue levels of cellular oxidative stress by the comet 95ºC for 45 minutes. For the study of tissue β-catenin
assay. In the animals of the control group, the same expression, the anti-β-catenin primary antibody was
number of fragments was collected from the left co- used (Dako — Denmark A/S, Glostrup, DE  — Ref.
lon, also 20 mm long, 10 mm above the Peyer’s patch. M3539, Lot 10025022) diluted at 1:50 in bovine al-
For those addressed to measuring the levels of cellular bumin (1%). The slides were covered with 100 µL
oxidative stress, the mucosa was separated from the of the solution containing the primary antibody and
other layers of the wall by microdissection. The  re- stored at 4ºC for 24 hours. After the conclusion of this
moved part was immediately stored in eppendorf, with stage, they were washed with PBS, incubated with
freezing solution and at -80ºC. the secondary antibody and submitted to the complex
biotin-streptavidin peroxidase staining for 45  min-
Histological analysis utes, prepared with 1:100 dilution in PBS. The slides
For the histological analysis, the fragments of were developed with a solution of diaminobenzidine
colons with and without stream of each animal in the tetrahydrochloride (DAB, 10 mg in 10  mL of PBS
experiment group, and of the left colon of animals in with 3 mL H2O2), which was dropped over the blades
the control group, were fixated onto a flat cork surface and incubated for 3 minutes. Afterwards, they were
with the mucus side facing up. After identification, washed and counterstained with methyl green, and
they were stored in a 10% buffered formaldehyde so- again washed in distilled water. After the counter-
lution, and remained there for 72 hours. After this pe- staining, there was dehydration by immersion in in-
riod, they were washed in running and distilled water, creasing solutions of ethanol and xylene. Finally,
and then dehydrated in successive increasing concen- they were set, labeled and stored in the horizontal
trations of alcohol and clarified in xylene. Afterwards, position for 24 hours.

346
J Coloproctol Oxidative stress and changes in the content and pattern of tissue expression of β-catenin Vol. 32
October/December, 2012 protein in diversion colitis Nº 4
Carlos Augusto Real Martinez et al.

Measuring the content and evaluating the protein, and black represented the rest of the field.
pattern of β-catenin expression The values found for the total content of β-catenin
The presence of β-catenin was considered as pos- were expressed as percentage per field. The final num-
itive when the brownish coloration was diffusely pres- ber adopted for the animals of subgroups control and
ent, with variable intensity regions and fine granular experiment (segments with and without intestinal
distribution in the apical and basolateral membrane, stream) was always represented by median, with the
cytoplasm and cell nucleus. According to the recom- respective standard deviation.
mendation of the manufacturer, the negative control Figure 1A exemplifies the expression of β-catenin
of immunocoloration was performed without the addi- protein in the mucosal layer of the colon with fecal
tion of the primary antibody, and the positive one used stream after 18 weeks of bypass, while Figure 1B
the neoplastic colonic tissue, which is positive for the shows the quantification of protein in the same field
protein. The analysis of the β-catenin expression was shown by Figure 1A, in binary image, using the com-
performed with a common optical microscope, Nikon puter-assisted image processing.
Eclipse DS-50 (Nikon Inc., Osaka, Nippon), with fi-
nal 200x magnification, by an experienced pathologist evaluation of oxidative stress levels
in immunohistochemical techniques. He did not know The quantification of oxidative stress levels by
the origin of the material and objectives of the study. gel electrophoresis of isolated cells (comet assay) was
The photographic documentation was obtained performed according to the previously described tech-
with a video capture camera DS-Fi-50 (Nikon Inc., nique42. Briefly, all the samples from animals in the
Osaka, Nippon), previously attached to the micro- control and experiment groups, with colon with or
scope, and the images were digitized, identified without intestinal stream, underwent triplicate analy-
and filed in a computer. sis. The specimens were incubated in 3 mL of Hank’s
The pattern of expression of β-catenin protein buffered solution (Invitrogen, Carlsbad, CA, USA),
was evaluated according to the place of greater ex- with 5.5 mg of proteinase K (Sigma Chemical, CO, St.
pression along the colonic crypts (apex or base), clas- Louis, MO, USA) and 3 mg collagenase for 45 minutes
sifying the intensity of immunocoloration in each of at 37ºC for the isolation of colonic mucosal cells. Parts
the sites into crosses: + mild expression; ++ moder- were removed and the cellular viability was assessed.
ate expression; and +++ intense expression. The pat- Finally, the fluorescein diacetate (FDA) / ethidium bro-
tern of final tissue expression for each slide was the mide (EtBr) method (Sigma-Aldrich, St. Louis, MO,
median found after reading three different fields with USA) was used. The solution of cell coloration was
at least three full and contiguous crypts. The grading prepared immediately before its use, and it contained
intensity expressed into crosses was performed by 30 mL of FDA in acetone (5 mg/mL), 200 mL of EtBr
two independent observers, and the conflicting results in phosphate buffered solution (PBS; 200 mg/mL), and
were analyzed afterwards. 4.8 mL of PBS.
The total tissue content of β-catenin was mea-
sured by computer assisted image analysis (comput-
A B
erized morphometry) in three fields, which showed,
in a longitudinal cut, three contiguous and full crypts.
The selected image was captured by the camera, pro-
cessed and analyzed by the software NIS-Elements
(Nikon Inc., Osaka, Nippon). For the quantification
of β-catenin content in each chosen Field, in 100 mi-
crometers rgb wavelength filter was selected contain-
Figure 1. (A) Pattern of β-catenin expression in the mucosa of
ing the brown color (which identified the tissue immu-
the colonic segment with fecal steram after 18 weeks of intestinal
noexpression of β-catenin). Afterwards, the software bypass (immunohistochemistry 400x). (B) Tissue β-catenin content
transformed the captured content into a binary image (white color) by binary analysis of computer assisted image in the
in which the white color represented the presence of same field described in Figure 1A (400x).

347
J Coloproctol Oxidative stress and changes in the content and pattern of tissue expression of β-catenin Vol. 32
October/December, 2012 protein in diversion colitis Nº 4
Carlos Augusto Real Martinez et al.

The suspension containing isolated cells was β-catenin, comparing animals from the control and ex-
isolated, and then mixed to 25 mL of stain solution, periment groups. The median test was used to analyze
placed over the slide, covered with glass slides and the intensity of expression of β-catenin protein in the
read in fluorescence microscope. The nuclei of viable apical and basal regions of the colonic glands in con-
cells were stained green, and those of unviable cells trol and experiment groups. The inflammation grading
were stained red. After the analysis of the slides, only scale in the different times of exclusion was assessed
tissue samples that presented more than 75% of the by the Main-Whitney test. We applied the ANOVA
viable cells were selected. For the alkaline version test for the analysis of variance in relation with time
of the comet assay in the viable samples, 15 ml of of exclusion of stream and total tissue protein content.
the previously obtained cell suspension were mixed Kruskal-Wallis was used to evaluate the variation in
to the  0.5% low melting point agarose placed onto the protein expression in apical and basal regions of
a blade and covered with a glass slide. Finally, they the colonic glands in relation to the time of experiment.
were immersed in cold lysis solution (2.5 M NaCl, The established significance level was 5%
100 mM EDTA, 10 mM Tris, 1º SDS, pH10 with 1% (p<0.05) for all the tests. Statistical analysis was per-
Triton X-100 and 10% DMSO) and remained at 4ºC formed with the software SPSS (SPSS Inc., Chicago,
for 12 hours. Subsequently, they were exposed to an USA version 13.0).
alkaline buffer (1 mM EDTA and 300 mM NaOH, pH
13.4) for 40 minutes at 4ºC. Electrophoresis was per- RESULTS
formed in this buffer, inside the refrigerator, at 4ºC,
for 30 minutes at 25 V and 300 mA. After electropho- Figure 2A shows the epithelial surface of the
resis, the slides were neutralized (0.4 M Tris, pH 7.5), colonic mucosa with fecal stream, while Figure 2B
stained with Sybr Safe (Invitrogen, Carlsbad, CA, shows the colon without stream after 18 weeks of ex-
USA) and analyzed at the fluorescence microscope. clusion. It was possible to observe that in segments
The whole material was processed and verified at the without stream the colonic glands were dilated, with
same time to avoid technical variations. Two hundred a great amount of mucus in the lumen. The caliciform
cells were randomly selected (100 of each intestinal cells are dilated and replace the cells with absorptive
segment, with and without stream and of animals in function in the apical surface, which no longer pres-
the control group), which were analyzed with the ent the same juxtaposition by the edema in the stroma,
Komet 5.5 software (Kinetic Imaging, NY, USA). So, thus configuring an aspect similar to a “brush border”.
the value of tail moment (TM) was obtained, and the Figure 3 indicates, by mean and the respective
means were determined. According to the manufac- standard deviation, the values found for the inflamma-
turer’s manual, TM is defined as the product between tion score, comparing animals in the control and ex-
the fragments of tail DNA and the mean distance of periment subgroups (segments with and without fecal
migration of the comet tail, which reflects the exten- stream) in the different proposed periods of exclusion.
sion of the rupture of DNA helix (oxidative stress). We found higher score for those without stream, re-
The value can be quantified by the intensification of gardless of considered time of exclusion. The inflam-
image and computational analysis. For each animal, mation score in the colon without stream after 6 weeks
the mean obtained from the reading of 100 cells of was 3±0.40, while after 12 and 18 weeks of bowel ex-
each colonic segment performed by the same techni- clusion these values were 8±0.37, presenting statistical
cian, was used. The technician did not know about the significance when compared to the colon with stream
origin of the material and the objectives of the study. and to the animals in the control group (p<0.01). The
colon without stream presented increased inflamma-
Statistical method tion score in sacrificed animals in 12 and 18 weeks
The results were described by mean with the re- in relation to those sacrificed after 6 weeks (p<0.05).
spective standard deviation. The Student’s t-test was Figures 4A and 4B show, respectively, show the
used to assess the total content of oxidative stress, and tissue expression of β-catenin protein in the colonic
the Mann-Whitney test analyzed the total content of mucosa with and without fecal stream after 12 weeks

348
J Coloproctol Oxidative stress and changes in the content and pattern of tissue expression of β-catenin Vol. 32
October/December, 2012 protein in diversion colitis Nº 4
Carlos Augusto Real Martinez et al.

of fecal exclusion, while Fgures 4C and D present the When the total β-catenin tissue content was consid-
protein expression in segments with and without fecal ered in the glands of the colonic epithelium, a reduc-
stream after 18 weeks of exclusion. It is observed that tion in the segments without fecal stream was ob-
in the colon with stream (Figures 4A and C), the greater served in comparison to the colon with stream and the
protein expression is concentrated in cells of the apical animals of the control group after only six weeks of
surface of colonic glands, while the cells of deeper re- fecal exclusion. The total protein content in the colon
gions present with lower expression. On the contrary, in without stream did not range with the time of exclu-
segments without fecal stream (Figures 4B and D), the sion (Table 1).
expression of β-catenin protein is more intense in
the deep portions of the Lieberkühn glands, exactly
in the proliferative regions of colonic glands. A B
Figure 5 indicates, in average, with the respec-
tive standard deviation, the total tissue content of
β-catenin, comparing the control and experiment sub-
groups (with and without fecal stream) in the differ-
ent periods of fecal stream exclusion, measured by
computerized morphometry. In colonic glands, after
six weeks of intestinal exclusion, the mean percentage Figure 2. (A) Colonic mucosa with stream after 18 weeks of
of β-catenin tissue content was 23.30±3.00%, while fecal stream diversion (hematoxylin-eosin 200x); (B) Colonic
in animals submitted to bypass from 12 to 18 weeks mucosa without fecal stream after 18 weeks of intestinal diversion
it was 26.79±4.85% and 25.52±3.08%, respectively. (hematoxylin-eosin 200x).

escore 9
** **
8

7
Inflammation grade

0
6 weeks 12 weeks 18 weeks

Control With stream Without stream

** Significant (without stream X control and with stream) (p<0.01). Mann-Whitney test.
Figure 3. Inflammation score comparing the control and experiment subgroups (colons with and without stream) in the different periods
of exclusion.

349
J Coloproctol Oxidative stress and changes in the content and pattern of tissue expression of β-catenin Vol. 32
October/December, 2012 protein in diversion colitis Nº 4
Carlos Augusto Real Martinez et al.

Figure 4. (A) β-catenin expression in the mucosa of the colonic segment with fecal stream after 12 weeks of intestinal bypass
(immunohistochemistry 200x); (B) Protein expression in the mucosa of the colonic segment without fecal stream after 12 weeks of intestinal
bypass (immunohistochemistry 400x); (C) β-catenin protein expression in the mucosa of the colonic segment with fecal stream 18 weeks
after surgery (immunohistochemistry 400x); (D) Expression in the colonic mucosa without fecal stream 18 weeks after intestinal bypass
(immunohistochemistry 400x).

Table 1. Variation of cellular oxidative stress levels and β-catenin content in the colon without fecal stream in
relation to the different times of exclusion.
Colon without stream
Mean±SD.
6 weeks 12 weeks 18 weeks p-value
Oxidative stress (TM) 3.24±0.44 3.74±0.40 4.37±0.32 0.0007*
β-catenin 23.13±3.02 26.79±4.95 25.52±3.08 0.49
TM: Tail moment; SD: standard deviation; *Significant; ANOVA test.

Figure 6 shows, in median, the intensity of the sion, there was a significant reduction in the content
variation of β-catenin protein expression in the api- of β-catenin in the apical regions of colonic crypts, es-
cal regions of the colonic mucosal crypts in animals pecially after 12 and 18 weeks of exclusion (p<0.05).
of control and experiment groups (segments with and The protein content in the apical portions of the colonic
without fecal stream) in different times of exclusion. glands in the segments without stream did not show
It was observed that, regardless of the time of exclu- variation according to the time of exclusion.

350
J Coloproctol Oxidative stress and changes in the content and pattern of tissue expression of β-catenin Vol. 32
October/December, 2012 protein in diversion colitis Nº 4
Carlos Augusto Real Martinez et al.

35

30
*
25
Percentage per field

20

15

10

0
6 weeks 12 weeks 18 weeks

Control With stream Without stream


*without stream<Control and Proximal. (p<0.05). Mann-Whitney test.
Figure 5. Total β-catenin tissue content measured by computerized morphometry comparing animals from the control and experiment
subgroups (colons with and without stream) in the different periods of intestinal stream exclusion.

3.5

2.5
* * *
2
Escore

1.5

0.5

0
Control With stream Without stream

6 weeks 12 weeks 18 weeks


*Without stream 6, 12 and 18 weeks<control and with stream (p<0.05). Median test.
Figure 6. Variation of β-catenin tissue content in the apical region of the crypts, comparing the animals in control and experiment subgroups
(colons with and without stream) in the different periods of intestinal stream exclusion.

351
J Coloproctol Oxidative stress and changes in the content and pattern of tissue expression of β-catenin Vol. 32
October/December, 2012 protein in diversion colitis Nº 4
Carlos Augusto Real Martinez et al.

On the other hand, Figure 7 shows, in median, each other and to the basal blade11,43. These cells are
the variation of intensity in the β-catenin protein ex- gathered to one another by systems of cell-cell adhe-
pression in the basal regions of the colonic mucosa sion, which support most of the mechanical stress and
glands in animals from the control and experiment also work as a functional barrier. The specialized ICJs
groups (with and without fecal stream) in the dif- are located in places where there is no contact between
ferent considered times of exclusion. The increased two cells, or between one cell and the extracellular
β-catenin contentin the deeper regions of colonic matrix. In order for the cells to function in an inte-
glands was observed, regardless of time of exclusion, grated manner in a compact set, the already mentioned
and such increase was even more significant after 12 specialized ICJs, formed by group systems, are need-
and 18 weeks of exclusion. The increased protein ed43. There are three functional groups of ICJ: The OJs
content in the basal regions of the crypts was also ob- or zonula occludens, the AJs or the zonula adherens,
served after six weeks of exclusion, when these val- and the communicating or electrotonic ones. There are
ues started to stabilize. also specialized junctions in the adhesion of the cell
Figure 8 shows, in mean, with the respective with the extracellular matrix or basal membrane, rep-
standard deviation, the values found for the levels of resented by hemidesmosomes. All of these ICJs are
tissue oxidative stress, comparing the animals in the composed by different types of proteins, which have
control and experiment subgroups (with and without specific roles inside the complex that form them.
fecal stream) in the different times of fecal exclu- The AJs connect the internal cytoskeleton of a
sion. The levels of oxidative stress were similar in cell to its neighbor, by means of a protein complex
the subgroup control and in segments with stream, re- formed by the proteins in the cadherin, catenin, vin-
gardless of the considered time of exclusion. In the culin and actin families11. The AJs are also related to
colon without stream for 6 weeks, these values were the proteins of the intracellular signaling pathway,
3.24±0.44 TM, while, after 12 and 18 weeks of exclu- enabling them to participate in the communication
sion, they were 3.74±0.40 TM and 4.37±0.32 TM, re- mechanisms that are present inside the neighboring
spectively. The results showed that the levels of tissue cells, and the cadherins are the main proteins that form
oxidative stress were higher in the segments without AJs11. These are proteins dependent on calcium that
stream when compared to those with stream and to play an important role in intercellular adhesion, tis-
the subgroup control, and time of exclusion was not sue differentiation, polarization and epithelial stratifi-
relevant (p=0.0001). Table 1 indicates that levels of cation44. The cytoplasmic domain of E-cadherin joins
oxidative stress in the colon without stream increase one or more intracellular anchor protein, represented
with time of exclusion (p=0.0007). especially by β-catenin, while the extracellular do-
Table 2 presents the variation of β-catenin content main interacts with the domain of another homolo-
between the apical and basal regions of the colonic crypts gous molecule, from the neighbor cell11,43.
in segments without fecal stream, in relation to time of In order for the occurrence of the anchor between
exclusion. The variation in the pattern  of expression the E-cadherin and the actin protein, which is the most
of the tissue protein in the basal region of colonic glands important component of the cellular cytoskeleton, pro-
was observed, in comparison to colons without stream teins from the catenin family (α-catenin, β-catenin e
for 6 weeks and those for 12 and 18 weeks (p=0.04 and γ-catenin) are essential11. β-catenin is translated from
p=0.04, respectively). the transcription of the CTNNB1 gene, located on the
chromosome 8q32, with molecular weight of 88 kDa.
DISCUSSION The β-catenin isoform presents double cell function, be-
cause besides participating in the mechanisms of adhe-
Cell adhesion is a primary characteristic of the sion between two neighboring cells, it is important for
architecture of most of the tissues in the human body. the Wnt signaling11. When the protein system that form
The epithelium that covers the digestive tube is formed the AJs in the intercellular space breaks, there is the ac-
by an isolated layer of specialized cells, with absorp- cumulation of free β-catenin in the cell cytosol. With
tion and secretion functions, intimately adhered with the increased concentration of the protein inside the

352
J Coloproctol Oxidative stress and changes in the content and pattern of tissue expression of β-catenin Vol. 32
October/December, 2012 protein in diversion colitis Nº 4
Carlos Augusto Real Martinez et al.

3.5
** **
3

2.5
*
2
Escore

1.5

0.5

0
Control With stream Without stream
6 weeks 12 weeks 18 weeks
*Without stream 6 weeks > with stream 12 weeks (p<0.05); **Without stream 12 and 18 weeks > with stream
12 and 18 weeks (p<0.01). Median test
Figure 7. Variation of β-catenin tissue content in the deep region of the crypts, comparing the animals in control and experiment subgroups
(colons with and without stream) in the different periods of intestinal stream exclusion.

5
Arbitraty **
Units
4.5
**
4
**
3.5
Tail moment

3
2.5
2
1.5
1
0.5
0
6 weeks 12 weeks 18 weeks

Control With stream Without stream


**Significant (without stream X control and with stream) (p<0.01). Student’s t-test
Figure 8. Levels of cell oxidative stress comparing the control and experiment subgroups (colons with and without stream) in the different
times of exclusion.

353
J Coloproctol Oxidative stress and changes in the content and pattern of tissue expression of β-catenin Vol. 32
October/December, 2012 protein in diversion colitis Nº 4
Carlos Augusto Real Martinez et al.

Table 2. Variation of β-catenin content values in the of E-cadherin causes the accumulation of β-catenin
apical and basal regions of colonic glands in the segments cytoplasmic content, thus stimulating cellular divi-
without fecal stream in relation to the different times of sion1,11,20,21,46. The OFRs can also dissociate the junc-
exclusion. tions between E-cadherin and β-catenin in the cyto-
Colon without stream sol by a dependent tyrosine-kinase mechanism, which
Median leads to the cytoplasmic accumulation of β-catenin44.
(crosses) It was experimentally shown that the migration of
Apical Basal p-value
β-catenin from its membranous cytoplasmic domain
6 weeks ++ + to the inner nuclear cell is considered as the first event
12 weeks ++ +++ 0.04* in the animal models of chemically induced colitis,
18 weeks ++ +++ 0.04* which comes even before the neutrophilic infiltra-
*Significant; Kruskal-Wallis test.
tion19,47,48. However, it is difficult to demonstrate this
possibility in the models of chemical colitis, since the
cytosol, the ubiquitin system is unable to degrade the rupture of AJs could result from the action of harmful
β-catenin in the proteasome, and this way the excess agents, such as TNBS and DSS. With the DV mod-
protein migrates inside the nucleus and joins the gene el proposed in this study, it is possible to observe the
transcription factors, thus activating the transcription of role of OFR in the rupture of AJs30. Recent evidence
genes related to cell proliferation, such as C-MYC and shows that in experimental models of DC, despite the
cyclin-17,8,11,13. Therefore, β-catenin, besides being es- non existence of intestinal epithelium exposure to any
sential to AJs, actively participates in the Wnt signal- toxic substance, there is increased production of OFR,
ing, one of the main mechanisms responsible for the which determines the appearance of colitis by the rup-
induction of cell division. This double functional do- ture of different lines of defense of the colonic muco-
main is important for the renewal of cells in the colonic sal barrier29-31,37-40. Even though the relations between
epithelium, in constant replacement. the changes in content and pattern of tissue expres-
It has been shown that, in patients with URC, sion of E-cadherin and β-catenin in sick patients and
who suffers from constant apoptosis of the superficial experimental models of URC have been subjectively
cells of the colonic epithelium, the β-catenin protein demonstrated, this possibility had not been assessed in
presents more expression in the deep regions of colon- experimental models of DC19,23.
ic glands, where the germinative zone is located, and It is also worth mentioning that the evaluation of
is the main responsible for the process of cell prolif- tissue content of proteins that compose AJs in models
eration13,45. On the contrary, the substantial reduction of colitis is usually subjective, which depends on the
of β-catenin expression in cells of the mucosal surface pathologist’s experience. The possibility to use meth-
of subjects with URC was shown, and in this situation ods of image analysis with the assistance of computers
there is constant cellular death13,22,24. The comparison leads to more accuracy, uniformity and reliability in
between normal and sore tissues in subjects with URC relation to the results, since it quantifies the tissue con-
showed significant reduction of the tissue content of tent of the protein analyzed objectively. The analysis
E-cadherin and β-catenin proteins just in locations in of computer-assisted image, also known as computer-
which the disease is active, but not in normal tisses26. ized morphometry, presents additional advantages in
These results confirm the strong relation between the relation to conventional methods, such as the fast and
rupture of AJs and the development of colitis24. low cost quantitative evaluation of microscopic struc-
Many mechanisms are able to damage the AJs tures37-40. In this study, with the use of computerized
in the colonic epithelium. Among them, the oxidative morphometry, it was possible to determine the tissue
stress stands out20,21,32,45. Studies show that the colonic content of the β-catenin protein objectively, which
mucosa exposed to high concentrations of OFR oxi- enabled more precise comparisons between normal
dizes the Ca++ ions, which keep the E-cadherin mol- and sore tissues38. Computerized morphometry had
ecules together in the intercellular space20. The rupture not been previously used to quantify tissue levels of
of Ca++ molecules degrading the intercellular bridges β-catenin in models of colitis.

354
J Coloproctol Oxidative stress and changes in the content and pattern of tissue expression of β-catenin Vol. 32
October/December, 2012 protein in diversion colitis Nº 4
Carlos Augusto Real Martinez et al.

The evaluation of tissue oxidative stress levels ity, we found higher levels of oxidative stress in these
can also be performed by different techniques. Among segments, which increased with the experiment. It is
the most used ones are the malondialdehyde tissue possible that the increased production of OFR be re-
dosimetry, which is a product of the cell membrane sponsible for the larger number of ulcers, and, conse-
phospholipid peroxidation, the plasmatic and urinary quently, for the higher inflammation score observed in
dose of 8-hydroxyguanosine levels, and the advanced segments without stream after 12 and 18 weeks. When
oxidation protein products29,49. However, these are we measure the tissue levels of oxidative stress in the
sensitive biochemical techniques, subject to varia- segments without stream we observe that they were
tions, and they need a reasonable amount of tissue to directly related to the worst inflammation score. The
be executed42. With the advent of the single cell gel high levels of oxidative stress after six weeks of di-
electrophoresis (comet assay), it became possible to version may be related to the increased production of
quantify the oxidative stress levels in the whole tis- OFR, both for the presence of neutrophils – cells that
sue50. The technique enables the comparison of oxi- produce OFR – and for the changes in cell metabolism
dative damage levels in cells of the normal colonic resulting from SCFA deficiency.
mucosa and the sore epithelium50. When we measure the tissue content of β-catenin
The comet assay is one of the most sensitive in animals submitted to bypass for six weeks, we find
methods to assess levels of oxidative stress, present- reduction in the segments without fecal stream in re-
ing greater accuracy when compared to other tech- lation to those in the control group and the segments
niques50. Because of its high sensitivity, allied to its with preserved stream. When we study the β-catenin
low cost, it has been more and more used30,31,40,42,50. content separating the apical and basal regions of the
The comet assay had not been employed to assess the colonic glands, we notice the reduction of content in
relation between tissue oxidative stress and changes in the apical region, and, on the other hand, its increase
tissue content and expression of the β-catenin protein in the basal region. These findings suggest that the re-
in DC models. duction of β-catenin expression in cells of the epithe-
At first, with the objective to confirm if animals lial surface may be related to higher levels of damage
used for experimentation developed colitis in seg- to the cells in this region, probably due to greater lo-
ments without stream, we evaluated the histological cal oxidative stress. The worsened inflammation in the
changes in the diverted colon. We observed the pres- segments without stream could lead to the degradation
ence of colitis in this segment for all rats, regardless of β-catenin, and consequently to the greater produc-
of diversion time, when compared to segments with tion of OFR. It is possible that cytokines and proteases
preserved stream30,31. In the control group and in co- produced by activated neutrophils, which are present
lonic segments with fecal stream in the animals from at this stage of the experiment, could also be respon-
the experiment group, even though we did not find the sible for the greater degradation of β-catenin, and also
formation of epithelial ulcers, we identified some de- that the rupture of E-cadherin/β-catenin bridges in the
gree of inflammatory infiltrate, especially those con- cells of the epithelial surface could lead to the migra-
stituted of neutrophils. Differently, in the colon with- tion of β-catenin free of cytosol to the inner part of
out stream there was the formation of more epithelial the nucleus in cells of the germinative zone, with the
ulcers, sometimes deep, destroying the whole epithe- objective to increase the transcription of genes related
lial surface, and larger tissue inflammatory infiltrate, to cellular division. It is also possible that the greater
regardless of considered time. It is worth mentioning β-catenin content found in deep cells of the colonic
that in segments without stream, after 12 and 18 weeks glands can be explained by the greater need for cell
of intestinal exclusion, the inflammation grading scale proliferation, with the goal to replace the dead cells
increased in relation to animals submitted to bypass from the apical surface, destroyed by tissue stress.
for 6 weeks, thus suggesting that the worsened epithe- However, only the analysis of cell division genes,
lial aggression could be related to the deficient supply such as C-myc or Ciclyn-1, and the β-catenin expres-
of SCFA, modifying the cellular energetic metabolism sion, comparing apical and basal cells from the co-
for a longer period of time. Confirming this possibil- lonic glands, could confirm this possibility11.

355
J Coloproctol Oxidative stress and changes in the content and pattern of tissue expression of β-catenin Vol. 32
October/December, 2012 protein in diversion colitis Nº 4
Carlos Augusto Real Martinez et al.

In animals submitted to intestinal bypass for The total β-catenin tissue content in segments
12  weeks, we found worsened inflammation score in without fecal stream, diverted for 18 weeks, was similar
the colonic segments without fecal stream, when com- to that of animals with bypass for 6 and 12 weeks. The
pared to those with bypass for six weeks. This is mainly intensity of β-catenin expression in the apical regions
due to the greater presence of epithelial ulcers, once we of colonic glands was similar to that of animals submit-
found lower neutrophilic infiltrate. The levels of oxida- ted to bypass for 6 and 12 weeks. However, in the basal
tive stress in these segments were higher when compared region, the intensity of the expression remained high,
to those found in animals with bypass for six weeks, and with values similar to those found in the colon without
were directly related to the worst inflammation score. stream for 12 weeks, thus suggesting the greater need
The worsened levels of tissue oxidative stress in for gene activation related to cell division by β-catenin.
the colon without stream in animals with bypass for As what happened with diverted colons for 12 weeks,
12 weeks could also be a result of the presence of neu- the intensity of β-catenin expression in segments with-
trophils. However, it is likely that for these animals, out stream presented significant variation when com-
the greater formation of OFRs because of the SCFA paring apical and basal regions. The greater β-catenin
deficiency is more relevant for tissue damage when expression in the proliferative zone of colonic glands
compared to animals with bypass for six weeks. after 18 weeks reaffirms the need to maintain the cell
The total β-catenin content in segments without division process in the cells by the germinative zone.
stream after 12 weeks was similar to that of animals Studies have shown the important role of SCFA to
in the control groups and segments with fecal stream. maintain the proper tropism of epithelial cells from the
In the diverted colon, there was no variation in protein colonic mucosa35-38. They are important substracts to pre-
content when compared to that found in animals with serve the integrity of barrier mechanisms, since they in-
bypass for six weeks. When analyzing the β-catenin duce the expression of genes that form the proteins that
expression separately in the apical and basal regions are responsible for the selective permeability of AJs and
of colonic glands, we noticed the reduction of con- avoid oxidative stress, which cause lesions in these de-
tent in the apical region, while the basal one presented fense systems35-38. The inhibition of SCFA metabolization
with increase. We found significant variation in pro- leads to the appearance of colitis36, while the establishment
tein content between the apical and basal regions of of fecal stream and the administration of SCFA, mixed
colonic glands in relation to time of exclusion. These nutritional solutions and omega-3 and omega-6 rich poly-
findings reinforce our suspicion that the proportional unsaturated fatty acids, improve histological alterations,
increase of β-catenin concentration in the proliferative probably by diminishing tissue oxidative stress30.
zones of the crypts is related to the greater need for The results found in this study add new evidence
cell division in the proliferative zones of crypts, with to support the theory of colitis induction by OFR. In
the goal to replace the cells from an increasingly dam- this paper, it was possible to demonstrate that cells
aged epithelial surface. from the colonic mucosa without regular SCFA sup-
The inflammation score of the colon without ply suffer from more oxidative stress, especially in the
stream in animals with bypass for 18 weeks did not late stages of fecal diversion. It was possible to show
increase in relation to those with bypass for 12 weeks. that colonic segments without stream present histo-
However, in the diverted segments for 18 weeks, de- logical changes that are indistinguishable from those
spite the major presence of epithelial ulcers, the neu- found in human DC, and similar to those described in
trophilic infiltrate was insignificant. These findings experimental models of chemically induced colitis37-40.
suggest that the worsened epithelial lesion cannot be The results also showed that SCFA deficiency, despite
related to the higher presence of neutrophils. In these practically keeping the total β-catenin tissue content,
segments, we found higher levels of oxidative stress drastically changes the place of protein expression, re-
than for animals with bypass for 12 weeks, suggesting ducing its content in the damaged epithelial surface
that after 18 weeks, the greater tissue oxidative stress and increasing it in the proliferative region. These find-
caused by energy deficiency can be the main respon- ings are in accordance with previous studies, which
sible for the worsened epithelial lesion. demonstrated the double functional β-catenin domain,

356
J Coloproctol Oxidative stress and changes in the content and pattern of tissue expression of β-catenin Vol. 32
October/December, 2012 protein in diversion colitis Nº 4
Carlos Augusto Real Martinez et al.

favoring the mechanisms of cellular adhesion to the practical point of view, the findings suggest that the
epithelial surface and leading to cellular proliferation reestablishment of SCFA supply to the diverted colon,
in germinative zones of colonic glands. Finally, the re- be it by the reconstitution of fecal stream or by the ad-
sults in this study show, for the first time in literature, ministration of nutritional solutions rich in SCFA, or
that the content and place of β-catenin expression is even the use of antioxidant substances, can be consid-
changed in DC, as it happened with URC. From the ered as a valid strategy to prevent and treat DC.

REFERENCES 13. Aust DE, Terdiman JP, Willenbucher RF, Chew K, Ferrell L,
Florendo C, et al. Altered distribution of β-catenin, and its
1. Pravda J. Radical induction theory of ulcerative colitis. World binding proteins E-cadherin and APC, in ulcerative colitis-
J Gastroenterol 2005;11(16):2371-84. related colorectal cancers. Mod Pathol 2001;14(1):29-39.
2. Gaudier E, Hoebler C. Physiological role of mucins in 14. Kucharzik T, Walsh SV, Chen J, Parkos CA, Nusrat A. Neutrophil
the colonic barrier integrity. Gastroenterol Clin Biol transmigration in inflammatory bowel disease is associated with
2006;30(8-9): 965-74. differential expression of epithelial intercellular junction proteins.
3. Laukoetter MG, Nava P, Nusrat A. Role of the intestinal Am J Pathol 2001;159(6):2001-9.
barrier in inflammatory bowel disease. World J Gastroenterol 15. Laukoetter MG, Nava P, Nusrat A. Role of the intestinal
2008;14(3):401-7. barrier in inflammatory bowel disease. World J Gastroenterol
4. Berkes J, Viswananthan VK, Savkovic SD, Hecht G. 2008;14(3):401-7.
Intestinal epithelial responses to enteric pathogens: effects on 16. Gassler N, Rohr C, Schneider A, Kartenbeck J, Bach
the tight junction barrier, iron transport, and inflammation. A, Obermüller N, et al. Inflammatory bowel disease is
Gut 2003;52(3):439-51. associated with changes of enterocytic junctions. Am J
5. Clayburgh DR, Shen L, Turner JR. A porous defense: the Physiol Gastrointest Liver Physiol 2001;281(1):G216-28.
leaky epithelial barrier in intestinal disease. Lab Invest 17. Ozawa M, Ringwald M, Kemler R. Uvomorulin-catenin
2004;84(3):282-91. complex formation is regulated by a specific domain in the
6. Usami Y, Chiba H, Nakayama F, Ueda J, Matsuda Y, Sawada cytoplasmic region of the cell adhesion molecule. Proc Natl
N, et al. Reduced expression of claudin-7 correlates with Acad Sci USA 1990;87(11):4246-50.
invasion and metastasis in squamous cell carcinoma of the 18. Schmitz H, Barmeyer C, Fromm M, Runkel N, Foss HD,
esophagus. Hum Pathol 2006;37(5):569-77. Bentzel CJ, et al. Altered tight junction structure contributes
7. Gumbiner B, Stevenson B, Grimaldi A. The role of the to the impaired epithelial barrier function in ulcerative colitis.
cell adhesion molecule uvomorulin in the formation and Gastroenterology 1999;116(2):301-9.
maintenance of the epithelial junctional complex. J Cell Biol 19. Takahashi M, Fukuda K, Sugimura T, Wakabayashi K.
1988;107(4):1575-87. Beta-catenin is frequently mutated and demonstrates altered
8. Gumbiner BM, McCrea PD. Catenins as mediators of cellular localization in azoxymethane-induced rat colon
the cytoplasmic functions of cadherins. J Cell Sci Suppl tumors. Cancer Res 1998;58(1):42-6.
1993;17:155-8. 20. Parrish AR, Catania JM, Orozco J, Gandolfi AJ. Chemically
9. Yeager M, Unger VM, Falk MM. Synthesis, assembly and induced oxidative stress disrupts the E-cadherin/catenin cell
structure of gap junction intercellular channels. Curr Opin adhesion complex. Toxicol Sci 1999;51(1):80-6.
Struct Biol 1998;8(6):810-1. 21. Meyer TN, Schwesinger C, Ye J, Denker BM, Nigam
10. Hynes RO, Zhao Q. The evolution of cell adhesion. J Cell SK. Reassembly of the tight junction after oxidative
Biol 2000;150(2):F89-96. stress depends on tyrosine kinase activity. J Biol Chem
11. Kypta R, Bernfield M, Burridge K, Geiger B, Goodenough 2001;276(25):22048-55.
D, Humphries M, Hynes R, Reichardt L, Rosenbaum J, 22. Dorudi S, Sheffield JP, Poulsom R, Northover JM,
Rucislahti E, Sanes J, Springer T, Yurchenco P. Junções Hart IR. E-cadherin expression in colorectal cancer. An
celulares, adesão celular e matriz extracelular. In: Alberts immunocytochemical and in situ hybridization study. Am J
B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. (eds.). Pathol 1998;142(4):981-6.
Biologia Molecular da Célula. Porto Alegre: ARTMED; 23. Chen J, Huang XF. The signal pathways in azoxymethane-
2006. p. 1065-1125. induced colon cancer and preventive implications. Cancer
12. Demetter P, De Vos M, Van Damme N, Baeten D, Elewaut Biol Ther 2009;8(14):1313-7.
D, Vermeulen S, et al. Focal up-regulation of E-cadherin- 24. Jankowski JA, Bedford FK, Boulton RA, Cruickshank
catenin complex in inflamed bowel mucosa but reduced N, Hall C, Elder J, et al. Alterations in classical cadherins
expression in ulcer-associated cell lineage. Am J Clin Pathol associated with progression in ulcerative and Crohn’s colitis.
2000;114(3):364-70. Lab Invest 1998;78(9):1155-67.

357
J Coloproctol Oxidative stress and changes in the content and pattern of tissue expression of β-catenin Vol. 32
October/December, 2012 protein in diversion colitis Nº 4
Carlos Augusto Real Martinez et al.

