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GeneralSurgeryNews.com
MAY 2006
Fibrin Glue
Newest Treatment for Anal Fistulas: the
When it was first cited regularly in the colorectal literature at Surgisis AFP Plug
the beginning of the 1990s, fibrin glue was reported to be supe-
rior to other approaches in the treatment of anal fistulas. The The FDA cleared the Surgisis AFP plug, Cook Incorporated,
use of fibrin glue also is relatively simple and noninvasive. Bloomington, Ind., March 9, 2005, as the first surgical device for
Everyone thought this might be the holy grail for fistulas, the repair of anal fistulas. The slender, cone-shaped device is
remarked Dr. Sklow, noting that early, short-term studies indi- made from porcine small intestinal submucosa. It is placed in the
cated very high closure rates, which made fibrin glue a serious fistula channel, where it serves as a bio-scaffold for native tissue
contender for taking the top spot in surgeons treatment choic- regeneration, and hence safely closes the fistula tract. Some sur-
es for anal fistulas. geons have been using the Surgisis AFP plug for as long as 4
One of the earliest studies of fibrin glue in the treatment of years and appear to be very satisfied with it.
anal fistulas was conducted by a team of Danish surgeons.8 In Dr. Sklow was highly involved in the development of the Sur-
a series of 23 patients, 12 patients (52%) showed complete and gisis AFP plug. He has been using it since April 2002, when the
permanent fistula closure after 1 application of fibrin glue. device was in its earliest formhe rolled a sheet of porcine mate-
Another 5 (22%) showed fistula healing after 2 or 3 attempts. rial before insertion into the fistula. At the American Society of
The method failed in the remaining 6 patients (26%). Colon and Rectal Surgeons 2004 annual meeting, Dr. Sklow
Jose R. Cintron, MD, and his colleagues at the University of and his colleagues reported on the rolled form of the plug in 17
Illinois Medical Center, Chicago, had similar results in their patients.15 The patients were treated between April 2002 and
study, published 9 years later in 2000. Patients treated with May 2003, their average age at diagnosis was 53.8 years
autologous fibrin glue (14/26) had a 54% complete-closure (range, 28-79 years), and 14 (82%) were men. One of the sub-
rate at 1 year, and there was a 64% rate among those treated jects had Crohns disease, another had ulcerative colitis, and
with commercial fibrin sealant (34/53).9 Moreover, Ian Lindsey, one more had a restorative proctocolectomy for ulcerative coli-
MD, and his team in Oxford, England, completed a small ran- tis. Sixteen of the 18 simple or complex fistulas (88.9%) were fis-
domized, controlled trial that revealed fibrin glue healed 50% tulas in ano, while 1 (5.6%) was a pouch-cutaneous fistula, and
(3/6) of simple fistulas and 69% (9/13) of complex fistulas.10 the remaining fistula (5.6%) was of the recto-pelvic form. There
The respective numbers for fistulotomy were 100% (7/7) and had been previous attempts to close 5 of the fistulas (27.8%).
13% (2/16). A higher closure rate of anal fistulas85% The mean fistula length was 5.9 cm (range, 3-10 cm).
(17/20)was documented after a mean follow-up of 10 months The investigators documented a 61% closure rate (11/18) of
by Stephen M. Sentovich, MD, and colleagues, in 2001.11 How- the patients after an average of 12 months. Four of the patients
ever, Dr. Sentovich noted the healing rate dropped to 69% (24%) required only local anesthesia, 11 (65%) required spinal
(33/48) after a mean follow-up of 22 months.12 anesthesia, and the remaining 2 (12%) were given general
Indeed, other research corroborates the finding that healing anesthesia.
rates decrease as follow-up times increase. One randomized Of the fistulas, 13 (72%) were closed with insertion of the
study of anal fistulas with a mean 27-month follow-up by a team plug combined with closure of the internal opening with
that included Dr. Cintron and Herand Abcarian, MD, FACS, Turi sutures. Seven of these patients (54%) successfully healed.