25. Hermiston ML, Gordon JI. Inflammatory bowel disease with and without intestinal transit in rats. Acta Cir Bras
and adenomas in mice expressing a dominant negative 2008;23(5):417-24
N-cadherin. Science 1995;270(5239):1203-7. 40. Caltabiano C, Máximo FR, Spadari AP, Miranda DDC,
26. Karayiannakis AJ, Syrigos KN, Efstathiou J, Valizadeh Serra MM, Ribeiro ML, et al. 5-aminosalicylic (5-ASA)
A, Noda M, Playford RJ, et al. Expression of catenins and can reduce the levels of oxidative DNA damage in cells of
E-cadherin during epithelial restitution in inflammatory colonic mucosa with and without fecal stream. Dig Dis Sci
bowel disease. J Pathol 1998;185(4):413-8. 2011;56(4):1037-46.
27. Nollet F, Berx G, van Roy F. The role of the E-cadherin/ 41. Gupta RB, Harpaz N, Itzkowitz S, Hossain S, Matula S,
catenin adhesion complex in the development and progression Kornbluth A, et al.. Histologic inflammation is a risk factor
of cancer. Mol Cell Biol Res Commun 1999;2(2):77-85. for progression to colorectal neoplasia in ulcerative colitis: a
28. Sheehan JF, Brynjolfsson G. Ulcerative colitis following cohort study. Gastroenterology 2007;133(4):1099-105.
hydrogen peroxide enema: case report and experimental 42. Ribeiro ML, Priolli DG, Miranda DD, Arçari DP, Pedrazzoli
production with transient emphysema of colonic wall and gas J Jr. Martinez CA. Analysis of oxidative DNA damage in
embolism. Lab Invest 1960;9:150-68. patients with colorectal cancer. Clin Colorectal Cancer
29. Marques LHS, Silva CMG, Lameiro TMM, Almeida MG, 2008;7(4):267-72.
Cunha FL, Pereira JA, et al. Avaliação dos níveis de peroxidação 43. Lodish H, Berk A, Zipursky SL, Matsudaira P, Baltimore D,
lipídica em células da mucosa cólica após aplicação de enemas Darnell J. A integração das células nos tecidos. In: Lodish H,
com peróxido de hidrogênio: estudo experimental em ratos. Rev Berk A, Zipursky SL, Matsudaira P, Baltimore D, Darnell J.
bras colo-proctol 2010;30(3):272-80. (eds.). Biologia celular e molecular. Rio de Janeiro: Revinter;
30. Martinez CA, Ribeiro ML, Gambero A, Miranda DD, Pereira 2004. p.968-1002.
JA, Nadal SR. The importance of oxygen free radicals in the 44. Duband JL, Thiery JP. Spatio-temporal distribution of the
etiopathogenesis of diversion colitis in rats. Acta Cir Bras adherens junction-associated molecules vinculin and talin in
2010;25(5):387-95. early avian embryo. Cell Differ Dev 1990;30(1):55-76.
31. Longatti TS, Acedo SC, de Oliveira CC, Miranda DD, Priolli 45. Rao RK, Basuroy S, Rao VU, Karnaky Jr KJ, Gupta A.
DG, Ribeiro ML, et al. Inflammatory alterations in excluded Tyrosine phosphorylation and dissociation of occludin-ZO-1
colon in rats: a comparison with chemically induced colitis. and E-cadherin-b-catenin complexes from the cytoskeleton
Scand J Gastroenterol 2010;45(3):315-24. by oxidative stress. Biochem J 2002;368(Pt 2):471-81.
32. Damiani CR, Benetton CA, Stoffel C, Bardini KC, Cardoso 46. Schmehl K, Florian S, Jacobasch G, Salomon A, Körber
VH, Di Giunta G, et al. Oxidative stress and metabolism in J. Deficiency of epithelial basement membrane laminin
animal model of colitis induced by dextran sulfate sodium. J in ulcerative colitis affected human colonic mucosa. Int J
Gastroenterol Hepatol 2007;22(11):1846-51. Colorectal Dis 2000;15(1):39-48.
33. Liu Q, Shimoyama T, Suzuki K, Umeda T, Nakaji S, Sugawara 47. Cooper HS, Murthy S, Kido K, Yoshitake H, Flanigan A.
K. Effect of sodium butyrate on reactive oxygen species Dysplasia and cancer in the dextran sulfate sodium mouse colitis
generation by human neutrophils. Scand J Gastroenterol model. Relevance to colitis-associated neoplasia in the human:
2001;36(7):744-50. a study of histopathology, B-catenin and p53 expression and the
34. Glotzer DJ, Glick ME, Goldman H. Proctitis and colitis role of inflammation. Carcinogenesis 2000;21(4):757-68.
following diversion of the fecal stream. Gastroenterology 48. Fodde R, Tomlinson I. Nuclear beta-catenin expression
1981;80(3):438-41. and Wnt signalling: in defence of the dogma. J Pathol
35. Agarwal VP, Schimmel EM. Diversion colitis: a nutritional 2010;221(3):239-41.
deficiency syndrome? Nutr Rev 1989;47(9):257-61. 49. Baskol M, Baskol G, Koçer D, Ozbakir O, Yucesoy M.
36. Butzner JD, Parmar R, Bell CJ, Dalal V. Butyrate enema Advanced oxidation protein products: a novel marker of
therapy stimulates mucosal repair in experimental colitis in oxidative stress in ulcerative colitis. J Clin Gastroenterol
the rat. Gut 1996;38(4):568-73. 2008;42(6):687-91
37. Nonose R, Spadari AP, Priolli DG, Máximo FR, Pereira 50. Glei M, Hovhannisyan G, Pool-Zobel BL. Use of Comet-fish
JA, Martinez CA. Tissue quantification of neutral and acid in the study of DNA damage and repair: review. Mutat Res
mucins in the mucosa of the colon with and without fecal 2009;681(1):33-43.
stream in rats. Acta Cir Bras 2009;24(4):267-75.
38. Martinez CA, Nonose R, Spadari AP, Máximo FR, Priolli
DG, Pereira JA, et al. Quantification by computerized
morphometry of tissue levels of sulfomucins and sialomucins Correspondence to:
in diversion colitis in rats. Acta Cir Bras 2010;25(3):231-40. Carlos Augusto Real Martinez
39. Sousa MV, Priolli DG, Portes AV, Cardinalli IA, Pereira JA, Rua José Raposo de Medeiros
Martinez CA. Evaluation by computerized morphometry of CEP: 12914-450 – Bragança Paulista (SP), Brazil
histopathological alterations of the colon wall in segments E-mail: caomartinez@uol.com.br

358
Original Article

Role of bowel preparation on colocolonic anastomosis:


experimental study in dogs
Francisco Sérgio Pinheiro Regadas1, Welligton Ribeiro Figueiredo2,
Miguel Augusto Arcoverde Nogueira3, Carlos Renato Sales Bezerra4, Péricles Cerqueira de Sousa5

1
Full Professor at Faculty of Medicine, Universidade Federal do Ceará (UFC) – Fortaleza (CE), Brazil. 2Digestive Tract
Surgeon, Master student in Surgery, UFC – Fortaleza (CE), Brazil. 3Coloproctologist, Doctoral candidate in Surgery,
UFC – Fortaleza (CE), Brazil. 4Digestive Tract Surgeon, Doctoral candidate in Surgery, UFC – Fortaleza (CE), Brazil.
5
Digestive Tract Surgeon, Master student in Surgery, UFC – Fortaleza (CE), Brazil.

Regadas FSP, Figueiredo WR, Nogueira MAA, Bezerra CRS, Sousa PC. Role of bowel preparation on colocolonic anastomosis:
experimental study in dogs. J Coloproctol, 2012;32(4): 359-364.
Abstract: The aim of the present study was to evaluate the efficacy of colocolonic anastomosis with and without preoperative bowel
preparation. Methods: The study compared 42 female dogs (Canis familiaris), divided into 2 groups of 21 animals: Group I (control) –
submitted to bowel preparation – and Group II (study) – without previous bowel preparation –. All animals were submitted to laparotomy
with sectioning of the descending colon and primary anastomosis using polypropylene thread. Following euthanasia on the 21st postopera-
tive day (POD), a second laparotomy was performed to evaluate the anastomosis with regard to complications, intra-abdominal adhesions
and anastomotic burst pressure. Results: One animal from each group (4.5%) died. The death in Group I occurred on seventh POD due
to anastomotic dehiscence. The death in Group II occurred on tenth POD due to deep incisional infection at the surgical site and complete
dehiscence of the abdominal wall. The groups did not differ significantly with regard to adhesion grade or anastomotic burst pressure (one
specimen burst in each group) (p>0.05). Conclusion: Colocolonic anastomosis without previous bowel preparation was shown to be safe
and efficacious, suggesting it is not an indispensable procedure in colorectal anastomosis surgery.
Keywords: colorectal surgery; postoperative complications; anastomotic leak.

Resumo: Esse estudo avaliou a eficácia da anastomose colocólica sem preparo intestinal prévio comparando-a com a anastomose
realizada com preparo. Método: Foram utilizados 42 animais (Canis familiares) fêmeas distribuídos em 2 grupos com 21 animais em
cada: Grupo I (controle) – com preparo intestinal – e Grupo II (estudo) – sem preparo intestinal prévio –. Os animais de ambos os grupos
foram submetidos à laparotomia com secção do cólon descendente e à anastomose primária com fio de polipropileno, bem como à euta-
násia no 21º dia de pós-operatório com laparotomia e à avaliação da anastomose colocólica quanto à presença de complicações, grau de
aderências intestinais e pressão de ruptura da anastomose. Resultados: Ocorreu um (4,5%) óbito em cada grupo, sendo o do Grupo I no
sétimo dia pós-operatório em decorrência da deiscência da anastomose colocólica e o do Grupo II no décimo dia de pós-operatório por
causa de infecção em sítio cirúrgico com deiscência total da parede abdominal. Não foi observada diferença estatisticamente significante
no grau de aderências intestinais tampouco no teste de pressão de ruptura entre os grupos (um espécime sofreu ruptura em casa grupo)
(p>0,05). Conclusão: A anastomose colocólica sem preparo intestinal apresentou a mesma segurança e eficácia da anastomose realizada
com preparo prévio, sugerindo não ser indispensável na cirurgia colorretal com anastomose.
Palavras-chave: cirurgia colorretal; complicações pós-operatórias; fístula anastomótica.

Study carried out at Post-graduation program stricto sensu in Surgery, Surgery Department, School of Medicine, Universidade Federal do Ceará –
Fortaleza (CE), Brazil.
Financing source: none.
Conflict of interest: nothing to declare.

Submitted on: 11/27/2011


Approved on: 11/06/2011

359
J Coloproctol Role of bowel preparation on colocolonic anastomosis: experimental study in dogs Vol. 32
October/December, 2012 Francisco Sérgio Pinheiro Regadas et al. Nº 4

INTRODUCTION tic complications from colorectal surgery12. Other


researchers believe mechanical colon preparation
Colorectal surgery with primary anastomo- does not improve postoperative morbidity rates
sis is associated with a range of mild to severe and may even increase the incidence of infectious
complications, from simple surgical site infection complications, fistulas and hydroelectrolyte im-
to anastomotic dehiscence and fistula. Thus, the balance10. In a study with five years of follow-up,
postoperative recovery of patients submitted to Fillmann, in 2001, reported lower fistula and in-
colorectal surgery remains a major challenge for fection rates among patients who were not submit-
surgeons. ted to preoperative bowel preparation13. Thus, to a
Mechanical bowel preparation of the colon number of authors, anastomosis may be performed
prior to elective surgery was first proposed over safely without preoperative bowel preparation14,15.
a hundred years ago. It has since been used to re- The aim of the present study was to evalu-
duce or eliminate the fecal mass, thereby minimiz- ate the efficacy of colocolonic anastomosis in dogs
ing infection and complications in perianastomotic with and without preoperative bowel preparation.
tissues and ensuring more esthetic outcomes1.
Bowel preparation involves a set of proce- MATERIALS AND METHODS
dures designed to completely remove fecal resi-
dues and significantly reduce the bacterial flora in This study included 42 female dogs (Canis fa-
the colon with the least possible discomfort and miliaris) weighing 8.4–16.9 kg, distributed at ran-
risk for the patient2. dom in two groups of 21 animals each:
Thorough bowel cleansing is by most sur- • Group I (control) – animals with preoperative
geons considered one of the most important fac- bowel preparation;
tors in the prevention of complications3. In fact, • Group II (study) – animals not submitted to
since the days of Halsted, the presence of feces in- preoperative bowel preparation.
side the colon has been viewed as a major cause of
anastomotic dehiscence4. Not surprisingly, many The animals in Group I (control) were sub-
authors believe preoperative bowel preparation is mitted to preoperative bowel preparation with a
essential in the prevention of infectious complica- 12% glycerin solution administered rectally one
tions following colorectal surgery5-8. day before surgery.
Based on the literature, it is difficult to de- Surgical technique — once the animals
termine exactly when preoperative bowel prepa- were anesthetized, a digital rectal examination
ration became a standard procedure in colorectal was performed individually to determine bowel
surgery, but the earliest studies on colon and rec- preparation according to the classification pro-
tum cleansing were carried out by Maunsell in the posed by O’Dweyr: excellent (absence of feces);
early 1890s9. good (presence of minimal fecal residue); accept-
However, in the 1990s, the use of bowel prep- able (presence of liquid feces); soiled (presence of
aration as an indispensable preoperative procedure solid feces)16. The procedure consisted of a medi-
came into question, and criteria for when it ought an transumbilical laparotomy, identification of the
to be avoided was proposed10. In addition, a num- descending colon at 20 cm from the anal margin,
ber of studies documented the favorable evolution and colotomy with sectioning of the entire colon
of patients submitted to emergency left colon re- circumference. In both groups, the colotomy was
section with primary anastomosis without previous closed manually with a continuous single-layer ex-
colon preparation, raising doubts about its indis- tramucosal suture using polypropylene 3–0 thread.
pensability11. It has been shown that under certain The animals were evaluated during the first
circumstances mechanical bowel preparation can 21 days after surgery concerning the presence of
actually stimulate bacterial growth and transloca- signs and symptoms of surgical site infection and
tion, both of which favor the emergence of sep- other complications. On the 21st postoperative day

360
J Coloproctol Role of bowel preparation on colocolonic anastomosis: experimental study in dogs Vol. 32
October/December, 2012 Francisco Sérgio Pinheiro Regadas et al. Nº 4

(POD 21), the animals were euthanized and a sec- RESULTS


ond laparotomy was performed through the same
incision. The anastomoses were evaluated with re- One animal in each group (4.5%) died. The death
gard to integrity and the presence of fistulas and in Group I (study) occurred on POD 7 due to anas-
dehiscence, while the abdominal cavity was eval- tomotic dehiscence. The death in Group II (control)
uated for adhesions using the classification pro- occurred on POD 10 due to deep incisional infection
posed by Knightly: 0=no adhesions, 1=single thin at the surgical site and complete dehiscence of the ab-
and easily separable adhesion, 2=less extensive dominal wall with evisceration and intact anastomo-
but weak adhesions which withstand traction poor- sis. The two groups did not differ with regard to de-
ly, 3=extensive visceral adhesions extending to ab- hiscence (p>0.05). Likewise, the observed difference
dominal wall, 4=numerous extensive and visceral in average weight did not reach statistical significance
adhesions involving the mesentery, bowel, omen- (p>0.05).
tum and abdominal wall17. A 6 cm-colon segment According to the O’Dweyr classification, bowel
centered on the anastomosis was resected and cau- preparation was considered good in 70% and excellent
terized at the proximal extremity using a urethral in 30% of the animals in Group II.
probe (#8.0). In order to determine the anastomot- The distribution of the animals according to in-
ic bursting pressure, the proximal extremity of the tra-abdominal adhesion grade is shown in Graph 1.
colon segment was tied to a sphygmomanometer In Group I, adhesions were predominantly grade
with two cotton threads (size 2–0) while the distal 2 (35%) and grade 3 (25%), while the distribution
extremity was closed with Kelly forceps to prevent
air from escaping (Figure 1).
Then the colon segment was inflated continu-
ously with a manual bulb to a maximum pressure
of 300 mmHg, or until the suture burst (Figure 2).
The site of anastomotic disruption, if any, was ex-
amined and the respective pressure was registered.
The weight, colon preparation, postoperative
clinical evolution, intra-abdominal adhesion score and
anastomotic bursting pressure were registered for all
the animals, and the two groups were compared.

Figure 1. System used to test the bursting strength of colon Figure 2. System used to test the bursting strength of colon
segment prior to inflation (animal #23). segment, with segment fully inflated at 300 mmHg (animal #23).

361
J Coloproctol Role of bowel preparation on colocolonic anastomosis: experimental study in dogs Vol. 32
October/December, 2012 Francisco Sérgio Pinheiro Regadas et al. Nº 4

Group II (control)
Group I (study) 100 95 95*
40 Group II (control)
35 80 Group I (study)
Frequency (%)

30

Frequency (%)
25 25 25 25 60
20 20
20
15 40

10 20
5 5
5 5
0 0
Absence Grade 1 Grade 2 Grade 3 Grade 4 No disruption Disruption
*p=0,5685 *p=0,9714
Figure 3. Disttribution of animals according to intra-abdominal Figure 4. Disruption of anastomosis submitted to inflation at up
adhesion grade. to 300 mmHg.

was more homogenous in Group II (grades 1, 2 and er to use a continuous single-layer suture or sepa-
3=25%; grade 4=20%). However, the difference was rate stitches, and which thread to use. The method
not statistically significant (p=0.5685). (Figure 3) a­dopted in this study (continuous single-layer ex-
When testing the bursting strength by inflation at tramucosal suture) is simple, swift and inexpensive.
up to 300 mmHg, one colon segment from each group It is associated with impermeability and low levels of
(5.0%) was disrupted, one at 270 mmHg (Group I) and tissue inflammation, and is considered as safe as sep-
one at 220 mmHg (Group II). The difference was not arate stitches20,21. Monofilament thread is preferred
statistically significant (p>0.05) (Figure 4). to multifilament thread which is known to favor the
development of infections and inflammatory reac-
DISCUSSION tions14. The polypropylene thread used in this study
is monofilament, has high tensile strength and is as-
Female dogs were used in this study because sociated with very little inflammatory reaction22.
they are easy to obtain and handle, their bowels are The mortality rate was similar in the two groups.
relatively similar to human bowels, and the size of the Both the observed deaths were the result of infectious
pelvic cavity is appropriate to test the procedure18. In complications. One animal in Group I presented anas-
addition, canine and human bowels also feature rela- tomotic dehiscence evolving towards peritonitis and
tively similar intestinal microflora, blood supply and died on POD 7. Another animal in Group II presented
descending colon anatomy16. deep incisional infection at the surgical site leading
On the average, the animals in Group I weighed to complete dehiscence of the abdominal wall and
more than the animals in Group II, but the difference died on POD 10. These results suggest that mechani-
was not statistically significant. Thus, body weight cal bowel preparation prior to surgery does not reduce
cannot be considered a determining factor in our sam- mortality in dogs submitted to colorectal anastomosis
ple. surgery14,15,23.
The bowel preparation of the animals in Group I The grade of adhesions is an indirect measure
was successful, indicating that bowel cleansing with of anastomotic complications and, consequently, of
12% glycerin solution 24 hours prior to surgery is ef- wound healing. Based on Knightly’s classification
ficient in dogs19. of adhesions17, no significant differences between
There is still some discussion about the most the groups were observed, indicating that mechani-
appropriate way to perform anastomosis, wheth- cal bowel preparation did not influence the devel-

362
J Coloproctol Role of bowel preparation on colocolonic anastomosis: experimental study in dogs Vol. 32
October/December, 2012 Francisco Sérgio Pinheiro Regadas et al. Nº 4

opment of adhesions. This  finding contradicts the were carefully centered on the anastomosis. Burst
notion that preoperative colon cleansing reduces the pressure is an efficient parameter to evaluate the heal-
risk of contamination of the peritoneum and perian- ing of intestinal anastomoses provided the disruption
astomotic tissues, thereby minimizing the develop- occurs at the site of the anastomosis17,24. In our study,
ment and severity of adhesions2. disruption occurred in one specimen from each group,
Studies on healing of intestinal sutures often em- thus no significant difference was observed. In conclu-
ploy mechanical parameters such as burst tension test- sion, colocolonic anastomosis without previous bowel
ing in which a bowel segment is distended with liquid preparation was shown to be safe and efficacious, sug-
or air up to a predetermined pressure level, or until gesting it is not an indispensable procedure in colorec-
it bursts17,24. In this study, the bowel segments tested tal anastomosis surgery.

REFERENCES the management of left-sided large bowel emergencies. Br J


Surg 1985;72(9):708-11.
1. Hares MM, Alexander-Williams J. The effect of 12. Valarini R, Lemos R, Quintana LFC, Cordova LF, Cabrera
bowel preparation on colonic surgery. World J Surg PFA, Repka JD, et al. Estudo da translocação bacteriana após
1982;2(6):175-81. sutura primária do colo com e sem limpeza mecânica: trabalho
2. Habr-Gama A, Gama-Rodrigues JJ, Teixeira MG, Alves experimental em cães. Rev Bras Coloproct 1998;18(1):22-9.
PRA, Ventura TCM, Quintanilha AG, et al. Preparo intestinal 13. Fillmann LS, Perondi F, Fillmann HS, Fillmann EEP. Cirurgia
pela ingestão de manitol a 10%. Rev Bras ­­ Coloproct eletiva para o câncer colo-retal sem preparo mecânico da luz
1981;1(2):84-94. intestinal: Análise após 5 anos de acompanhamento. Rev
3. Güenaga KF, Matos D, Wille-Jørgensen P. Preoperative Bras Coloproct 2001;4(21):246-9.
mechanical bowel preparation in elective colorectal surgery. 14. Torres Neto JR, Fakhouri R, Menezes MVA, Santos JS,
An update of systematic review of the literature and meta- Prudente ACL, Monteiro JTS, et al. Estudo Histomorfométrico
analysis. J Coloproctol 2012;1(32):7-17. de Anastomoses Primárias de Cólon em Coelhos, Com e Sem
4. Ravo B, Metwally N, Castera P, Polasnky PJ, Ger R. The Preparo Intestinal. Rev Bras Coloproct 2007;4(27):384-90.
importance of intraluminal anastomotic fecal contact and 15. Scabini S, Rimini E, Romairone E, Scordamaglia R, Damiani
peritonitis in colonic anastomotic leakages. An experimental G, Pertile D, et al. Colon and rectal surgery for câncer without
study. Dis Colon Rectum 1988;1(31):868-71. mechanical bowel preparation: onecenter ramdomized
5. Rosenberg IL, Graham NG, Dombal FT, Goligher JC. prospective trial. World J Surg Oncol 2010;8:35.
Preparation of the intestine in patients undergoing major 16. O’Dwyer PJ, Conway MC, McDermott EW, O’Higgins
large-bowel surgery, mainly for neoplasmas of the colon and NJ. Effect of mechanical bowel preparation on anastomotic
rectum. Br J Surg 1971;58(4):266-9. integrity following low anterior resection in dog. Br J Surg
6. Irvin TT, Goligher JC. Aetiology of disruption of intestinal 1989;76(7):756-8.
anastomoses. Br J Surg 1973;60(6):461-4. 17. Knigthly JJ, Agostino D, Cliffton EE. The effect of
7. Buffara JR, Brenner S, Souza FJ, Marchesini JB, Malafia fibrinolisyn and heparin on the formation of peritoneal
O. Infecção em cirurgia colorretal. Estudo retrospectivo de adhesions. Surgery 1962;52(4):250-8.
621 casos. Rev Bras Colo-Proct 1988;3(8):94-7. 18. Regadas SMM, Regadas FSP, Rodrigues LV, Carvalho
8. Pitrez FAB. Pré e pós-operatório em cirurgia geral e MCGS, Regadas Filho FSP. Modelo experimental de sutura
especializada. 2a ed. Porto Alegre: Artmed; 2003. 266 p. manual em cólon de cão por vídeo-laparoscopia. Acta Cir
9. Graney MJ, Graney CM. Colorectal surgery from antiquity Bras 2005;20(4):323-8.
to the modern era. Dis Colon Rectum 1980;23(6):432-41. 19. Bezerra CRS. Fechamento do coto distal do cólon sigmóide
10. Fillmann EEP, Fillmann LS, Fillmann HS. Cirurgia comparando sutura contínua com lacre plástico. Estudo
colorretal eletiva sem preparo. In: Habr-Gama A, experimental em cães. [dissertation]. Fortaleza (CE):
Barone B. Atualização em coloproctologia. São Paulo: Universidade Federal do Ceará; 2010.
Sociedade Brasileira de Coloproctologia e Associação 20. Regadas FSP, Castro Filho HF, Nicodemo AM, Morano
Latino-americana de Coloproctologia; 1995. p. 269-71. JCOD, Sampaio ZS. Estudo comparativo entre sutura
11. Koruth NM, Krukowski ZH, Youngson GG, Hendry WS, contínua e separada em anastomose cólica. Estudo
Logie JR, Jones PF, et al. Intra-operative colonic irrigation in experimental em ratos. Acta Cir Bras 1990;4:141-5.

363
J Coloproctol Role of bowel preparation on colocolonic anastomosis: experimental study in dogs Vol. 32
October/December, 2012 Francisco Sérgio Pinheiro Regadas et al. Nº 4

21. Figueiredo AF. Efeitos da suplementação nutricional com 24. Gonçalves CG. Cicatrização de anastomose colônica
glicina e com glutamina na cicatrização colônica em coelhos e nutrição pré-operatória em ratos desnutridos: estudo
[dissertation]. Belo Horizonte (MG): Universidade Federal tensiométrico e de deposição de colágeno [dissertation].
de Minas Gerais; 2007. Curitiba (PR): Universidade Federal do Paraná; 2005.
22. Ribeiro FJC. Avaliação qualitativa e quantitativa da resposta
inflamatória comparando a ação do fio de polipropileno com
o fio de poligliconato em anastomoses realizadas em colon de Correspondence to:
ratos [dissertation]. Fortaleza (CE): Universidade Federal do Francisco Sergio Pinheiro Regadas
Ceará; 1998. Faculdade de Medicina da Universidade Federal do Ceará
23. Feres O, Santos Jr JCM, Andrade JI. The role of mechanical Avenida Atilano de Moura, 430, apto. 200
bowel preparation for colonic resection and anastomosis: an CEP: 60810-180 – Fortaleza (CE), Brazil
experimental study. Int J Colorectal Dis 2001;16(6):353-6. E-mail: sregadas@hospitalsaocarlos.com.br

364
Original Article

Anthropometric assessment of men with colorectal cancer


after dietary supplement with Agaricus sylvaticus fungus
Renata Costa Fortes1,2, João Rodrigo de Lavor e Silva1, Maria Rita Carvalho Garbi Novaes3

1
Nutrition course, Institute of Health Sciences, Universidade Paulista (UNIP) – Brasília (DF), Brazil. 2Residency Program
in Clinical Nutrition, Hospital Regional da Asa Norte, State Secretariat of Health of Distrito Federal – Brasília (DF),
Brazil. 3Medical course, Escola Superior de Ciências da Saúde (ESCS), Fundação de Ensino e Pesquisa em Ciências da
Saúde (FEPECS), State Secretariat of Health of Distrito Federal – Brasília (DF), Brazil.

Fortes RC, Lavor e Silva JR, Novaes MRCG. Anthropometric assessment of men with colorectal cancer after dietary supplement with
Agaricus sylvaticus fungus. J Coloproctol, 2012;32(4): 365-371.
ABSTRACT: Introduction: Cancer is the second cause of death in Brazil, coming after cardiovascular disease. Medicinal fungi have been
used in cancer patients due to their immunomodulatory effects. Objective: To evaluate the anthropometric status of men with colorectal
cancer after supplementation with Agaricus sylvaticus. Methods: Randomized, double-blind, placebo-controlled clinical trial conducted in
a public hospital in the Federal District. The sample consisted of 24 male patients with colorectal cancer, separated into Agaricus sylvaticus
(30 mg/kg/day) and placebo groups. Weight, height, body mass index, arm circumference, triceps skinfold, arm muscle circumference and fat
percentage were evaluated during treatment. The results were analyzed before treatment and after three and six months of supplementation
with the Student’s t test and F test, with 5% significance. Results: The Agaricus sylvaticus group showed significant increase in arm muscle
circumference after six months of supplementation, but not in the placebo group. There were significant changes in both groups as to body
mass index, arm circumference, percent body fat and triceps skinfold thickness during treatment. Conclusion: The dietary supplement with
Agaricus sylvaticus is able to significantly improve muscle mass in male patients with colorectal cancer.
Keywords: anthropometry; colorectal neoplasms; neoplasms; Agaricales; Agaricus sylvaticus.

Resumo: Introdução: O câncer é a segunda causa de óbitos no Brasil, subsequente às doenças cardiovasculares. Fungos medicinais têm
sido utilizados em pacientes oncológicos devido a seus efeitos imunomoduladores. Objetivo: Avaliar o estado antropométrico de homens com
câncer colorretal após suplementação com fungos Agaricus sylvaticus. Métodos: Ensaio clínico randomizado, duplo-cego, placebo-controlado
realizado em um hospital público do Distrito Federal. Amostra de 24 pacientes com câncer colorretal, sexo masculino, separados em grupos
Agaricus sylvaticus (30 mg/kg/dia) e placebo. Foram avaliados peso, estatura, índice de massa corporal, circunferência do braço, dobra
cutânea tricipital, circunferência muscular do braço e percentual de gordura durante o tratamento. Os resultados foram analisados antes do
tratamento, com três e seis meses de suplementação, por meio dos testes t de Student e F, com significância de 5%. Resultados: O grupo
Agaricus sylvaticus apresentou aumento significativo da circunferência muscular do braço após seis meses de suplementação, fato não obser-
vado no grupo placebo. Não foram encontradas, em ambos os grupos, alterações significativas no índice de massa corporal, circunferência do
braço, percentual de gordura corporal e dobra cutânea tricipital ao longo do tratamento. Conclusão: A suplementação dietética com Agaricus
sylvaticus é capaz de melhorar significativamente a massa muscular de pacientes do sexo masculino com câncer colorretal.
Palavras-chave: antropometria; neoplasias colorretais; neoplasias; Agaricales; Agaricus sylvaticus.

INTRODUCTION interaction of endogenous and environmental factors.


The main factors related to oncogenesis are: heredity,
Cancer is the second cause of death in Brazil, af- physical inactivity, exposure to some kinds of viruses,
ter heart diseases. Its development is a result of the bacteria and parasites, frequent contact with carcino-

Study carried out at the Coloproctology oupatient clinic of Hospital de Base from the Federal District – Brasília (DF), Brazil.
Financing source: none.
Conflict of interest: nothing to declare.

Submitted on: 08/01/2012


Approved on: 25/04/2012

365
J Coloproctol Anthropometric assessment of men with colorectal cancer after dietary supplement Vol. 32
October/December, 2012 with Agaricus sylvaticus fungus Nº 4
Renata Costa Fortes et al.

genic substances, smoking, drinking, overweight or The work was conducted at the outpatient Coloproctol-
obesity, old age and improper diets1. ogy clinic of Hospital de Base of the federal district,
Studies show that 25 to 50% of oncologic pa- from November 2004 to July 2006.
tients present with malnutrition at the time of diag-
nosis, and that 100% are malnourished at the time Sample
of death. Clinical manifestations, such as anorexia, The sample consisted of patients with colorec-
weight loss, depletion of fat and muscle tissues, ane- tal cancer separated into the groups placebo (Gp) and
mia, hypoalbuminemia, glucose intolerance, among supplements with A. sylvaticus fungi (Gf), respecting
others, are common among patients with cancer2,3. the following inclusion criteria: male patients with
Combat therapies itself, as well as those that in- confirmed diagnosis of colorectal cancer, at postop-
hibit tumor growth, (chemotherapy, radiotherapy and erative phase, from 3 months to 2 years after surgical
surgery) exhibit different degrees of malnutrition due intervention, older than 20 years of age. Exclusion cri-
to complications and/or side effects such as nausea, teria were: bedridden patients, with physical impair-
vomit, diarrhea and anorexia, which makes the pa- ment, on alternative therapy, with other chronic non-
tients more prone to infections, causing a negative im- communicable diseases and with metastasis.
pact on their nutritional status3.
Nutritional evaluation is relevant for patients with Extract of Agaricus sylvaticus
cancer, whose changes in nutritional status are mostly The A. sylvaticus fungus was first described in
established during the course of the disease. Its main Switzerland and has a broad geographic distribu-
objectives are to define the degree of malnutrition, to tion, occurring naturally in Brazil. Its identification
identify patients who are at risk of developing compli- has been confirmed by the Royal Botanic Gardens of
cations resulting from nutritional deficit and to moni- London, and the document was provided by the Insti-
tor nutritional support. Maintaining a proper nutritional tute of Botanics at the State Environment Secretariat
status is an important goal to be reached4. of Sao Paulo on November 10, 1995.
Scientific evidence show that the Agaricus The fungus from the Agaricaceae family, whose
sylvaticus fungus (A. sylvaticus), which belongs to popular name is sun mushroom, was obtained from a
the order Agaricales and the family Agaricaceae, producer registered at the Brazilian Agricultural Re-
presents possible inhibiting effects on tumor growth, search Corporation (EMBRAPA), from the Tapiraí
tumor regression and stimulation of both immune and region, in the state of São Paulo. The fungus extract
hematopoietic systems, besides the beneficial effects was obtained by immersing the dehydrated material
on the improvement of quality of life and on the into hot water for 30 minutes, liquefied, sieved and dry
prognosis of oncologic patients5. with a dissector. The analysis of the composition of
The objective of this study was to analyze, by A. sylvaticus was performed by Japan Food Research
means of anthropometric measurements, the effects of Laboratories Center and showed the presence of car-
supplement nutritional therapy with A. sylvaticus fungi bohydrates (18.51 g/100 g), lipids (0.04 g/100 g), er-
on male oncologic patients assisted at a public hospital in gosterol (624 m/100 g), proteins (4.99 g/100 g), amino
Brasília (DF), Brazil. acids — arginine (1.14%), lysine (1.23%), histidine
(0.51%), fenilalanin (0.92%), tyrosine (0.67%), leu-
MATERIALS AND METHODS cine (1.43%), methionine (0.32%), valine (1.03%), ala-
nine (1.28%), glycine (0.94%), proline (0.95%), glu-
Study design tamic acid (3.93%), serine (0.96%), threonine (0.96%),
The study consists of a randomized, double-blind, aspartic acid (1.81%), tryptophan (0.32%) and cysteine
placebo-controlled clinical trial. It was approved by the (0.25%) — and micronutrients in minute quantities.
Human Research Ethics Committee of the State Health The dry extract was transformed into pills, ac-
Secretariat of the federal district (CEP/SES/DF), proto- cording to the pharmacotechnical procedure. The dose
col n. 051/04. The free informed consent form was ob- of fungus administered to the patients in the supple-
tained from the patients, who participated voluntarily. ment group was equal to 30 mg/kg/day, fraction-

366
J Coloproctol Anthropometric assessment of men with colorectal cancer after dietary supplement Vol. 32
October/December, 2012 with Agaricus sylvaticus fungus Nº 4
Renata Costa Fortes et al.

ated into two daily intakes (six pills a day, three in To measure the height, patients were in ortho-
the morning and three in the afternoon, in between static position, barefoot, with the body extended
meals), considering the mean weight of the studied to the maximum, straight head, looking ahead, in
population during a period of six months. The group Frankfört position, with the back and the back part
of patients who took the placebo received the same of the knees touching the wall, and the feet together6.
amount of pills, with the same excipient and energetic The Frankfört anatomical position extends from the
value, however, without the extract of A. sylvaticus, lower margin of the ocular orbit to the upper margin
which was replaced by starch. of the auditory meatus7. Height was measured once
in centimeters (cm) with inelastic metric tape mea-
Clinical evolution suring 150 cm, fixed on a plane wall, without skirt-
Patients were followed-up for six months. Dur- ing, 50 cm from the ground. It was set in a square on
ing the three first months, appointments took place ev- the upper part of the head, thus obtaining a 0.1 cm
ery 15 days for clinical assessment. In the last three precision measurement.
months, appointments were monthly. After obtaining data such as weight and height,
Patients remained with their routine diet, even BMI was measured by the division of the weight, in
though they received general guidance on how to keep kilograms, by the square of the height, in meters.
a healthy diet during treatment. After six months of The value of BMI <18.5 kg/m2 was used to char-
follow-up, an individual diet was recommended for acterize thinness; 18.5 kg/m2 <BMI<25 kg/m2, eu-
each patient, and they were referred to other profes- trophy; 25 kg/m2<BMI<30 kg/m2, overweight; and
sionals from the health field when necessary. >30 kg/m2, obesity, according to the classification
The anthropometric evaluation took place by suggested by the World Health Organization8.
means of body mass index (BMI), triceps skinfold TSF was measured with the speed reading Cescorf®
(TSF), arm circumference (AC), arm muscle circum- compass, with scale of up to 60 mm and a ±1 mm pre-
ference (AMC) and fat percentage. The means of re- cision. Three consecutive measurements of TSF were
sults were assessed in three distinct moments: before taken, considering the arithmetic mean of the measured
the beginning of supplementation, and after three and values. In order to measure AC, a metric tape with un-
six months of treatment. extendable material with up to 150 cm, 1cm scale, was
All patients were followed-up every week by used. The value of AMC was obtained with the formula:
the researchers for doubt clarification, analysis of the AMC=AC–(0.314 x TSF)8.
proper use of the mushroom and the confirmation of TSF, AM and AMC measurements were com-
schedule, thus ensuring highest adhesion to treatment pared to the reference pattern by Frisancho9, and the
and control as to the continuity of the study. adjustment was calculated with the division of ob-
Patients who gave up were those who did not at- tained values by the percentile 50, multiplied by 100.
tend the appointments during the whole six-month pe- In order to classify the nutritional status, the following
riod. Those who died before the end of treatment were values were considered: >120% obesity; 110–120%
excluded from the sample. overweight; 90–110% eutrophy; 80–90% mild mal-
nutrition; 70–80% moderate malnutrition; e <70% se-
Anthropometric evaluation vere malnutrition10. Fat percentage was obtained with
A special file was used for the anthropometric the digital scale Plenna®.
evaluation, which should be filled up in all appoint-
ments. Weight was measured with the patient barefoot, Statistical analysis
wearing light clothes, with no jewelry that could inter- The presented values were compared and ana-
fere with the measurement, standing in the center of the lyzed by means of statistical tests such as Student’s t
scale with the body weight equally distributed on both and F, using the softwares Microsoft Excel 2007 and
feet6. The scale was the digital Plenna® (Resolve), with Statistical Package of the Social Sciences (SPSS<SPSS
bioimpedance (BIA), model MEA-02500, capacity for Inc, Chicago, EUA) for Windows, version 19.0. The
150 kg and variation of 0.1 g, properly calibrated. probability of statistical significance was p≤0.05.

367
J Coloproctol Anthropometric assessment of men with colorectal cancer after dietary supplement Vol. 32
October/December, 2012 with Agaricus sylvaticus fungus Nº 4
Renata Costa Fortes et al.

RESULTS In Gif no significant changes were observed in TSF


after 3 months (from 13.94±9.80 to 14.02±9.06 mm,
After a six-month follow-up at the outpatient p=0.33), and 6 months (from 13.94±9.80 to
Coloproctology clinic at Hospital Base in the fed- 13.44±8.69 mm, p=0.20) of supplements (Figure 3).
eral district, 24 male patients with colorectal can- After calculating AMC, in Gp a non-sig-
cer, mean age of 61.5±13 years, stages I (n=08), II nificant decrease was observed after 3 months
(n=04) and III (n=12), separated into the groups who (from 24.65±2.67 to 24.59±1.72 cm, p=0.50), and
took placebo (n=12) and A. sylvaticus (n=12), con- 6 months (from 24.65±2.67 to 24.53±1.62 cm,
cluded the study. p=0.40), (Figure 4).
Mean age of Gp was 58.63±14.41 years, and Gf presented differences concerning AMC after 3
56.87±15.16 years in the Gf (p=0.38). months (from 25.28±2.74 to 24.82±2.06 cm, p=0.28),
When analyzing BMI, it was observed that Gp pre- however, with significant increase after 6 months of
sented initial BMI of 23.52±4.45 kg/m2; after 3 months, supplements (from 25.28±2.74 to 26.59±2.67 cm,
23.80±3.96 kg/m2 (p=0.15); and, in the sixth month, p=0.04), (Figure 4).
24.80±3.80 kg/m2 (p=0.11), however, these changes As to the analyses of fat percentage, Gp initial-
were not statistically significant (Figure 1). ly presented mean value of 26.60±8.50% (p=0.50);
The Gf presented initial BMI of 25.05±3.62 kg/m2; after 3 months, of 26.60±5.45% (p=0.50), be-
after 3 months, 25.03±3.74 kg/m2 (p=0.44); and in the ing constant until the sixth month, 26.60±8.50%
sixth month, 25.23±3.58 kg/m2 (p=0.18), results with no (p=0.50), however, these changes were not statisti-
significant statistical difference (Figure 1). cally significant (Figure 5).
Concerning AC, the Gp had initial mean of
29.30±4.32 cm; after 3 months, 30.00±2.62 cm 30.2
Arm circumference (cm)

(p=0.29), and after 6 months, 29.62±2.50 cm (p=0.40), 30


however, these changes were not statistically signifi- 29.8
cant (Figure 2). 29.6
Gf presented initial values for AC of 29.68±3.26 29.4
cm; after 3 months with supplements, 29.47±3.58 cm 29.2
(p=0.27), and after 6 months, 29.66±3.44 cm (p=0.47), 29
and these results do not differ statistically (Figure 2). 28.8
Beginning 3 months 6 months
As to TSF, it was observed that Gp pre- Placebo group A. Sylvaticus group
sented mean initial value of 14.40±6.69 mm; af-
Figure 2. Arm circumference (cm) of men with colorectal cancer
ter 3 months, 14.40±5.89 mm (p=0.40), and, after from the placebo (n=12) and Agaricus sylvaticus (n=12) groups,
6 months, 14.30±5.82 mm (p=0.09), however, these assisted in a public hospital of the federal district during the
changes were not statistically significant (Figure 3). whole follow-up period.

25.5
Body mass index (kg/m2)

14.6
Triceps skinfold (mm)

25 14.4
14.2
24.5 14
24 13.8
13.6
23.5 13.4
23 13.2
13
22.5
Beginning 3 months 6 months 12.8
Beginning 3 months 6 months
Placebo group A. Sylvaticus group Placebo group A. Sylvaticus group
Figure 1. Body mass index (kg/m2) of men with colorectal cancer Figure 3. Triceps skinfold (mm) of men with colorectal cancer
in groups placebo (n=12) and Agaricus sylvaticus (n=12) of the placebo (n=12) and Agaricus sylvaticus (n=12) groups,
assisted at a public hospital in the federal district during the assisted in a public hospital of the federal district during the
whole clinical follow-up. whole follow-up period.

368
J Coloproctol Anthropometric assessment of men with colorectal cancer after dietary supplement Vol. 32
October/December, 2012 with Agaricus sylvaticus fungus Nº 4
Renata Costa Fortes et al.

In patients with malignant neoplasms, it is ob-


Arm muscle circumference (cm)

27 served that the depletion of the fat tissue is responsible


26.5 for most of the weight loss. The loss of body nitrogen
26 has also been reported in 50 to 70% of the malnour-
25.5
ished oncologic patients, and the depletion of muscle
25
24.5
tissue is considered as the main cause of the reduction
24 of survival in these patients1.
23.5 In this study, no statistically significant changes
23 were observed in both groups in relation to the ana-
Beginning 3 months 6 months
Placebo group A. Sylvaticus group lyzed anthropometric parameters (BMI, AC, TSF, fat
Figure 4. Arm muscle circumference (cm) of men with colorectal percentage), except concerning the thin mass (AMC),
cancer of the placebo (n=12) and Agaricus sylvaticus (n=12) which increased significantly in Gf after six months of
groups, assisted in a public hospital of the federal district during supplements, which was not observed in Gp. Scientific
the whole follow-up period. evidence points out that medicinal fungi have bioac-
tive compounds that can avoid muscle protein catabo-
29 lism, which is commonly present in these patients1-3,5,11,16,
which partly explain the observed results.
Body fat percentage

28.5
28 Catalano et al.14 evaluated the nutritional sta-
27.5 tus of patients with cancer by means of bioimped-
27 ance and anthropometric variables. They noticed
26.5
that even though the anthropometric indexes pre-
26
sented normal values, bioimpedance revealed mal-
25.5
Beginning 3 months 6 months nutrition with changes in the ratio of extracellular
Placebo group A. Sylvaticus group and intracellular mass.
Figure 5. Body fat percentage of men with colorectal cancer of the The use of arm circumference and skin folds can
placebo (n=12) and Agaricus sylvaticus (n=12) groups, assisted in a be important to diagnose the nutritional status of a
public hospital of the federal district during the whole follow-up period.
patient, especially when there is no body weight. AC
represents the sum of bone, muscle and fat tissues; tri-
DISCUSSION ceps skinfold refers to the estimate of layers and/or
compromise of the fat tissue; and arm muscle circum-
In this study, mean age of patients was 58 and ference shows the quantity or degree of depletion of
56 years old in both Gp and Gf, respectively. Stud- muscle layers14.
ies show that colorectal cancer affects mostly the age Protein depletions are manifested especially by
group equal or superior to 50 years1,11,12. the atrophy of the skeletal muscle, atrophy of visceral
Both Gp and Gf presented initial BMI within the organs, myopathy and hypoalbuminemia. The reduc-
eutrophy range, with a tendency to overweight. Sci- tion of protein mass and the skeletal atrophy predis-
entific research has shown a positive relation between pose patients with cancer to an increased risk of infec-
overweight, obesity and risk of developing several tions, difficulties to heal wounds, increased asthenia
types of cancer, and also mortality due to this disease13. and decreased functional capacity1-3.
Anthropometry is a technique developed to assess There is also a positive association between ex-
body composition in a more complete manner14. It is cessive weight and risk of colorectal cancer among men
characterized by a simple and low cost method, which when compared to women. This shows that abdominal
is non-invasive and highly reliable. The objective is to distribution or central body fat, which is mostly a male
identify the quantity and the distribution of the main de- characteristic, is the main component of the increased
terminers of body composition15. Therefore, anthropo- risk for heart disease, once it is connected to the periph-
metric data should be obtained to check for depletion, eral resistance to insulin and hyperinsulin13. However,
repletion and maintenance of studied compartments14. visceral fat was not assessed in this study.

369
J Coloproctol Anthropometric assessment of men with colorectal cancer after dietary supplement Vol. 32
October/December, 2012 with Agaricus sylvaticus fungus Nº 4
Renata Costa Fortes et al.

Scientific evidence proves that medicinal fungi people with malignant neoplasms after diet supplement
have anabolic effects, once they contain all the nec- with A. sylvaticus fungi and other medicinal fungi.
essary amino acids, besides arginine and glutamine, However, scientific studies prove that medicinal fun-
which, in moments of metabolic stress, become condi- gi are able to cause beneficial changes in the metabo-
tionally essential, thus contributing with improvements lism of nutrients and in the hematopoietic, immune and
in the nitrogen balance1,16,17. Other bioactive substances gastrointestinal systems of patients with cancer, which
that are present in medicinal fungi also stand out, such reflects positively on their quality of life1,3,5,11,16-23.
as: glucans, proteoglucans, lectins, ergosterol and trit-
erpenes, both able to modulate the different metabolic CONCLUSION
and immune actions in these patients1,3,16-21.
The mechanisms of action of the bioactive com- The results show that diet supplement with
pounds that are present in the fungi are not fully clear A. sylvaticus fungi is able to significantly improve the
in literature yet, but scientific studies suggest that muscle mass of male patients with colorectal cancer.
these substances can modulate the carcinogenesis in However, more clinical controlled and randomized
all stages of the disease, especially by stimulating the trials are necessary to clarify the mechanisms of ac-
immune system18,21,22. tion of the bioactive principles that are present in the
In literature, no scientific articles were found that A. sylvaticus and the different clinical situations that
evaluated the nutritional or anthropometric status of could benefit from this supplement.

REFERENCES 8. World Health Organization. Obesity: preventing and


managing the global epidemic. Geneva: WHO, 1997.
1. Fortes RC, Recôva VL, Melo AL, Novaes RC. Life 9. Frisancho AR. Anthropometric standards for the assesment
quality of postsurgical patients with colorectal cancer after of growth and nutritional status. Michigan: University of
supplemented diet with Agaricus sylvaticus fungus. Nutr Michigan, 1990.
Hosp 2010;25(4):586-96. 10. Blackburn GL, Thornton PA. Nutrition assessment of the
2. Fortes RC, Recôva VL, Melo AL, Novaes MRCG. Hábitos hospitalized patients. Med Clin North Am 1979;63:1103-15.
dietéticos de pacientes com câncer colorretal em fase pós- 11. Fortes RC, Recôva VL, Melo AL, Novaes MRCG. Qualidade
operatória. Rev Bras Cancerol 2007;53(3):277-89. de vida de pacientes com câncer colorretal em uso de
3. Fortes RC, Novaes MRCG. Efeitos da suplementação suplementação dietética com fungos Agaricus sylvaticus após
dietética com cogumelos Agaricales e outros fungos seis meses de segmento: ensaio clínico aleatorizado e placebo-
medicinais na terapia contra o câncer. Rev Bras Cancerol controlado. Rev Bras Coloproctol 2007;27(2):130-8.
2006;52(4):363-71. 12. Kimura CA, Kamada I, Fortes RC, Monteiro PS. Reflexões para
4. Castione MF, Garcia PPC, Sousa AS. Perfil nutricional em os profissionais de saúde sobre a qualidade de vida de pacientes
pacientes oncológicos no período pré–operatório em uma oncológicos estomizados. Com Ciências Saúde 2009;20(4):333-40.
unidade hospitalar da rede pública do Distrito Federal. 13. Cozerattolini R, Gallon CW. Qualidade de vida e
Ensaios e Ciência: C. Biológicas, Agrárias e da Saúde perfil nutricional de pacientes com câncer colorretal
2010;14(1):29-40. colostomizados. Rev Bras Coloproctol 2010;30(3):289-98.
5. Fortes RC, Novaes MRCG, Recôva VL, Melo AL. 14. Catalano G, Della Vittoria Scarpati M, De Vita F, Federico
Immunological, hematological and glycemia effects of dietary P, Guarino G, Perrelli A, et al. The role of “bioelectrical
supplementation with Agaricus sylvaticus on patients’ colorectal impedance analysis” in the evaluation of the nutritional status
cancer. Exp Biol Med (Maywood) 2009; 234(1):53-62. of cancer patients. Adv Exp Med Biol 1993;348:145-8.
6. Lohman TG, Roche AF, Martorell R. Anthropometric 15. Waitzberg DL, Ferrini MT. Exame físico e antropometria. In:
standardization reference manual. Champaing/Illinois: Waitzberg DL. Nutrição oral, enteral e parenteral na prática
Human Kinetics Books, 1988. clínica. São Paulo: Atheneu, 2000. p. 255-78.
7. Shils ME, Olson JA, Shike M, Ross AC. Tratado de nutrição 16. Fortes RC, Novaes MRCG. The effects of Agaricus
moderna na saúde e na doença. 9a. ed. São Paulo: Manole, 2003. sylvaticus fungi dietary supplementation on the metabolism

370
J Coloproctol Anthropometric assessment of men with colorectal cancer after dietary supplement Vol. 32
October/December, 2012 with Agaricus sylvaticus fungus Nº 4
Renata Costa Fortes et al.

and blood pressure of patients with colorectal cancer during 21. Fortes RC, Taveira VC, Novaes MRCG. The immunomodulator
post surgical phase. Nutr Hosp 2011;26(1):176-86. role of β–D-glucans as co-adjuvant for cancer therapy. Rev
17. Novaes MRCG, Fortes RC, Garcez LC. Cogumelos comestíveis da Bras Nutr Clin 2006;21(2):163-8.
família Agaricaceae: aspectos nutricionais e atividade farmacológica 22. Novaes MRCG, Fortes RC. Efeitos antitumorais de
no câncer. Rev Soc Bras Farm Hosp 2004;5(4):15-20. cogumelos comestíveis da família Agaricaceae. Rev Nutr
18. Fortes RC, Novaes MRCG. Terapia nutricional com fungos Bras 2005;4(4):207-17.
medicinais em pacientes oncológicos: uma perspectiva no
23. Fortes RC, Recôva VL, Melo AL, Novaes MRCG. Alterações
tratamento adjuvante do câncer. Nutrição Brasil 2010;9(5):310-9.
gastrointestinais em pacientes com câncer colorretal em
19. Taveira VC, Novaes MRCG, Reis MA, Silva MF. Hematologic
ensaio clínico com fungos Agaricus sylvaticus. Rev Bras
and metabolic effects of dietary supplementation with
Agaricus sylvaticus fungi on rats bearing solid walker tumor. Coloproctol 2010;30(1):45-54.
Exp Biol Med (Maywood) 2008;233(11):1341-7.
20. Fortes RC, Recôva VL, Melo AL, Novaes MRCG. Effects Correspondence to:
of dietary supplementation with medicinal fungus in Renata Costa Fortes
fasting glycemia levels of patients with colorectal cancer: a QI 14. CJ J. CS 26 – Guará 1
randomized, double-blind, placebo-controlled clinical study. CEP: 71015-100 – Brasília (DF), Brazil
Nutr Hosp 2008;23(6):591-8. E-mail: fortes.rc@gmail.com

371
Original Article

Doppler-guided hemorrhoidal artery ligation with


rectal mucopexy technique: initial evaluation of 42 cases
Carlos Mateus Rotta1, Fernando Oriolli de Moraes2, Araripe Fernandez Varella Neto3, Thereza Cristina Ariza Rotta4,
João Vitor Antunes Marques Gregório4, Alfredo Luiz Jacomo6, Carlos Augusto Real Martinez7

Professor Doctor of Coloproctology at the Surgical Clinic of the Medical School at Universidade de Mogi das Cruzes
1

(UMC) – Mogi das Cruzes (SP), Brazil .2Digestive Tract surgeon at Hospital e Maternidade Mogi D’or – Mogi das
Cruzes (SP), Brazil. 3Digestive Tract surgeon at Hospital Nove de Julho – São Paulo (SP), Brazil. 4Student at the 6th
year of the Medical School of UMC – Mogi das Cruzes (SP), Brazil. 5Associate Professor by the Department of Surgery
at Universidade de São Paulo (USP) — São Paulo (SP), Brazil. 6Associate Professor by the Department of Surgery at
USP — São Paulo (SP), Brazil; 7Adjunct Professor of the Health Sciences Post-Graduation Program of Universidade São
Francisco (USF) — Bragança Paulista (SP), Brazil.

Rotta CM, Moraes FO, Varella Neto AF, Rotta TCA, Gregório JVAM, Jacomo AL, Martinez CAR. Doppler-guided hemorrhoidal artery
ligation with rectal mucopexy technique): initial evaluation of 42 cases. J Coloproct, 2012;32(4): 372-384.
ABSTRACT: The treatment of hemorrhoidal disease (HD) by conventional hemorrhoidectomy is associated with significant morbidity,
mainly represented by the postoperative pain and the late return to daily activities. Doppler-guided hemorrhoid artery ligation (DGHAL)
is a minimal-invasive surgical treatment for HD that has been used as an alternative method in order to reduce these inconveniences.
Objective: To analyze the initial results of the DGHAL technique associated with rectal mucopexy in the treatment of HD.
Methods: Forty-two patients with stage I, III and IV hemorrhoids who were submitted to DGHAL were analyzed from December 2010
to August 2011. Eleven patients (26%) were stage II; 21 (50%), stage III; and 10 (24%), stage IV HD. All patients were operated by the
same surgeon under spinal anesthesia and using the same equipment and technique to perform the procedure. The 42 patients underwent
ligation of six arterial branches followed by rectal mucopexia by uninterrupted suture. Nine patients needed concomitant removal of
perianal skin tag. In the postoperative, the following parameters were evaluated: pain, tenesmus, bleeding, itching, prolapse, mucus
discharge and recurrence. The mean postoperative follow-up lasted four months (one to nine months). Results: Tenesmus was the most
common postoperative complaint for 85.7% of patients followed by pain, in 28.6%, perianal burning, in 12.3%, mucus discharge and
perianal hematoma in 4.7%. Two patients had severe postoperative bleeding and required surgical haemostasis, one of which needed
blood transfusion. Ninety-five percent of the patients declared to be satisfied with the method. Conclusion: Even though DGHAL has
complications similar to those of other surgical methods, its results present less postoperative pain, allowing faster recovery and return
to work. Studies with more cases and a longer follow-up are still necessary to assess the late recurrence.

Keywords: hemorrhoids; hemorrhoids/surgery; ligation; ultrasonography, doppler.

Resumo: O tratamento da doença hemorroidária (DH) pelas técnicas convencionais cursa com significante morbidade principalmen-
te relacionada à dor pós-operatória e ao considerável tempo de afastamento do trabalho. A técnica de desarterialização hemorroidária
transanal guiada por doppler (DHGD) associada à mucopexia retal é uma opção cirúrgica menos invasiva que vem sendo utilizada como
método alternativo com objetivo de reduzir esses inconvenientes. Objetivo: Analisar os resultados iniciais com a técnica da DHGD
associada à mucopexia retal no tratamento da DH. Método: Foram estudados 42 pacientes, portadores de DH de graus II, III e IV
submetidos à técnica da DHGD, durante o período de dezembro de 2010 a agosto de 2011. Onze pacientes (26%) apresentavam DH do
grau II, 21(50%) do III e 10 (24%) do IV. Todos os pacientes foram operados pelo mesmo cirurgião, sob anestesia raquidiana e sempre
utilizando o mesmo equipamento e técnica para realização do procedimento. Os 42 pacientes foram submetidos à desarterialização de

Study carried out at the Department of Surgery of the Medical School of Universidade de Mogi das Cruzes (UMC); Department of Surgery at Hospital e
Maternidade Mogi-D’or – Mogi das Cruzes (SP), Brazil; Hospital Nove de Julho – São Paulo (SP), Brazil; Health Sciences Post-Graduation Program of
Universidade São Francisco (USP) – Bragança Paulista (SP), Brazil.
Financing source: none.
Conflict of interest: nothing to declare.

Submitted on: 03/06/2012


Approved on: 15/09/2012

372
J Coloproctol Doppler-guided hemorrhoidal artery ligation with rectal mucopexy technique: Vol. 32
October/December, 2012 initial evaluation of 42 cases Nº 4
Carlos Mateus Rotta et al.

6 ramos arteriais seguida de mucopexia retal por sutura contínua. Nove necessitaram remoção concomitante de plicomas perianais. No
pós-operatório, foram avaliados os parâmetros: dor, tenesmo, sangramento, prurido, prolapso, perda de muco e recidiva. O seguimento
médio foi de quatro meses (um a nove meses). Resultados: O tenesmo foi a queixa pós-operatória referida por 85,7% dos pacientes,
seguida da dor 28,6%, ardor perianal 12,3%, perda de muco e formação de hematoma perianal 4,7%. Dois pacientes apresentaram
sangramento pós-operatório de maior intensidade necessitando hemostasia cirúrgica, sendo que em um houve necessidade de reposição
sanguínea. Noventa e cinco por cento dos pacientes declararam-se satisfeitos com o método. Conclusão: A técnica da DHGD, apesar
de apresentar complicações semelhantes a outros métodos cirúrgicos, apresenta bons resultados com pouca dor pós-operatória, possibi-
litando retorno rápido ao trabalho. Estudos com maior número de casos e tempo de seguimento mais prolongado ainda são necessários
para avaliar a recidiva tardia.
Palavras-chave: hemorroidas; hemorroidas/cirurgia; ligadura; ultrassonografia doppler.

INTRODUCTION means of mechanical circular suture6,7. Since no inci-


sions are performed in the mucosa of the anal canal,
Hemorrhoidal disease (HD) is one of the most patients evolved with few painful postoperative symp-
common illnesses in a specialized doctor’s office.It toms. The lower need to care for the surgical wounds
is estimated that in industrialized countries, approxi- enables the fast return to daily activities7. However,
mately 50% of the individuals aged more than 50 years despite these benefits, MA is not free of postoperative
develop some of its main symptoms throughout life1,2. complications, and recent studies have shown high-
Even though people with HD in its early stage may er recurrence rates at long term when compared to
temporarily benefit from conservative measures, most those of CH8-10. The presence of severe complications,
of the times, when the disease is at a more advanced such as major postoperative hemorrhage and perfora-
stage, they need some sort of surgical treatment3,4. The tion in the rectal wall, has also been described, and it
most frequent conventional surgical methods to treat was probably related to the impossibility to standard-
for HD are Milligan-Morgan or Ferguson hemorrhoid- ize the depth with which the purse-string suture was
ectomy. In the hands of an expert, both present with placed into the rectal wall before stapling10. When it
few postoperative complications, excellent results in is too superficial, it might not comprehend the arterial
terms of healing the HD and acceptable recurrence branches present in the submucosa, thus increasing
rates. However, conventional hemorrhoidectomy the chances of postoperative bleeding; when too deep,
(CD) presents some main limitations, such as severe it might comprehend the whole rectal wall, causing
postoperative pain and a prolonged period away from the confection of low rectorectal anastomosis during
work because of the surgical anodermal wound, since stapling without the protection of a stoma10.
this region has a lot of sensitive nervous terminations. Aiming to interrupt the blood flow directly onto
The fear of postoperative pain leads many patients the branches of hemorrhoidal arteries and to avoid the
to avoid surgical treatment, choosing to live with the deep penetration of the suture in the rectal wall, the
limiting symptoms of HD for the rest of their lives. technique of doppler-guided hemorrhoid artery liga-
With the objective to reduce the inconvenience tion (DGHAL)11 was proposed. With this method, it
of CD, from the 1990s on new methods have been is possible to interrupt the blood flow onto the arte-
proposed to treat HD. Among them, mechanical an- rial branches, thus avoiding surgical incisions below
orectopexy (MA) became the most diffuse surgical the dentate line, which is the main cause of postopera-
procedure as an alternative method to conventional tive pain in CH12,13. The DGHAL technique, when as-
techniques5-7. In MA, the irrigation is interrupted and sociated with rectal mucopexy, also enables the high
there is the fixation of the mucosa through the resec- fixation and, therefore, the correction of prolapsed in-
tion of mucosal and submucosal cuff in the lower rec- ternal hemorrhoids13-24. However, despite being used
tum, above the pectineal line, reconstituting and fix- for years, especially in Europe, the DGHAL technique
ating the borders of the remaining rectal mucosa by has been little diffused in Brazil. The objective of

373
J Coloproctol Doppler-guided hemorrhoidal artery ligation with rectal mucopexy technique): Vol. 32
October/December, 2012 initial evaluation of 42 cases Nº 4
Carlos Mateus Rotta et al.

this study is to present the initial experience with the Table 1. Characteristic of the studied sample.
DGHAL technique associated with rectal mucopexy Characteristic n %
in the surgical treatment of HD. Gender
Men 29 69.04
METHODS Women 13 30.96
Hemorrhoid stage
Table 1 shows the characteristics of the studied II 11 26
patients. Fourty two of them (29 men), with mean age III 21 50
IV 10 24
of 42.3 years (31 to 64) with HD were included in this
Presence of
study. Eleven (26%) presented with HD in stage II, re- associated skin tags
fractory to conservative treatment, 21 (50%), stage III, Without skin tags 33 78.57
and 10 (24%), stage IV. No patient had recurrence and With skin tags 9 21.43
nine of them presented with associated anal skin tags. Mean age (years) 42.3 (31–64) –
Patients who were excluded presented with other as- Total of patients 42 100
sociated anorectal disease, such as: anal fissure, peri-
anal fistula, external hemorrhoid thrombosis, hidrad-
enitis suppurativa, neoplastic disease of any origin or holder and the standardization of the stitch depth pen-
those who were on anticoagulants. etration performed through the lateral window. Su-
All patients were enlightened as to the surgical ture thread with a knot threader and the optical fiber
procedure to which they would be submitted and, af- cable accompany the equipment. The double crystal
ter agreeing to participate in the study, they signed an transducer captures sonic waves emitted by the arte-
informed consent form. rial branches located on the surface of the rectal wall.
All surgeries were elective and performed by the When connected to the unit, the sound is amplified.
same surgeon (CMR) from December 2010 to August It is a sliding transducer, so it can be freely removed
2011. Before the procedure, all volunteers were sub- by the surgeon and addressed towards the operating
mitted to anamnesis with special focus on the time of window of the anoscope. Therefore, it is possible to
evolution of the HD, frequency of bleeding, presence identify the sound coming exclusively from the arte-
of pain, mucosal prolapsed, anal incontinence and his- rial branches.
tory of prior hemorrhoid thrombosis. All of them were
submitted to a full rectal examination with static and Doppler guided transanal hemorrhoidal
dynamic inspection, rectal touch and rigid proctosig- dearterialization surgical technique
moidoscopy. No patient underwent anorectal manom- All patients were admitted to the hospital in the
etry. Patients aged more than 50 years were submitted morning and submitted to mechanical bowel prepara-
not only to rectal examination, but also to colonosco- tion with enema containing 118 mL of dibasic sodium
py to track for colorectal cancer. All patients were fol- phosphate 0.06 g/mL and monobasic sodium phos-
lowed-up for about four months (one to nine months). phate 0.16 g/mL (Fleet-enema® from Fleet Laborato-
ries, Lynchburg, Virginia, USA), used three hours be-
Equipment fore the procedure. Surgeries were always performed
The system used was composed of a doppler- with spinal anesthesia and all patients received anti-
fluxometry unit associated with a cold light source biotic prophylaxis with metronidazole (Sanofi-Aven-
(THD UK Ltd., Worcester, United Kingdom). The tis Farmacêutica Ltda., Suzano, São Paulo, Brazil),
unit has two exits to which a transducer that captures 500 mg intravenously during anesthetic induction, re-
sonic waves and an optical fiber cable are connected. peated every 8 hours during the first 24 hours. All in-
An anoscope comes with the equipment, and it is espe- terventions were performed with patients in the lithot-
cially confectioned for the procedure. It is comprised omy position.
of a fixed part and a sliding bar to perform mucopexy, After rectal touch and gentle anal dilation, the
a central pivot at the extremity to couple the needle anoscope was lubricated with gel and used to for ul-

374
J Coloproctol Doppler-guided hemorrhoidal artery ligation with rectal mucopexy technique: Vol. 32
October/December, 2012 initial evaluation of 42 cases Nº 4
Carlos Mateus Rotta et al.

trasound. The anoscope was previously coupled to the evacuations. All patients were discharged on non-hor-
doppler equipment and introduced carefully, until it monal anti-inflammatories (Tenoxicam – 60 mg/day)
reached the lower portion of the rectum, approximately and tramadol chlorhydrate (200 mg/day) in case of se-
seven centimeters above the anal border. Afterwards, vere pain. Postoperative follow-up took place in the
the set was moved to the craniocaudal and laterolateral first and fourth weeks and, afterwards, once a month,
direction until it was possible to hear the best intensity so there was no loss to follow-up in the considered pe-
of the acoustic signal coming from the arterial branch riod. After one month, all patients were interviewed in
identified in the upper lateral rectal wall. After identi- relation to the satisfaction with the method.
fying the cranial branch, the transducer was guided to
the rectal direction identifying the segment of the rec- RESULTS
tal wall where there was no emission of sound waves
(non-acoustic window). The traction progressed and The main symptoms mentioned before surgery
was interrupted when finding a second point of sound were: bleeding (97%), anal discomfort (95%), hemor-
emission located in the lower portion of the rectum. rhoid prolapse (92%), anal pruritus (53%) and mucus
At this point, located above the dentate line, the mu- discharge (23%). Mean surgery time was 35±10 min-
cosa was marked with an electric scalpel. Afterwards, utes to perform dearterialization and mucopexy. All
the anoscope was repositioned in the cranial portion of patients were submitted to rectal mucopexy and de-
the rectum and the needle-holder was introduced until arterialization of six arterial branches. In 9 of them
its extremity was firmly coupled to the pivot, placed to (21.43%), besides dearterialization and mucopexy,
the distal extremity of the anoscope. In its extremity, the there was the need to resect skin tags (one or more).
needle-holder clenched a cylindrical curved needle with Skin tag resection was performed by elliptical incision
a 5/8 circumference, 2.65 of length, already coupled to and afterwards it was sutured with absorbable mono-
the thread, monofilamental (2–0), absorbable and pro- filament thread (3–0). After dearterialization, there
vided with the system. Dearterialization began at the was the need for complementary haemostatic suture
cranial sound emission point by applying two trans- during surgery in five patients (8.4%). Figures 1 and 2
fixion X stitches manually tied. The depth of needle show the patients with HD before and after DGHAL
penetration in the rectal wall through the lateral win- with rectal mucopexy.
dow of the anoscope was limited by the pivot. After Figure 3 represents the main complaints in the
the ligation of the cranial branch, the mucosal prolapse fourth week after surgery. Thirty six patients (85.71%)
was corrected by continuous suture (three to four) per- complained of tenesmus, 12 (28.6%), of anorectal
formed with straight vision from the rectum to the anal pain, 8 (19.5%), of burning sensation, 6 (12.3%) of
canal, going through the region without sound emis- mucus discharge, 2 (4.76%), of anal pruritus. Two pa-
sion (non-acoustic window). The suture progressed to tients progressed with perianal hematoma (4.76%),
the place previously marked with the electric scalpel, and in one of them, full thrombus regression remained
where the second point of sound emission was located. for 30 days. All patients who underwent skin tag re-
Rectal mucopexy was concluded by tying the first to section complained of more frequent anal pain at the
the last stitch. Dearteralization always began by the postoperative period. Twenty percent of patients de-
branch located at three hours clockwise. An identical veloped urinary retention at the immediate postop-
procedure was repeated at 1, 5, 7, 8 and 11 hours, and erative period, requiring the use of probe. In one of
six arterial branches were always dearterialized. After them, who also evolved with concomitant external
the procedure was finished, a healing patch was made hematoma, the retention lasted for seven days requir-
by introducing a homeostatic sponge in the anal canal. ing repeated bladder probes during this period. Two
At the postoperative period, patients were recom- patients (4.76%) presented with postoperative bleed-
mended to have a diet rich in fibers, liquids and Psyl- ing, therefore needing surgical haemostasis, which
lium fiber twice a day. The recommendations for pa- was performed on the fifth and ninth postoperative
tients who were submitted to concomitant resection of days; one of them required blood replacement. One
skin tags were to have hip baths with warm water after patient mentioned fecal incontinence for one day, and

375
J Coloproctol Doppler-guided hemorrhoidal artery ligation with rectal mucopexy technique): Vol. 32
October/December, 2012 initial evaluation of 42 cases Nº 4
Carlos Mateus Rotta et al.

A B

Figure 1. (A) Preoperative aspecto f patient with hemorrhoid disease in stage III. (B) Immediate postoperative of the same patient submitted
to the doppler-guided transanal hemorrhoidal dearterialization with mucopexy.

A B

Figure 2. (A) Preoperative aspect of patient with hemorrhoidal disease. (B) Immediate postoperative of the same patient submitted to the
doppler-guided transanal hemorrhoidal dearterialization with mucopexy.

two others (4.76%) developed anal fissure between remission of symptoms, be of simple technical execu-
the 7th and 15th postoperative days, which healed with tion and financially accessible, be well tolerated by the
clinical treatment. No recurrence was observed in the patients and progress with low rates of postoperative
follow-up period. complications and recurrence24,25. The great number of
surgical procedures that are currently available to treat
DISCUSSION HD shows that until now none of the proposed tech-
niques can gather all of these items. Nowadays, CH is
The best surgical choice to treat symptomatic still the most used surgical choice around the world for
HD must consider the following: it should provide full the treatment of HD. Despite being effective to control

376
J Coloproctol Doppler-guided hemorrhoidal artery ligation with rectal mucopexy technique: Vol. 32
October/December, 2012 initial evaluation of 42 cases Nº 4
Carlos Mateus Rotta et al.

40

35

30
Number of patients

25

20

15

10

0
Tenesmus Pain Burning Mucus Pruritus Hematoma Hemorrhage Fissure
discharge
Figure 3. Main symptoms reported until the fourth week after the surgery.

symptoms and evolving with low recurrence rates, its mucosal prolapse, resecting it and fixating it (MA), or
main limitations are the severe postoperative pain and just by fixating it inside the rectum (DGHAL)14.
the necessary care during convalescence, and because The MA technique proposed by Longo6, in 1998,
of that the patient is away from daily activities for a interrupts the blood flow to the hemorrhoidal plexus
considerable amount of time24,25. Aiming to come up and reduces prolapsed by the resection of a circular
with alternative methods that are able to minimize the mucosal and submucosal segment above the dentate
inconvenient of CH, new surgical options have ap- line, and fixating the remaining mucosa at a higher sit-
peared to treat HD6,11. In the modern group of thera- uation by means of mechanical circular suture24. The
pies to treat HD, MA and DGHAL represent the most resection of the excess of mucosa with posterior re-
used alternatives23,25. Despite the advantages of both placement inside the rectum, besides correcting hem-
methods concerning reduced postoperative pain and orrhoidal prolapsed, also has the advantage to improve
faster return to the patient’s social daily life, the main the mechanisms of continence since it normalizes the
limiting factors for the greater acceptance of such pro- anal pressure at rest. Since there are no incisions below
cedures are related to higher costs for the health sys- the dentate line, which is an anatomic region rich in
tems (both public and private), which certainly do not sensitive terminations, the MA technique significantly
cover all necessary expenses to perform these meth- reduces the intensity of postoperative pain when com-
ods, thus condemning the patients to pay for part of pared to conventional techniques25. The absence of sur-
them, and to the yet minor postoperative follow-up. gical wound in the anoderm decreases the need for fre-
The proposal of both techniques is to treat HD quent postoperative care and enables the patient to get
by the interruption of blood flow to the hemorrhoid- back to daily activities faster25. However, despite these
al plexus and the reduction of mucosal prolapse with undeniable advantages, recent sample reviews have
rectal mucopexy, thus restablishing the regular an rec- shown that the MA technique evolves with long term
tal anatomy6,11. Both procedures try to achieve these recurrence rates up to 5.5 times higher than CH8,25,26.
objectives by interrupting the blood flow to the hem- The reduction of blood flow to the hemorrhoid-
orrhoidal plexux and by fixating the excess of rectal al plexus, with the MA technique, is obtained by the

377
J Coloproctol Doppler-guided hemorrhoidal artery ligation with rectal mucopexy technique): Vol. 32
October/December, 2012 initial evaluation of 42 cases Nº 4
Carlos Mateus Rotta et al.

transaction of caudal branches of the upper rectal ar- advantages in relation to CH concerning the less in-
tery during the resection of the mucosal and submu- tense postoperative pain and the faster return to daily
cosal cuff followed by mechanical stapling23. How- activities, the MA technique costs more and probably
ever, a recent study evaluating arterial blood flow in has higher recurrence rates at long term.
the hemorrhoidal plexus, before and after the proce- The DGHAL technique, in theory, presents the
dure, did not find significant differences, thus suggest- same technical proposal of MA: the interruption of
ing that the MA technique is not able to completely blood flow through the distal branches of the upper
interrupt the blood flow by the intramural branches rectal artery by the application of transfixion stitches
of the upper rectal artery, located below the point directly over these branches and posterior fixation of
where the stapling was performed27. It is possible that prolapsed hemorrhoids inside the rectum at a higher
the height the rectum where the stapling is performed situation11. Unlike MA, the use of a Doppler equipment
in the rectum may be involved in the lower dearteri- associated with a light source attached to an anoscope,
alization. The maintenance of blood supply by these especially designed for the procedure, enables the pre-
caudal branches may be one of the factors responsi- cise location of the arterial branches that are present
ble for higher rates of late recurrence when compared in the rectal wall11,23. Therefore, these arteries are in-
to CH27. Concerning the complications of MA, ma- dividually identified, which not only enables the em-
jor postoperative bleeding and pain resulting from the ployment of the transfixion stitch directly over these
stapling being too close to the dentate line or because arteries, but also allows verifying if the blood flow has
of the presence of the surgical staples are usually de- been completely stopped after the conclusion of the su-
scribed7,25. The urge to evacuate, tenesmus, sensation ture. The technological characteristics of the system is
of a foreign body in the rectum, persisten proctalgia comprised of a double crystal echo acoustic transducer
and incomplete evacuation have been increasingly de- that can capture sonic waves emitted by the smallest
scribed, while stenosis and lack of stapling are rarer branches located on the surface of the rectal wall, thus
complications26,28. However, the most feared compli- increasing the precision of the ligation of these vessels.
cation from MA is the risk of potential pelvic infec- The exact location through which an arterial branch
tions when the full resection of the whole rectal wall passes enables the suture and the posterior mucopexy
takes place during mechanical stapling8-10. The result to be performed exactly onto the vessel throughout the
of the complication is similar to performing an ultra longitudinal axis of the rectum, thus leaving free room
low rectal anastomosis, in a rectum without mechani- between each stitch. This detail decreases the chance,
cal preparation, and without the protection of a proxi- at least in theory, as with MA, of the full blockage of
mal stoma, which can evolve to severe abdominal and the venous flow by the hemorrhoidal venous plexus,
pelvic infections, mostly fatal8-10. Since this kind of which is responsible for postoperative cases of ex-
complication can happen with surgeons at different ternal hemorrhoid thrombosis. The space between
stages in relation to learning the method, it is possi- stitches also reduces the chance of the total oblitera-
ble that it occurs due to the confection of suture in tion of the rectal lumen, which is a complication de-
a purse string without the standardization of depth to scribed after the use of MA28. Another advantage of
penetrate the stitches into the rectal wall10. In favor of DGHAL in relation to MA is that the provided ano-
this probability is the constant presence of segments scope already coupled to the transducer and cable light
of muscle layers from the rectal wall in the resected enables the application of transfixion stitches to be per-
specimens, submitted to histopathological analysis29. formed with straight view, and its depth is guided by
Changes in the initially designed equipment and new the pivot placed in the equipment. Such details also
devices have been proposed in order to decrease the help to decrease the chance of reaching the deeper lay-
possibility of such a severe complication11,30,31. As to ers of the rectal wall. Since the depth of the stitches
the costs of MA, when compared to CH there is still becomes standardized, and there is no resection of the
controversy. Two studies demonstrated that MA costs rectal mucosal and submucosal cuff, the possibility to
more in relation to CH, while a third analysis showed completely cut the rectal wall, which is one of the main
the opposite32-34. With these considerations, despite the concerns with MA, is minor with DGHAL. However,

378
J Coloproctol Doppler-guided hemorrhoidal artery ligation with rectal mucopexy technique: Vol. 32
October/December, 2012 initial evaluation of 42 cases Nº 4
Carlos Mateus Rotta et al.

it is worth to mention that despite the greater risk of was less than the findings in this study. At a mean
lesion in the rectal wall with MA, the possibility to re- postoperative follow-up of 10 months (2-28 months),
sect and fixate a considerable segment of the prolapsed there was a significant improvement of symptoms in
mucosa at a higher situation inside the rectum brings 33 patients (94%). Nine patients (25.7%) evolved with
theoretical advantages to MA as to the lower chance of irregular bleeding when evacuating in the first weeks
prolapsed recurrence at long term. they evacuated spontaneously, 3 (8.6%) had mild anal
The possibility to identify and perform the indi- pain, 4 (11.4%) felt transitory anal burning, and 4
vidual dearterialization of each arterial branch (5–9 (11.4%) had tenesmus. Ten patients (28.6%) present-
branches) may explain the different number of liga- ed with some degree of residual prolapsed and only 2
tions when comparing the DGHAL technique with (5.7%) had a more significant mucosal prolapse and
other methods of elastic ligation of HD, in which it needed surgery. Despite the short follow-up period,
is not possible to identify exactly where the arterial the authors could not find anal stenosis or inconti-
branch passes15,19-23,27,32-34. Because of the greater se- nence. After applying a satisfaction questionnaire with
lectivity as to the location of arterial branches, the the method, they noticed that after a ten-month fol-
number of stitches (ligations) ranges from three to low-up, there was significant number of patients who
nine, according to different authors in most published were happy about it39. However, even though some
articles12-16. In this study, six arterial branches were li- suggest the DGHAL technique can be used in patients
gated and identified in positions 1, 3, 5, 7, 9 and 11 with stage IV HD, the postoperative results, like with
hours. The patient was in the lithotomy position. MA, do not present the same degree of satisfaction
In this study, the DGHAL technique was indicat- when compared to patients with less advanced stages
ed for patients with hemorrhoids in stage II, III and IV. of HD39. A second multicenter study analyzing 507 pa-
Similarly to MA, the DGHAL technique was initially tients with HD in stages II (28.4%), III (63%) and IV
used with patients with stage II HD who were refrac- (8.6%), who were submitted to the DGHAL technique
tory to conservative treatment or those at the stage III and followed-up for one year, found good results with
of the disease19,23,25,35. Afterwards, with the addition of the procedure with 69.2% of the patients, and accept-
mucopexy to surgical time, enabling the reduction and able in the remaining 4.8%40. However, when gather-
fixation of prolapsed hemorrhoids, it was possible to ing the patients according to the stage of HD, they ob-
indicate the method for patients with stage IV HD36-38. served that 92.4% of those with stage II hemorrhoids
Unlike what happens with MA, that is, the amount of and 84% of patients with stage III were satisfied with
resected tissue and the height of stapling range from the method, whilst only 41% of those with stage IV
case to case, with DGHAL it is possible to define the HD felt the same way40.
places where mucopexy will begin and end, as well Studies have clearly shown the advantages of the
as the amount of tissue involved, even for those with MA technique in relation to CH, especially concern-
stage IV HD. A study assessed the DGHAL technique ing the intensity of postoperative pain and the early
associated with rectal mucopexy in 35 patients with return to daily activities7,41-43. A review of 12 studies
the objective to decrease the need to perform CH and, that compared CH with MA, with follow-up between 6
consequently, also decrease the intensity of postopera- months to 4 years, showed that CH is more efficient to
tive pain in patients with non-fibrous stage IV HD39. reduce long term recurrence (OR=3.85; 95%CI 1.47–
The authors dearterialized six arterial branches and 10.07; p<0.006)43. CH also prevented the develop-
average surgical time was of 33±12 minutes. They ment of new hemorrhoids after 12 or more months of
also checked that during postoperative follow-up, postoperative follow-up (OR=3.6; 95%CI 1.24–10.49;
three patients (8.6%) presented with external hemor- p<0.02). CH was better in relation to preventing pro-
rhoid thrombosis; one of them needed additional sur- lapsed (OR=2.96; 95%CI 1.33–6.58; p<0.008), as well
gical treatment and two (5.7%) evolved with postop- as to avoid the development of prolapse after one or
erative bleeding. One of the latter needed haemostasis more years of follow-up (OR=2.68; 95%CI 0.98–7.34;
surgery. Five patients (14.3%) presented with urinary p<0.05). There were no significant differences favoring
retention and required an intravesical probe, which CH when the following was analyzed: the proportion of

379
J Coloproctol Doppler-guided hemorrhoidal artery ligation with rectal mucopexy technique): Vol. 32
October/December, 2012 initial evaluation of 42 cases Nº 4
Carlos Mateus Rotta et al.