Josefsen professor and chairman, Department of Surgery, Uni- The remaining 5 involved using the plug together with an
versity of Illinois College of Medicine at Chicago, revealed a advancement flap, after failure of the internal opening to close
40% (10/25) healing rate at an average of 27 months when sur- with sutures. All 5 were posterior midline fistulas. Four of these
gical closure of the internal fistula opening was used.13 How- 5 fistulas (80%) healed. Four of the successfully healed
ever, there was only a 31% healing rate with the combination of patients had failed previous surgical attempts at closure. One
surgical closure and fibrin sealant (8/26) and a 21% rate when patient required an additional surgical procedure for a second
fibrin glue and cefoxitin were used (5/24). missed fistula tract. The average time to closure was 4.9 weeks
Similarly, a team of St. Louis researchers documented a 38% (range, 2-9 weeks). There was only 1 complication: a patient
success rate at an average of 26 months among complex-fis- with Crohns disease developed an abscess at the external
tula patients given a first treatment with fibrin glue, and a 22% opening. The abscess was drained, and the fistula healed.
healing rate among those with previously treated fistulas.14 The overall rate of closure after the first attempt at plug
Most of the failures occurred within 3 months. placement was 44% (8/18). Dr. Sklow explained that this low
So glue may not be as great as we once thought, but it cer- rate can be partly explained by the fact that 3 of the patients
tainly has a role [in first-line treatment of anal fistulas], Dr. whose fistulas failed to heal after the first attempt should not
Sklow concluded. have been given the Surgisis AFP plug because they had short,
Dr. Abcarian agreed. superficial fistulas. The explanation for most of the other fail-
Is glue past its due? No, he said. It has its place in the sur- ures was surgeon technique; it should be noted that these sur-
geons armamentarium. It is definitely ineffective in rectovaginal geons were early in the learning curve.
fistulas[that is], it is ineffective in short, wide tracts. But it is The installation of the Surgisis AFP plug is easy to perform,
much more effective in long, complex tracts, and may be used safe, noninvasive, and associated with few complications and
in Crohns disease. You have nothing to lose if you use it as minimal discomfort for the patient, Dr. Sklow said. It certainly
first-line treatment. If it fails, repeat it once. If it fails again or the can be repeated if it fails initially and may be the procedure of
fistula recurs, move to endorectal advancement flap, dermal- choice for reoperative complex fistulas. Moreover, the com-
island flap anoplasty, seton drainage, or the anal fistula plug. mercially available conical shape may yield superior results.
2
Surgisis AFP The next step was a prospective comparison of the Surgisis
Anal Fistula Plug. AFP plug to fibrin glue for the closure of anal fistulas, under-
taken by Dr. Armstrong and his team. They have been using the
Surgisis AFP plug for more than 2 years for complex fistulas
that have failed at least 1 previous attempt at closure.
We were exploring ways to work with patients with these
complex fistulas, explained Dr. Armstrong. We decided on the
Photo courtesy of Cook Biotech, Inc. Surgisis AFP plug because it seemed like it was made from an
ideal material. It comes from porcine small intestinal submu-
The plug is rehydrated cosawhich is very similar to the human equivalent. Theres no
and inserted into the foreign-body reaction, [so] it allows tissue ingrowth and its
primary opening until resistant to infection.
resistance is first met. Dr. Armstrong and his colleagues enrolled 25 patients in a
prospective trial. The team used the Surgisis AFP plug on 15
patients and treated 10 with fibrin glue. Patients with Crohns
disease were excluded from the study. There were no signifi-
cant differences between the 2 groups in average age, number
of men and women, number of prior fistula surgeries, or num-
The excess plug is
ber of secondary fistula openings. All of the patients underwent
trimmed at the level of the mechanical bowel preparation accompanied by application of
primary opening and enteric antibiotics.
sutured in place with a Of the 15 patients treated with the Surgisis AFP plug, 13
deep figure-of-eight suture,
using 2-0 Vicryl. It is
(87%) had complete closure of all fistula tracts. Only 4 patients
essential to use a deep, treated with fibrin glue (40%) showed complete closure of all
secure suture at the fistula tracts (P<0.05). Most of the failures with the Surgisis AFP
primary opening to prevent plug or with fibrin glue occurred within the first 4 weeks after
extrusion of the plug.
surgery. These results were presented at the American Society
of Colon and Rectal Surgeons 2005 annual meeting16 and
The plug undergoes subsequently published.17
resorption and remodeling
into the native tissue, and
Dr. Armstrong and his colleagues now have treated 35 high
six weeks later the fistula anorectal fistulas with the Surgisis AFP plug, yielding an 80%
is firmly closed. healing rate after an average of 12 months. This includes clo-
sure of all fistulas in 8 Crohns patients. They also have had
success using the Surgisis AFP plug to replace setons, as well
as with healing an anastomotic fistula, anterior radial fistulas,
hemi-horseshoe and horseshoe fistulas, and in patients who
Photos courtesy of David N. Armstrong, MD. are morbidly obese or who have HIV/AIDS.