asymptomatic patients, presence of postoperative bleed- needing to consume painkillers for longer48. Probably,
ing, mucus discharge, difficulties with hygiene and fecal the most intense postoperative pain is related to the
incontinence, presence of perianal skin tags and need for larger number of ligations performed with DGHAL
future surgeries. As to MA, the authors could not find and to the association of rectal mucopexy. One year
advantages concerning pain, anal pruritus, symptoms of after surgery, recurrence rates were similar48. The au-
obstructed evacuation or stenosis43. thors concluded that the simple elastic ligation of HD
However, few studies have compared the DGHAL is a simple and cost effective method to treat the dis-
technique with other surgical options to treat HD, ease in stage III, so there are no advantages to use the
which makes it difficult to conduct a more precise whole equipment of DGHAL to assist the ligation of
evaluation44,45. Bursics et al.14, in 2004, compared the hemorrhoidal vessels before mucopexy48. Spyridakis
DGHAL technique with CH after a one-year follow-up. et al.49, in 2011, studied 90 patients who underwent the
They showed that the patients submitted to the DGHAL DGHAL technique and observed that the recurrence
technique required less postoperative analgesia and less rate assessed by the presence of bleeding or muco-
days to return to work faster14. These results were con- sal prolapse was identified in 6.6% of patients, being
firmed by other authors27,45. Avital et al.46, in 2001, com- more common in patients with stage IV hemorrhoids.
pared the MA and DGHAL techniques in 63 patients The results found in this study showed that even
and found that those submitted to DGHAL presented though all patients were discharged still on anti-in-
less pain after evacuating (2.1±1.4 versus 5.5±1.9) and flammatories, 85.71% of them complained of tenes-
were on less painkillers. The length of hospital stay, the mus at the postoperative period which regressed after
interval for the first evacuation and the complete func- the second week. Despite the use of anti-inflamma-
tional recovery to evacuate were shorter for those sub- tory, eight patients (19.5%) complained of anal pain,
mitted to DGHAL46. However, 18% of patients treated and six (12.30%) mentioned constant burning, which
with DGHAL remained with bleeding or hemorrhoidal also regressed after the second and third weeks, re-
prolapse and needed complementary surgical resec- spectively. In three patients, the pain was prolonged
tion, compared to only 3% of those submitted to MA46. for one month and required the use of painkillers for
When the questionnaire to assess the satisfaction of pa- longer. These results are different from those found
tients with the procedure was applied, it was observed by other authors, showing that 72% of patients sub-
that those submitted to MA were happier in relation to mitted to DGHAL did not need postoperative anal-
those who underwent DGHAL. As previously suggest- gesia21,35. It is likely that these discomforts are owed
ed it is likely that the higher incidence of prolapse after to suture and fixation of the prolapsed hemorrhoid,
DGHAL is associated with the performance of a less which leads to ischemia, necrosis with a consequent
effective rectal mucopexy. inflammatory process at the site of mucopexy21. That
A recently published systematic literature re- is why most of the patients followed-up in this study,
view, whicht selected only randomized and controlled as well as those described by other authors, presented
studies showed, in 150 patients (80 of them submit- with more intense pain and tenesmus in the first week
ted to DGHAL and 70 to MA), that both procedures after surgery, which disappeared as the days passed
were similar in terms of satisfaction, length of opera- by35. Most authors describe the occurrence of mi-
tion, recurrence and postoperative complications47. nor bleeding associated with evacuations in the first
However, the DGHAL technique proved to be supe- days after surgery, similarly to other techniques35.
rior in relation to the intensity of postoperative pain47. Data from literature report that postoperative bleed-
A double blind randomized study compared the sim- ing takes place in 1 to 20.9% of the patients submit-
ple elastic ligation from the hemorrhoidal plexus as- ted to DGHAL12-15,17,18,34,49-51. A randomized study
sociated with mucopexy without using the DGHAL comparing patients submitted to MA and DGHAL re-
equipment with the conventional DGHAL method in port that 12% of those who underwent MA presented
patients with stage III HD48. Results shows that the with more intense bleeding, thus requiring readmis-
DGHAL technique presented longer surgical time, sion to control the hemorrhage, compared to only 4%
and patients presented more postoperative pan, thus of the patients submitted to DGHAL52. In this study,

380
J Coloproctol Doppler-guided hemorrhoidal artery ligation with rectal mucopexy technique: Vol. 32
October/December, 2012 initial evaluation of 42 cases Nº 4
Carlos Mateus Rotta et al.

in the first two weeks most patients (68%) presented mitted to DGHAL and 83% of those submitted to
with minor bleeding during evacuations. However, for MA presented with complete healing of symptoms 6
two patients rectal bleeding was major and required weeks after the intervention52. In this study, the persis-
reintervention for the hemostasis of the bleeding ves- tence of the mucosal prolapse was higher in patients
sel. In one of them there was the need for blood re- who underwent DGHAL, however, most patients with
placement in order to control acute anemia. In one of stage IV hemorrhoids were placed in the DGHAL
the patients, bleeding came from one of the transfixion group, which may have influenced the results. In this
stitches, while in the second, with the major bleeding, study, it was observed that most patients who pre-
it was originated from the site where pexy had been sented with postoperative discomfort had stage IV
performed in one of the prolapsed hemorrhoids. It is hemorrhoids or were submitted to skin tag resection.
probable that the hemorrhage is a result of necrosis, A recent study assessed 244 patients submitted to
and consequent dehiscence of mucopexy, and that the DGHAL and confirmed these observations53. By us-
continuous use of non-hormonal anti-inflammatory in ing the multivariate logistic regression analysis, the
the first week, since in interferes with the blood pro- authors concluded that the presence of mucosal pro-
file, may also have contributed for the bleeding. Other lapse is considered as a risk factor for the persistence
less frequent symptoms were mucus discharge in 6 of symptoms (OR=2.38; 95%CI 1.10–5.15). They
(14.30%) patients, urinary retention in 8 (19.4%) and also observed that patients with HD in stages III and
anal pruritus in 2 (4.76%). Two patients evolved with IV had higher risks of recurrence (OR=4.94; 95%CI
the formation of perianal hematoma at the postopera- 0.67–36.43) and concluded that DGHAL should be
tive period, and in one of them, with stage III HD, the carefully indicated for more advanced HD53. In this
perianal hematoma presented a larger proportion, last- study, it was noticed that the larger number of patients
ing for 3 weeks and associated with prolonged urinary who referred being little satisfied with the technique
retention; however, it was healed after 30 days. These also presented stage IV HD. They were submitted to
results are similar to those described by other au- concomitant perianal skin tag resection or presented
thors who followed-up a larger sample34. Even though with complications (hemorrhage, perianal hematoma
DGHAL preserves the venous drainage between mu- or postoperative anal fissure).
copexy sutures, which is not true for MA, it can also When considering the costs, one article compar-
evolve with external hemorrhoid thrombosis associ- ing the conventional elastic ligation and DGHAL re-
ated with the difficulty of venous return. In this study, ports that even though the doppler-guided dearterial-
for 38 patients (90.5%) postoperative complaints did ization is more efficient than elastic ligation to reduce
not prevent the return to regular activities one week postoperative pain, recurrence and also to improve the
after intervention. quality of life of patients with stage II and III hemor-
A systematic literature review considering all rhoids without mucosal prolapse, it costs more54.
published DGHAL cases, and included 2,000 patients, Even with the reduced number of patients and
showed recurrence rate of 10.8% for mucosal pro- the short follow-up at the postoperative period, the re-
lapse, 9.7% for postoperative bleeding and 8.7% for sults of this study suggest that DGHAL can be con-
pain when evacuating51. When considering only pa- sidered as a valid choice to treat for HD. Despite the
tients followed-up for more than one year, the recur- advantages in relation to the less intense postoperative
rence of prolapse and bleeding increased to 10.8 and pain and faster return to daily activities, the DGHAL
9.7%, respectively51. A recent randomized study that technique may present the same postoperative com-
assessed patients submitted to CH, MA and DGHAL plications described in other methods. As in other
did not find differences between the techniques con- techniques, the postoperative results of DGHAL in
cerning the improvement of symptoms such as bleed- stage IV HD seem to be worse, as well as when there
ing or pain52. However, as to the healing of the pro- is the need to perform procedures that include inci-
lapse, CH proved to be superior to MA and DGHAL52. sions in the perianal skin or the anal canal. Perianal
Another study comparing DGHAL associated with incisions increase postoperative discomfort and de-
pexy and MA showed that 78% of the patients sub- crease the degree of satisfaction with the method. The

381
J Coloproctol Doppler-guided hemorrhoidal artery ligation with rectal mucopexy technique): Vol. 32
October/December, 2012 initial evaluation of 42 cases Nº 4
Carlos Mateus Rotta et al.

results show that DGHAL is a simple surgical proce- verify if recurrence and satisfaction rates concerning
dure to perform, with a small learning curve due to the the method remain stable throughout the years.
possibility to repeat the procedure many times in the
same patient. The technique provides the remission of CONCLUSION
symptoms, especially for those with HD in stages II
and III, and is well tolerated. It evolves with accept- The DGHAL technique is a valid alternative to
able short term recurrence rates. At the moment, the treat for HD in stages II and III, and its main benefits
development of a multicenter national study is pro- are to evolve with little postoperative pain and to en-
posed in order to evaluate more patients with longer able the fast return of the patient to daily activities.
follow-up to confirm the validity of this new option of Studies involving more cases and with longer follow-
treatment for HD. Only this way it will be possible to up are still necessary to assess late recurrence.

REFERENCES 12. Sohn N, Aronoff JS, Cohen FS, Weinstein MA. Transanal
hemorrhoidal dearterialization is an alternative to operative
1. Kaidar-Person O, Person B, Wexner SD. Hemorrhoidal hemorrhoidectomy. Am J Surg 2001;182(5):515-9.
disease: a comprehensive review. J Am Coll Surg 2007;204(1): 13. Charúa Guindic L, Fonseca Muñoz E, García Pérez NJ, Osorio
102-17. Hernández RM, Navarrete Cruces T, Avendaño Espinosa O,
2. Johanson JF, Sonnenberg A. The prevalence of hemorrhoids et al. Hemorrhoidal desarterialization guided by Doppler. A
and chronic constipation. An epidemiologic study. surgical alternative in hemorrhoidal disease management.
Gastroenterology 1990;98(2):380-6. Rev Gastroenterol Mex 2004;69(2):83-7. [Spanish].
3. Altomare DF, Roveran A, Pecorella G, Gaj F, Stortini E. The 14. Bursics A, Morvay K, Kupcsulik P, Flautner L. Comparison
treatment of hemorrhoids: guidelines of the Italian Society of of early and 1-year follow-up results of conventional
Colorectal Surgery. Tech Coloproctol 2006;10(3):181-6. hemorrhoidectomy and hemorrhoid artery ligation: a
4. Cataldo P, Ellis CN, Gregorcyk S, Hyman N, Buie WD, randomized study. Int J Colorectal Dis 2004;19(2):
Church J, et al. Practice parameters for the management 176-80.
of hemorrhoids (revised). Dis Colon Rectum 2005;48(2): 15. Ramirez JM, Gracia JA, Aguilella V, Elia M, Casamayor
189-94. MC, Martinez M. Surgical management of symptomatic
5. Sobrado CW, Cotti GCC, Coelho FF, Rocha JRM. Initial haemorrhoids: to cut, to hang or to strangle? A prospective
experience with stapled hemorrhoidopexy for treatment of randomized controlled trial. Colorectal Dis 2005;7:52.
hemorrhoids. Arq Gastroenterol 2006;43(3):238-42. 16. Felice G, Privitera A, Ellul E, Klaumann M. Doppler-
6. Longo A. Treatment of haemorrhoids disease by reduction guided hemorrhoidal artery ligation: an alternative to
of mucosa and hemorrhoidal prolapse with circular suturing hemorrhoidectomy. Dis Colon Rectum 2005;48(11):
device: a new procedure. 6th World Congress of Endoscopic 2090-3.
Surgery; Rome; 1998:777-84. 17. Scheyer M, Antonietti E, Rollinger G, Mall H, Arnold S.
7. Tjandra JJ, Chan MK. Systematic review on the procedure Doppler-guided hemorrhoidal artery ligation. Am J Surg
for prolapse and hemorrhoids (stapled hemorrhoidopexy). 2006;191(1):89-93.
Dis Colon Rectum 2007;50(6):878-92. 18. Greenberg R, Karin E, Avital S, Skornick Y, Werbin N. First
8. Kornaros S, Dalamangas K, Zisi-Sermpetzoglou A. Fulminant 100 cases with Doppler-guided hemorrhoidal artery ligation.
intra-abdominal sepsis after stapled hemorrhoidectomy. Surg Dis Colon Rectum 2006;49(4):485-9.
Infect (Larchmt) 2011;12(2):145-8. 19. Wallis de Vries BM, van der Beek ES, de Wijkerslooth LR,
9. Cirocco WC. Life threatening sepsis and mortality following van der Zwet WC, van der Hoeven JA, Eeftinck Shattenkerk
stapled hemorrhoidopexy. Surgery 2008;143(6):824-9. M, et al. Treatment of grade 2 and 3 hemorrhoids with
10. Crepaldi Filho R, Martinez CAR, Palma RT, Priolli DG, Doppler-guided hemorrhoidal artery ligation. Dig Surg
Rezende Júnior HC, Waisberg J. Modificação do anuscópio 2007;24(6):436-40.
auxiliar (PSA 33) do PPH para facilitar a realização da sutura 20. Abdeldaim Y, Mabadeje O, Muhammad KM, Mc Avinchey D.
em bolsa na hemorroidectomia por grampeamento. Rev Bras Doppler-guided haemorrhoidal arteries ligation: preliminary
Colo-proct 2004;24(4):365-71. clinical experience. Ir Med J 2007;100(7):535-7.
11. Morinaga K, Hasuda K, Ikeda T. A novel therapy for internal 21. Ratto C, Donisi L, Parello A, Litta F, Doglietto GB.
hemorrhoids: ligation of the hemorrhoidal artery with a Evaluation of transanal hemorrhoidal dearterialization as a
newly devised instrument (Moricorn) in conjunction with a minimally invasive therapeutic approach to hemorrhoids. Dis
Doppler flowmeter. Am J Gastroenterol 1995;90(4):610-3. Colon Rectum 2010;53(5):803-11.

382
J Coloproctol Doppler-guided hemorrhoidal artery ligation with rectal mucopexy technique: Vol. 32
October/December, 2012 initial evaluation of 42 cases Nº 4
Carlos Mateus Rotta et al.

22. Dal Monte PP, Tagariello C, Sarago M, Giordano P, Shafi A, II and III degree haemorrhoids: a prospective multicentric
Cudazzo E, et al. Transanal haemorrhoidal dearterialization: study. Colorectal Dis 2010;12(8):804-9.
nonexcisional surgery for the treatment of haemorrhoidal 36. Theodoropoulos GE, Sevrisarianos N, Papaconstantinou
disease. Tech Coloproctol 2007;11(4):333-8. J, Panoussopoulos SG, Dardamanis D, Stamopoulos
23. Giordano P, Nastro P, Davies A, Gravante G. Prospective P, et al. Doppler-guided haemorrhoidal artery ligation,
evaluation of stapled haemorrhoidopexy versus transanal rectoanal repair, sutured haemorrhoidopexy and minimal
haemorrhoidal dearterialisation for stage II and III mucocutaneous excision for grades III-IV haemorrhoids:
haemorrhoids: three-year outcomes. Tech Coloproctol a multicenter prospective study of safety and efficacy.
2011;15(1):67-73. Colorectal Dis 2010;12(2):125-34.
24. Lienert M, Ulrich B. Doppler-guided ligation of the 37. Satzinger U, Feil W, Glaser K. Recto Anal Repair (RAR):
hemorrhoidal arteries. Report of experiences with 248 a viable new treatment option for high-grade hemorrhoids.
patients. Dtsch Med Wochenschr 2004;129(17):947-50. One year results of a prospective study. Pelviperineology
[German]. 2009;28(2):37-42.
25. Giordano P, Gravante G, Sorge R, Ovens L, Nastro P. Long- 38. Zagriadskii EA. Trans-anal disarterization of internal
term outcomes of stapled hemorrhoidopexy vs conventional hemorrhoids under Doppler control with mucopexy and
hemorrhoidectomy: a meta-analysis of randomized controlled lifting in treatment of stage III-IV hemorrhoids. Khirurgiia
trials. Arch Surg 2009;144(3):266-72 (Mosk) 2009;2:52-8. [Russian].
26. Pescatori M, Gagliardi G. Postoperative complications after 39. Ratto C, Giordano P, Donisi L, Parello A, Litta F, Doglietto
procedure for prolapsed hemorrhoids (PPH) and stapled GB. Transanal haemorrhoidal dearterialization (THD) for
transanal rectal resection (STARR) procedures. Tech selected fourth-degree haemorrhoids. Tech Coloproctol
Coloproctol 2008;12(1):7-19. 2011;15(2):191-7.
27. Aigner F, Bodner G, Conrad F, Mbaka G, Kreczy A, Fritsch 40. Wałega P, Scheyer M, Kenig J, Herman RM, Arnold S,
H. The superior rectal artery and its branching pattern with Nowak M, et al. Two-center experience in the treatment of
regard to its clinical influence on ligation techniques for hemorrhoidal disease using Doppler-guided hemorrhoidal
internal hemorrhoids. Am J Surg 2004;187(1):102-8. artery ligation: functional results after 1-year follow-up. Surg
28. Büyükaşik O, Hasdemir OA, Cöl C. Rectal lumen obliteration Endosc 2008;22(11):2379-83.
from stapled hemorrhoidopexy: can it be prevented? Tech 41. Shao WJ, Li GC, Zhang ZH, Yang BL, Sun GD, Chen YQ.
Coloproctol 2009;13(4):333-5. Systematic review and meta-analysis of randomized controlled
29. Naldini G, Martellucci J, Moraldi L, Romano N, Rossi M. trials comparing stapled haemorrhoidopexy with conventional
Is simple mucosal resection really possible? Considerations haemorrhoidectomy. Br J Surg 2008;95(2):147-60.
about histological findings after stapled hemorrhoidopexy. 42. Nisar PJ, Acheson AG, Neal KR, Scholefield JH.
Int J Colorectal Dis 2009;24(5):537-41. Stapled hemorrhoidopexy compared with conventional
30. Regadas FS, Regadas SM, Rodrigues LV, Misici R, hemorrhoidectomy: systematic review of randomized,
Tramujas I, Barreto JB, et al. New devices for stapled rectal controlled trials. Dis Colon Rectum 2004;47(11):1837-45.
mucosectomy: a multicenter experience. Tech Coloproctol 43. Jayaraman S, Colquhoun PH, Malthaner RA. Stapled
2005;9(3):243-6. hemorrhoidopexy is associated with a higher long-term
31. Rebuffat C, Porta MD, Ciccarese F, Rosati R. A new anoscope recurrence rate of internal hemorrhoids compared with
for transanal surgery. Am J Surg 2008;196(3):e12-5 conventional excisional hemorrhoid surgery. Dis Colon
32. Ho YH, Cheong WK, Tsang C, Ho J, Eu KW, Tang CL, Rectum 2007;50(9):1297-305.
et al. Stapled hemorrhoidectomy: cost and effectiveness. 44. Wałega P, Scheyer M, Kenig J, Herman RM, Arnold S,
Randomized controlled trial including incontinence scoring, Nowak M, et al. Two-center experience in the treatment of
anorectal manometry, and endoanal ultrasound assessments hemorrhoidal disease using Doppler-guided hemorrhoidal
at up three months. Dis Colon Rectum 2000;43(12):1666-75. artery ligation: functional results after 1-year follow-up. Surg
33. Kirsch JJ, Staude G, Herold A. The Longo and Milligan- Endosc 2008;22(11):2379-83.
Morgan hemorrhoidectomy. A prospective comparative study 45. Faucheron JL, Poncet G, Voirin D, Badic B, Gangner
of 300 patients. Chirurg 2001;72(2):180-5. [German]. Y. Doppler-guided hemorrhoidal artery ligation and
34. Wilson MS, Pope V, Doran HE, Fearn SJ, Brough WA. rectoanal repair (HAL-RAR) for the treatment of grade IV
Objective comparison of stapled anopexy and open hemorrhoids: long-term results in 100 consecutive patients.
hemorrhoidectomy: a randomized, controlled trial. Dis Colon Dis Colon Rectum 2011;54(2):226-31.
Rectum 2002;45(11):1437-44. 46. Avital S, Itah R, Skornick Y, Greenberg R. Outcome of stapled
35. Infantino A, Bellomo R, Dal Monte PP, Salafia C, Tagariello hemorrhoidopexy versus doppler-guided hemorrhoidal
C, Tonizzo CA, et al. Transanal haemorrhoidal artery artery ligation for grade III hemorrhoids. Tech Coloproctol
echodoppler ligation and anopexy (THD) is effective for 2011;15(3):267-71.

383
J Coloproctol Doppler-guided hemorrhoidal artery ligation with rectal mucopexy technique): Vol. 32
October/December, 2012 initial evaluation of 42 cases Nº 4
Carlos Mateus Rotta et al.

47. Sajid MS, Parampalli U, Whitehouse P, Sains P, McFall with PPH or THD. A randomized trial on postoperative
MR, Baig MK. A systematic review comparing transanal complications and short-term results. Int J Colorectal Dis
haemorrhoidal de-arterialisation to stapled haemorrhoidopexy 2009;24(12):1401-5.
in the management of haemorrhoidal disease. Tech 53. Pol RA, van der Zwet WC, Hoornenborg D, Makkinga
Coloproctol 2012;16(1):1-8. B, Kaijser M, Eefitinck Schattenkerk M, et al. Results of
48. Gupta PJ, Kalaskar S, Taori S, Heda PS. Doppler-guided 244 consecutive patients with hemorrhoids treated with
hemorrhoidal artery ligation does not offer any advantage Doppler-guided hemorrhoidal artery ligation. Dig Surg
over suture ligation of grade 3 symptomatic hemorrhoids. 2010;27(4):279-84.
Tech Coloproctol 2011;15(4):430-44. 54. Giamundo P, Salfi R, Geraci M, Tibaldi L, Murru L, Valente
49. Spyridakis M, Christodoulidis G, Symeonidis D, Dimas D, M. The hemorrhoid laser procedure technique vs rubber
Diamantis A, Polychronopoulou E, et al. Outcomes of Doppler- band ligation: a randomized trial comparing 2 mini-invasive
guided hemorrhoid artery ligation: analysis of 90 consecutive treatments for second- and third-degree hemorrhoids. Dis
patients. Tech Coloproctol 2011;15(Suppl 1):S21-4. Colon Rectum 2011;54(6):693-8.
50. Cantero R, Balibrea JM, Ferrigni C, Sanz M, García Pérez
JC, Pérez R, et al. Doppler-guided transanal haemorrhoidal
dearterialization: an alternative treatment for haemorrhoids.
Cir Esp 2008;83(5):252-5. [Spanish].
51. Giordano P, Overton J, Madeddu F, Zaman S, Gravante Correspondence to:
G. Transanal hemorrhoidal dearterialization: a systematic Carlos Mateus Rotta
review. Dis Colon Rectum 2009;52(9):1665-71. Rua Julio Prestes, 240
52. Festen S, van Hoogstraten MJ, van Geloven AA, Gerhards CEP: 08780-110 – Mogi das Cruzes (SP), Brazil
MF. Treatment of grade III and IV haemorrhoidal disease E-mail: dr.mateusrotta@hotmail.com

384
Original Article

Knowledge and practice of physicians


regarding colorectal cancer screening
Elziane da Cruz Ribeiro e Souza1, Marina Lise1, Thalita Pereira dos Santos1, Luciano Pinto de Carvalho2

Physicians graduated by Universidade Luterana do Brasil – Canoas (RS), Brazil.


1

2
PhD in Gastroenterology Sciences; Expert in Coloproctology; Adjunct Professor at
Universidade Luterana do Brasil – Canoas (RS), Brazil.

Cruz ERS, Lise M, Santos TP, Carvalho LP. Knowledge and practice of physicians regarding colorectal cancer screening.
J Coloproctol, 2012;32(4): 385-394.
ABSTRACT: Introduction: Despite the high prevalence and high rates of mortality of colorectal cancer, it is likely to be a
secondary prevention disease due to the presentation of characteristics that are ideal for a successful screening program, with a
proven positive impact on its outcome. Objective: To describe the knowledge and practice of physicians concerning screening
tests for the prevention of colorectal cancer. Methods: Cross-sectional study carried out between November 2011 and February
2012, through a questionnaire administered to 83 physicians who assist adult patients at the University Hospital of Universidade
Luterana do Brasil and at basic health units of Canoas, Rio Grande do Sul, Brazil. Results: From the number of physicians par-
ticipating in the survey, only 35 (42.0%) reported prescribing tests for colorectal cancer screening. Out of these, only 21 used the
screening on patients aged 50 years old or more, as recommended by the guidelines. Only 65.0% of the physicians reported inves-
tigating family history of colorectal cancer, and surgical experts were the ones who least investigated this risk factor (p=0.005),
when compared with clinical and gynecology specialties. Conclusions: The number of physicians who reported ordering tests
for the prevention of colorectal cancer is still low, and their knowledge regarding the recommendations of the guidelines is very
limited. The results indicate the immediate need for investment in professional formation and medical staff training concerning
preventive measures for colorectal cancer.
Keywords: colorectal cancer; prevention; screening; physicians.

RESUMO: Introdução: O câncer colorretal, apesar de apresentar alta prevalência e elevadas taxas de mortalidade, é uma doença
passível de prevenção secundária, devido ao fato de possuir características ideais para um programa de rastreamento bem-sucedi-
do. Objetivo: Estudar o conhecimento e a prática dos médicos sobre o rastreamento e a prevenção secundária do câncer colorretal.
Métodos: Estudo transversal, realizado entre novembro de 2011 e fevereiro de 2012, por meio de um questionário aplicado a 83
médicos que atendem diretamente pacientes adultos no Hospital Universitário da Universidade Luterana do Brasil e em unidades
básicas de saúde de Canoas, no estado do Rio Grande do Sul. Resultados: Do total de médicos participantes da pesquisa, ape-
nas 35 (42,0%) afirmaram solicitar exames de rastreamento do câncer colorretal e desses somente 21 iniciam o rastreamento a
partir dos 50 anos, que é a idade recomendada pelas diretrizes. Apenas 65% dos médicos declararam investigar história familiar
de câncer colorretal, sendo os especialistas cirúrgicos os que menos afirmaram investigar tal fator de risco (p=0,005), quando
comparados com as especialidades clínica e ginecológica. Conclusões: O número de especialistas que afirmaram solicitar exa-
mes de prevenção do câncer colorretal foi baixo, e seu conhecimento quanto às recomendações das diretrizes se mostrou muito
limitado. Os resultados apontam para uma necessidade imediata de capacitação e treinamento da classe médica sobre prevenção
do câncer colorretal.
Palavras-chave: câncer colorretal; prevenção; rastreamento; médicos.

Study carried out at the Universidade Luterana do Brasil – Canoas (RS), Brazil.
Financing source: none.
Conflict of interest: nothing to declare.

Submitted on: 02/06/2011


Approved on: 29/07/2011

385
J Coloproctol Knowledge and practice of physicians regarding colorectal cancer screening Vol. 32
October/December, 2012 Elziane da Cruz Ribeiro e Souza et al. Nº 4

INTRODUCTION ity rate by CRC in the total of deaths caused by can-


cer in Brazil has increased. Rates ranged from 11.6%,
Colorectal cancer (CRC) involves malignant tu- from 1989 to 1993, to 14.5%, from 2003 and 200714.
mors that affect the colon and the rectum, thus consti- The increasing rates of this type of cancer in Bra-
tuting all over the world the third most common cause zil and the higher mortality levels throughout the years
of cancer among males and the second among fe- indicate a flaw in screening and prevention. Among
males1. The National Cancer Institute (Inca) estimates the explanations for this situation, there are medical
that, in 2010, the Brazilian population was affected by unawareness and/or the non-application of recom-
more than 28,000 new cases of such cancer and, in mended preventive measures.
2012, 30,1402,3. A study conducted in São Paulo concerning the
Mostly (70 to 90% of the cases), CRC comes doctors’ attitude towards prevention and screening of
from adenomatous polyps, according to the adenoma- the most prevalent types of cancer showed that CRC
carcinoma sequence, which slowly progresses in about was the type that doctors were less concerned about in
ten yeras4,5. Even though this long period of evolution terms of prevention. When performing it, the adopted
offers an opportunity to prevent CRC, it is clinically screening methods were those that most diverged in
silent; that is, diagnosis and the consequent interrup- relation to the recommendations in the guidelines15.
tion of the evolution to a malignant lesion can only A research aiming to determine the obstacles to
happen by the performance of screening tests, which CRC screening showed that the indication from a doc-
are able to identify the adenomas, or even the carcino- tor is the factor that most influences the adhesion of
mas, in early stages6. the patient to screening tests for this type of cancer16.
Screening is a secondary form of prevention that Considering that the medical class constitutes the
uses tests of asymptomatic subjects for the presumptive main instrument of CRC prevention, and that the un-
identification of the disease, which is still unknown7. awareness of these professionals concerning screen-
A study from 2010 pointed CRC screening as the can- ing is one of the barriers to control the incidence and
cer with greater chances of success, in terms of preven- mortality caused by this cancer, this study aimed to
tion and early detection8. This is due to the oncogenic analyze the medical knowledge and practice in rela-
peculiarities of this type of cancer and the availability tion to CRC screening and secondary prevention.
of effective screening methods, which allow the identi-
fication and, consequently, the treatment both for pre- METHODS
cursor lesions (preventing CRC) and malignant tumors
at early stages, with the confirmed reduction of mortal- It is a cross-sectional study performed between
ity incidence and rates caused by the disease9. November 2011 and February 2012. The study popu-
Literature shows that the incidence of CRC can lation was comprised of 83 doctors who assisted adult
be reduced in up to 90% when the detection and the patients in the University Hospital of Universidade
removal of pre-malignant lesions occur10. Likewise, Luterana do Brasil (ULBRA) and in basic health units
the survival of patients submitted to screening tests di- of Canoas, Rio Grande do Sul, who agreed to partici-
agnosed with malignant lesions at early stages reaches pate in the study. Doctors were randomly selected.
90% in five years11,12. Data collection was based on a self-employment
In the United States, which has an effective sys- questionnaire composed of open and closed questions
tem of prevention and vigilance, it was observed that concerning the characterization of the study popula-
between 2003 and 2007 there was a 13% decrease tion and the medical knowledge and practice related
in CRC incidence, and a 12% decrease in mortality, to CRC prevention.
which means the reduction of about 66,000 cases and The analyzed variables to characterize the study
32,000 deaths in comparison with 200213. population were: year and university of graduation, spe-
Contrarily to what is observed in the USA, data cialty, place of work (University Hospital – ULBRA and
from the Department of Data Processing of the Uni- basic health units of Canoas); place of assistance (outpa-
fied Health System (DATASUS) show that the mortal- tient client and admission) and income source of medi-

386
J Coloproctol Knowledge and practice of physicians regarding colorectal cancer screening Vol. 32
October/December, 2012 Elziane da Cruz Ribeiro e Souza et al. Nº 4

cal care. The other variables included: ordering tests Data collection and analysis were conducted only
for CRC screening and the indication factor of the after the approval from the Human and Animal Research
request, requested examinations, reason to choose Ethics Committee of ULBRA, protocol 2011-248H.
the exam, investigation of family history of colorec- The participants were enlightened as to the nature
tal cancer, screening for other types of cancer and of the study, the voluntariness of the participation, and
heart disease. then they signed the informed consent form and re-
Time of formation was described by median and ceived a copy of it. Identity preservation was assured
interquartile amplitude (percentiles 25–75), due to the by such term. The study followed the determinations
asymmetric distribution of such variable. The other of Resolution 196, from the National Health Council.
variables were described by absolute and relative fre-
quencies and the association between them was as- RESULTS
sessed by the χ2, Pearson or Fisher’s exact test.
The analysis of the answers concerning the The questionnaire was answered by 83 doctors;
knowledge about CRC prevention was based on guide- 76% of them worked at the University Hospital, and 24%
lines of polyp and CRC screening from the Agency for in basic health units of Canoas. As to the characterization
Health Care Policy and Research (Chart 1)17. of the sample, 100% of the doctors graduated in medi-
The adopted significance level was 5% (p≤0.05), cal schools from Rio Grande do Sul and presented with
and the analyses were performed with the software Sta- median nine after graduation (P25–P75=3–20). Around
tistical Package for the Social Sciences (SPSS), 18.0. 60% of them had clinical formation, with specialties dis-

Chart 1. Recommendations by the Agency for Healthcare Policy and for colorectal cancer and polyp screening.
Risk category Screening method Age to start screening
Medium risk Choose one of the following:
(without associated risk Annual fecal occult blood test (FOBT); 50 years.
factors) Sigmoidoscopy every 5 years;
Annual FOBT and sigmoidoscopy every 5 years;
Barium enema every 5–10 years†;
Colonoscopy every 10 years.
With family history Choose one of the following 40 years of age or 10 years
Colonoscopy every 10 years; before the age the youngest
Barium enema every 5 years. member of the family was
diagnosed, whatever comes first.
Hereditary nonpolyposis Colonoscopy every 1–3 years; 21 years.
colorectal cancer (HNPCC) Genetic assistance;
Consider genetic tests.
Familial adenomatous Flexible sigmoidoscopy or colonoscopy every 1 Puberty
polyposis (FAP) to 3 years;
Genetic assistance;
Consider genetic tests.
Ulcerative colitis Colonoscopy with biopsy for dysplasia every 7 to 8 years after the pancolitis
1–2 years. diagnosis, 12 to 15 years after
left-sided colitis diagnosis.
†: in 2008, guidelines from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer and the American College
of Radiology were published concerning colorectal cancer screening and prevention tests for people with medium risk, as follows:
Tests to detect adenomatous polyps and cancer: flexible sigmoidoscopy (FSIG) every five years; colonoscopy every tem years; barium
enema every five years; computed tomographic colonography every five years.
Tests to detect especially cancer: stool guaiac test for fecal occult blood (gFOBT) – with high sensitivity for cancer, each year; fecal
immunochemical testing (FIT) with high sensitivity for cancer, each year; stool DNA, with high sensitivity for cancer, uncertain interval20.

387
J Coloproctol Knowledge and practice of physicians regarding colorectal cancer screening Vol. 32
October/December, 2012 Elziane da Cruz Ribeiro e Souza et al. Nº 4

tributed according to Table 1, and 72.3% of them had Among the 35 doctors who reported ordering
professional connections with the medical school insti- tests for CRC screening, most of them stated this re-
tution. Most of them worked concomitantly in outpa- quest was based on family history of this type of can-
tient clinics and admission and, at the same time, both cer. However, only 60% of them reported ordering it
for the Unified Health System (SUS) and for private for the population aged 50 years or older, according
health insurance companies (Table 1). to what is recommended by the guidelines (Chart 1)17.
Out of the total number of doctors participating When these doctors were asked about which CRC
in the study, about 80% confirmed they knew about prevention tests they order, most of them chose more
CRC screening, but only 35 of them (42.2%) declared than one option. The most indicated examinations
ordering any prevention examination for this cancer were colonoscopy and the fecal occult blood test, 83
during routine elective care. and 73%, respectively. Efficiency was the most indi-
cated reason for choosing these examinations (Table 2).
Table 1. Characterization of doctors who answered the However, at the separate analysis of how many doctors
questionnaire of the study as to year and university of order only colonoscopy as a test to prevent CRC, the
graduation, specialty, work place (university hospital frequency decreased from 83 to 40%.
or basic health unit), place of medical care (outpatient Out of all the doctors who answered the ques-
clinic or admission) and income source of medical tionnaire, only 65% stated investigating family history
care, in Canoas, RS, 2012. of CRC in patients without bowel complaints. More
Variables n=83 (%) than 90% said they knew which the examination of
Work place choice for CRC prevention was and 82.7% mentioned
University hospital 63 (75.9) colonoscopy as the examination of choice.
Basic health unit 20 (24.1) Most doctors, 84%, declared ordering tests or re-
Graduation university ferring asymptomatic patients to screen for other types
Private 43 (51.8) of cancer, and breast, uterine and prostate cancer are
Public 40 (48.2) the ones that are mostly screened for: 88.7, 84.5 and
Time of graduation conclusion (years) – 9 (3–20.0) 69%, respectively. Likewise, almost 90% of the doc-
median (P25–P75) tors reported screening for heart disease in asymptom-
<5 25 (30.1) atic patients during routine care (Table 3).
5–10 18 (21.7) It was observed that doctors who performed CRC
10-15 11 (13.3) screening were the ones who mostly responded having
>15 29 (34.9) knowledge concerning screening (p=0.043), and also
Specialty the ones who mostly stated investigating family histo-
Clinical 49 (59.0) ry of this cancer (p=0.002) in relation to other doctors.
Surgical 18 (21.7) It was also found that 98.5% of the doctors with
Obstetrics-Gynecology 16 (19.3) knowledge concerning CRC declared to know the ex-
Connection with medical school amination of choice for screening, while amongst the
institution ones who claimed not having this knowledge, only
Yes 60 (72.3) 62.5% reported knowing which was the examination
No 23 (27.7) of choice to prevent this cancer (p<0.001).
Place of medical care All variables were analyzed according to the
Only outpatient clinic 23 (27.7) specialties, and those which presented a statistically
Only admission 2 (2.4) significant difference are shown in Table 4. Surgical
Both 58 (69.9) experts, when compared to the others, are the ones
Income source of medical care who least analyze family history of CRC (p=0.005).
Only the Unified Health System 25 (30.1) Obstetrician-gynecologists pointed the efficiency as
Only private 2 (2.4) a reason to choose the screening test with less fre-
Both 56 (67.5) quency (p=0.016). Besides, they mentioned more

388
J Coloproctol Knowledge and practice of physicians regarding colorectal cancer screening Vol. 32
October/December, 2012 Elziane da Cruz Ribeiro e Souza et al. Nº 4

Table 2. Medical knowledge and practice at the university hospital and the basic health unit concerning colorectal
cancer screening in Canoas, RS, 2012.
Total sample – University Basic health
Variables p-value
n=83 (%) hospital – n=63 (%) unit** – n=20 (%)
Is aware of CRC screening? 0.339
Yes 66 (79.5) 52 (82.5) 14 (70.0)
No 17 (20.5) 11 (17.5) 6 (30.0)
Orders any colorectal cancer screening test for patients without bowel complaints?
Yes 35 (42.2) 27 (42.9) 8 (40.0) 1.000
No 48 (57.8) 36 (57.1) 12 (60.0)
If so, in which situation?*
According to age 31 (88.6) 24 (88.9) 7 (87.5) 1.000
Does not order according to age 4 (11.4) 3 (11.1) 1 (12.5) 1.000
Aged > 40 years old 5 (16.1) 3 (12.5) 2 (28.6) 0.562
Aged > 50 years old 21 (67.7) 18 (75.0) 3 (42.9) 0.172
Aged > 60 years old 5 (16.1) 3 (12.5) 2 (28.6) 0.562
According to family history of 33 (94.3) 25 (92.6) 8 (100) 1.000
colorectal cancer
Routine for all 3 (8.6) 3 (11.1) 0 (0.0) 1.000
According to associated pathologies 14 (40.0) 9 (33.3) 5 (62.5) 0.221
Ordered examinations*
Fecal occult blood test 13 (37.1) 10 (37.0) 3 (37.5) 1.000
Performs rectal touch 2 (5.7) 2 (7.4) 0 (0.0) 1.000
Rectosigmoidoscopy 1 (2.9) 1 (3.7) 0 (0.0) 1.000
Colonoscopy 29 (82.9) 23 (85.2) 6 (75.0) 0.602
Opaque enema 1 (2.9) 0 (0.0) 1 (12.5) 0.229
Refers to specialist 10 (28.6) 8 (29.6) 2 (25.0) 1.000
Reasons for choosing screening test for colorectal cancer*
Efficiency 28 (80.0) 21 (77.8) 7 (87.5) 1.000
Availability 8 (22.9) 6 (22.2) 2 (25.0) 1.000
Cost 7 (20.0) 5 (18.5) 2 (25.0) 0.648
Others 3 (8.6) 3 (11.1) 0 (0.0) 1.000
Routine investigation of family history of colorectal cancer?
Yes 54 (65.1) 40 (63.5) 14 (70.0) 0.793
No 29 (34.9) 23 (36.5) 6 (30.0)
Knows which is the examination of choice for the prevention of colorectal cancer?***
Yes 75 (91.5) 57 (91.9) 18 (90.0) 1.000
No 7 (8.5) 5 (8.1) 2 (10.0)
If so, what is the examination?*
Colonoscopy 62 (82.7) 48 (84.2) 14 (77.8) 0.499
Fecal occult blood test 7 (9.3) 3 (5.3) 4 (22.2) 0.053
Rectal touch 2 (2.7) 2 (3.5) 0 (0.0) 1.000
Rectosigmoidoscopy 4 (5.3) 4 (7.0) 0 (0.0) 0.567
Anamnesis 1 (1.3) 0 (0.0) 1 (5.6) 0.240
CEA 1 (1.3) 1 (1.8) 0 (0.0) 1.000
Tumor marker 1 (1.3) 1 (1.8) 0 (0.0) 1.000
CRC: colorectal cancer; CEA: carcinoembryonic antigen; *multiple choice question; **basic health units; ***one subject who did not
answer this question (1.2%); p-value: Fisher’ test.