The message is: superficial fistulas are not good candi-
Multiple perianal fistulas dates for the Surgisis AFP plug, said Dr. Armstrong. Those
and extensive perianal you can unzip with a simple fistulotomy. But the deeper the fis-
induration after multiple tulas are, the longer they are, the better candidates they are for
(failed) procedures (see
radial incision in the right
the plug. This is a safe modality with no septic complications,
gluteal region). Setons are and obviously no incontinence. I think the reason the plug
inserted to decrease the seems to be a little better than glue is because you can actual-
induration, and to ly suture it to the primary opening.
mature the fistula tracts.
3
Table. Dos and Donts of the Surgisis AFP Plug Technique
of-eight suture is inserted through the primary opening, deep
DOs to the internal sphincter, getting another 1 or 2 bites of the
Rehydrate the plug for 5 minutes in saline.
plugs head. Resistance is felt when the suture passes
through the plug. Finally, the primary opening is closed over
Use a 2-0 Vicryl suture. the plugs head by tying the suture to the 6-inch tail. This
Insert a figure-of-eight suture through the primary opening, deep to buries the head of the plug, closes the primary opening and
the internal sphincter and try to get another 1 or 2 bites of the secures the head of the plug deep to the primary opening to
plugs head. prevent extrusion.
Advise patients to avoid strenuous activity for at least 2 weeks after Dr. Armstrong emphasized the need for a deep suture to
the procedure. secure the head of the plug because of the high pressures that
are generated in the pelvic floor during straining and exercise.
DONTs This has to be a real stitch, he said. Youve got to get a
Dont mechanically debride the fistula tract in such a way that would good, solid, deep bite through the internal sphincter, and also
likely make the tract wider and harder to close. through the head of the plug and out through the other side of
the internal sphincter. You want to try and stitch this plug so its
Dont use the entire plug. Pull the plug into the fistula tract until
deep to the internal opening. You need to bury it. At the end of
resistance is first met, and trim the excess plug at the level of the
the procedure, you dont want to see any plug.
primary opening. If the primary opening is too large, insert a seton
The tip of the plug is sutured to the edge of the secondary
for 6 to 8 weeks to narrow the tract and mature the fistula.
opening and the excess is trimmed at skin level. The sec-
Dont leave any of the plugs head exposed. Pull the plug into the ondary opening should not be completely closed, as this will
tract just deep to the primary opening. prevent drainage from the fistula tract, and possibly result in an
Dont close the secondary opening. Suture the end of the plug to abscess. Some drainage from the tract generally persists for 2
the edge of the secondary opening to secure tip. This will help to 4 weeks after the proceduresometimes longeras the plug
prevent a closed space infection. undergoes reabsorption and remodeling into native tissue. As
the fistula closes, the drainage decreases and eventually dries
up. This is more a biological closure of the fistula than a
Suture a 6-inch tail to the tip of the plug and cut the excess. mechanical closure, Dr. Armstrong explained. After the proce-
This helps prevent the tie from slipping off as the plug is pulled dure, patients should be told to avoid any strenuous activity for
into the tract. Pull the plug into the primary opening until resis- at least 2 weeks, bathe standing up (they should not sit in the
tance is met. This can be done by a variety of means, such as bathtub) 2 or 3 times a day, and apply topical 10% metronida-
tying the tail of the suture to the fistula probe. If there is already zole externally to help prevent any septic complications. They
an indwelling seton in the tract, the tail of the suture can be tied should also be instructed to avoid straining during bowel move-
to the seton, which is then cut and used to pull the plug into the mentstaking a stool softener will helpand be instructed to
primary opening of the tract. The cut seton method is very eat a high fiber diet. Patients are reviewed in the office 2 to 4
simple and straightforward, and avoids having to find the pri- weeks after the procedure.
mary opening again.