389
J Coloproctol Knowledge and practice of physicians regarding colorectal cancer screening Vol. 32
October/December, 2012 Elziane da Cruz Ribeiro e Souza et al. Nº 4

times the fecal occult blood test as the method of doctors concerning CRC screening and prevention,
choice for the secondary prevention of CRC, to the university of graduation, professional connections
detriment of colonoscopy. with the medical school institution, work place (out-
An association between knowledge concerning patient clinic, admission) and the income source of
CRC declared by the professional and time of grad- medical care (SUS, private health insurance).
uation was found (p=0.028). Doctors who had been
graduated for more than 15 years were the ones who DISCUSSION
mostly declared not knowing about CRC screening,
as presented in Figure 1. They also investigated Despite presenting high incidence and mortality
uterine cancer less frequently when compared to rates, colonic and rectal cancer can really be prevented
other doctors, who had been graduated for a fewer by means of screening tests, which are able to detect
years (p=0.048). and remove pre-malignant lesions1,6. However, this
Doctors graduated more recently (less than form of prevention is conditioned to a proper medi-
five years) were the ones who mostly stated order- cal knowledge and application of the recommended
ing screening tests for prostate cancer (95.2%), when screening examinations.
compared to those who have been graduated from five Out of the doctors who participated in this study,
to ten years (55.6%), from 10 to 15 years (66.7%) and only 42% stated ordering CRC screening and preven-
more than 15 years (56.5%), with p=0.019. tion tests. This result corresponds approximately to
Concerning work location, it was observed that the double of the data found in 2004 by Tucundava
doctors from basic health units declared ordering more et al., who analyzed doctors in a medical school of São
examinations to prevent uterine and prostate cancer Paulo (20.30%)15. However, it is a much lower result
than the doctors in the university hospital (p=0.030; than that found in the United States, which has an ef-
p=0.011). However, no significant differences were fective CRC vigilance and screening system. There,
found between these work places and CRC screening. Klabunde et al. found that only 2% of primary care
This study did not find statistically significant doctors do not order prevention examinations for this
differences between the knowledge and practice of type of cancer18.

Table 3. Attitude of the doctors who work in the university hospital and in basic health units as to screening for
other types of cancer and heart disease in Canoas, RS, 2012.
Total sample – University hospital Basic health
Variables p-value
n=83 (%) – n=63 (%) unit** – n=20 (%)
Orders tests or refers asymptomatic patients to screen for other types of cancer?
Yes 70 (84.3) 51 (81.0) 19 (95.0) 0.173
No 13 (15.7) 12 (19.0) 1 (5.0)
What type of cancer?*
Breast 63 (88.7) 44 (84.6) 19 (100) 0.099
Uterine 60 (84.5) 41 (78.8) 19 (100) 0.030
Stomach 14 (19.7) 11 (21.2) 3 (15.8) 0.745
Prostate 49 (69.0) 31 (59.6) 18 (94.7) 0.011
Lung 20 (28.2) 15 (28.8) 5 (26.3) 1.000
Skin 19 (26.8) 14 (26.9) 5 (26.3) 1.000
Orders prevention tests for heart diseases in asymptomatic patients?
Yes 73 (88.0) 53 (84.1) 20 (100) 0.108
No 10 (12.0) 10 (15.9) 0 (0.0)
*multiple choice question; **basic health units; p-value: Fisher’s test.

390
J Coloproctol Knowledge and practice of physicians regarding colorectal cancer screening Vol. 32
October/December, 2012 Elziane da Cruz Ribeiro e Souza et al. Nº 4

The age to start CRC screening ranges, espe- vention tests, 40% of them do not request it for pa-
cially at the presence of family history for such dis- tients aged 50 years old or more. This information
ease (Chart 1)17. However, when this peculiarity is not points to the low level of knowledge of the doctors as
present, it is common sense among the organizations to the CRC screening indications recommended by the
involved in CRC prevention and control that everyone guidelines, and it also confirms the data from a North-
should start screening at the age of 50, period when American study, which also found many doctors rec-
its increased incidence is observed9,19,20. In this study, ommending this screening test for patients outside the
among the 35 doctors who stated ordering CRC pre- suggested age group1,18.

Table 4. Medical knowledge and practice concerning colorectal cancer according to specialty in Canoas, RS, 2012.
Obstetrics-
Clinical – n=31 Surgical – n=18
Variables Gynecology** – p-value
(%) (%)
n=16 (%)
Reason for choosing the colorectal cancer screening test*
Efficiency 18 (85.7) 7 (100) 3 (42.9) 0.016
Availability 5 (23.8) 0 (0.0) 3 (42.9) 0.159
Cost 6 (28.6) 0 (0.0) 1 (14.3) 0.240
Others 2 (9.5) 0 (0.0) 1 (14.3) 0.615
Routine investigation of family history of colorectal cancer?
Yes 35 (71.4) 6 (33.3) 13 (81.3) 0.005
No 14 (28.6) 12 (66.7) 3 (18.8)
Knows which is the examination of choice for the prevention of colorectal cancer?
Yes 44 (89.8) 16 (88.9) 15 (100) 0.422
No 5 (10.2) 2 (11.1) 0 (0.0)
Examinations of choice for colorectal cancer prevention*
Colonoscopy 38 (86.4) 15 (93.8) 9 (60.0) 0.028
Fecal occult blood test 3 (6.8) 0 (0.0) 4 (26.7) 0.026
Rectal touch 0 (0.0) 2 (12.5) 0 (0.0) 0.023
Rectosigmoidoscopy 1 (2.3) 1 (6.3) 2 (13.3) 0.254
Anamnesis 1 (2.3) 0 (0.0) 0 (0.0) 0.700
CEA 1 (2.3) 0 (0.0) 0 (0.0) 0.700
Tumor marker 1 (2.3) 0 (0.0) 0 (0.0) 0.700
Orders tests or refers asymptomatic patients to screen for other types of cancer?
Yes 44 (89.8) 12 (66.7) 14 (87.5) 0.065
No 5 (10.2) 6 (33.3) 2 (12.5)
Which type of cancer?*
Breast 42 (93.3) 7 (58.3) 14 (100) 0.001
Uterine 41 (91.1) 5 (41.7) 14 (100) <0.001
Stomach 9 (20.0) 5 (41.7) 0 (0.0) 0.029
Prostate 40 (88.9) 7 (58.3) - <0.001
Lung 13 (28.9) 6 (50.0) 1 (7.1) 0.052
Skin 9 (20.0) 6 (50.0) 4 (28.6) 0.112
Orders prevention tests for heart diseases in asymptomatic patients?
Yes 47 (95.9) 10 (55.6) 16 (100) <0.001
No 2 (4.1) 8 (44.4) 0 (0.0)
CEA: carcinoembryonic antigen; *multiple choice question; **obstetricians-gynecologists; statistical analysis for prostate cancer was
performed only amongst clinical and surgical specialties

391
J Coloproctol Knowledge and practice of physicians regarding colorectal cancer screening Vol. 32
October/December, 2012 Elziane da Cruz Ribeiro e Souza et al. Nº 4

this cancer. These results show the deficient investiga-


100 94.4 90.9 tion of this factor, once first degree relatives of people
90 84 with CRC have twice or three times the chance to de-
% of the sample

80 velop this type of cancer in comparison with the Con-


70 62.1
60 trol Group. Therefore, a positive family history deter-
50 mines age anticipation to start screening7,17,19,22.
40 37.9 More than 90% of the doctors participating in
30 this study said they knew which the examination of
20 16 choice for CRC prevention was, mentioning colo-
10 5.6 9.1
0 noscopy80% of the time. This result is similar to that
Yes No found by Klabunde et al. with doctors in the United
Is aware of colorectal cancer screening States, who also see colonoscopy as the most effi-
<5 years 5-10 years 10-15 years >15 years cient screening method18. Even though there are no
randomized prospective clinical trials analyzing
Figure 1. Association between colorectal cancer screening
declared by the doctors and time of graduation conclusion,
colonoscopy as a method to reduce the incidence
Canoas, RS, 2012. and/or mortality by CRC, it is based on indirect but
substantial evidence, which recognizes colonoscopy
as the most efficient prevention method. The advan-
tages of colonoscopy include the complete colon and
Generally, CRC screening tests can be divided rectum examination, the possibility to diagnose pre-
into two categories. One of them is composed by malignant lesions (main objective of CRC screen-
stool tests, which are more adequate to detect can- ing), the performance of biopsy, as well as the re-
cer, once the pre-malignant lesions, especially small moval of adenomas, being the only test that is able
polyps, tend not to bleed, and the larger ones can to reduce the incidence of this cancer in 66 to 90%
present intermittent bleeding or simply not be de- of the cases20,23.
tectable in a stool sample. The other category is rep- In most studies, the coverage rates concern-
resented by endoscopic examinations, especially ing CRC screening are low, usually much lower than
colonoscopy, which reaches the double objective of those related to other cancer prevention programs7,15.
detecting adenocarcinoma and adenomatous polyps, This data was confirmed in this study. While only 42%
thus enabling the treatment of these lesions and, con- of all the participating doctors stated conducting CRC
sequently, CRC prevention20. screening, which is similar to the double, 84% report-
Since the primary objective of CRC screening is ed ordering tests or referring asymptomatic patients to
preention, tests that are able to detect both cancer in screen for other types of cancer.
early stages and pre-malignant lesions should be indi- Breast and uterine cancers are the ones doctors
cated20. Among the doctors who stated ordering CRC mostly screen for, which confirms the results of an-
prevention tests in this study, 82.9% indicated colonos- other study from São Paulo, which found these two
copy as an alternative for screening. However, with the cancers as being the ones doctors are more concerned
analysis of which ones among them indicate this test about preventing15.
exclusively as a prevention method, the frequency de- Proportionally to the screening for other cancers,
creased to 40%. This information differs from the result more than the double of doctors participating in the
found in the United States, where 95% of the doctors research declared ordering prevention tests for heart
order colonoscopy for CRC prevention21. diseases in asymptomatic patients. These results are
From all the doctors who answered the question- in accordance with the analysis of mortality rates by
naire, only 65% stated investigating family history of chronic diseases in Brazil, which point to a 31% re-
CRC in patients without bowel complaints, and an duction in mortality by heart disease between 1996
even lower frequency was found among surgeons and and 2007, and an increased mortality rate by CRC,
doctors who declared not performing screening for both for men and women24.

392
J Coloproctol Knowledge and practice of physicians regarding colorectal cancer screening Vol. 32
October/December, 2012 Elziane da Cruz Ribeiro e Souza et al. Nº 4

Nowadays, CRC affects women more than gy- related to the fact that guidelines and screening meth-
necological cancers. Epidemiological studies demon- ods have been improved in the past decade, when these
strated the increased risk of colonic and rectal cancer doctors had already finished their basic graduation.
from 1.5 to 3.0 times in women who have previously The methodological limitations of this study
had primary malignant neoplasm of endometrium or should be mentioned. As demonstrated in previous
ovary25. This information points to the need for even studies, there is a gap between what the doctors report
more attention from gynecologists to CRC preven- doing and what he or she actually does27. However, in
tion. The American College of Obstetricians and Gy- Brazil there are no studies that assess knowledge and
necologists (ACOG) published, in the beginning of practice of the doctors specifically as to CRC screen-
2011, a report encouraging doctors in this specialty to ing and prevention. Besides, the found results confirm
order screening and prevention CRC tests for women the findings in other studies, suggesting that the infor-
aged more than 50 years old, or earlier, according mation presented is valid and interpretable.
to the risk. This report also recommends colonos-
copy as the method of choice for prevention26. De- CONCLUSION
spite that, out of the 16 doctors with this specialty
who answered the questionnaire in this study, 56% A small number of doctors participating in this
stated not ordering screening tests for CRC. Besides, study adopt CRC screening and prevention methods.
when compared to other specialties, they were the Besides, they demonstrated low level of knowledge
ones who most indicated the fecal occult blood test concerning the recommendations in the guidelines for
to the detriment of colonoscopy as the examination the prevention of this cancer, especially as to the age
of choice to prevent such cancer. to start screening.
In this study, the association between time of grad- The results in this study point to the need to in-
uation and knowledge concerning CRC declared by the vest in professional formation and training of the med-
Professional stood out. Doctors graduated for more ical class, emphasizing the importance and the effi-
than 15 years were the ones who mostly declared not cacy of secondary prevention to control the incidence
knowing about CRC screening (Figure 1). This can be and mortality by this cancer.

REFERENCES 6. Lux G, Stabenow-Lohbauer U. Cancer prevention with the


endoscope. Search not only for polyps. MMW Fortschr Med
1. Jemal A, Bray F, Center M, Ferlay J, Ward E, Forman D. 2002;144(51-52):29-33.
Global Cancer Statistics. CA Cancer J Clin [homepage on 7. Secretaria de Estado da Saúde. Grupo Técnico de Avaliação
the Internet]. 2011 Dec [cited 2011 Nov 28]; 61:69-90. e Informações de Saúde. A relevância do câncer colorretal.
Available from: http://onlinelibrary.wiley.com/doi/10.3322/ BEPA, Bol Epidemiol Paul [periódico na Internet]. 2009
caac.20107/pdf Nov [cited 2011 Nov 12];6(68):01-14. Available from:
2. Instituto Nacional de Câncer [homepage on the Internet]. http://periodicos.ses.sp.bvs.br/scielo.php?script=sci_
Estimativa 2010. Incidência do câncer colorretal no Brasil. arttext&pid=S1806-42722009000800006&lng=pt
[cited 2011 Oct 13]. Available from: http://www2.inca.gov. 8. Edwards BK, Ward E, Kohler BA, Eheman C, Zauber
br/wps/wcm/connect/tiposdecancer/site/home/colorretal/ AG, Anderson RN, et al. Annual report to the nation on the
definicao status of cancer 1975–2006, featuring colorectal cancer trends
3. Instituto Nacional de Câncer [homepage on the Internet]. and impact of interventions (risk factors, screening, and
Estimativa 2012- Incidência do câncer no Brasil. [cited treatment) to reduce future rates. Cancer 2010;116(3):544-573.
2011 Dec 02]. Available from: http://www.inca.gov.br/ 9. Burt RW. Colorectal cancer screening. Curr Opin
estimativa/2012/index.asp?ID=5 Gastroenterol 2010;26(5):466-70.
4. Bond J. Clinical evidence for the adenoma-carcinoma 10. Wehrmann K, Frühmorgen P. Removing adenomas reduces colon
sequence, and the management of patients with colorectal carcinoma risk up to 90%. MMW Fortschr Med 2000;142(8):26-9.
adenomas. Semin Gastrointest Dis 2000;11(4):176-84. 11. O’Connell JB, Maggard MA, Ko CY. Colon cancer survival
5. Leslie A, Carey FA, Pratt NR, Steele RJ. The colorectal rates with the new American Joint Committee on Cancer
adenoma-carcinoma sequence. Br J Surg 2002;89(7):845-60. sixth edition staging. J Natl Cancer Inst 2004;96(19):1420-5.

393
J Coloproctol Knowledge and practice of physicians regarding colorectal cancer screening Vol. 32
October/December, 2012 Elziane da Cruz Ribeiro e Souza et al. Nº 4

12. Vasconcelos TA. Pólipos e Cancro do Cólon e Recto. Arq 22. World Gastroenterology Organization/International Digestive
Med 2009;23(6):209-16. Cancer [homepage on the Internet]. Alliance Practice
13. Richardson LC, Tai E, Rim SH, Joseph D, Plescia M. Guidelines: triagem do câncer colorretal. 2007. [cited 2011
Vital Signs: Colorectal Cancer Screening, Incidence, and Nov 15]. Available from: http://www.worldgastroenterology.
Mortality. United States, 2002—2010. Centers for Disease org/assets/downloads/pt/pdf/guidelines/06_colorectal_
Control and Prevention (CDC). MMWR Morb Mortal Wkly cancer_screening_pt.pdf
Rep 2011;60(26):884-9. 23. Sonnenberg A, Delco F, Inadomi JM [hompage on the
14. Departamento de Informático do SUS [homepage on the Internet]. Cost-Effectiveness of Colonoscopy in Screening for
Internet]. Taxas de mortalidade por câncer no Brasil [cited Colorectal Cancer. 2000; [cited 2011 Nov 15]; 133;8:573-84.
2011 Oct 15]. Available from: http://www.datasus.gov.br Available from: http://www.annals.org/content/133/8/573.sh
15. Tucunduva LTCM, Sá VHLC, Koshimura ET, Prudente ort?relatedurls=yes&legid=annintmed;133/8/573
FVB, Santos ESTS, Samano EST, et al. Estudo da atitude e 24. Schmid MI, Duncan BD, Silva GA, Menezes AM,
do conhecimento dos médicos não oncologistas em relação Monteiro CA, Barreto SM, et al. Doenças crônicas não
às medidas de prevenção e rastreamento do câncer. Rev transmissíveis no Brasil: carga e desafios atuais. Séries.
Assoc Med Bras 2004;50(3):257-62. Saúde no Brasil 4 [série na Internet]. 2011 [cited 2011 Nov
16. Sarfaty M, Wender R. How to increase colorectal cancer screening 13];6736(11):60135-9. Available from: http://download.
rates in practice. CA Cancer J Clin 2007;57(6):354-66. thelancet.com/flatcontentassets/pdfs/brazil/brazilpor4.pdf
17. Read E, Thomas F, Caushaj P. Screening for Colorectal 25. Mahayri N, Moreira DCF. A importância dos registros
Neoplasms. In: American Cancer Society. Cancer Facts and de câncer de base populacional para identificar casos de
Figures 2004. Atlanta, GA: American Cancer Society; 2004. câncer ginecológico relacionados com câncer colorretal
p. 353-8. em população de risco. Rev Bras Cancerologia [série
18. Klabunde CN, Frame PS, Meadow A, Jones E, Nadel M, na Internet] 2002 [cited 2011 Nov 25];48(3):349-56.
Vernon SW. A national survey of primary care physicians’ Available from: http://www.inca.gov.br/rbc/n_48/v03/pdf/
colorectal cancer screening recommendations and practices. artigo3.pdf
Am J Prev Med 2003;36(3):352-62. 26. American College of Obstetricians and Gynecologists.
19. Sociedade Brasileira de Endoscopia Digestiva [homepage Committee Opinion No. 482: Colonoscopy and colorectal
on the Internet]. Rastreamento e Vigilância do Câncer Colo- cancer screening strategies. Obstetrics & Gynecology
retal. Prevenção secundária e detecção precoce. Projeto [série na internet]. 2011 [cited 2011 Nov 30];117(3):766-
Diretrizes. SOBED. 2008. [cited 2011 Nov 15]. Available 71. Available from: http://www.mendeley.com/research/
from: http://www.sobed.org.br/web/arquivos_antigos/pdf/ committee
diretrizes/Screening.pdf 27. Ganry O, Boche T. Prévention des cancers par les médecins
20. Levin B, Lieberman DA, McFarland B, Andrews KS, Brooks généralistes de Picardie : résultats d’une enquête de type
D, Bond J, et al. Screening and Surveillance for the Early déclarative. Bulletin du Câncer [série na Internet]. 2004
Detection of Colorectal Cancer and Adenomatous Polyps, [cited 2011 Nov 13];91(10):785-91. Available from: http://
2008: A Joint Guideline From the American Cancer Society, www.jle.com/fr/revues/medecine/bdc/e-docs/00/04/09/59/
the US Multi-Society Task Force on Colorectal Cancer, article.phtml
and the American College of Radiology. Gastroenterology
2008;134(5):1570-95. Correspondence to:
21. Klabunde CN, Lanier D, Nadel MR, McLeod C, Yuan G, Elziane da Cruz Ribeiro e Souza
Vernon SW. Colorectal Cancer Screening by Primary Care Rua Bolívia, 1.122, apto. 216 – São Luis
Physicians Recommendations and Practices, 2006–2007. Am CEP: 92420-170 – Canoas (RS), Brazil
J Prev Med 2009;37(1):8-16. E-mail: cruz.elziane@yahoo.com.br

394
Original Article

Epidemiological profile of 175 patients with


Crohn’s disease submitted to biological therapy
Marcelo Rassweiler Hardt1, Paulo Gustavo Kotze1, Fabio Vieira Teixeira2, Juliano Coelho Ludvig3,
Everson Fernando Malluta4, Harry Kleinubing Junior5, Eron Fábio Miranda1, Wanessa Bertrami Tonini1,
Márcia Olandoski6, Lorete Maria da Silva Kotze7, Claudio Saddy Rodrigues Coy8

1
Colorectal Surgery Unit at Cajuru University Hospital, at Pontifícia Universidade Católica do Paraná (PUC-PR) – Curitiba
(PR), Brazil. 2Clínica Gastrosaúde – Marília (SP), Brazil. 3Institute Espaço de Saúde do Aparelho Digestivo (ESADI) – Blumenau
(SC), Brazil. 4Universidade do Vale do Itajaí (UNIVALI) – Itajaí (SC), Brazil. 5Universidade de Joinville (UNIVILLE) – Joinville
(SC), Brazil. 6Discipline of Biostatistics at PUC-PR – Curitiba (PR), Brazil. 7Gastroenterology Unit at PUC-PR – Curitiba (PR),
Brazil. 8Coloproctology Unit at Universidade Estadual de Campinas (UNICAMP) – Campinas (SP), Brazil.

Hardt MR, Kotze PG, Teixeira FV, Ludvig JC, Malluta EF, Kleinubing Jr H, Miranda EF, Tonini WB, Olandoski M, Kotze LMS, Coy CSR.
Epidemiological profile of 175 patients with Crohn’s disease submitted to biological therapy. J Coloproct, 2012;32(4): 395-401.
ABSTRACT: Introduction: There is currently an increasing use of biological agents in the management of Crohn’s disease (CD).
There is lack of data regarding the epidemiological profile of patients on infliximab (IFX) and adalimumab (ADA) for CD in Brazil.
Objective: To identify the epidemiological characteristics of patients with CD who underwent biological therapy. Method: Retro-
spective multicenter study, with CD patients on biological therapy. Analyzed variables: gender, age at treatment initiation, Montreal
classification, concomitant perianal disease and smoking status. Results: 175 patients without previous exposure to biological agents
were included, 93 (53%) were male. The mean age at treatment initiation was 35.5 (2-79) years old an the mean disease duration was
46.9 (0-480) months. Overall, 117 (66.9%) patients used IFX and 58 (33.1%), ADA. Montreal classification: age at diagnosis ― A1
(n=21; 12%), A2 (n=102; 58.3%), and A3 (n=52; 29.7%). CD location ― L1 (n=42; 24%), L2 (n=51; 29.1%), L3 (n=81; 46.3%), and
L4 (n=1, 0.6%). Phenotype ―B1 (n=59; 33.7%), B2 (n=46; 26.3%), and B3 (n=70; 40%). Perianal disease was found in 89 (50.9%)
patients. Conclusions: The epidemiological profile of patients was similar to the literature. There was a high prevalence of patients
with fistulizing CD.
Keywords: Crohn’s disease; tumor necrosis factor-alpha; epidemiology.
RESUMO: Introdução: Atualmente há uso crescente dos agentes biológicos no manejo da doença de Crohn (DC). Há escassez de dados
referentes ao perfil epidemiológico dos usuários de infliximabe (IFX) e adalimumabe (ADA) para DC no Brasil. Objetivo: Identificar as
características epidemiológicas dos pacientes com DC submetidos à terapia biológica. Método: Estudo retrospectivo, multicêntrico, com
portadores de DC que utilizaram terapia biológica. Variáveis analisadas: gênero, idade ao início do tratamento, classificação de Montreal,
doença perianal concomitante e tabagismo. Resultados: Foram incluídos 175 pacientes, sem exposição prévia a biológicos, sendo 93
(53%) homens. A média de idade no início do tratamento biológico foi de 35,5 (2-79) anos. O tempo médio de doença ao início do trata-
mento foi de 46,9 (0-480) meses. Do total da amostra, 117 (66,9%) utilizaram IFX e 58 (33,1%) ADA. Classificação de Montreal: idade
ao diagnóstico ― A1 (n=21; 12%), A2 (n=102; 58,3%) e A3 (n=52; 29,7%). Localização da DC ― L1 (n=42; 24%), L2 (n=51; 29,1%),
L3 (n=81; 46,3%) e L4 (n=1; 0,6%). Forma de apresentação ― B1 (n=59; 33,7%), B2 (n=46; 26,3%) e B3 (n=70; 40%). Doença perianal
foi encontrada em 89 (50,9%) dos pacientes. Conclusões: Os dados epidemiológicos dos pacientes foram compatíveis com os da literatura
internacional. Houve uma alta prevalência de pacientes com a forma fistulizante da DC.
Palavras-chave: Doença de Crohn; fator de necrose tumoral alfa; epidemiologia.

Study carried out at the Colorectal Surgery Unit of the University Hospital Cajuru, from Pontifícia Universidade Católica do Paraná (PUC-PR) –
Curitiba (PR), Brazil.
Financing source: none.
Conflict of interest: nothing to declare.

Submitted on: 22/10/2012


Accepted on: 15/12/2012

395
J Coloproctol Epidemiological profile of 175 patients with Crohn’s disease submitted to biological therapy Vol. 32
October/December, 2012 Marcelo Rassweiler Hardt et al. Nº 4

INTRODUCTION the ability to prevent long term complications has been


more and more discussed5. The drugs that are most
Crohn’s Disease (CD) is a chronic transmural likely to meet these objectives are the anti-TNF anti-
inflammatory disease that may affect the whole gas- bodies, infliximab (IFX), adalimumab (ADA) and cer-
trointestinal tract, and is characterized by alternate tolizumab pegol (CER), which are the only biological
episodes of remission and reactivation. Its evolution agents available in Brazil to handle the disease. Today,
throughout the years, due to its natural history, can a great proportion of the patients with CD in outpatient
cause complications such as stenosis, fistulas or ab- clinics, doctors offices or reference centers, use these
scesses1. Nowadays, there is a global tendency that the drugs. Due to the recent approval of CER in Brazil to
CD incidence will increase, and this is confirmed by manage CD, the number of patients being treated with
important retrospective epidemiological studies from this third agent is still small, but it should increase in
the 1980’s2-4. the next years.
The pathogenesis of CD is not well understood, Currently, the incidence of CD in the United
so there is no defined etiology for the disease5. Some States is approximately 15 to 20 cases per 10 thou-
believe in the existence of complex genetic and envi- sand inhabitants2. It is difficult to measure this number
ronmental interactions that eventually predispose and in countries of Africa or Latin America, like Brazil,
trigger its pathological manifestations6. Its clinical pre- since the epidemiological data of the disease are only
sentation varies according to location, extension and in- available in few publications. Therefore, there is no
tensity of the inflammation of compromised sites5. national prevalence or incidence rate that is officially
CD occurs mainly among adolescents and young acknowledged.
adults, and represents an important social, psychologi- Even with data from isolated regions, it is pos-
cal and labor impact since it affects this age group of sible to observe the increasing number of CD cases
great productivity7. Because of this recurring pattern diagnosed in the past few decades in South America
of symptoms and the evolution to the already men- and Brazil2. Studies performed in the 1980s and 1990s
tioned complications, which lead more than 70% of in some states of Brazil showed dozens of new diag-
patients to surgery and 30% to repeated resections, nosed cases, with much higher numbers in compari-
CD causes a significant impact on the physical and son to previous decades2.
psychological quality of life of patients7,8. In the international literature, many papers analyze
The proper treatment for CD is yet significantly isolated factors such as ethnicity, age, gender, medica-
limited, since there is no type of clinical or surgical in- tion, association with smoking and other variables. How-
tervention that can cure the disease5. Therefore, there ever, none of them have designed an epidemiological
is a constant search for new forms of treatment. In the profile, including only patients with CD on anti-TNF
past few years, the management of CD has evolved, therapy. In Brazil, both epidemiological data of patients
especially due to the increasing use of biological with CD and on biological therapy are lacking.
agents all over the world1. With this scenario of limited data, this study
Until the end of the 1990s, when the first bio- aimed to identify the epidemiological characteristics
logical drug was approved for CD, the conventional of Brazilian patients with CD submitted to biologi-
therapeutic arsenal was composed of corticosteroids, cal therapy, based on baseline characteristics and the
antibiotics, aminosalicylates and immunomodulators Montreal classification. Morover, it aims to determine
(azathioprine, 6-mercaptopurine and methotrexate)5,8. which is the most frequent phenotype of the disease in
Nowadays, the objectives of CD treatment include this sample of patients and to compare this informa-
the fast induction to clinical remission, with the effi- tion with data from the international literature.
cient maintenance of remission without the use of corti-
costeroids, as well as mucosal healing, closure of fistu- METHOD
las, prevention and reduction of the number of hospital
admissions and surgeries, besides the improvement in This study was carried out after the approv-
the quality of life of patients. As an additional objective, al by the Research Ethics Committee of Pontifícia

396
J Coloproctol Epidemiological profile of 175 patients with Crohn’s disease submitted to biological therapy Vol. 32
October/December, 2012 Marcelo Rassweiler Hardt et al. Nº 4

Universidade Católica do Paraná (PUC-PR), pro- Table 1. Detailed Montreal Classification, adapted
tocol number 0005580/11. from Silverberg et al.0.
This was a retrospective, transversal multicenter Montreal Classification
study with patients with CD who were on biological ther- A1 ≤16 years old
apy from May 2000 to May 2012, coming from five dif- Age at
A2 17–40 years old
ferent reference centers of inflammatory bowel disease diagnosis (A)
A3 ≥40 years old
(IBD) from the South and Southeast of Brazil. L1 Terminal ileum
The study included: patients with CD, users of Disease L2 Colon
IFX, ADA or CER as the first anti-TNF agent, who location (L) L3 Ileum-colon
had not previously been on biological therapy, at any L4 Upper gastrointestinal tract
age. The study excluded: patients with ulcerative coli- B1 Nonstenotic /non-penetrating
tis or indeterminate IBD, and those who were using a Behavior (B) B2 Stenotic
second biological drug in the treatment (patients with B3 Penetrating
previous exposure to a first biological agent).
The study sample was not calculated, but per- cal data to the analyzed ones were selected for fur-
formed by means of a convenience sample, including ther comparison.
the actual number of patients coming from the men- With complete protocols and literature review,
tioned reference centers. A data review was conduct- data were compiled and organized in frequency tables.
ed with information from medical files and posterior The obtained results from this sample were expressed
completion of a specific protocol, with previously by means, medians, minimum values, maximum val-
chosen variables to be analyzed. When necessary, the ues and standard deviation (quantitative variables) or
patient received a phone call in case there was con- by frequencies and percentages (qualitative variables).
flicted or missing information, to clear any doubts or Each variable was individually analyzed with the ob-
to request any additional information. After the revi- jective to compare them with data found in literature.
sion of medical files and data collection, 175 patients
met the criteria and were included in this study. RESULTS
All reference centers of IBD that offered their pa-
tients data manage CD according to the guidelines by The study included 175 patients, 93 (53%) were
the European Crohn’s and Colitis Organization (ECCO), male and 82 (47%) female. In relation to age at the be-
which standardizes specially the indication to biological ginning of biological treatment, a mean of 35.5 years
treatment in the included subjects9. old (2–79; SD=13.9) was found. The mean time of
The analyzed variables were gender, age at biologi- duration of CD at the beginning of treatment was
cal therapy initiation, time of diagnosis, associated perianal 46.9 months (0–480; SD=69.6). However, it was ob-
disease, concomitant medications, smoking, type of anti- served that most cases (55.4%) started biological treat-
TNF agent anti-TNF (IFX, ADA or CER) and Montreal ment less than 24 months after the onset of the disease.
classification (age at diagnosis of CD, location of disease One hundred and forty-six patients (83.4%) were
and phenotype). The Montreal classification is detailed in on concomitant use of azathioprine (AZA), using the
Table 1. Protocols were fulfilled based on the compiled strategy of combo therapy, more recently described1.
data concerning the beginning of biological treatment, and Corticosteroids were used at the beginning of biologi-
not the time of diagnosis of CD. cal treatment in 102 patients (58.3%). No patient used
Literature review was based on searches in the fol- methotrexate. There were only 11 smoking patients,
lowing databases: PubMed, MEDLINE and SciELO. which corresponded to 6.3% of the total sample. Peri-
The searched terms were: “infliximab”, “adalimumab”, anal disease was found in 89 patients (50.9%). The
“certolizumab pegol”, “anti-TNF”, “biologics” and biological therapies used were IFX in 117 (66.9%)
“epidemiology”, always combined with “Crohn’s dis- patients and ADA in 58 (33.1%). No patient was on
ease”. All relevant articles published until July 2012 CER. Table 2 summarizes the baseline characteristics
were reviewed, and those with similar epidemiologi- of the analyzed patients.

397
J Coloproctol Epidemiological profile of 175 patients with Crohn’s disease submitted to biological therapy Vol. 32
October/December, 2012 Marcelo Rassweiler Hardt et al. Nº 4

According to the Montreal classification, the fol- Table 2. Baseline characteristics of the 175 analyzed
lowing results were obtained for each of the variables: patients.
age at diagnosis A1 (n=21; 12%), A2 (n=102; 58.3%) n (%)
and A3 (n=52, 29.7%). CD location: L1 (n=42; 24%), Gender
L2 (n=51, 29.1%), L3 (n=81, 46.3%), and L4 Male 93 (53)
(n=1, 0.6%). So, there was a higher prevalence of pa- Female 82 (47)
tients diagnosed with CD between 17 and 40 years old Used biological drug
(A2), patients with ileocolic location (L3) and with ADA 58 (33.1)
fistulizing disease (B3). Figure 1 illustrates these data. IFX 117 (66.9)
Time of diagnosis (months)
DISCUSSION <24 97 (55.4)
24 to 60 36 (20.6)
The determination of epidemiological characteris- >60 42 (24.0)
tics in patients with CD is very difficult, in Brazil and in Mean±SD 46.9±69.6
other developing countries, due to the deficient registra- Median (range) 12.0 (0.0~480.0)
tion systems. It is more difficult to characterize patients Age at treatment initiation (years)
with CD on biological therapy, because even in devel- Mean±SD 35.5±13.9
oped countries these data are controversial, and ana- Median (range) 34.0 (2.0~79.0)
lyzed in different manners by the studies that are avail- Azathioprine
able in literature2. Some assess only isolated users of Yes 146 (83.4)
biological therapy, most of the time analyzing its effica- No 29 (16.6)
cy, safety or loss of response11-16,18. Therefore, this study Corticosteroids
aimed to assess data from subjects coming from five Yes 102 (58.3)
reference centers of IBD from the South and Southeast No 73 (41.7)
of Brazil in order to present a general epidemiological Smoking
profile of these patients, which is more adequate to our Yes 11 (6.3)
reality, and compare them with other studies conducted No 164 (93.7)
in Brazil and in other parts of the world. Perianal CD
The findings in this study demonstrated the Yes 89 (50.9)
greater prevalence of CD in young patients – A2 in
No 86 (49.1)
the Montreal classification, and mean age of 35.5 years
old – in accordance with national and international lit- SD: Standard deviation; CD: Crohn’s Disease; ADA: adalimumab;
IFX: infliximab.
erature2,11-18. This fact reveals the great importance of
diagnosis and adequate management of these patients,
70
since it’s a period of major activity and productivity
of subjects. Since the disease is considerably debilitat- 60 58.3%
ing, both physically and emotionally, and because the 50 46.3%
% of patients

treatment is long, these years in the patient’s life end 40


40%
up being compromised11,13. 33.7%
29.7% 29.1%
30 26.3%
The higher prevalence of male (53 versus 47%) 24%
was a bit different than findings from literature, 20
12%
which presents 45 to 61.8% of female patients and 10
32.8 to 55% of male patients2,11-18. According to
0
Cosnes et al.17, in countries with low incidence of A1 A2 A3 L1 L2 L3 L4 B1 B2 B3
CD, in Europe and North America, the prevalence Montreal Classification
of the disease has increased among men, being simi- Figure 1. Montreal Classification of the 175 patients submitted to
lar or even superior to women. biological therapy.

398
J Coloproctol Epidemiological profile of 175 patients with Crohn’s disease submitted to biological therapy Vol. 32
October/December, 2012 Marcelo Rassweiler Hardt et al. Nº 4

The other two analyzed variables that presented of the patients were on the medication. These data may
different numbers than those found in literature were seem to reflect the tendency of the great use of cortico-
the presence of perianal disease and smoking. Since steroids in Brazil in relation to the other countries2,19,20.
the study was performed in specialized IBD centers, It is very difficult to define which biological
especially coloproctology units, more than half of the agent is more used nowadays. The most relevant in-
patients (50.9%) had associated perianal disease. This ternational studies on the subject aim to assess the
percentage was significantly different when compared safety and efficacy of each isolated drug2,11-16. National
to other papers in literature, which showed 13.1–42% studies and other case series do not present these data
patients affected by perianal disease2,11-13,16,17. Howev- comparatively2,19,20. Even though, a significantly high-
er, it is important to notice the increase of severe and er prevalence of IFX is still observed, maybe for its
complicated forms of CD, such as perianal compro- longer presence in the market or because of its avail-
mise or other conditions2. The presence of fistulae is ability in some centers. It could also be due to the ex-
especially emphasized, since they have a significant perience of professionals who prescribe it and handle
impact on the quality of life of patients and make the it. However, ADA is being more and more used, so
treatment for CD even more challenging13,15. this difference is being reduced as observed in publica-
Regarding smoking, the difference was even tions throughout the years1,2,15. It is certain that within
greater. In this study, only 6.3% of patients smoked, a few years there will be a greater number of patients
while in literature this habit was present in 19 to 47.8% on CER, which was recently approved in Brazil to
of the cases2,12,13,15-17. Maybe this fact is justified by the treat CD patients. The results in this study demonstrated
greater announcement of the relation between smok- 66.85% of patients on IFX and 43.15% on ADA, with
ing and the worse evolution of the disease, especially a clear progression on the use of ADA each year during
in patients’ associations and reference services. the analyzed period. No patient was on CER. The main
In relation to immunosuppressive drugs, distinct epidemiological data found in this study in comparison
values were found in comparison to the literature when to data from literature are described on Table 3.
analyzing only the use of AZA: 83.4% in this study and Concerning the Montreal classification, many
percentages between 25 and 49.7% in the international studies were analyzed; however, those that described
literature. However, in relation to the use of concomitant the samples with this system were not only studies with
drugs, such as methotrexate, 6-mercaptopurine and ami- patients on biological treatment, but with CD in gener-
nosalicylates, which are common in Europe and in the al. Some analyses that assessed only patients on ADA
United States, if added to the use of AZA, the per- or IFX did not use this classification, since their objec-
centage is close to 70%2,11-16. These values suggest tives were not related to epidemiological variables. So,
that even with adverse effects and slow action onset, the values found in this study were comparable to those
there are benefits to the combined treatment with anti- of Brazilian analyses reflecting a reality closer to ours,
TNF that overcome its disadvantages1,14. The results besides an international study that aimed to expose the
presented by Colombel et al.1, in the SONIC study, evolution of the incidence and prevalence of IBD, CD
demonstrated that the combined therapy of IFX and and ulcerative colitis, separately, throughout the years,
AZA presented better clinical remission rates for CD which consistently demonstrated the prevalence of each
as well as mucosal healing, in comparison to mono- one of the classifications2,17,19-21.
therapy with IFX or AZA. Group A2 in the Montreal classification (age
By analyzing the use of corticosteroids at the begin- at diagnosis between 17 and 40 years) was the most
ning of biological treatment, 58.3% of the patients in this prevalent in this study, accounting for 58.3% of the
study used them. In the national and international litera- patients. This number was similar to that of papers
ture, these values ranged from 26 to 77% of the cases, in literature analyzed in this comparison (between
which demonstrates one of the great indications to use 59 and 73%), which shows the great prevalence of CD
biological drugs for the treatment of CD, the corticoste- and the biological treatment in this age group17,19-21.
roid dependency2,11-18. Brazilian studies that also reported The disease location was also shown in this study,
the analysis of this variable, demonstrated that 67 to 77% and the percentages were in accordance with literature.

399
J Coloproctol Epidemiological profile of 175 patients with Crohn’s disease submitted to biological therapy Vol. 32
October/December, 2012 Marcelo Rassweiler Hardt et al. Nº 4

The most prevalent type was L3 (ileocolic CD), in 46.3% CONCLUSIONS


of the cases. In the literature, this was also the most com-
mon form observed in most of the reviewed studies, with Patients with CD on biological treatment, who
percentages ranging from 34.5 and 47%2,17,19-21. had not been previously on anti-TNF therapy, had
Regarding the behavior of CD, differences be- mean age of 35.5 years old, and most of them were
tween the findings in this sample were found in com- male (53%). The subtype A2, from the Montreal clas-
parison to literature. The B3 type (penetrating CD) was sification, was the most found one (68.3%), and ileo-
described as being the most frequent one, representing colic segment (L3) as the most frequent compromised
40% of the cases. In most studies, the B1 type was more location in 46.3% of the cases. Most patients were on
prevalent (luminal CD), ranging between 29.2 and 71%. treatment with AZA or corticosteroids together with
This fact can be explained by the conduction of studies the biological treatment. These data characterize an
in colorectal surgery units, instead of gastroenterology epidemiological profile compatible with that found in
clinics, where the reference and indications for patients international literature.
with fistulizing perianal CD is more prevalent2,17,19,20. The presence of perianal disease was shown in
The comparative data in the present sample in relation 50.9% of the cases, and the subtype B3 from the Mon-
to the Montreal classification and other studies in litera- treal classification was present in 40% of the cases,
ture are detailed in Table 4. with higher prevalence comparing to the literature.

Table 3. Clinical and epidemiological basal characteristics of patients in comparison to papers from the national
and international literature.
Gender (%) Perianal Concomitant Concomitant
Smoking
Author Mean age Disease AZA corticosteroid
Male Female (%)
(%) (%) (%)
Panaccione et al. 11
43.1 56.9 37 22.4 – 46.4 47.4
Colombel et al.12 38.2 61.8 37.1 15.2 35.5 32.2 44.0
Lichtiger et al.13 40.9 59.1 40.8 13.1 23.5 41.2 42.3
Hanauer et al.14 42.0 58.0 35 – – 25.0 51.0
Sands et al.15 55.0 45.0 37 – 45.0 30.0 26.0
Schnitzler et al.16 39.0 61.0 33.9 28.0 47.8 49.7 32.2
Cosnes et al.17 54.0 46.0 33 31.0 19.0 – –
Souza et al.2 44.0 56.0 32 42.0 – 48.8 77.0
Kotze et al.8 46.3 53.7 36.7 50.0 – – 55.5
This study 53.0 47.0 35.5 50.9 6.3 83.4 58.3
AZA: azathioprine.

Table 4: Montreal classification: data found in this study compared with data from national and international literature.
Montreal
Author
A1 A2 A3 L1 L2 L3 L4 B1 B2 B3
Teixeira et al. 21
10.0% 72.0% 18.0% 34.5% 31.0% 34.5% 0.0% - - -
Souza et al.20 - - - 22.0% 29.0% 47.0% 2.0% 58.0% 19.0% 23.0%
Poli et al.19 8.0% 73.0% 19.0% 34.0% 15.0% 45.0% 1.0% 38.0% 26.0% 36.0%
Souza et al. 2
8.0% 59.0% 33.0% 46.0% 10.0% 43.0% 1.0% 71.0% 8.0% 21.0%
Cosnes et al. 17
11.0% 72.0% 17.0% 25.3% 27.2% 34.6% 13.1% 29.2% 33.6% 37.2%
This study 12.0% 58.3% 29.7% 24.0% 29.1% 46.3% 0.6% 33.7% 26.3% 40.0%

400
J Coloproctol Epidemiological profile of 175 patients with Crohn’s disease submitted to biological therapy Vol. 32
October/December, 2012 Marcelo Rassweiler Hardt et al. Nº 4

REFERENCES 12. Colombel JF, Sandborn WJ, Rutgeerts P, Enns R, Hanauer SB,
Panaccione R, et al. Adalimumab for maintenance of clinical
1. Colombel JF, Sandborn WJ, Reinisch W, Mantzaris GJ, response and remission in patients with Crohn’s disease: the
Kornbluth A, Rachmilewitz D, et al. Infliximab, azathioprine, CHARM trial. Gastroenterology 2007;132(1):52–65.
or combination therapy for Crohn’s disease. N Engl J Med 13. Lichtiger S, Binion DG, Wolf DC, Present DH, Bensimon AG,
2010;362(15):1383-95. Wu E,  et  al. The CHOICE trial: adalimumab demonstrates
2. Souza MHLP, Troncon LEA, Rodrigues CM, Viana CFG, safety, fistula healing, improved quality of life and increased
Onofre PHC, Monteiro RA,  et  al. Evolução da ocorrência work productivity in patients with Crohn’s disease who
(1980-1999) da doença de Crohn e da retocolite ulcerativa failed prior infliximab therapy. Aliment Pharmacol Ther
idiopática e análise das suas características clínicas em um 2010;32(10):1228-39.
hospital universitário do sudeste do Brasil. Arq Gastroenterol 14. Hanauer SB, Feagan BG, Lichtenstein GR, Mayer LF,
2002;39(2):98-105. Schreiber S, Colombel JF, et al. Maintenance infliximab for
3. Sedlack RE, Whisnant J, Elveback LR, Kurland LT. Incidence Crohn’s disease: the ACCENT I randomised trial. Lancet
of Crohn’s disease in Olmsted County, Minnesota, 1935- 2002;359(9317):1541-9.
1975. Am J Epidemiol 1980;112(6):759-63. 15. Sands BE, Anderson FH, Bernstein CN, Chey WY,
4. Sonnenberg A. Geographic variation in the incidence of Feagan BG, Fedorak RN,  et  al. Infliximab maintenance
and mortality from inflammatory bowel disease. Dis Colon therapy for fistulizing Crohn’s disease. N Engl J Med
Rectum 1986;29(12):854-61. 2004;350(9):876-85.
5. Yanai H, Hanauer SB. Assessing response and loss of 16. Schnitzler F, Fidder H, Ferrante M, Noman M, Arijs I,
response to biological therapies in IBD. Am J Gastroenterol Van Assche G, et al. Long-term outcome of treatment with
2011;106(4):685-98. infliximab in 614 patients with Crohn’s disease: results from
6. Chaparro M, Panés J, García V, Merino O, Nos P, Domènech a single-centre cohort. Gut 2009;58(4):492-500.
E, et al. Long-term durability of response to adalimumab in 17. Cosnes J, Gower-Rousseau C, Seksik P, Cortot A.
Crohn’s disease. Inflamm Bowel Dis 2012;18(4):685-90. Epidemiology and natural history of inflammatory bowel
7. Rutgeerts P, Van Assche G, Vermeire S. Optimizing anti-TNF diseases. Gastroenterology 2011;140(6):1785-94.
treatment in inflammatory bowel disease. Gastroenterology 18. Kotze PG, Vieira A, Sobrado Jr CW, Salem JB, Kotze LMS.
2004;126(6):1593-610. Adalimumab in the induction of Crohn’s disease remission:
8. Wu EG, Mulani PM, Yu AP, Tang J, Pollack PF. Loss of results of a Brazilian multicenter case series. J Coloproctol
treatment response to infliximab maintenance therapy 2011;31(3):233-40.
in Crohn’s disease: a payor perspective. Value Health 19. Poli DD. Aspectos da raça e da ancestralidade na
2008;11(5):820-9. apresentação e evolução da DC no Brasil [Dissertação
9. Dignass A, Van Assche G, Lindsay JO, Lémann M, Söderholm de Mestrado]. São Paulo: Faculdade de Medicina da
J, Colombel JF,  et  al. The second European evidence-based Universidade de São Paulo; 2007. 51 p.
Consensus on the diagnosis and management of Crohn’s 20. Souza MM; Belasco AGS; Aguilar-Nascimento JE. Perfil
disease: Current management. J Crohns Colitis 2010;4(1):28-62 epidemiológico dos pacientes portadores de doença
10. Silverberg MS, Satsangi J, Ahmad T, Arnott ID, Bernstein inflamatória intestinal do estado de Mato Grosso. Rev Bras
CN, Brant SR, et al. Toward an integrated clinical, molecular Colo-proctol 2008;28(3):324-8.
and serological classification of inflammatory bowel 21. Teixeira MG, Habr-Gama A, Takiguti CK, Brunetti Netto
disease: Report of a Working Party of the 2005 Montreal C, Pinotti HW. Aspectos epidemiológicos da doença de
World Congress of Gastroenterology. Can J Gastroenterol Cröhn em 140 pacientes do serviço de Colo-Proctologia do
2005;19 (Suppl A):5-36. HCFMUSP. Rev Bras Colo-Proctol 1993;13(4):128-32.
11. Panaccione R, Loftus Jr EV, Binion D, McHugh K, Alam S,
Chen N, et al. Efficacy and safety of adalimumab in Canadian Correspondence to:
patients with moderate to severe Crohn’s disease: results of Paulo Gustavo Kotze
the Adalimumab in Canadian SubjeCts with ModErate to Rua Mauá, 682
Severe Crohn’s DiseaSe (ACCESS) trial. Can J Gastroenterol CEP: 80030-200 – Curitiba (PR), Brazil
2011;25(8):419-25. E-mail: pgkotze@hotmail.com

401
Original Article

Transanal minimally invasive surgery with single-port (TAMIS)


for the management of rectal neoplasms: a pilot study
Eduardo Fonseca Alves Filho1, Paulo Frederico de Oliveira Costa2, João Cláudio Guerra3

1
Titular Member of Sociedade Brasileira de Coloproctologia (SBCP) – Rio de Janeiro (RJ), Brazil. 2Affilieted Member of
SBCP – Rio de Janeiro (RJ), Brazil. 3Associate Member of SBCP – Rio de Janeiro (RJ), Brazil.

Alves Filho EF, Costa PFO, Guerra JC. Transanal minimally invasive surgery with single-port (TAMIS) for the management of rectal
neoplasms: a pilot study. J Coloproctol, 2012;32(4): 402-406.
ABSTRACT: Transanal endoscopic microsurgery (TEM) has been used since the 1980’s for the treatment of selected rectal cancers,
with clear benefits regarding morbidity and mortality, and good oncological outcomes when compared to radical surgery and conven-
tional local resections. The high cost of equipment and the need for long learning curve did not allow the spread of the technique. The
aim of this study was to describe the technical characteristics and outcomes of 4 patients operated by this technique, 3 with histologi-
cally confirmed adenomas and 1 carcinoid rectal tumor, with no recurrence after an average ­follow-up of 12 months. The use of single
port devices for transanal surgery is a safe method with good oncological results and allows a faster learning curve, by the similarity
with conventional laparoscopic procedures and the availability of devices commonly used in laparoscopy.
Keywords: colorectal surgery; rectal neoplasms; TAMIS; laparoscopy.

Resumo: A microcirurgia endoscópica transanal (TEM) é usada desde a década de 80 para o tratamento de neoplasias retais se-
lecionadas, com claros benefícios relacionados à mortalidade e morbidade, e com bons resultados oncológicos, em comparação à
cirurgia radical e a ressecções locais convencionais. O custo alto de equipamento de TEM e a necessidade de uma curva de aprendi-
zagem longa ainda não permitiram a propagação da técnica. O objetivo deste estudo foi descrever a técnica cirúrgica e os desfechos
oncológicos em 4 pacientes operados por esta técnica, 3 com diagnóstico final de adenomas e 1 de tumor carcinoide, sem recorrência
após seguimento médio de 12 meses. A utilização de dispositivos de portal único para a cirurgia transanal é um método seguro e com
bons resultados oncológicos, permitindo uma curva de aprendizado mais rápida pela semelhança com os procedimentos laparoscó-
picos convencionais e pela disponibilidade de dispositivos comumente utilizados em laparoscopia.
Palavras-chave: cirurgia colorretal; neoplasias retais; TAMIS; laparoscopia.

INTRODUCTION rectum, access to higher lesions and better ability to ob-


tain clear margins with the possibility of excision with-
Since the introduction of transanal endoscopic mi- out fragmentation of the surgical specimen1-13.
crosurgery (TEM) by Buess in 1985, there was a change The high cost of the equipment and surgical
in the paradigms for the treatment of several rectal neo- instruments added to the limited number of indica-
plasms. This technique has proven to be effective and tions for its use, consequently, lead to a long learn-
safe in treating early rectal tumors and polyps. When ing curve. This led TEM to remain a restricted meth-
compared with traditional techniques as local excision, od, preventing the spread of the technique among
TEM has the advantages of better visualization of the colorectal surgeons.

Studiy carried out at the Coloproctology Service of Hospital Português da Bahia – Salvador (BA), Brazil.
Financing source: none.
Conflict of interest: nothing to declare.

Submitted on: 11/06/2012


Approved on: 02/08/2012

402
J Coloproctol Transanal minimally invasive surgery with single-port (TAMIS) Vol. 32
October/December, 2012 for the management of rectal neoplasms – a pilot study Nº 4
Eduardo Fonseca Alves Filho et al.

From the development of surgical techniques, eral, anterior and posterior stitches were performed
such as Natural Orifice Transluminal Endoscop- to maintain proper placement. Rectal insufflation
ic Surgery (NOTES), and the use of single portal with carbon dioxide was performed, with an aver-
devices for laparoscopic surgery, a new alternative age pressure of 12 to 15 mmHg. Three trocars were
for resection of rectal lesions by transanal surgery then introduced on the SILS device. Superiorly, an
called Transanal endoscopic microsurgery per- optics with 5 mm and 30 degrees was introduced,
formed by single port (TAMIS) was introduced1-3, and inferiorly one ordinary laparoscopic forceps of
combining the TEM traditional technique with other 5 mm was placed. On the third port, a hook, scis-
instruments commonly used in laparoscopic surgery. sor or sealing clamp was placed, according to the
The aim of this study was to describe a case se- surgical needs. A conventional monopolar cautery
ries of the first four patients operated by the ­TAMIS was connected to these previous laparoscopic in-
technique in our service, with emphasis on technical struments, as needed.
details and surgical oncological outcomes. After its identification, the lesions were
bounded and the disection was started ­(Figure 2).
METHODS One crutial step of the procedures was to outline
partial or total commitment of the rectal wall. De-
This is a retrospective description (case series) of pending on the size of the lesion, it was removed
four patients submitted to rectal neoplasms resection along with the device withdrawal, which could
by the TAMIS technique. All patients were operated again be introduced and fixed. Then, the wound
with the SILS® device (Covidien, USA) (Figure 1), an could be reviewed and its primary closure could
equipment primarily developed for single-port lapa- be performed in cases of full thickness resection
roscopic surgery, made of flexible synthetic materi- of the rectal wall.
al, with three openings for the introduction of 5 and
12 mm trocars and a CO2 connection for insufflation RESULTS
and pneumorectum achievement.
All patients underwent colonoscopy and biopsy Four patients were treated with this method and
previously. As a preparation for the operations, they represented our initial experience, three women and
underwent mechanical anterograde bowel prepara- one man. The average age was 55 years old. Regard-
tion, antibiotic prophylaxis and were operated on ing the preoperative diagnosis, three rectal adenomas
lithotomy position under general anesthesia, with with low grade dysplasia were identified and one rec-
uniform technique. The device was introduced into tal submucosal tumor whose chromogranin A serum
the anal canal after its lubrification (Figure 2). Lat- level confirmed the diagnosis of carcinoid tumor.

Figure 1. SILS port Figure 2. Introdução do dispositivo SILS

403
J Coloproctol Transanal minimally invasive surgery with single-port (TAMIS) Vol. 32
October/December, 2012 for the management of rectal neoplasms – a pilot study Nº 4
Eduardo Fonseca Alves Filho et al.

Three patients underwent magnetic resonance imag- hand, the method also proved to have lower mor-
ing (MRI) of the pelvis preoperatively, and there was bidity and no difference in overall survival rates.
no evidence of invasion of the rectal wall. This can be explained by the fact that patients with
The average size of the lesions was 1.5 cm, and recurrent T1 tumors after TEM are often referred
the median distance from the anal margin was 6.5 cm. to radical surgery and chemoradiation. When com-
The mean duration of the procedures was 110 minutes. pared to local resection, TEM had better results
All operations were carried out successfully, without in achieving negative margins and disease-free
conversion for conventional transanal resection. There survival, however no differences in complication
were no complications and no need for new interven- rates and overall recurrence were demonstrat-
tions. There were two submucosal resection and two ed 15,16. TEM is also described as inadequate for the
full-thickness resection with primary closure of the treatment of T2 rectal tumors15.
wound with separate stitches. The submucosal invasion and tumor size are
In all cases, the lateral and deep margins were considered the most important predictors of local
clear, and the postoperative diagnosis were three recurrence. Tumors smaller than 3 cm and without
tubule-villous adenomas with low grade displasia submucosal invasion have recurrence rates of 7%,
and one carcinoid tumor measuring 1 cm. No ad- as compared to up to 38% in lesions larger than
ditional therapy was needed for all cases. With an 3 cm with invasion of the submucosal layer17.
average follow-up of 12 months, no recurrences In selected cases of early rectal adenocarcino-
were detected. mas with certain features such as superficial inva-
sion of submucosa (pT1 SM1), histologically well
DISCUSSION differentiated, with <3 cm of diameter and without
lymphatic or vascular invasion, a local recurrence
TEM has been accepted as a safe alternative rate of less than 5% can be demonstrated when
when colonoscopic rectal adenomas resections or treated by TEM. In these cases, TEM had similar
conventional transanal local resections are not fea- recurrence and disease-free survival, with fewer
sible or appropriate from the oncologic standpoint. rates of mortality and morbidity, when compared
Colonoscopic resection may be associated with to radical surgery18.
high rates of recurrence (21 to 33%) for polyps In patients with suspected partial response af-
whose resection margins are positive or less than ter neoadjuvant treatment, where any lump or ir-
1 mm. This is most likely to happen in polyps larg- regularity in the rectal wall can be identified, re-
er than 2 cm and in piecemeal resections14. TEM section by TEM of these suspicious lesions with
provides larger resections with adequate margins adequate lateral and deep margins, can confirm a
and encompassing the whole rectal wall. This pro- complete pathologic response (ypCR), allowing
vides a recurrence rate of aproximately 5%, with the inclusion of these patients in Watch and Wait
conversion rates of 5.7% and complications in 3 protocols19.
to 7% of the cases14. Recurrence is particularly in- TEM can also be used to resect submuco-
creased in patients who previously underwent a re- sal rectal neoplasms such as carcinoids tumors20.
section by both TEM and colonoscopy15,16. In all These must be smaller than 2 cm without any evi-
cases of our initial experience, no recurrence and dence of muscular invasion to be considered a good
no morbidity was demonstrated, possibly due to indication for the method. When these lesions are
patient selection. removed by colonoscopy, usually they result in
Recent meta-analysis that evaluated the re- positive margins, compromising the oncological
sults of TEM in the treatment of T1 and T2 rec- radical profile of the procedure. Our patient with
tal tumors demonstrated that when compared with the carcinoid tumor presented with this features
radical surgery, TEM has higher chances of posi- and had no complications on the follow-up.
tive margins, higher rates of local recurrence and Some degree of anorectal dysfunction can oc-
lower disease-free survival rates15. On the other cur in more than 50% of the patients undergoing

404
J Coloproctol Transanal minimally invasive surgery with single-port (TAMIS) Vol. 32
October/December, 2012 for the management of rectal neoplasms – a pilot study Nº 4
Eduardo Fonseca Alves Filho et al.

Table 1. Resections by TAMIS.


Number of Positive
Conversions Complications Deaths
resections margins
Lorenz, Nimmesgern and Langwieler13 13 0 0 0 0
Atallah, Albert and Larach3 6 1 0 0 0
Cid et al.5 5 0 0 0 0
Van den Boezem et al.7 12 0 2 0 0
Matz and Matz8 3 0 0 0 0
Lim et al.10 16 0 0 0 0
Barendse et al.12 15 0 2 2 0
Total 70 1 (1.4%) 4 (5.6%) 2 (2.8%) 0

TEM. Decreased resting pressures and contraction struments, a partial loss of insufflation (pneumor-
can be presented until one year after these proce- ectum) can also occur. The visibility of the rectum
dures, causing temporary incontinence. The main is generally excellent. Lower lesions, nearby the
risk factor for this complication was the duration dentate line, are not generally resectable by both
of the procedure1. It was demonstrated by endorec- TEM and TAMIS, being conventional local re-
tal ultrasound that partial lesions of the internal section the most appropriate method indicated7.
anal sphincter can occur in up to 29% of patients 1. ­TAMIS, when compared to TEM, does not allow
Other studies have shown no significant changes access to higher rectal lesions (15 to 20 cm ver-
in incontinence scores or in quality of life ques- sus 18 to 25 cm). Currently, more than one single
tionnaires in the long term evaluation21,22. Despite portal device have been tested for the resection
the fact that our patients were not submitted to of rectal lesions, and it seems to be no difference
sphincter evaluation with ultrasound, no anal in- among the different equipments tested13.
continence was referred in this initial experience. The main question that exists with TAMIS
Unlike what is done in TEM and local resec- is if this new adapted technique will have simi-
tions, the positioning of the patients in TAMIS is lar results as compared to TEM. TAMIS is not the
independent of the location of the lesion. The li- first modification of the TEM method. Other ap-
thotomy position is suitable for most tumor resec- paratus as TEO, using 2D optical systems, in con-
tions, even in lesions of the anterior rectal wall1,3,4. trast to the three-dimensional view of TEM, are
The attachment of an external arm to the surgical also used with similar results to TEM23. Based on
table is also not needed. The instruments needed reports in the literature, we could identify more
are the same commonly used in laparoscopic pro- than 70 patients treated by TAMIS (Table 1), with
cedures, like cholecystectomies and appendecto- results comparable to those of TEM for negative
mies. The costs of the TEM surgical rectoscope margins, conversion and complication rates. There
and its instruments is estimated by US$ 85,000 in were no reported deaths related to the procedure.
Europe, while the single port devices cost around Long term results regarding recurrence and over-
US$ 500. This makes TAMIS a feasible alterna- all survival rates may answer these questions in a
tive in any center with regular laparoscopic equip- near future.
ments and experienced professionals in colorectal The initial experience of this pilot study, in
laparoscopic surgery14. accordance to the literature, suggests that TAMIS,
The technical limitations of TAMIS are simi- as a new adaptation of TEM, can be safely per-
lar to those of laparoscopic surgery. There is a ten- formed with similar results. Due to its lower costs,
dency when using conventional electric cautery to and the possible shorter learning curve, this adapt-
produce smoke that impairs the view of the opera- ed technique can contribute to the dissemination
tive field. Depending on the mobilization of the in- of minimally invasive treatment for rectal lesions.

405
J Coloproctol Transanal minimally invasive surgery with single-port (TAMIS) Vol. 32
October/December, 2012 for the management of rectal neoplasms – a pilot study Nº 4
Eduardo Fonseca Alves Filho et al.

REFERENCES 14. Mulsow J, Winter DC. Sphincter preservation for distal


rectal cancer – a goal worth achieving at all costs? World J
1. Lorenz C, Nimmesgern T, Back M, Langwieler TE. Transanal Gastroenterol 2011;17(7):855-61
single port microsurgery (TSPM) as a modified technique 15. Middleton PF, Sutherland LM, Maddern GJ. Transanal
of transanal endoscopic microsurgery (TEM). Surg Innov endoscopic microsurgery: a systematic review. Dis Colon
2010;17(2):160-3. Rectum 2005;48(2):270-84.
2. Khoo RE. Transanal excision of a rectal adenoma using 16. Nahas SC, Nahas CSR, Marques CFS, Dias AR, Pollara WM,
single-access laparoscopic port. Dis Colon Rectum Cecconello I. Transanal endoscopic microsurgery (TEM): a
2010;53(7):1078-9. minimally invasive procedure for treatment of selected rectal
3. Atallah S, Albert M, Larach S. Transanal minimally invasive neoplasms. ABCD 2010;23(1):35-9.
surgery: a giant leap forward. Surg Endosc 2010;24(9):2200-5. 17. Sgourakis, Lanitis S, Gockel I, Kontovounisios C, Karaliotas
4. Ragupathi M, Haas EM. Transanal endoscopic video- C, Tsiftsi K, et al. Transanal endoscopic microsurgery for T1
assisted excision: application of single-port access. JSLS and T2 rectal cancers: a meta-analysis and meta-regression
2011;15(1):53-8. analysis of outcomes. Am Surg 2011;77(6):761-72.
5. Cid RC, Pérez JC, Elosua TG, Pinto FL, Alegre JM, Martín 18. Doornebosch PG, Zeestraten E, de Graaf EJ, Hermsen
R, et al. [Transanal resection using a single port trocar: a new P, Dawson I, Tollenaar RA, et al. Transanal endoscopic
approach to NOTES]. Cir Esp 2011;89(1):20-3. microsurgery for T1 rectal cancer: size matters! Surg Endosc
6. Dardamanis D, Theodorou D, Theodoropoulos G, Larentzakis 2012;26(2): 551-7.
A, Natoudi M, Doulami G, et al. Transanal polypectomy 19. Habr-Gama A, Perez R, Proscurchin I, Gamarodriguez J.
using single incision laparoscopic instruments. World J Complete clinical response after neoadjuvant chemoradiation
Gastrointest Surg 2011;3(4):56-8. for distal rectal cancer. Surg Oncol Clin N Am 2010;19:829-45.
7. Van den Boezem PB, Kruyt PM, Stommel MW, Tobon 20. Moraes RS, Malafaia OT, Queiroz JE, Trippia MA, Buess
Morales R, Cuesta MA, Sietses C. Transanal single-port GF, Coelho JCU. Transanal endoscopic microsurgery in the
surgery for the resection of large polyps. Dig Surg 2011;28(5- treatment of rectal tumors: a prospective study in 50 patients.
6):412-6. Arq Gastroenterol 2008;45(4):268-74
8. Matz J, Matz A. Use of a SILS port in transanal endoscopic 21. Doornebosch PG, Gosselink MP, Neijenhuis PA, Schouten
microsurgery in the setting of a community hospital. J WR, Tollenaar RA, de Graaf EJ. Impact of transanal
Laparoendosc Adv Surg Tech A 2012;22(1):93-6. endoscopic microsurgery on functional outcome and quality
9. Demirbas S, Cetiner S, Ozer TM, Oztas M, Duran E. The use of life. Int J Colorectal Dis 2008;23(7):709-13.
of single port surgery for polyps located in the rectum.Turk J 22. Allaix ME, Rebecchi F, Giaccone C, Mistrangelo M,
Gastroenterol 2012;23(1):66-71. Morino M. Long-term functional results and quality of
10. Lim SB, Seo SI, Lee JL, Kwak JY, Jang TY, Kim CW, et al. life after transanal endoscopic microsurgery. Br J Surg
Feasibility of transanal minimally invasive surgery for mid- 2011;98(11):1635-43.
rectal lesions. Surg Endosc 2012. [Epub ahead of print] 23. Rocha JJR, Féres O. Transanal endoscopic operation: a new
11. Smith RA, Anaya DA, Albo D, Artinyan A. A stepwise proposal. Arq Gastroenterol 2008;45(4):268-74.
approach to transanal endoscopic microsurgery for rectal
cancer using a single-incision laparoscopic port. Ann Surg
Oncol 2012. [Epub ahead of print]
12. Barendse RM, Verlaan T, Bemelman WA, Fockens P, Dekker
E, Nonner J, et al. Transanal single port surgery: selecting Correspondence to:
a suitable access port in a porcine model. Surg Innov 2011. Eduardo Fonseca Alves Filho
[Epub ahead of print] Centro Médico do Hospital Português
13. Lorenz C, Nimmesgern T, Langwieler TE. Transanal Avenida Princesa Isabel, 914, sala 208, Barra Avenida
endoscopic surgery using different single-port devices. Surg CEP: 40144900 – Salvador (BA), Brazil
Technol Int 2012;XXI:107-111. [Epub ahead of print] E-mail: eduardoalvesfh@hotmail.com

406
Original Article

Clinical outcomes of Fournier’s gangrene from a tertiary hospital


Isaac José Felippe Corrêa Neto1, Otávio Nunes Sia2, Alexander Sá Rolim3, Rogério Freitas Lino Souza4,
Hugo Henriques Watté5, Laércio Robles6

1
Assistant Physician at the Service of Coloproctology at the Hospital Santa Marcelina (HSM) – São Paulo (SP), Brazil;
Associate member of the Sociedade Brasileira de Coloproctologia (SBCP) – São Paulo (SP), Brazil. 2Former Resident
Physician at the Service of Coloproctology, HSM – São Paulo (SP), Brazil; Affiliate member of the SBCP – São Paulo (SP),
Brazil. 3Assistant Physician at the Service of Coloproctology at the HSM – São Paulo (SP), Brazil. 4Assistant Physician at
the Service of Coloproctology at the HSM – São Paulo (SP), Brazil. 5Assistant Physician at the Service of Coloproctology
at the HSM – São Paulo (SP), Brazil; Full member at the SBCP – São Paulo (SP), Brazil. 6Physician, Head of the
Department of Surgery and Coordinator of the Medical Residency Program in Coloproctology at the HSM – São Paulo
(SP), Brazil.

Corrêa Neto IJF, Sia ON, Rolim AS, Souza RFL, Watté HH, Robles L. Clinical outcomes of Fournier’s gangrene from a tertiary hospital.
J Coloproctol, 2012;32(4): 407-410.
ABSTRACT: Fournier’s gangrene is a progressive polymicrobial necrotizing fasciitis, caused by aerobic and anaerobic organisms. It causes
an endarteritis obliterans leading to vessel thrombosis and subsequent cutaneous and subcutaneous necrosis of the perineal region. Objective:
It was to describe the clinical outcomes of Fournier’s gangrene treated at the Hospital Santa Marcelina, São Paulo (SP), Brazil. Methods:
This was a retrospective study conducted at the Hospital Santa Marcelina, in São Paulo (SP), Brazil, with patients with necrotizing fasciitis
from September 2008 to March 2011. Results: We included 13 patients, most were males, and the mean age was 51.8 years old. Five of them
presented with systemic inflammatory response syndrome, only two had no comorbidities and 23% were obese. The most prevalent etiologic
agent was E. coli, and the most common antibiotic regimen consisted of a combination of metronidazole with ciprofloxacin. The average
number of surgical procedures performed by patient was 2.07, and 7 patients (53.8%) underwent colostomy formation. The mortality rate was
30.8%. Conclusions: Fournier’s gangrene is a severe disease, with high mortality rates. The physician should suspect its diagnosis early and
have an aggressive treatment approach to achieve better outcomes.
Keywords: Fournier gangrene; perineum; colostomy; bacterial infections; necrosis.

Resumo: A gangrena de Fournier representa uma fasceíte necrotizante e progressiva de origem polimicrobiana, causada por organismos ae-
róbios e anaeróbios. Tem como fisiopatologia a endarterite obliterante, que leva à trombose dos vasos cutâneos e subcutâneos e à consequente
necrose da região perineal. Objetivo: Foi descrever os casos de gangrena de Fournier atendidos no Hospital Santa Marcelina, São Paulo (SP),
Brasil. Métodos: Este estudo retrospectivo foi realizado no Hospital Santa Marcelina, em São Paulo (SP), com pacientes portadores de fasceíte
necrotizante no período de setembro de 2008 a março de 2011. Resultados: Este estudo incluiu 13 pacientes, a maioria do sexo masculino,
com média de idade de 51,8 anos. Cinco apresentavam síndrome da resposta inflamatória sistêmica e somente dois não tinham comorbidades,
sendo 23% deles obesos. O agente etiológico mais prevalente foi a E.coli, e o esquema de antibiótico mais utilizado foi a associação de me-
tronidazol e ciprofloxacina. A média foi de 2,07 cirurgias por paciente, com realização de ostomia derivativa em 7 dos 13 pacientes (53,8%).
A taxa de mortalidade foi de 30,8%. Conclusão: A gangrena de Fournier é uma doença grave, com alto índice de mortalidade. O médico
assistente deve suspeitar precocemente essa afecção e realizar conduta terapêutica agressiva visando a melhores resultados.
Palavras-chave: gangrena de Fournier; períneo; colostomia; infecções bacterianas; necrose.

Study carried out at the Coloproctology Medical Residency Program of the Department of General Surgery at the Hospital Santa Marcelina – São Paulo
(SP), Brazil.
Financing source: none.
Conflict of interest: nothing to declare.

Submitted on: 01/06/2012


Approved on: 13/09/2012

407
J Coloproctol Gangrena de Fournier: revisão de literatura e experiência de serviço terciário Vol. 32
October/December, 2012 Isaac José Felippe Corrêa Neto et al. Nº 4

INTRODUCTION neal and scrotal region, indicating cellulitis. Tissue


crepitus is found in 50 to 62% of the cases20. After 48
Fournier’s gangrene (FG) was reported for the to 72 hours, necrotic areas appear in the infected tis-
first time in 1764 by Baurienne1 and initially described sue, making local gangrene evident after 4 to 5 days.
in 1883 by Fournier2. It is a progressive polymicrobial Most authors consider three principles when se-
necrotizing fasciitis, caused by aerobic and anaerobic lecting the treatment option9,21,22: clinical stabilization,
organisms3 that act synergistically, affecting the peri- broad-spectrum antibiotics and surgical debridement
anal, perineal, genital and abdominal regions4. with excision of affected tissues, as broad as necessary,
Other terms have been used to describe this con- complemented or not by urinary and fecal diversion.
dition, such as idiopathic gangrene, spontaneous ful-
minant gangrene of the scrotum, streptococcal scrotal METHODS
gangrene and gangrenous erysipelas of the scrotum,
among other names. This is a retrospective descriptive study that ana-
This infectious process caused by endarteritis lyzed the electronic records of patients with necrotizing
obliterans leads to thrombosis of cutaneous and sub- fasciitis from September 2008 to March 2011, at the
cutaneous vessels and consequent necrosis of the skin Hospital Santa Marcelina, in São Paulo (SP), Brazil.
in the affected region.3,5 Necrosis dissemination may The following variables were collected: age and
reach 2 to 3 cm per hour6. In addition, tissue edema, gender of patients, comorbidities, obesity, symptom
hypoxia and difficult blood supply contribute to an- duration, signs of systemic inflammatory response
aerobic bacteria development and proliferation7. syndrome (SIRS), etiology, prior surgical procedures
FG affects around 1:7,5008, mostly men, at mean and how many, use of colostomy, etiological agent,
age of 50 years old5,9 and at the ratio of 10:1. Risk antibiotic regimen, hospital length-of-stay and mortal-
factors for FG include: diabetes mellitus, found in 40 ity rate.
to 60% of the patients10-12, alcohol abuse (25 to 50% This study was evaluated and approved by the
of the cases), arterial hypertension, renal and hepatic Research Ethics Committee of the Hospital Santa
failure, obesity, senility, smoking, immunodeficiency Marcelina.
diseases and other conditions, such as infection by hu-
man immunodeficiency virus (HIV), radiotherapy and RESULTS
chemotherapy, leukemia, neoplasm and surgical pro-
cedures13-15. Our study included 13 patients with FG admit-
Regarding its etiology, a careful investigation ted to the Hospital Santa Marcelina in the studied pe-
should be performed to determine the disease ori- riod, 77% (10) were males, mean age of 51.8 years old
gin, which may be especially located in the urogeni- (24–67), and the most affected age group was that of
tal tract, digestive tract or in skin infections. A recent patients in the 5th decade.
study that analyzed 1,726 cases determined that skin Most patients were admitted several days after
infections may be the site of infection in 24% of the disease onset, ranging from 1 to 15 days, mean period
patients16. of 7.6 days, and 5 of them (38.5%) already presenting
The most commonly isolated microorganisms signs of systemic inflammatory response syndrome.
are species that usually colonize the urethra, rectum Regarding the predisposing factors, only 2 patients
and skin of the affected region17, including aerobic (15%) did not present any comorbidity. Diabetes
gram-negative, Escherichia coli and Pseudomonas mellitus and arterial hypertension were present in 6
aeruginosa, aerobic gram-positive, Staphylococcus (46%) patients, and neurological sequelae and neo-
aureus and Staphylococcus epidermidis, Clostridium plasm in 15%. Morbid obesity was observed in 23%
difficile and Bacteroides fragilis anaerobic bacilli and of the patients.
gram-positive spore-forming bacilli8,18,19. Regarding the probable initial infection origin, the
Its clinical aspects involve an area of hyperemia, most common was perianal abscess in 7, scrotal abscess
pain and swelling, that may affect the perianal, peri- in 4 and cutaneous infections in 2 patients (Figure).

408
J Coloproctol Gangrena de Fournier: revisão de literatura e experiência de serviço terciário Vol. 32
October/December, 2012 Isaac José Felippe Corrêa Neto et al. Nº 4

The most prevalent etiological agent was E. coli, The main infection origin found in this study
found in 57.1% of the cases, followed by Enterococcus, was: anorectal and genitourinary tracts, followed by
in 28.6%. The most frequent used antibiotic regimen cutaneous infections. Data obtained from this study
was a combination of metronidazole with ciprofloxa- agree with those presented in the literature, which
cin, and it was changed according to the clinical prog- shows involvement of anorectal tract in 30–70% of
ress and culture results. the cases, involvement of genitourinary tract in 13–
Average number of surgical procedures was 2.07 70% and cutaneous infections in around 24%16,25,26.
per patient (ranging from 1 to 7 surgeries), and diversion FG is usually a result of polymicrobial infection,
colostomy was performed in 7 patients (53.8%). The caused by aerobic and anaerobic organisms. E. coli is
average hospital length-of-stay was 14.4 days (ranged the most commonly isolated microorganism, also in
from 4 to 39 days). Mortality rate was 30.8%, and the agreement with our study.
clinical features of these 4 patients can be seen in Table. The Fournier’s gangrene severity index (FGSI)22
analyzes the following parameters: temperature, heart
DISCUSSION ratio, respiratory rate, levels of sodium, potassium,
creatinine, bicarbonate, hematocrit and leukocyte
Like most studies in the medical literature, we count. We did not use this index as an assessment pa-
observed greater incidence of Fournier’s gangrene in rameter in this study, since this is from a retrospective
men4,23, with predominance of patients in the fifth de- report without a well-defined standardized protocol.
cade of life. Diabetes was present in almost half of the The treatment of FG involves hemodynamic sup-
cases, in agreement with other studies that report 40– port, rigorous intravenous hydration, broad-spectrum
60% incidence, and it was considered the main reason antibiotics, debridement of non-living tissues, with sus-
for poor response to treatment24. picion of necrosis with doubtful viability, primary site
investigation and, when required, urinary or fecal diver-
sion. Urethral stenosis or genitourinary source of infec-
8 tion are indications for cystostomy, while colostomy is
7 indicated in case of infection involving the anal sphinc-
6 ter or in the presence of large perineal wound with per-
5 sistent fecal contamination4,23,27. If necrotic areas still
4 persist after 24 to 48 hours from the initial procedure, a
3 new surgical debridment should be performed4.
2 FG may progress at the speed of 2 to 3 cm per
1 hour6, therefore, a precise and quick diagnosis associated
0 with an effective surgical treatment are very important
Perianal abscess Scrotal abscess Skin infections and can determine the disease prognosis and mortality.
Figure. Primary infection origin of Fournier’s gangrene. Initially considered as a process limited to men,
idiopathic and fulminant in its original description, FG

Table. Clinical features associated with mortality.


Age (years) Gender Comorbidities Infection origin Fecal diversion
Hypertension, diabetes,
Patient 1 58 Male Perianal abscess Yes
smoking, alcoholism
Cutaneous
Patient 2 24 Male None No
infection
Cutaneous
Patient 3 53 Male Spinal trauma, schizophrenia No
infection
Mesenchymal neoplasm
Patient 4 56 Male Perianal abscess No
recurrence

409
J Coloproctol Gangrena de Fournier: revisão de literatura e experiência de serviço terciário Vol. 32
October/December, 2012 Isaac José Felippe Corrêa Neto et al. Nº 4

is today a well-known disease, but still presenting with CONCLUSION


high mortality rates5,13,17. In our analysis, the mortality
rate was of 30.8%, according to the previous literature, Fournier’s gangrene is a severe disease with high
in which can range from 3 to 67%4,24,25. Factors of even mortality rates. The physician should suspect its diag-
worse prognosis include: sepsis at hospital admission, nosis early and have an aggressive treatment approach
late referral to medical support and diabetes. to achieve better outcomes.