The surgeon notes where the plug enters the primary open-
ing. The plug is withdrawn several millimeters and the excess is Conclusion
trimmed. It is not unusual to trim as much as half the length of
the plug, as the plugs are oversized. Colorectal surgeons have several options for treating simple
A 2-0 Vicryl suture is inserted into the head of the plug. The and complex fistulas. The most common procedure remains fis-
suture is then tied, leaving a 6-inch tail that will later be used tulotomy, although fibrin glue has a role in long, complex tracts
to close the primary opening. This is best done under direct and Crohns disease. The Surgisis AFP plug is gaining notable
visualization to ensure the surgeon gets a good bite of the favor for complex fistulas and repeat surgery. By following the
plug. The plug is pulled back into the tract, just deep to the procedure for insertion of the plugs advised by field leaders,
primary opening. No part of the plug is left exposed. A figure- surgeons can have considerable success in difficult patients.
References
1. Gonzalez-Ruiz C, Kaiser AM, Vukasin P, et al. Intra- 2005;7:513-518. intra-adhesive antibiotics and/or surgical closure of
operative physical diagnosis in the management of 7. Dixon M, Root J, Grant S, et al. Endorectal flap the internal fistula opening. Dis Colon Rectum.
anal fistula. Am Surg. 2006;72:11-15. advancement repair is an effective treatment for 2005;48:799-808.
2. Perez F, Arroyo A, Serrano P, et al. Fistulotomy with selected patients with anorectal fistulas. Am Surg. 14. Loungnarath R, Dietz DW, Mutch MG, et al. Fibrin
primary sphincter reconstruction in the manage- 2004;70:925-927. glue treatment of complex anal fistulas has low suc-
ment of complex fistula-in-ano: prospective study of 8. Hjortrup A, Moesgaard F, Kjaergard J. Fibrin adhe- cess rate. Dis Colon Rectum. 2004;47:432-436.
clinical and manometric results. J Am Coll Surg. sive in the treatment of perianal fistulas. Dis Colon 15. Robb BW, Vogler SA, Nussbaum MN, et al. Early
2005;200:897-903. Rectum. 1991;34:752-754. experience using porcine small intestinal submu-
3. Theerapol A, So BY, Ngoi SS. Routine use of setons cosa to repair fistulas-in-ano. Paper presented at:
9. Cintron JR, Park JJ, Orsay CP, et al. Repair of fistu-
for the treatment of anal fistulae. Singapore Med J. American Society of Colon and Rectal Surgery
las-in-ano using fibrin adhesive: Long-term follow-
2002;43:305-307. 2004 annual meeting; May 8-13, 2004;
up. Dis Colon Rectum. 2000;43:944-949.
4. Hasegawa H, Radley S, Keighley MR. Long-term Dallas,Texas. Abstract P9.
10. Lindsey I, Smilgin-Humphreys MM, Cunningham C,
results of cutting seton fistulotomy. Acta Chir Iugosl. 16. Johnson EK, Gaw JU, Armstrong D. Efficacy of
et al. A randomized, controlled trial of fibrin glue vs.
2000;47(suppl 1):19-21. biodegradable collagen plug versus fibrin glue in
conventional treatment for anal fistula. Dis Colon
5. Joy HA, Williams JG. The outcome of surgery for closure of anorectal fistulas. Paper presented at:
Rectum. 2002;45:1608-1615.
complex anal fistula. Colorectal Dis. 2002;4: American Society of Colon and Rectal Surgery
254-261. 11. Sentovich SM. Fibrin glue for all anal fistulas. J Gas- 2005 annual meeting; April 30-May 5, 2005;
6. van der Hagen SJ, Baeten CG, Soeters PB, et al. trointest Surg. 2001;5:158-161. Philadelphia, Pa. Abstract S51.
Staged mucosal advancement flap for the treat- 12. Sentovich SM. Fibrin glue for anal fistulas: long-term 17. Johnson EK, Gaw JU, Armstrong DN. Efficacy of
SR604
ment of complex anal fistulas: pretreatment with results. Dis Colon Rectum. 2003;46:498-502. anal fistula plug vs. fibrin glue in closure of anorec-
noncutting setons and in case of recurrent multiple 13. Singer M, Cintron J, Nelson R, et al. Treatment of fis- tal fistulas. Dis Colon Rectum. 2006 Jan. 29 [Epub
4 abscesses a diverting stoma. Colorectal Dis. tulas-in-ano with fibrin sealant in combination with ahead of print].