REFERENCES 17. Smith GL, Bunker CB, Dinneen MD. Fournier’s gangrene.
Br J Urol 1998;81(3):347-55.
1. Baurienne H. Sur une plaie contuse qui s’est terminee par le 18. Yaghan RJ, Al-Jaberi TM, Bani-Hani I. Fournier’s
sphacele de le scrotumi. J Med Chir Pharm 1764;20:251-6. gangrene: changing face of the disease. Dis Colon Rectum
2. Fournier JA. Gangrene foudroyante de la verge. Med Pract 2000;43(9):1300-8.
1883;4:589-97. 19. Chinchilla RM, Morejona EI, Pietricicâ BN, Franco EP,
3. Laucks SS 2nd. Fournier’s gangrene. Surg Clin North Am Albasini JLA, López BM. Fournier’s gangrene. Descriptive
1994;74(6):1339-52. analysis of 20 cases and literature review. Actas Urol Esp
4. Navarro-Vera JA. Gangrena de fournier. Rev Eviden Invest 2009;33(8):873-80.
Clin 2010;3(1):51-7. 20. Almanza JM, Martín JAR, Latif já, Zuccollo S. Infecciones
5. Yaghan RJ, Al-Jaberi TM, Bani-Hani I. Fournier’s necrotizantes del perine: gangrena de Fournier. Rev argent cir
gangrene: changing face of the disease. Dis Colon Rectum 1993;64(3/4):122-8.
2000;43(9):1300-8. 21. Cabral AA, Pineda GA, Domingues J, Cattaneo D, Gordillo L,
6. Fajdic J, Bukovic D, Hrgovic Z, Habek M, Gugic D, Jonas D, De Barrio J, et al. Celulitis necrotizante del periné (Gangrena
et al. Management of Fournier’s gangrene – report of 7 cases de Fournier). Rev Argent Coloproct 1997;8(1):60-3.
and review of the literature. Eur J Med Res 2007;12(4):169-72. 22. Laor E, Palmer LS, Tolia BM, Reid RE, Winter HI. Outcome
7. Burgl JCZ, Silva JG, Parra BJ. Gangrena de Fournier: prediction in patients with Fournier’s gangrene. J Urol
presentación de caso. Univ Med 2007;48(4):487-92. 1995;154(1):89-92.
8. Nisbet AA, Thompson IM. Impact of diabetes mellitus on the 23. Gamagami RA, Mostafavi M, Gamagami A, Lazorthes
presentation and out­comes of Fournier’s gangrene. Urology F. Fournier’s gangrene: an unusual presentation for rectal
2002;60(5):775-9. carcinoma. Am J Gastroenterol 1998;93(4):657-8.
9. Schaeffer AJ. Infections of the urinary tract. In: Walsh PC, 24. Mehl AA, Nogueira Filho DC, Mantovani LM, Grippa MM,
Retik AB, Vaughan ED Jr, Wein AJ, editors. Campbell’s Berger R, Krauss D, et al. Manejo da gangrena de Fournier:
Urology. 8th ed. Philadel­ phia: WB Saunders Company; experiência de um hospital universitário de Curitiba. Rev Col
2002. p. 515-602 Bras Cir 2010;37(6):435-41.
10. Norton KS, Johnson LW, Perry T, Perry KH, Sehon JK, 25. Irazu JC, de Miceu S, Salas J, Katz ON, Eche-guren ES,
Zibary GB. Management of Fournier’s gangrene: an eleven Blundo OA. Gangrena de Fournier: nuestra experiencia
year retrospective analysis of early recognition, diagnosis, clinica, etiopatogenia y tratamiento. Actas Urol Esp
and treatment. Am Surg 2002;68(8):709-13. 1999;23(9):778-83.
11. Féres O, Andrade JI, Rocha JJR, Aprilli F. Fournier’s 26. Czymek R, Hildebrand P, Kleemann M, Roblick U, Hoffmann
gangrene: a new anatomic classification. In: Reis Neto M, Jungbluth T, et al. New insights into the epidemiology
JA, editor. Proceedings of the 18th Biennial Congress of and etiology of Fournier’s gangrene: a review of 33 patients.
the International Society of University Colon and Rectal Infection 2009;37(4):306-12.
Surgeons. Bologna: Monduzzi Editore; 2000. p. 103-7. 27. Barreda JT, Scheiding MM, Fernández CS, Campaña
12. Thambi Dorai CR, Kandasami P. Fourniers gangrene: its JMC, Aguilera JR, Miranda EF, et al. Fournier gangrene. A
aetilogy and management. Aust N Z J Surg 1991;61(5):370-2. retrospective study of 41 cases. Cir Esp 2010;87(4):218-23.
13. Eke N. Fournier’s gangrene: a review of 1726 cases. Br J
Surg 2000;87(6):718-28.
14. Paty R, Smith AD. Gangrene and Fournier’s gangrene. Urol Correspondence to:
Clin North Am 1992;19(1):149-62. Isaac José Felippe Corrêa Neto
15. Chang IJ, Lee CC, Cheng SY. Fulminant gangrenous and Hospital Santa Marcelina
crepitating scrotum. Arch Dermatol 2006;142(6):767-8. Rua Santa Marcelina, 177
16. Ahrenholz DH. Necrotizing soft-tissue infections. Surg Clin CEP: 08270-070 – São Paulo (SP), Brazil
North Am 1988;68(1):199-214. E-mail: isaacneto@hotmail.com

410
Original Article

Transanal endoscopic microsurgery (TEM): initial experience


Carlos Ramon Silveira Mendes1, Luciano Santana de Miranda Ferreira2, Ricardo Aguiar Sapucaia1
Meyline Andrade Lima1, Sergio Eduardo Alonso Araujo3, Mauricio Jose de Matos e Silva4, Jose Figueiroa Filho4,
Joaquim Herbenildo Costa Carvalho4, Maurilio Toscano de Lucena4, Orcina Fernandes Duarte4,
Raquel Kelner Silveira4, Anna Christina Cordeiro da Silva4, Carolina Araujo Guenes5

1
Doctor at the Coloproctology Service of Hospital Santa Izabel da Santa Casa de Misericórdia da Bahia – Salvador
(BA), Brazil; Associate Member of the Brazilian Society of Coloproctology – Rio de Janeiro (RJ), Brazil. 2Head of the
Coloproctology Service at Hospital Santa Izabel da Santa Casa de Misericórdia da Bahia – Salvador (BA), Brazil;
Titular at the Brazilian Society of Coloproctology – Rio de Janeiro (RJ), Brazil. 3Titular at the Brazilian Society of
Coloproctology – Rio de Janeiro (RJ), Brazil. 4Doctor at the Coloproctology Service of Hospital Barão de Lucena – Recife
(PE), Brazil; Titular at the Brazilian Society of Coloproctology – Rio de Janeiro (RJ), Brazil. 5Doctor of the Coloproctology
Service of Hospital Barão de Lucena – Recife (PE), Brazil.

Mendes CRS, Ferreira LSM, Sapucaia RA, Lima MA, Araujo SEA, Silva MJM, Filho JF, Carvalho JHC, Lucena MT, Duarte OF, Silveira
RK, Silva ACC, Guenes CA. Transanal endoscopic microsurgery (TEM): initial experience. J Coloproctol, 2012;32(4): 411-415.
ABSTRACT: Introduction: Transanal endoscopic microsurgery is a technique created in the 1980’s for resections of rectal tumors. This tech-
nique is a good option for the resections of rectal tumors, with low morbidity and mortality. Objective: To report the initial experience of two
different services in the Brazilian Northeast, Bahia and Pernambuco. Methods: Retrospective and descriptive data collected from January
2010 to June 2012 regarding the postoperative outcomes of patients who underwent transanal endoscopic microsurgery for rectal tumor resec-
tion in these services. Results: Our initial experience consisted of 52 patients, being 59.6% males; 71.2% were benign diseases, and the mean
distance from the anal margin was 5.6 cm. Mean hospital stay was 1.2 days. Complications included bleeding, perforation and entry to the
abdominal cavity in three cases, as well as suture dehiscence and neoplasm recurrence in an advanced adenocarcinoma. Conclusion: Transanal
endoscopic microsurgery is an excellent technical option for the resection of rectum adenomas, which are not feasible for endoscopic resection.
The procedure may be used for other indications, as the resection of anal fistulae, being an useful instrument in colorectal surgery.
Keywords: TEM; adenocarcinoma; rectal neoplasms.

Resumo: Introdução: A microcirurgia endoscópica transanal é uma técnica minimamente invasiva criada nos anos de 1980 para ressecção
local de tumores retais. Essa técnica tem se mostrado uma boa opção para as ressecções de tumores retais, com morbidade baixa e mortalidade
praticamente nula. Objetivo: Relatar a experiência inicial de dois serviços localizados no Pernambuco e na Bahia, Nordeste do Brasil. Méto-
dos: Estudo retrospectivo e descritivo realizado de janeiro de 2010 a junho de 2012 dos resultados pós-operatórios de pacientes submetidos
à microcirurgia endoscópica transanal nestes dois serviços. Resultados: Cinquenta e dois pacientes consecutivos submetidos a tratamento
cirúrgico por meio de TEM foram revisados, 59,6% dos quais eram do sexo masculino. Em 71,2% dos casos, o procedimento foi realizado
para lesões benignas, e a distância média dos tumores da borda anal foi de 5,6 cm. A média do período de internação foi de 1,2 dias. Das
complicações encontradas, podemos citar sangramento, perfuração e entrada na cavidade abdominal em três casos, bem como deiscência de
sutura e recidiva tumoral em um adenocarcinoma avançado. Conclusão: A microcirurgia endoscópica transanal é uma excelente alternativa
técnica para os casos de ressecção de adenomas de reto que não são possíveis por colonoscopia. O procedimento pode ser utilizado em outras
indicações, como a ressecção de fístulas anais, mostrando-se um instrumental útil na cirurgia colorretal.
Palavras-chave: TEM; adenocarcinoma; neoplasias retais.

Study carried out at the Hospital Santa Izabel of Santa Casa de Misericórdia da Bahia – Salvador (BA), Brazil, and at Hospital Barão de Lucena – Recife
(PE), Brazil.
Financing source: none.
Conflict of interest: nothing to declare.

Submitted on: 01/09/2012


Approved on: 01/02/2013

411
J Coloproctol Transanal endoscopic microsurgery (TEM): initial experience Vol. 32
October/December, 2012 Carlos Ramon Silveira Mendes et al. Nº 4

INTRODuCTION toscope, it is possible to perform dissection by us-


ing curved instruments in its distal portion due to the
The transanal endoscopic microsurgery (TEM) is its broad view9,10. TEM makes it possible to magnify
a minimally invasive surgical technique introduced in the image of the lesion with endoscopic view, thus
the 1980s by Dr. Gerhard Buess, which enables the improving the visualization of the neoplasm. When
excision of rectal neoplasms with excellent exposure performing pneumorectum with the equipment, it is
of the surgical field and minimum morbidity1-3. possible to obtain a better definition of the margins
In the lower third of the rectum, the endoanal of the lesion, which facilitates the use of instruments
resection is among the classic surgical techniques and manipulation. Therefore, it is possible to remove
employed to treat rectal neoplasm4,5. This technique the whole specimen, which will then be analyzed
presents difficulties concerning the control of resec- by the pathologist.
tion margins, hemostasis, full-thickness resection of Moore et al.5 demonstrated that the fragmenta-
the rectal wall, and also regarding the definition of the tion of the specimen and compromised surgical mar-
proximal margin. In the medium third, Mason’s trans- gins occurred in 35 and 29% of the cases, respectively,
sphincteric-transrectal approach has become obso- when the conventional endoanal resection was per-
lete due to its high morbidity and anal incontinence. formed. In that same study, it was observed that such
Kraske procedure enables the access to the upper values decreased to 6 and 10% with TEM, also show-
third of the rectum, but it has also been neglected due ing reduced rates of local recurrence with this tech-
to poor results and high morbidity6. The alternative to nique (24% versus 4%).
these techniques for major adenomatous lesions used TEM has been more and more used for other
to be the low anterior resection or abdominoperineal procedures other than the resection of rectal tu-
resection, which present with high morbidity and mor- mors, as shown by Zoller et al. 11, who performed
tality3,7. On the other hand, TEM leads to less compli- the resection of retrorectal tumor. Another op-
cations in comparison to other technoques, also reduc- tion for using TEM is the correction of stenosis in
ing hospital stay1,8. colorectal anastomoses12.
TEM is performed with a rectoscope (Figure 1)
measuring approximately 15 cm in length and 4 cm OBJeCTIVe
in diameter. This set is introduced in the anus, af-
ter dilation, and placed in the rectum according to The aim of this article was to demonstrate the
the location and height of the lesion. With the rec- initial experience with transanal endoscopic microsur-
gery performed by two teams of the Northeast of Brazil
(Bahia and Pernambuco) during two years.

MeTHOD

All patients who underwent TEM for benign


and malignant neoplasms in Salvador (Bahia) and
Recife (Pernambuco), from January 2010 to June
2012, were included. These patients were retrospec-
tively reviewed and analyzed regarding demographic
data such as age, gender, distance from the anal verge
and type of resected lesion. Complications related to
the procedure, both during surgery and postoperative-
ly, were evaluated.
The available long-term results of patients were
also reported, such as neoplasm recurrence and appro-
Figure 1. Surgical instruments. TEO - Karl Storz®. priate treatment.

412
J Coloproctol Transanal endoscopic microsurgery (TEM): initial experience Vol. 32
October/December, 2012 Carlos Ramon Silveira Mendes et al. Nº 4

RESULTS transanal primary closure. In the other one, the patient


was already diverted with a colostomy and a laparo-
Fifty-two patients who underwent TEM for scopic approach was performed to assess the defect.
resection of benign and malignant lesions were in- Perineal sepsis was reported in one case (1.9%), and
cluded. Most procedures were performed to treat be- it was treated with antibiotics. Wound dehiscence was
nign disease (71.2%). General characteristics of the observed postoperatively in three patients (5.8%). No
patients included are demonstrated in Table 1. The other complications were reported during the surgical
preoperative pathology submitted to surgical resec- procedure and at the initial follow-up (Table 2).
tion was benign in 71.2% of the cases, and 28.8% Recurrence of benign lesions was demonstrated
accounted for malignant lesions. The full-thickness in two cases, which were submitted to new resection
resection was performed in 80.8% of the proce- by TEM. In one patient with rectal adenocarcinoma
dures, and partial-thickness resection or mucosec- who refused undergoing radical surgery, local resec-
tomy, in 19.2%. The closure of the rectal wall was tion by TEM was performed, and she presented with
performed in 84.6% of the lesions, not being carried local recurrence eight months after surgery, not ac-
out in eight cases due to the difficulty caused by the cepting other treatments.
proximity to the anal verge, aiming not to cause tis-
sue tension, and in cases of mucosectomy of small DISCUSSION
diameter lesions.
Nine cases (17.3%) presented with intraopera- The studied population does not differ much
tive and postoperative complications, Two patients from the literature. As to gender, it has been observed
had bleeding (3.8%), solved during surgery, and three that mostly females undergo TEM, ranging from 51
patients (5.8%) had perforation and entry into the to 65%5,8,10,13,14. In our population, the prevalence was
abdominal cavity. In two of the latter we performed of 59.6% (Figure 2), and this correlation was not as-
sociated with any specific characteristic of patients
who underwent this treatment. We observed that the
Table 1. Patients characteristics. mean age (57.1 years old) was apparently lower than
n=52 (100%) of the age seen in the literature (Figure 3). Regard-
21/31 ing the distance of the lesion from the anal verge, our
Gender M/F
(40.4/59.6%) mean distance was 5.7 cm, similar to the population
Mean age (years) 57.2 (16–92) studied by Barendse et al.10, which presented with an
Distance from anal verge (cm) 5.7 (1–15) average of 6 cm. Gonzalez et al.14 reported a mean
Resected lesion distance of 9.1 cm (Figure 4). The distance of the le-
Benign 37 (71.2) sion to the anal verge is probably related to the rates
Malignant 15 (28.8) of peritoneal invasion. However, this was not the ob-
Full-thickness resection 42 (80.8) jective of this study.
Wound closure 44 (84.6)
Time of hospital stay (days) 1.2 (1–3)
M: male; F: female. 65.0 63.6
58.5 59.6
54.0 51.2
46.0 48.8
41.5 40.4
% 35.0 36.4
Table 2. Complications.
Intraoperative complications
Bleeding 2 (3.8%)
Perforation of intraperitoneal rectum 3 (5.8%)
Guerrieri Moore Barendse Gonzalez Graff Mendes
Postoperative complications et al.8 et al.5 et al.10 et al.14 et al.13 et al.
Dehiscence 3 (6.8%) Female Male
Perineal sepsis 1 (1.9%) Figure 2. Distribution by gender.

413
J Coloproctol Transanal endoscopic microsurgery (TEM): initial experience Vol. 32
October/December, 2012 Carlos Ramon Silveira Mendes et al. Nº 4

TEM proved to be a safe technique with low rates In the study by Gonzalez et al.14, the percentage
of severe complications. In our study, the total compli- of patients with benign lesion submitted to TEM was
cation rate was 17.3%, regardless of the etiology of 72.8%, which is very similar to our results (71.2%).
the resected lesion. It is a known fact that patients with This same study reported the complication rate after
malignant neoplasm submitted to neoadjuvant chemo- TEM including rectovaginal fistula in 3% and perfora-
therapy and radiotherapy, followed by TEM, present tion associated with entry into the abdominal cavity in
with higher complication rates than those with no pre- 6.1%, which is similar to our study, especially in lesions
vious treatment15. The indication of TEM for malig- located 10 cm above the anal verge. The recurrence of
nant neoplasm should be highly selective, since there a rectal lesion previously resected by TEM does not
is no lymph node resection, which might compromise contraindicate the recommendation of the same method
the final oncologic result. to treat the recurrence, as observed in this sample, ap-
parently without increasing the complication rate. Due
to the restricted number of patients in this sample who
66 66
64
were submitted to re-resection by TEM, the evaluation
62.3 of complications could not be objectively assessed.
Guerrieri et al.8 reported a median time of hos-
57.1 pital stay of 3.5 days, more than our median hospi-
tal stay of 1.2 days (1 to 3 days). This study8, with
590 patients, also reported two rectovaginal fistula
requiring diversion ostomy, complication not seen in
Barendse Gonzalez Mendes Moore Guerrieri our sample.
et al.10 et al.14 et al. et al.5 et al.8
Figure 3. Mean age. CONCLUSION

The transanal endoscopic microsurgery is a safe


9.1 procedure with low morbidity and pratically null mor-
8 tality. This technique can be an excellent alternative
6
to resect benign rectal adenomas and neuroendocrine
5.67
tumors placed in the rectum. For the adenocarcinoma,
new studies should be analyzed in order to better define
it indication instead of performing a total mesorectal
excision, and also the role of neoadjuvant and adjuvant
treatment associated with the resection of malignant
Graff Barendse Gonzalez Mendes rectal tumors. Nonetheless, TEM is a very powerful
et al.13 et al.10 et al.14 et al.
tool whose indications may include other anorectal pa-
Figure 4. Mean distance to anal verge (cm). thologies, besides benign and malignant rectal tumors.

REFERENCES 3. Atallah S, Albert M, Larach S. Transanal minimally


invasive surgery: a giant leap forward. Surg Endosc
1. Buess G, Mentges B, Manncke K, Starlinger M, Becker 2010;24:2200-5.
HD. Technique and results of transanal endoscopic 4. Endreseth BH, Wibe A, Svinsas M, Marvik R, Myrvold HE.
microsurgery in early rectal cancer. Am J Surg Postoperative morbidity and recurrence after local excision
1992;163:63-9; discussion 9-70. of rectal adenomas and rectal cancer by transanal endoscopic
2. Cataldo PA, O’Brien S, Osler T. Transanal endoscopic microsurgery. Colorectal Dis 2005;7:133-7.
microsurgery: a prospective evaluation of functional results. 5. Moore JS, Cataldo PA, Osler T, Hyman NH. Transanal
Dis Colon Rectum 2005;48:1366-71. endoscopic microsurgery is more effective than traditional

414
J Coloproctol Transanal endoscopic microsurgery (TEM): initial experience Vol. 32
October/December, 2012 Carlos Ramon Silveira Mendes et al. Nº 4

transanal excision for resection of rectal masses. Dis Colon 12. Moraes RS, Buess G, Lima JHF, Morgenstern AG, Campos
Rectum 2008;51:1026-30; discussion 30-1. ACL, Coelho JCU, et al. Transanal endoscopic microsurgery
6. Nahas SC, Nahas CSR, Marques CFS, Dias AR, Pollara WM, (TEM) in the treatment of postoperative colorectal stenosis.
Cecconello I. Transanal endoscopic microsurgery (TEM): A Arq Bras Cir Dig 2008;21:147-9.
minimally invasive procedure for treatment of selected rectal 13. de Graaf EJ, Doornebosch PG, Tetteroo GW, Geldof H,
neoplasms. Arq Bras Cir Dig 2010;23:35-9. Hop WC. Transanal endoscopic microsurgery is feasible for
7. Lezoche G, Baldarelli M, Guerrieri M, Paganini AM, De Sanctis adenomas throughout the entire rectum: a prospective study.
A, Bartolacci S, et al. A prospective randomized study with a Dis Colon Rectum 2009;52:1107-13.
5-year minimum follow-up evaluation of transanal endoscopic 14. Gonzalez JEB, Zulueta AF, Alfonso MAM, Díaz OFC, Faife
microsurgery versus laparoscopic total mesorectal excision after BF, Hernández JMG, et al. Cuban experience and the future
neoadjuvant therapy. Surg Endosc 2008;22:352-8. perspectives of transanal endoscopic microsurgery. Rev
8. Guerrieri M, Baldarelli M, Morino M, Trompetto M, Da Rold Cubana Cir 2009;48.
A, Selmi I, et al. Transanal endoscopic microsurgery in rectal 15. Perez RO, Habr-Gama A, Sao Juliao GP, Proscurshim I,
adenomas: experience of six Italian centres. Dig Liver Dis Scanavini Neto A, Gama-Rodrigues J. Transanal endoscopic
2006;38:202-7. microsurgery for residual rectal cancer after neoadjuvant
9. Middleton PF, Sutherland LM, Maddern GJ. Transanal chemoradiation therapy is associated with significant
endoscopic microsurgery: a systematic review. Dis Colon immediate pain and hospital readmission rates. Dis Colon
Rectum 2005;48:270-84. Rectum 2011;54:545-51.
10. Barendse RM, Doornebosch PG, Bemelman WA, Fockens
P, Dekker E, de Graaf EJ. Transanal employment of
single access ports is feasible for rectal surgery. Ann Surg Correspondence to:
2012;256:1030-3. Carlos Ramon Silveira Mendes
11. Zoller S, Joos A, Dinter D, Back W, Horisberger K, Post S, Rua São Domingos Savio, 150 – Nazaré
et al. Retrorectal tumors: excision by transanal endoscopic CEP: 40050-520 – Salvador (BA), Brazil
microsurgery. Rev Esp Enferm Dig 2007;99:547-50. E-mail: proctoramon@hotmail.com

415
Case Report

Sacrococcygeal hernia: a challenge for the coloproctologist


Eron Fábio Miranda1, Ilario Froehner Junior2, Juliana Stradiotto Steckert2, Cristiano Denoni Freitas3,
Juliana Ferreira Martins4, Paulo Gustavo Kotze5

Master in Surgery by Pontifícia Universidade Católica do Paraná (PUC-PR); Titular at the Brazilian Society of
1

Proctology (SBCP); Doctor at the Coloproctology Service at the University Hospital Cajuru from PUC-PR – Curitiba
(PR), Brazil. 2Resident of Coloproctology by the University Hospital Cajuru from PUC-PR; Affiliated to SBCP; Former
resident of the Coloproctology Service at PUC-PR – Curitiba (PR), Brazil. 3Resident of Coloproctology at the University
Hospital Cajuru from PUC-PR; Affiliated to SBCP; Surgeon of the Digestive System and Coloproctologist at Hospital
Governador Celso Ramos and Imperial Hospital de Caridade – Florianópolis (SC), Brazil. 4 Resident of Coloproctology
at the University Hospital Cajuru from PUC-PR; Titular at SBCP; Doctor of the Coloproctology Service at the
Coloproctology Service of the University Hospital Cajuru from PUC-PR – Curitiba (PR), Brazil. 5Master in Surgery by
PUC-PR; Titular at SBCP; Head of the Coloproctology Service at the Coloproctology Service of the University Hospital
Cajuru from PUC-PR – Curitiba (PR), Brazil.

Miranda EF, Froehner Junior I, Steckert JS, Freitas CD, Martins JF, Kotze PG. Sacrococcygeal hernia: a challenge for the coloproctologist.
J Coloproctol, 2012;32(4): 416-421.
ABSTRACT: Sacrococcygeal hernia consists of the protrusion of abdominal and pelvic structures through the sacrococcygeal
region, an uncommom complication of coccygectomy and sacral coccygectomy. Its surgical treatment is based on perineal her-
nia repair, by means of abdominal, perineal or abdominoperineal access. Perineal (local or sacrococcygeal) access avoids the
laparotomy morbidity and is indicated to patients that are not exposed to radiation or those who had not undergone oncological
surgery, allowing local tissue to reconstruct, as in myocutaneous advancement flaps, associated or not to prosthetic mesh, be-
cause of the low complication rates and favourable outcomes. The aim of this article is to report the case of a female patient who
had undergone sacral coccygectomy due to refractory coccygodynia and developed a symptomatic sacrococcygeal hernia. She
underwent polytetrafluoroethylene mesh herniorrhaphy followed by soft tissue closure and gluteal myocutaneous V-Y advance-
ment flap. The authors emphasize technical details and the difficulty of the procedure itself. After three years of follow-up, no
recurrence was found.
Keywords: sacrococcygeal region; polytetrafluoroethylene; rectum; prostheses and implants.

Resumo: As hérnias sacrococcígeas são protrusões de estruturas pélvicas e abdominais pela topografia do sacro e cóccix, sendo
complicação incomum após coccigectomias ou sacrococcigectomias. O tratamento é cirúrgico e baseado na correção das hérnias
perineais, e pode ser realizado por acesso perineal, abdominal ou abdominoperineal. O perineal (local ou sacrococcígeo), sem a
morbidade da laparotomia, é viável para os pacientes não submetidos à cirurgia oncológica ou radioterapia, permitindo a recons-
trução com tecidos locais, como no avanço miocutâneo, associado ou não ao uso de telas, com baixa incidência de complicações
e bons resultados. O objetivo deste artigo é apresentar o caso de uma paciente submetida à sacrococcigectomia por coccigodinia
refratária ao tratamento clínico, que evoluiu com hérnia sacrococcígea sintomática tratada com a correção do defeito com tela de
politetrafluoretileno e síntese das camadas suprajacentes, associada ao avanço miocutâneo bilateral tipo V-Y, com o glúteo maior.
Serão enfatizados detalhes técnicos e o grau de dificuldade da reconstrução. Após seguimento de três anos, a paciente se encontra em
acompanhamento ambulatorial sem recidiva.
Palavras-chave: hérnia; região sacrococcígea; politetrafluoretileno; reto; próteses e implantes.

Study carried out at the Coloproctology Service of the University Hospital Cajuru from Pontifícia Universidade Católica do Paraná (PUC-PR) – Curitiba
(PR), Brazil.
Financing source: none.
Conflict of interest: nothing to declare.

Submitted on: 11/10/2012


Approved on: 21/12/2012

416
J Coloproctol Sacrococcygeal hernia: a challenge for the coloproctologist Vol. 32
October/December, 2012 Eron Fábio Miranda et al. Nº 4

INTRODUCTION Up until now, there is no consensus on the sur-


gical techniques to be employed in order to correct
The sacrococcygeal hernia consists of the pro- these hernia6. The bases to treat sacrococcygeal come
trusion of pelvic and abdominal structures by the to- from the perineal repair techniques3,4. Balkenende
pography of the sacrococcygeal region, which is an et al16. Described, in 1996, the first report of coccy-
uncommon complication after coccygectomy and geal hernia, after coccygectomy and refractory coc-
sacral coccygectomy1. Perineal hernias, although be- cygodynia. Herniorrhaphy occurred due to the ap-
ing considered as similar by some authors2, consist of proximation and suture of the borders of the hernia
the protrusion of the pelvic floor limited by ischial tu- ring.  Maguina and Kalimuthu17 reported sacrococcy-
berosities, coccyx and the pubic bone, which results, geal hernia in an elderly patient with sacral pressure
for instance, from the abdominoperineal amputation ulcer, being submitted to debridement. The patches
of the rectum or pelvic exenteration3,4. under negative pressure to optimize the healing were
It is known that symptomatic perinal hernias oc- pointed as the causers of the formation of a hernia bag
cur in at least 1% of the abdominoperineal resections and rectal protrusion.
of the rectum3-5, while the sacrococcygeal hernia is The second report of coccygeal hernia is from
even less seen, only described in case reports6,7, and 1988, which is the first case in which the polytetrafluo-
none of them is from Latin America. roethylene prosthesis (PTFE) was used11 to correct the
Coccyx resections are common for the surgical hernia defect. Chernyi et al.18, in 1988, described the
treatment of coccygodynia8-11, whereas the sacral coc- first sacral hernia repair by means of superimposing
cygectomy is performed in cases of local primary neo- tissure sutures by local access. The use of non ab-
plasms, such as chordoma, chondrosarcoma, giant cell sorbable mesh in sacral hernias (polypropylene) was
tumor, osteosarcoma and invasive or recurring rectal only described eight years later14. Cancrini et al.19, in
tumors12-14. These operations result in large surgical 1997, report the first use of an absorbable prosthesis
wounds, which bring the challenge of local recon- (polyglactin) in sacral hernias. As observed, there are
struction to the surgeon. The extensive tissue removal, different techniques described to correct this defect,
the lack of local muscular aponeurotic tissue, the dif- which leaves many doubts to the surgeon.
ficulty to obtain large flaps and preoperative radiother- The objective of this article is to describe a pa-
apy are among the factors involved in the genesis of tient submitted to surgical repair of a sacrococcygeal
the condition6,15. hernia by placing the PTFE mesh associated with V-Y
The complications of the sacral coccygectomy myocutaneous flaps, emphasizing the technical details
include hemorrhage, infection, local healing disor- and showing the great challenge that is such a condi-
ders, change in the pelvic statics and neurological tion for the colorectal surgeon.
deficit, such as: sexual, vesical and bowel dysfunc-
tion13,15. The hernias in this topography constitute a CASE REPORT
rare complication of this surgical procedure2,12.
Sacrococcygeal hernias are not believed to be A 68-year-old female patient, complaining of
only a consequence of the primary reconstruction painful protusion in the sacrococcygeal region start-
method15. The increased abdominal pressure at the ing four years ago. She mentioned coccyx resection
immediate postoperative, associated with the gravi- and, afterwards, partial sacrectomy five years ago to
tational action, would insinuate the bowel loops and treat for coccygodynia refractory to clinical treatment
the omentum to the pelvis, keeping them in touch by the orthopedics service. She reported that 30 days
with the pelvic floor13. Sacrectomy causes lesions after the last surgery, there was a clinically suspected
on the nervous branches corresponding to the height abscess and the site was punctured and fecal content
of the osteotomy. The muscles in the pelvic floor are was vacuumed. At inspection, she presented with a
innervated by sacral branches S2 to S5, whose sepa- scar in the sacrococcygeal region and local bulge, es-
ration predisposes to muscular atrophy, which favors pecially to the Valsalva maneuver (Figure 1). Digital
herniation2,13,15. rectal exam showed a normotonic anal sphincters, no

417
J Coloproctol Sacrococcygeal hernia: a challenge for the coloproctologist Vol. 32
October/December, 2012 Eron Fábio Miranda et al. Nº 4

bleeding or anorectal tumors. The exam also showed treatment of this sacrococcygeal herniation3,4. Three
a protrusion in the posterior wall due to the sacrococ- accesses are described: perineal (local or sacrococ-
cygeal defect, being a part of the hernia sac content. cygeal, for sacrococcygeal hernia), abdominal and
At the anoscope and rigid proctosigmoidoscopy, the combined abdominoperineal. The repair per se can be
rectal mucosa was normal; in the anal canal, only first performed by the simple suture of the hernia ring15;
degree internal hemorrhoids were found. the use of prosthesis (absorbable or non absorbable
Computed tomography of the pelvis showed the meshes)14; and the mobilization and fixation of struc-
densification of perirectal fat and protrusion of the tures placed on the pelvis, such as bladder, uterus13 or
posterior rectal wall to the sacral region (Figure 1). omentum1. Myocutaneous flaps can be used12, such
Surgical treatment was performed by the posterior ap- as: gluteus maximus muscle6,7, rectus abdominis mus-
proach (sacrococcygeal), with the patient in ventral cle20, thigh muscles (vastus lateralis or gracilis)21. This
decubitus position (penknife position) under spinal range of reconstructive techniques demonstrates the
anesthesia (Figure 2). It began by the removal of the real challenge in the treatment of such condition.
scar covering the surgical wound, followed by dissec- The local or sacrococcygeal access is interesting
tion, isolation and opening of the hernia sac. Through because it prevents the penetration of the abdominal
the hernia ring, a PTFE mesh was introduced and fix- cavity. However, exposure is limited, which can make
ated with absorbable suture (polyglactin 2.0) inside it difficult to evaluate recurrent disease in cases of
the hernia defect. The synthesis of the surgical wound neoplasm and to mobilize adhesions from the bowel
was performed by the superimposition of superjacent and the hernia sac13. Zook et al.7 reported a case of
tissues and the creation of V-Y bilateral myocutane- coccygeal hernia submitted to herniorrhaphy with sa-
ous advancement flaps (gluteus), sutured with 3.0 ny- croperineal access using a prosthesis, presenting with
lon. A closed suction drain was used below the flap to local recurrence caused by possible technical issues.
drain any possible accumulated fluid collection. Post- The second repair on the same topography received
operative evolution was excellent, without complica- a PTFE prosthesis, and there was no success due to
tions. The patient has been on outpatient follow-up, local infection. The referred causes for hernia recur-
without recurrence, for 36 months. rence are factors that are possible to prevent, and also
because they exist regardless of the access or repair
DISCUSSION technique, thus not being exclusive to the sacrococ-
cygeal access.
The treatment for perineal hernias, which is The abdominal access is useful in patients submit-
a more common condition, served as a base for the ted to previous oncological operations, in the evaluation

A B
Figure 1. (A), patient in dorsal decubitus seen from the sacral region; and the local bulge caused by the sacrococcygeal hernia.
(B), computed tomography showing rectal protrusion by the sacrococcygeal defect (indicator).

418
J Coloproctol Sacrococcygeal hernia: a challenge for the coloproctologist Vol. 32
october/December, 2012 Eron Fábio Miranda et al. Nº 4

A B

C D
Figure 2. Aspects of the surgical technique: (A) exposure of the hernia bag with tweezers; (B) polytetrafluoroethylene mesh is adjusted to
the sacrococcygeal defect and fixated o the borders of the hernia ring; (c) after the suture of the mesh and the synthesis of superjacent plans,
the V-Y myocutaneous advancement flap is prepared; (D) final aspect of the sacrococcygeal herniorrhaphy.

of recurrence and in those who need laparotomy due to Miles et al.6, after a retrospective analysis of 27 pri-
other indications. The access to the pelvis enables the mary repairs with myocutaneous flaps, proposed three
fixation of the prosthesis to the pelvic ring from the in- technical options. One of them indicates that for pa-
side of the abdominal cavity, with direct vision13. tients who were not submitted to radiotherapy and
The combined abdominoperineal access, con- those with an intact vascularization of the gluteal re-
sidered as gold standard, allows the complementary, gion, the V-Y bilateral gluteus maximus myocutane-
abdominal and perineal intervention, which is useful ous advancement flaps should be considered, which
for cases associated with important technical diffi- is well accepted because of the possibility to cover
culty, such as intense adherence between abdominal a great area of the subcutaneous mesh and because
and pelvic structures and with the hernia bag. Repair it is close to the resected area1,22. This technique was
is made possible by both accesses, suggesting lower chosen for the case reported in this study, due to the
risk of recurrence6. patient’s history and characteristics.
There are many descriptions of primary recon- In cases submitted to previous radiotherapy or
struction after sacral coccygectomy, with vascular lesions of the gluteal region, the verti-
including case series, and there is no estab- cal rectus abdominis myocutaneous flaps are a good
lished consensus for the most adequate technique. option. The contraindications for abdominal flaps are

419
J Coloproctol Sacrococcygeal hernia: a challenge for the coloproctologist Vol. 32
October/December, 2012 Eron Fábio Miranda et al. Nº 4

history of laparotomy or previous ostomies; in such of the basement membrane, with collagen and elastin
cases, crural flaps can be used6. fibers, in order to shape the local tissue growth. Due to
Kaplan and Santora14, in 1996, described the the fragility of this material, it is used as adjuvant to
first use of non absorbable mesh to repair sacral her- hernia repair, and not as an isolated technique.
nias. They suggested the use of prostheses for cases In this case, the indication for sacral coccygecto-
in which large resection prevented the approxima- my was the coccygodynia refractory to clinical treat-
tion of tissues that compose the hernia ring and when ment. Since the primary disease that motivated this
there were contraindications for the creation of bilat- resection was benign, the sacrococcygeal access was
eral gluteus maximus myocutaneous advancement chosen (local). The existence of a posterior rectal wall
flaps (radiotherapy and with vascular lesions of the composing the hernia sac led to the use of a PTFE
gluteal region). Polypropylene meshes were used and mesh to avoid rectal erosions and the consequent de-
fixated with sutures made of the same material in the velopment of complex enteric fistula. The intention to
borders of the hernia ring, approximation of the glu- complement the application of the prosthesis led to the
teus with continuous suture and absorbable sutures V-Y bilateral gluteus maximus myocutaneous ad-
and cutaneous synthesis with intradermal stitch with vancement flaps, with the proper occlusion of the cu-
absorbable material. taneous defect and important cosmetic increment. The
After reports of enterocutaneous fistula in pa- patient has been on outpatient follow-up with no sug-
tients with non absorbable meshes1, the use of a poly- gestive signs or symptoms of local recurrence.
propylene mesh with the abdominal side covered with The wide experience in the use of absorbable or
myofascial tissue (sublay technique) was proposed, or non absorbable prostheses (mesh) to repair different
also the application of the PTFE mesh, polyester cov- types of hernia, their easy application, low complica-
er, acellular human dermal matrix or animal submuco- tion rates and good results make them an important
sa (onlay technique), aiming to avoid adherence with option in the treatment and prevention of sacrococcy-
the bowel2,11. Korn et al.1 considered the relative ri- geal hernias, which correspond to a significant chal-
gidity of polypropylene meshes and the possibility of lenge to the coloproctologist. The knowledge of the
enteric erosion when the material is in direct contact existing techniques enables to choose them wisely,
with intestinal loops. They described the use of acel- thus reducing the morbimortality of the procedure and
lular human dermal matrix, which keeps the structure benefiting the patient.

REFERENCES 7. Zook NL, Zook EG. Repair of a long-standing coccygeal


hernia and open wound. Plast Reconstr Surg 1997;100(1):96-9.
1. Korn JM, Connolly MM, Walton RL. Single-stage sacral 8. Chueire AG, Carvalho Filho G, Souza LB. Coccigodinia:
coccygectomy and repair using human acellular dermal Tratamento cirúrgico. Acta Ortop Bras 2002;10(4):26-30.
matrix (AlloDerm) with bilateral gluteus maximus flaps for 9. Cebesoy O, Guclu B, Kose KC, Basarir K, Guner D, Us AK.
hernia prophylaxis. Hernia 2009;13(3):329-32. Coccygectomy for coccygodynia: do we really have to wait?
2. Al-Haddad AA, Hellinger MD, Akerman SC. Surgisis Injury. 2007;38(10):1183-8.
mesh repair of a postsacrectomy perineal hernia along with 10. Kumar A, Reynolds JR. Mesh repair of a coccygeal
posterior proctosigmoidectomy for concomitant stricture. hernia via an abdominal approach. Ann R Coll Surg Engl
Am Surg 2007;73(11):1129-32. 2000;82(2):113-5.
3. So JB, Palmer MT, Shellito PC. Postoperative perineal 11. García FJ, Franco JD, Márquez R, Martínez JA, Medina J.
hernia. Dis Colon Rectum 1997;40(8):954-7. Posterior hernia of the rectum after coccygectomy. Eur J Surg
4. Rayhanabad J, Sassani P, Abbas MA. Laparoscopic repair of 1998;164(10):793-4.
perineal hernia. JSLS 2009;13(2):237-41. 12. Lehto SA, Vakharia MR, Fernando TL, Mohler DG.
5. Salum MR, Prado-Kobata MH, Saad SS, Matos D. Primary Polypropylene mesh repair of sacroperineal hernia following
perineal posterior hernia: an abdominoperineal approach for sacrectomy with long-term follow-up. A case report and
mesh repair of the pelvic floor. Clinics 2005;60(1):71-4. literature review. Bull Hosp Jt Dis 2000;59(2):113-5.
6. Miles WK, Chang DW, Kroll SS, Miller MJ, Langstein 13. Atkin G, Mathur P, Harrison R. Mesh repair of sacral hernia
HN, Reece GP, et al. Reconstruction of large sacral following sacrectomy. J R Soc Med 2003;96(1):28-30.
defects following total sacrectomy. Plast Reconstr Surg 14. Kaplan LJ, Santora TA. Technique of sacral repair. Am Surg
2000;105(7):2387-94. 1996;62(9):762-4.

420
J Coloproctol Sacrococcygeal hernia: a challenge for the coloproctologist Vol. 32
October/December, 2012 Eron Fábio Miranda et al. Nº 4

15. Junge K, Krones CJ, Rosch R, Fackeldey V, Schumpelick defects with a transabdominal vertical rectus abdominis
V. Mesh reconstruction preventing sacral herniation. Hernia myocutaneous flap. Ann Plast Surg 2006;56(5):526-30.
2003;7(4):224-6. 21. Wong S, Garvey P, Skibber J, Yu P. Reconstruction of pelvic
16. Balkenende U, Van Leeuwen BP, Ginai AZ. Hernia through a exenteration defects with anterolateral thigh-vastus lateralis
scar on the posterior rectal wall. Eur J Surg 1996;162(4):347-8. muscle flaps. Plast Reconstr Surg 2009;124(4):1177-85.
17. Maguina P, Kalimuthu R. Posterior rectal hernia after 22. Bebenek M. Abdominosacral amputation of the rectum for
vacuum-assisted closure treatment of sacral pressure ulcer. low rectal cancers: ten year experience. Ann Surg Oncol
Plast Reconstr Surg 2008;122(1):46e-7e. 2009;16(8):2211-7.
18. Chernyi VA, Shchepotin IB, Klochko PI, Palivets AI. A
method of plastic surgery in postoperative sacro-perineal
hernia. Vestn Khir Im I I Grek 1998;140(5):88-9.
19. Cancrini A, Bellotti C, Santoro A, Ascenzi P, Cancrini Correspondence to:
G. Postoperative sacrocele: prevention and surgical Eron Fábio Miranda
considerations. G Chir 1997;18(10):488-92. Rua Brasílio Itiberê, 3909 — Água Verde
20. Glatt BS, Disa JJ, Mehrara BJ, Pusic AL, Boland P, Cordeiro CEP: 80240-060 – Curitiba (PR), Brazil
PG. Reconstruction of extensive partial or total sacrectomy E-mail: eronfabiomiranda@gmail.com

421
Case Report

Bezoar by mesalazine tablets:


cause of intestinal obstruction in Crohn’s disease
Idblan Carvalho de Albuquerque1, Mariana Andrade Carvalho2, Rodrigo Rocha Batista2, Galdino José Sitonio Formiga3

Doctor Assistant at the Coloproctology Service of Hospital Heliópolis – São Paulo (SP), Brazil.
1

Former resident at the Coloproctology Service of Hospital Heliópolis – São Paulo (SP), Brazil.
2

3
Head of the Coloproctology Service of Hospital Heliópolis – São Paulo (SP), Brazil.

Albuquerque IC, Carvalho MA, Batista RR, Formiga GJS. Bezoar by mesalazine tablets: cause of intestinal obstruction in Crohn’s disease.
J Coloproctol, 2012;32(4): 422-425.
ABSTRACT: The stricturing and fistulizing forms of Crohn’s disease (CD) exhibit many different results to clinical treatment and good
response to surgical therapy. The prevalence of strictures in CD ranges from 12 to 54% and they are more frequently in patients with longer
disease duration, and the terminal ileum is the most commonly affected location. The pharmacobezoars can be formed in any part of the gastro-
intestinal tract and are often associated with factors predisposing anatomic, functional or other concomitant conditions. The pharmacological
properties of drugs may contribute to the pathophysiology of bezoars. The objective of this case report is to alert for the importance of the qual-
ity of prescribed medications that are used by patients with CD, through the finding of more than 350 tablets of mesalazine during the surgical
treatment of a patient with the fibrostenotic pattern.
Keywords: Crohn’s disease; intestinal obstruction; constriction, pathologic; mesalazine; surgery.

Resumo: As formas estenosante e fistulizante da doença de Crohn (DC) apresentam resultado variável ao tratamento medicamentoso e boa
resposta à terapia cirúrgica. A prevalência da DC estenosante varia de 12 a 54%, mais frequente nos pacientes com maior tempo de doença,
sendo o íleo terminal o local mais acometido. Os farmacobenzoares podem se formar em qualquer porção do trato gastrointestinal e frequen-
temente estão associados a fatores anatômicos predisponentes, funcionais ou outras afecções concomitantes. As propriedades farmacológicas
dos medicamentos podem contribuir na fisiopatologia da formação dos benzoares. O objetivo deste trabalho é alertar para a importância da
qualidade dos fármacos prescritos e utilizados pelos pacientes com DC, por meio do achado de mais de 350 comprimidos de mesalazina du-
rante o tratamento cirúrgico de um paciente com o padrão fibroestenosante.
Palavras-chave: doença de Crohn; obstrução intestinal; constrição patológica; mesalamina; cirurgia.

INTRODUCTION gastrointestinal tract (GIT), shown by means of clini-


cal, radiological, endoscopic examinations or surgi-
Crohn’s disease (CD), in both stricturing and cal finding3.
fistulizing forms, presents a variable result to clini- Pharmacobezoars may be formed in any portion
cal treatment and good response to surgical thera- of the GIT and are frequently associated with pre-
py1,2. The presence of strictures in CD ranges from disposing anatomical and functional factors or other
12 to 54%, being most frequent in patients who have concomitant affections4. The pharmacological proper-
had the disease for longest. The terminal ileum is the ties of the drugs can contribute with the physiopathol-
most affected location1-3. The stricturing phenotype ogy of the formation of bezoars4. In literature, cases
is characterized by the inflammatory and/or fibrotic of bowel obstruction associated with undissolved pills
luminal reduction of one or more segments of the above the stenosis are rare.

Study carried out at the Coloproctology Service of Hospital Heliópolis – São Paulo (SP), Brazil.
Financing source: none.
Conflict of interest: nothing to declare.

Submitted on: 06/03/2012


Approved on: 09/15/2012

422
J Coloproctol Bezoar by mesalazine tablets: cause of intestinal obstruction in Crohn’s disease Vol. 32
October/December, 2012 Idblan Carvalho de Albuquerque et al. Nº 4

The objective of this study is to alert the medi- Ileocolectomy, sigmoidectomy and two enter-
cal community and health administrators as to the im- ectomies were performed with primary anastomoses.
portance of the quality of prescribed medicines used The patient is currently being followed-up at the in-
by patients with CD, by means of the finding of more flammatory bowel disease outpatient clinic and is as-
than 350 pills of mesalazine during enterectomy for ymptomatic, using biological therapy.
stricture in CD.
DISCUSSION
CASE REPORT
The Montreal classification establishes three pat-
A 28 year-old male patient diagnosed with CD was terns of behavior for Crohn’s disease: inflammatory,
referred to the inflammatory bowel disease outpatient stricturing and penetrating. The fibrostenotic type may
clinic of the Coloproctology Service at Hospital He- occur in up to half of the patients with CD. The forma-
liópolis, in São Paulo, . He had been using mesalazine
2.4 g/day for a year. One month earlier he had been com-
plaining of crampy abdominal pain and abdominal dis-
tension associated with weight loss of 8 kg. At physical
examination, he was thinner, with distended, tympanic
and painless abdomen, with a palpable mass in the right
iliac fossa (RIF). Rectal exam was consistent with nor-
mal mucosa up to 15 cm from the anal verge, and colo-
noscopy showed a stricture at the proximal sigmoid with
pseudopolyps and an orifice suggestive of fistula.
He underwent exploratory laparotomy, which
showed annular stenosis of the small bowel 150 cm
from the ligament of Treitz, proximal dilation and lu-
minal contents suggestive of a foreign body to palpa-
tion (Figure 1); ileosigmoid fistula 50 cm from the
ileocecal valve; and ileocolic fistula involving the
ascending colon and terminal ileum (Figure 2). After Figure 2. Fistula of the terminal ileum with the right colon.
the enterectomy, 350 pills of mesalazine were found
in the site of the stenosis (Figure 3).

Figure 1. Extensive dilation of the small bowel with mesenteritis. Figure 3. Enterectomy with the removal of pills.

423
J Coloproctol Bezoar by mesalazine tablets: cause of intestinal obstruction in Crohn’s disease Vol. 32
October/December, 2012 Idblan Carvalho de Albuquerque et al. Nº 4

tion of stenosis with decreased intestinal lumen due to A simple abdominal x-ray shows the disten-
fibrosis is a result of the wound repair process in the sion of bowel loops with hydroaeric levels, how-
transmural inflammation3. The clinical manifestations ever, 30% of the x-rays’ results are false negatives3.
of the fibrostenotic behavior vary according to the lo- The contrast imaging tests of the GIT may show the
cation of the disease, the intensity and extension of reduction or the stagnant contrast transit, changes in
stenosis and the general status of the patient. Peritone- the prominent mucous cell and areas of stenosis with
al irritation on physical examination means intestinal dilation above3,5. Currently, the computed tomogra-
perforation or ischemia3. phy of the upper abdomen and pelvis with contrast is
Bowel obstruction caused by fibrostenotic CD the most used examination to establish the diagnosis
has a differential diagnosis with postoperative ad- and treatment of fibrostenotic CD. With 92% sensi-
herence2,3, inflammatory parietal thickening3, entero- bility and 71% specificity, it identifies all the afore-
lytes3,5-9, bezoars3,10,11, seeds3,12, medications in the mentioned findings, besides showing parietal thick-
form of pills1, endometriosis3, hernias2,3, intussuscep- ening of the site affected by the disease, presence of
tion3, pseudopolyps13, tumors14 and biliary ileus3. intraluminal foreign body, signals of inflammatory
Bezoars are concretions of different materials, activity in the mesenterium and complications such
partially digested or not, which can be formed by as abscesses and fistula2,3,6,7,
fibers (phytobezoars), hair (trichobezoars), medi- Due to the advancements in imaging diagnostic
cations (pharmacobezoars), among others4. There tests and the poor response to drug therapy, the surgical
are few reports in literature concerning bowel ob- approach for the fibrostenotic behavior of CD has been
struction in patients with Crohn’s disease caused by indicated earlier for two decades. Trece et al.4, in 2010,
medications in form of pills1. The formation of phar- reported a case of pharmacobenzoars with mesalazine
macobezoars is related to the chemical and pharma- pills which, associated to the present description, points
cological properties of the pills, with formulas cov- to the importance of using the medications properly ac-
ered with late absorption or continuous liberation, cording to its pharmacological conditions, as well as to
besides individual predisposing factors, such as in- their adequate state of conservation, so that their active
flammatory, tumoral or post-surgical strictures4. principle may indeed function to control the disease.

REFERENCES 6. Khare DK, Bansal R, Doraisamy S, Gupta S. Crohn’s disease


presenting as enterolithic intestinal obstruction. Am J Surg
1. Piodi LP, Ulivieri FM, Carini M, Piccoli A, Bardella MT. 2004;187(3):408-9.
Iatrogenic ileal obstruction in a patient with Crohn’s disease. 7. Geoghegan T, Stunel H, Ridgeway P, Birido N, Geraghty
Dig Dis Sci 2004;49(7-8):1287-90. J, Torreggiani WC. Small bowel obstruction secondary to
2. Zissin R, Hertz M, Paran H, Bernheim J, Shapiro-Feinberg giant enterolith complicating Crohn’s disease. Ir J Med Sci
M, Gayer G. Small bowel obstruction secondary to Crohn 2005;174(2):58-9.
disease: CT findings. Adbom Imaging 2004;29(3):320-5. 8. Meade P, McDonnell B, Fellows D, Holtzmuller KC, Runke
3. Lahat A, Chowers Y. The patient with recurrent (sub) L. Enteroliths causing intermittent obstruction in a patient
obstruction due to Crohn’s disease. Best Pract Res Clin with Crohn’s disease. Am J Gastroenterol 1991;86(1):96-8.
Gastroenterol 2007;21(3):427-44. 9. García AB, Manrique HP, Sousa CN, Cuadrado MG, Esteban
4. Trece ASN, Netto LPP, Trece RL, Bravo FP, Castro Jr PC, MCG, Feria MR, et al. Intermittent small bowel obstruction
Paulo FL. Doença de Crohn e farmacobezoar intestinal: secondary to enterolithiasis in Crohn’s disease. Rev Esp
relato de caso. Rev Bras Colo-proctol 2010;30(2):215-20. Enferm Dig 2009;101(10):738-40.
5. Lichtenstein GR, Hanauer SB, Sandborn WJ. Management 10. Harrington S, Mohamed S, Bloch R. Small bowel obstruction
of Crohn’s disease in adults. Am J Gastroenterol 2009;104: by a primary phytobezoar in Crohn’s disease. Am Surg
465-83. 2009;75(1):93-4.

424
J Coloproctol Bezoar by mesalazine tablets: cause of intestinal obstruction in Crohn’s disease Vol. 32
October/December, 2012 Idblan Carvalho de Albuquerque et al. Nº 4

11. Siddiqua T, Easley D, Thomas S, Zenel JA, Pohl JF. 14. Albuquerque IC, Alves Filho EF, Paula Nunes BLBB,
Visual diagnosis: a small bowel obstruction. Pediatr Rev Nossa FLC, Barreto Neto PF, Silva JH, et al. Intussuscepção
2009;30(12):486-90. colônica por lipoma. Relato de dois casos. Rev bras Coloproct
12. Kaufman D, Lazinger M, Fogel S, Dutta SK. Fruit pit 1998;18(4):256-9.
obstruction leading to the diagnosis of Crohn’s disease. Am J
Surg 2001;182(5):530. Correspondence to:
13. Christianakis E, Pashalidis N, Kokkinou S, Pitiakoudis M, Idblan Carvalho de Albuquerque
Mplevrakis E, Chorti M, et al. Acute jejunoileal obstruction Rua Arruda Alvim, 161, apto. 102 – Pinheiros
due to a pseudopolyp in a child with undiagnosed Crohn CEP: 05410-020 – São Paulo (SP), Brazil
disease: a case report. J Med Case Rep 2008;2:54. E-mail: idblan@me.com

425
Technical Note

Operative Technique: Intersphincteric Resection


Marcus Valadão¹, Daniel Cesar², Guilherme Graziosi², Ricardo Ary Leal³

Doctoral student in Oncology by the National Cancer Institute; Oncologic Surgeon at


1

II Clínica Cirúrgica of Hospital Geral de Bonsucesso – Rio de Janeiro (RJ), Brazil.


2
Resident physician of General Surgery at II Clínica Cirúrgica of Hospital Geral de Bonsucesso – Rio de Janeiro (RJ), Brasil.
3
Expert in Coloproctology by the Brazilian Society of Coloproctology; Surgeon at II Clínica Cirúrgica
of Hospital Geral de Bonsucesso – Rio de Janeiro (RJ), Brazil.

Valadão M, Cesar D, Graziosi G, Leal RA. Operative Technique: Intersphincteric Resection. J Coloproctol, 2012;32(4): 426-429.
Abstract: Despite the technological advances over the last years, the treatment of low rectal cancer (extraperitoneal) remains as a surgical
challenge. Currently, the abdominoperineal resection is still the standard surgical treatment for most rectal lesions within 5 cm from the anal
verge with well-known physical and psychological consequences. On the other hand, the introduction of intersphincteric resection in clinical
practice has led to the possibility of sphincter preservation allied to satisfactory oncologic and functional outcomes in well selected cases. The
present paper describes the technical steps of an intersphincteric resection for the treatment of extraperitoneal low rectal cancer.
Keywords: surgery; neoplasms; rectum; anal canal.

Resumo: Apesar dos avanços tecnológicos dos últimos anos, o tratamento do câncer de reto inferior (extraperitoneal) continua sendo de-
safiador. Atualmente, a ressecção abdômino-perineal ainda é o tratamento padrão para lesões retais situadas a uma distância menor que 5 cm
da margem anal, sendo bem conhecidas suas sequelas físicas e psicológicas. Em contrapartida, a introdução da ressecção interesfincteriana
na prática clínica trouxe à tona a possibilidade da preservação anal aliada à obtenção de resultados oncológicos e funcionais satisfatórios em
casos bem selecionados. O presente estudo tem como objetivo descrever a técnica operatória da ressecção interesfincteriana no tratamento do
câncer de reto extraperitoneal.
Palavras-chave: cirurgia; neoplasias; reto; canal anal.

INTRODUCTION sphincter partially or completely and maintaining in-


testinal continuity in patients with rectal cancer close
The standard surgical treatment for rectal adeno- to the anal canal.
carcinoma located up to 5 cm from the anal verge is According to Akasu et al.3, the meticulous per-
the abdominoperineal resection (APR). This happens formance of the technique brings satisfactory results
because the length of the anal canal is from 2 to 4 cm, both for the anorectal function and the oncologic out-
and the disease-free longitudinal margin should have comes for T1 and T2 tumors, without increasing lo-
at least 1 cm (preferentially, 2 cm)1. In order to avoid cal or distant recurrence rates and without the need
the definitive colostomy in these patients, the inter- for association with radiotherapy. In the mentioned
sphincteric resection (IR) was first described in the study, 108 patients were submitted to IR. The local
1980s, and well established in the 1990s by Schiessel recurrence rate in 3 years for T1-T2 lesions was 0%,
et al.2. Nowadays, IR is defined as a procedure that can and for T3 lesions, 15%, while the distant recurrence
obtain satisfactory free margins removing the internal rate for T1, T2, T3 and T4 tumors was 4, 5, 18 and

Study carried out at the General Surgery Department of Hospital Geral de Bonsucesso – Rio de Janeiro (RJ), Brazil.
Financing source: none.
Conflict of interest: nothing to declare.

Submitted on: dd/mm/aaaa


Approved on: dd/mm/aaaa

426
J Coloproctol Operative Technique: Intersphincteric Resection Vol. 32
October/December, 2012 Marcus Valadão et al. Nº 4

33%, respectively3. The use of IR in T3 and T4 lesions the intersphincteric plane is dissected with the elec-
is still controversial, once the oncologic outcomes, in trocautery under direct vision. To facilitate the dis-
these cases, are not satisfactory when compared to the section and decrease bleeding, it is possible to infil-
abdominoperineal resection. trate a 1:200.000 adrenaline solution at this moment
The surgical planning for low rectal tumors is or before the incision. If the rectum is not closed in
complex. The decision to perform IR instead of ab- the abdominal stage, it should be closed with a suture
dominoperineal resection should be discussed with bag at the occasion. Dissection proceeds until the al-
the patient, and many factors should be analyzed4, ready dissected intraperitoneal portion of the rectum
such as: staging, ability to resect the tumor with free is found. Then, the rectum is resected and removed
radial margins, functional implications, desire of the through the abdomen when the access is made by
patient, distance from the tumor to the sphincter com- laparotomy, or through the anus with videolaparos-
plex, body mass index (BMI) and anatomy of the pel- copy. The pelvic cavity and the anal canal are irri-
vis (male x female). gated with 10% iodopovidone, followed by a saline
solution. The colon (especially after the confection
TECHNIQUE of a colonic J pouch) is brought through the hiatus
in the levator ani, and the coloanal anastomosis is
The principle of the technique is based on the performed with interrupted sutures (Figure 2). Usu-
dissection of the anatomical plane between the inter- ally the procedure is finished with a diverting loop
nal sphincter, which is the prolonged muscular layer ileostomy or colostomy to protect the anastomosis.
of the rectum, and the external sphincter.
Preferably, the surgical procedure is initiated by DISCUSSION
the abdominal approach, performing the high ligation
of the lower mesenteric vein and the lower mesenteric The success of the rectal cancer treatment in-
artery right after the emergence of the left colic artery. volves the combination of a good oncologic outcome
Afterwards, the mobilization of the splenic flexure is and an acceptable quality of life for the postopera-
performed, followed by total mesorectal excision by tive patient. APR is considered as gold standard in
means of the avascular embryological plane of areo- the treatment of low rectal tumors8, but it generates
lar tissue between the mesorectal fascia and the lateral outcomes that are followed by a compromised qual-
endopelvic fascia until the levator ani muscle and the ity of life.
anorectal junction5-7. Modern surgery should not be limited to curative
In most rectal tumor cases that demand IR, the tumor resections, since the functional result quality of
perineal time is necessary, which can be initiated after life of patients who suffer from colorectal cancer has
the mobilization of the rectum and sigmoid. A Gelpi become part of the primary treatment and has been
retractor or an autostatic Lone Star® retractor (Fig- assessed together with the oncologic outcomes. Engel
ure 1) is placed in the anal canal to expose the mu- et al.9 reported that patients with stoma have low self-
cosa, which is circumferentially opened, usually on esteem, altered body image and decreased sexual and
the dentate line or 1 cm from the distal margin of the physical activity when compared to the others.
tumor. If the incision is made on the dentate line or 1 Due to these reasons, it is possible to observe that
to 2 mm distal to it, the resection of the proximal half continuous efforts are being employed to preserve the
of the internal sphincter is considered. If the resec- anal sphincter in low rectal cancer. There is a new con-
tion is initiated above the dentate line, but below the cept according to which the resection with a 1 cm mar-
anorectal junction, the removal of the proximal third gin for rectal tumors located near the anal margin are
of the internal sphincter is considered. It is important known for presenting oncologic outcomes comparable
to remember that the resection with a 1 cm longitu- to larger margins10-13.
dinal macroscopic margin should always be the goal Such advances enabled the appearance of IR for
in this stage of the procedure. Like the mucosa, the tumors between 1 and 3 cm from the dentate line, and
internal sphincter is circumferentially incised, and the combination of chemotherapy and neoadjuvant

427
J Coloproctol Operative Technique: Intersphincteric Resection Vol. 32
October/December, 2012 Marcus Valadão et al. Nº 4

Figure 1. Eversion of the anal mucosa with the Lone Star® retractor. Figure 2. Manual coloanal anastomosis. Cardinal points visible
The level of mucosal incision was marked with the electrocautery. at 12h, 3h, 6h e 9h.

radiotherapy has been used with the objective to in- ing the anal sphincter in low and very low rectal
crease the opportunity to preserve the sphincter in pa- tumors14-22.
tients with very low rectal tumors2. Despite all the effort to develop new surgical
The benefits of IR compared to APR are still techniques and preoperative therapies, some patients
controversial. There are few studies comparing the with rectal cancer are not eligible for IR and, inevita-
oncologic outcomes of both techniques. Many of bly, APR will be indicated, especially for those with
them are retrospective, but even so they pointed out tumors in advanced stages, next to the anal margin and
there is good local control, with recurrence rates little responsive to neoadjuvant treatments23-26.
ranging from 0 and 12% after resections, preserv-

ReferENCES mesorectal excision in the operative treatment of carcinoma


of the rectum. J Am Coll Surg 1995;181(4):335-46.
1. Nicholls RJ, Hall C. Treatment of non-disseminated cancer 7. Heald RJ, Moran BJ, Ryall RD, Sexton R, MacFarlane JK.
of the lower rectum. Br J Surg 1996;83(1):15-8. Rectal cancer: the Basingstoke experience of total mesorectal
2. Schiessel R, Karner-Hanusch J, Herbst F, Teleky B, excision, 1978-1997. Arch Surg 1998;133(8):894-9.
Wunderlich M. Intersphincteric resection for low rectal 8. Rothenberger DA, Wong WD. Abdominoperineal resection
tumors. Br J Surg 1994;81(9):1376-8. for adenocarcinoma of the low rectum. World J Surg
1992;16(3):478-85.
3. Akasu T, Takawa M, Yamamoto S, Fujita S, Moriya Y.
9. Engel J, Kerr J, Schlesinger-Raab A, Eckel R, Sauer H,
Incidence and patterns of recurrence after intersphincteric
Hölzel D. Quality of life in rectal cancer patients: a four-year
resection for very low rectal adenocarcinoma. J Am Coll
prospective study. Ann Surg 2003;238(2):203-13.
Surg 2007;205(5):642-7.
10. Andreola S, Leo E, Belli F, Bonfanti G, Sirizzotti G,
4. Holzer B, Urban M, Hölbling N, Feil W, Novi G, Hruby W, et
Greco P, et al. Adenocarcinoma of the lower third of the
al. Magnetic resonance imaging predicts sphincter invasion
rectum surgically treated with a <10-MM distal clearance:
of low rectal cancer and influences selection of operation.
preliminary results in 35 N0 patients. Ann Surg Oncol
Surgery 2003;133(6):656-61.
2001;8(7):611-5.
5. Yoo JH, Hasegawa H, Ishii Y, Nishibori H, Watanabe M,
11. Minsky BD, Cohen AM, Enker WE, Paty P. Sphincter
Kitajima M. Long-term outcome of per anum intersphincteric preservation with preoperative radiation therapy and coloanal
rectal dissection with direct coloanal anastomosis for lower anastomosis. Int J Radiat Oncol Biol Phys 1995;31(3):553-9.
rectal cancer. Colorectal Dis 2005;7(5):434-40. 12. Janjan NA, Khoo VS, Abbruzzese J, Pazdur R, Dubrow
6. Enker WE, Thaler HT, Cranor ML, Polyak T. Total R, Cleary KR, et al. Tumor downstaging and sphincter

428
J Coloproctol Operative Technique: Intersphincteric Resection Vol. 32
October/December, 2012 Marcus Valadão et al. Nº 4

preservation with preoperative chemoradiation in 20. Prete F, Sebastiani R, Sammarco DF, Prete FP. Role of
locally advanced rectal cancer: the M. D. Anderson intersphincter resection among the surgical options for cancer
Cancer Center experience. Int J Radiat Oncol Biol Phys of the distal rectum. Chir Ital 2001;53(6):765-72.
1999;44(5):1027-38. 21. Rullier E, Goffre B, Bonnel C, Zerbib F, Caudry M, Saric
13. Rouanet P, Fabre JM, Dubois JB, Dravet F, Saint Aubert B, J. Preoperative radiochemotherapy and sphincter-saving
Pradel J, et al. Conservative surgery for low rectal carcinoma resection for T3 carcinomas of the lower third of the rectum.
after high-dose radiation. Functional and oncologic results. Ann Surg 2001;234(5):633-40.
Ann Surg 1995;221(1):67-73. 22. Rullier E, Laurent C, Zerbib F, Belleannée G, Caudry M,
14. Rullier E, Zerbib F, Laurent C, Bonnel C, Caudry M, Saric Saric J. Conservative treatment of adenocarcinomas of
J, et al. Intersphincteric resection with excision of internal the anorectal junction by preoperative radiotherapy and
anal sphincter for conservative treatment of very low rectal intersphincteral resection. Ann Chir 2000;125(7):618-24.
cancer. Dis Colon Rectum 1999;42(9):1168-75. 23. Tytherleigh MG, McC Mortensen NJ. Options for sphincter
15. Köhler A, Athanasiadis S, Ommer A, Psarakis E. Long- preservation in surgery for low rectal cancer. Br J Surg
term results of low anterior resection with intersphincteric 2003;90(8):922-33.
anastomosis in carcinoma of the lower one-third of 24. Kim NK, Baik SH, Seong JS, Kim H, Roh JK, Lee KY, et
the rectum: analysis of 31 patients. Dis Colon Rectum al. Oncologic outcomes after neoadjuvant chemoradiation
2000;43(6):843-50. followed by curative resection with tumor-specific mesorectal
16. Rullier E, Laurent C, Bretagnol F, Rullier A, Vendrely excision for fixed locally advanced rectal cancer: impact of
V, Zerbib F. Sphincter-saving resection for all rectal postirradiated pathologic downstaging on local recurrence
carcinomas: the end of the 2-cm distal rule. Ann Surg and survival. Ann Surg 2006;244(6):1024-30.
2005;241(3):465-9. 25. Crane CH, Skibber JM, Feig BW, Vauthey JN, Thames HD,
17. Vorobiev GI, Odaryuk TS, Tsarkov PV, Talalakin AI, Curley SA, et al. Response to preoperative chemoradiation
Rybakov EG. Resection of the rectum and total excision of increases the use of sphincter-preserving surgery in patients
the internal anal sphincter with smooth muscle plasty and with locally advanced low rectal carcinoma. Cancer
colonic pouch for treatment of ultralow rectal carcinoma. Br 2003;97(2):517-24.
J Surg 2004;91(11):1506-12. 26. Baik SH, Kim NK, Lee KY, Sohn SK, Cho CH. Analysis of
18. Saito N, Ono M, Sugito M, Ito M, Morihiro M, Kosugi anal sphincter preservation rate according to tumor level and
C, et al. Early results of intersphincteric resection for neoadjuvant chemoradiotherapy in rectal cancer patients. J
patients with very low rectal cancer: an active approach Gastrointest Surg 2008;12(1):176-82.
to avoid a permanent colostomy. Dis Colon Rectum
2004;47(4):459-66. Correspondence to:
19. Tiret E, Poupardin B, McNamara D, Dehni N, Parc R. Marcus Valadão
Ultralow anterior resection with intersphincteric dissection- Rua Dois de Dezembro, 78 – sala 403 – Catete
-what is the limit of safe sphincter preservation? Colorectal CEP: 22220-040 – Rio de Janeiro (RJ), Brazil
Dis 2003;5(5):454-7. E-mail: marcusvaladao@ig.com.br

429
SELF-ASSESSMENT QUIZ
Jorge Benjamin Fayad
Full Member of the Brazilian Society of Coloproctology

Fayad, JB. Self-Assessment Quiz. J Coloproctol, 2012;32(4): 430.

1 – Regarding the development of squamous cell 3 – According to the classification described by


carcinoma in the anal area, the following varia- Rodger Haggit for intestinal polyps, the invasive
bles are frequently reported: carcinomas in sessile polyps are described as:

a) HPV infection, immune status and sup- a) Level 1.


pressor genes. b) Level 2.
b) HPV infection, CMV ulceration and anal c) Level 3.
syphilis. d) Level 4.
c) HPV infection, anorectal fistula and alco-
holism.
d) HPV infection, herpes simplex ulcers and
chlamydial proctitis.

2 – These are criteria to evaluate the severity of


ulcerative colitis (UC):

a) Number of bowel movements, ESR and


blood in stool.
b) Heart rate, fever and CRP.
c) Abdominal pain, number of bowel move-
ments and ESR.
d) Blood in stool, heart rate and CRP.

430
Answers for the self-ASSESSMENT QUIZ
1 – Correct answer: a 3 – Correct answer: d
There are many factors associated with the develop- In 1985, Haggitt proposed the classification of
ment of carcinoma in the squamous cells of the anal polyps with adenocarcinoma according to the de-
canal, among which: uterine cervical carcinoma, gree of tumor invasion: level 0 – in situ or intra-
HPV infection, Hodgkin’s lymphoma, kidney trans- mucosal carcinoma; level 1 – the carcinoma sur-
plant, promiscuity, herpes type 2, HIV infection, passes the muscularis mucosa until the submucosa,
male homosexuality, positive serology for syphilis but restricted to the polyp head; level 2 – the carci-
and anal condyloma. Evidence shows that etiology noma invades up to the junction of the polyp head
comes from multifactorial interaction among envi- and pedicle; level 3 – the carcinoma invades the
ronmental factors, HPV infection, immune status and polyp pedicle; level 4 – the carcinoma invades
suppressor genes. the submucosa of the intestinal wall below the pe-
dicle. By definition, all invasive carcinomas in
• Corman ML. Colon and rectal surgery. 5th ed. sessile polyps are classified as level 4.
2005.
• Gordon PH, Nivatvongs S. Principles and practice
of surgery for the colon, rectum and anus. 3rd ed.
2 – Correct answer: a 2007.
In 1995, Truelove and Witts developed a severity in-
dex to evaluate the UC activity, considering parame-
ters such as the number bowel movements, presence
of blood in stool, fever, heart rate, serum hemoglo-
bin and ESR. C-reactive protein (CRP) and abdominal
pain are not considered as evaluation parameters.

• Wolff BG, Pemberton JH, Wexner SD, Fleshman


JW. The ASCRS textbook of colon and rectal
surgery. 2nd ed. 2011.

431
Accredited Services by the SBCP

Hospital Universitário C. Fraga Filho - UFRJ Fundação Ensino Superior Vale do Sapucai
Reg. Mec. 124 Hospital das Clínicas Samuel Libânio
Av. Brigadeiro Trompowsky - Ilha do Fundão Rua Comendador José Garcia, 777
21941-590 - Rio de Janeiro - RJ 36540-000 - Pouso Alegre - MG
Tel: (21) 2562-2010 - ramal 2719 Tel: (35) 3422-2345

Hospital Universitário Pedro Ernesto - UERJ Hospital Ernesto Dornelles


Reg. Mec 153 Av. Ipiranga, 1801
Av. 28 de Setembro, 77 96160-093 - Porto Alegre - RS
20551-030 - Rio de Janeiro - RJ Tel: (51) 3217-2002
Tel: (21) 2587-6100
Hospital Nossa Senhora da Conceição
Hospital de Ipanema Av. Francisco Trein, 596
Reg. Mec 156 91350-200 - Porto Alegre - RS
Rua Antonio Parreiras, 69 - Ipanema Tel: (51) 3341-1300
22411-020 - Rio de Janeiro - RJ
Tel: (21) 3111-2379 Hospital Barão de Lucena
Av. Caxangá, 3860 - Iputinga
Hospital dos Servidores do Estado 50731-000 - Recife - PE
Reg. Mec 160 Tel: (81) 3453-3566
Rua Sacadura Cabral, 178 - Saúde
22221-161 - Rio de Janeiro - RJ Hospital das Clínicas - UFCE
Tel: (21) 2291-3131 Rua Capitão Francisco Pedro, 1290
60430-370 - Fortaleza - CE
Hospital da Lagoa Tel: (85) 3243-9117
Reg. Mec 162
Irmandade da Santa Casa da Misericórdia de São Paulo
Rua Jardim Botânico, 501
Departamento de Cirurgia
22470-050 - Rio de Janeiro - RJ
Rua Cesário Mota Junior, 112
Tel.: (21) 3111-5100
01221-020 - São Paulo - SP
Tel.: (11)224-0122
Hospital Naval Marcílio Dias
Reg. Mec 171
Pontifícia Universidade Católica de Campinas
Rua César Zama, 185 - Lins de Vasconcelos
Rodovia D. Pedro I, Km 136
20725-090 - Rio de Janeiro - RJ
13020-904 - Campinas - SP
Tel: (21) 2599-5599 - ramal 5648 / 5428 Tel. (19)3252-0899 / 3729-8600
Hospital Heliópolis Hospital Municipal Miguel Couto - Rio
Reg. Mec 210 Rua Mário Ribeiro, 157 - Leblon
Rua Cônego Xavier, 276 22430-160 - Rio de Janeiro - RJ
Vila Heliópolis Tel. (21) 2274-6050
04231-030 - São Paulo - SP
Tel. (11) 2274-7600 (ramal 244) Santa Casa de Belo Horizonte
Grupo de Colo-Proctologia de Belo Horizonte
Hospital Universitário da Faculdade de Medicina Av. Francisco Sales, Praça Hugo Werneck, s/nº
PUC RS - Serviço de Coloproctologia 30150-300 - Belo Horizonte - MG
Av. Ipiranga, 6690 Tel. (31) 3238-8131
90610-000 - Porto Alegre - RS
Informações: COREME tel. 3339-1322 Ramal 2378 Hospital das Clínicas
Tel: (51) 3320-3000 Faculdade de Medicina da Universidade de São Paulo - SP
Av. Dr. Eneas de Carvalho Aguiar, 255
Hospital Clínicas da Universidade Federal do Paraná Cerqueira Cesar
Rua Gal. Carneiro, s/n 05403-000 - São Paulo - SP
80060-150 - Curitiba - PR Tel. (11)3069-6000
Tel: (41) 3360-1800
432
J Coloproctol Accredited services by the SBCP Vol. 32
October/December, 2012 Nº 4

Hospital de Base do Distrito Federal Hospital do Andaraí


S M H S , 101 BL. A Rua Leopoldo, 280 - 2º andar -Andaraí
Setor Hospitalar Sul 20541-170 - Rio de Janeiro - RJ
70335-900 - Brasília - DF (21) 2562-2719
Tel. (61) 3325-5050
Hospital Municipal São José
Real e Benemérita Sociedade Portuguesa de Beneficência - Av. Getúlio Vargas, 233
Hospital São Joaquim 89202-001 - Joinville - SC
Rua Maestro Cardim, 769 (47) 3441-6666
01323-001 - São Paulo - SP
Tel: (11) 3253-5022 Hospital Geral de Goiânia Dr. Alberto Rassi
Av. Anhanguera , 6379 - Setor Oeste
Hospital Universitário Evangélico de Curitiba 74043-011 - Goiânia - GO
Al. Augusto Stellfeld, 1908 Tel: (62) 3221-6031
80730-150 - Curitiba - PR
Tel. (41) 3222-0727 / 3322-4141 Santa Casa de Misericórdia - Fortaleza - CE
Serviço de Coloproctologia
Hospital do Servidor Público Estadual de São Paulo – “FMO” Rua Barão do Rio Branco, 1816
Serviço de Gastroenterologia Cirúrgica e Coloproctologia 60025-061 - Fortaleza - CE
Rua Pedro de Toledo, 1800 - 11º andar - Ala Central Tel: (85) 3211-1911
04029-000 - São Paulo - SP
Tel. (11) 5088-8117 / 5088-8119 Hospital do Serviço Público Municipal - SP
Serviço de Coloproctologia
Hospital Geral Roberto Santos Rua Castro Alves nº 60 - Liberdade
MEC/CNRM - PARECER Nº 98/99 01532 - São Paulo - SP
Est. do Saboeiro, S/N - Cabula Tel: (11) 3208-2211
41180-780 - Salvador - BA
Tel. (71) 3372-2849
Hospital Nossa Senhora das Graças
Serviço de Coloproctologia
Centro de Colo-Proctologia do Ceará
Rua Alcides Munhoz, 433 - Mêrces
Av. Pontes Vieira, 2551 (2º andar)
80810-040 Curitiba - PR
60130-241 - Fortaleza - CE
Tel: (41) 3240-6706 Fax. (41) 3240-6500
Tel. (85) 3257-6588 - 257-7728
Serviço de Coloproctologia
Hospital de Base da Faculdade de Medicina de São José do
Hospital das Clínicas da Faculdade de Medicina
Rio Preto
Av. Brigadeiro Faria Lima, 5416 Universidade Federal de Goiás
15090-000 - São José do Rio Preto - SP 1ª Avenida, s/nº
Tel. (17) 3201-5000 74650-050 - Goiânia - GO
Tel.: (62) 3202-1800 ramal 1094 - COREME
Hospital Felício Rocho Tel.: (62) 3202-4443
Av. Contorno, 9.530
30110-130 - Belo Horizonte - MG Hospital Universitário Prof. Alberto Antunes
Tel. (31) 3339-7142 Av. Lourival Melo Mota, s/n
Tabuleiro do Martins
Hospital de Jacarepaguá 57072-900 - Maceió - AL
Av. Menezes Cortes, 3245 Tel.: (82) 3322-2494
20715-190 - Rio de Janeiro - RJ
Tel. (21) 2425-2255 - R. 200 Hospital das Clínicas da Faculdade de Medicina de Ribei-
rão Preto - USP
Hospital Sírio Libanês Av. Bandeirantes, 3900
CNRN / MEC Nº 23/2002 14048-900 - Ribeirão Preto - SP
Rua Dona Adma Jafet, 91 Tel. (16) 3602-1000 / 3602-2509
01308-050 - São Paulo - SP
Tel. (11) 3155-0200
433
J Coloproctol Accredited services by the SBCP Vol. 32
October/December, 2012 Nº 4

Hospital Universitário da Universidade Federal de Sergipe Hospital São Rafael


Rua Cláudio Batista s/nº Serviço de Coloproctologia
Sanatório Av. São Rafael, 2152 - São Marcos
49060-100 - Aracajú - SE 41256-900 - Salvador - BA
Tel. (79) 3218-1738 Tel.: (71) 3281-6400

Hospital das Clínicas -UFMG Vitória Apart Hospital


Instituto Alfa de Gastroenterologia Serviço de Coloproctologia
Av. Prof. Alfredo Balena, 110 , 2º andar Rod. BR 101 Norte Km 2 - Carapina
Sta. Efigênia 29101-900 - Serra - ES
30130-100, Belo Horizonte, MG Tel.: (27) 3201-5555
Tel. (31) 3248-9403 / (31) 3248-9251
Hospital Municipal Dr. Mário Gatti
Clínica Reis Neto Serviço de Coloproctologia
Rua General Osório, 2273 Av. Prefeito Faria Lima, 340 - Parque Itália
12025-155 - Cambuí - Campinas - SP 13036-902 - Campinas - SP
Tel.: (19) 3252-5611 Tel.: (19) 3772-5700

Hospital Universitário Cajuru - Serviço de Coloproctologia Serviço de Coloproctologia


Reg. Mec. Parecer 43/06 Hospital de Clínicas de Porto Alegre
Av. São José, 300 Universidade Federal do Rio Grande do Sul
80050-350 - Cristo Rei - Curitiba - PR Rua Ramiro Barcelos, 2.350 / sala 600
Tel.: (41) 3271-3009 90035-903 - Porto Alegre - RS
Tel.: (51) 3359-8232

We require the Coloproctology services that have medical residency or internships related to this specialty to send their
program and schedule to the Society, so they can be publicized.
This section will be available to publicize rules and dates of selection.

Minimum program REQUIREMENTS to be accredited by the Brazilian Society of Coloproctology

Staff – Participation of at least two full members of SBCP.


Surgeries – Monthly mean of at least three colorectal surgeries and six anoperineal surgeries.
Ambulatory – Monthly mean of at least 50 appointments.
Endoscopies – Monthly mean of at least 20 rectosigmoidoscopies and five colonoscopies.
Available supporting units: Radiology, pathological anatomy, endoscopy, clinical analysis laboratory, ICU, Oncology,
Radiotherapy, Statistical and Medical Files.

Teaching – a) Weekly service meetings to discuss cases and also published articles;
b) To estimulate the production of scientific papers to be presented at the annual congress of the Brazilian Society of
Coloproctology and possible publication in the SBCP journal;
c) To send at least one original article per year for possible publication in the SBCP journal.

434

Você também pode gostar