34 l JANUARY JOGC JANVIER 2014

OBSTETRICS
Key Words: Gastric carcinoma, gastrointestinal stromal tumour,
GIST, hepatocellular carcinoma, anal melanoma, colorectal
carcinoma, rectal carcinoma, pregnancy
Competing Interests: None declared.
Received on June 17, 2013
Accepted on September 9, 2013
Pregnancy and Maternal Outcomes
in Women With Prior or Current
Gastrointestinal Malignancies
Ali Al-Ibrahim, MBBS, SSCOB, ABOG,
1
Jacqueline Parrish,
2
Evelyn Dunn, BScH, MD,
3

Carol Swallow, MD, PhD, FRCSC, FACS,
4
Cynthia Maxwell, MD, FRCSC, FACOG, RDMS
1
1
Maternal Disease in Pregnancy Program, Mount Sinai Hospital, University of Toronto, Toronto ON
2
Department of Biology, University of Toronto, Toronto ON
3
Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver BC
4
Division of General Surgery, Mount Sinai Hospital, University of Toronto, Toronto ON
J Obstet Gynaecol Can 2014;36(1):3441
Abstract
Objectives: To review the fetal and maternal outcomes of women
with a diagnosis of gastrointestinal (GI) cancer before or during
pregnancy.
Methods: We conducted a retrospective cohort study of pregnant
women referred to a single tertiary care centre with a current or
previous diagnosis of GI malignancy. Maternal, obstetric, and
infant data were recorded.
Results: We identifed 18 pregnancies in 13 women. Nine women
were found to have a GI malignancy during pregnancy (group 1).
There was an indirect maternal death in this group in a woman
with advanced gastric adenocarcinoma. Nine unique pregnancies
occurred in eight women with diagnosis and management of GI
malignancies before their pregnancies (group 2).
Conclusion: GI malignancies are diffcult to diagnose and manage
during pregnancy and are usually advanced at the time of
diagnosis. Surgery can be performed during pregnancy if
necessary, with chemotherapy and radiotherapy usually deferred
to the postpartum period. Women who have had a prior GI
malignancy have special circumstances related to the type of
surgery performed and previous exposure to chemotherapy.
These patients may beneft from a multidisciplinary team effort to
optimize their care.
Rsum
Objectifs : Analyser les issues ftales et maternelles des femmes
ayant reu un diagnostic de cancer gastro-intestinal (GI) avant ou
pendant la grossesse.
Mthodes : Nous avons men une tude de cohorte rtrospective
portant sur des femmes enceintes orientes vers un seul centre
de soins tertiaire en raison dun diagnostic actuel ou prcdent
de tumeur maligne GI. Les donnes maternelles, obsttricales et
infantiles ont t consignes.
Rsultats : Nous avons identif 18 grossesses chez 13 femmes.
Une tumeur maligne GI a t constate chez neuf de ces femmes
pendant la grossesse (groupe 1). Un dcs maternel indirect
a t signal dans ce groupe chez une femme prsentant un
adnocarcinome gastrique avanc. Neuf grossesses uniques ont
t constates chez huit femmes ayant obtenu un diagnostic de
tumeur maligne GI et ayant fait lobjet dune prise en charge avant
la grossesse (groupe 2).
Conclusion : Les tumeurs malignes GI sont diffciles
diagnostiquer et prendre en charge pendant la grossesse, et
se trouvent habituellement un stade avanc au moment du
diagnostic. Une chirurgie peut tre mene pendant la grossesse,
au besoin, les traitements de chimiothrapie et de radiothrapie
tant habituellement reports la priode postpartum. Les
femmes ayant dj prsent une tumeur maligne GI comptent
des circonstances particulires lies au type de la chirurgie
dont elles ont fait lobjet et leur exposition prcdente la
chimiothrapie. Ces patientes pourraient tirer avantage dune
approche dquipe multidisciplinaire pour optimiser les soins
quelles reoivent.
JANUARY JOGC JANVIER 2014 l 35
Pregnancy and Maternal Outcomes in Women With Prior or Current Gastrointestinal Malignancies
INTRODUCTION
C
ancer complicates approximately one in 1000
pregnancies, with the most common types being
cervical cancer, breast cancer, melanoma, lymphoma, and
leukemia.
1
Gastrointestinal (GI) malignancies are rare in
women of reproductive age and exceedingly rare during
pregnancy. For example, the incidence of colorectal cancer
is reported to be 2 per 100 000 pregnancies,
2
and only
10 cases of pancreatic cancer have been reported in the
literature.
3
Gastric cancer is slightly more common, with an
incidence of 0.1% in the Japanese population and probably
lower in other populations.
46
When malignancy is diagnosed during pregnancy, it has
major implications for the pregnant woman, her offspring,
her family, and her caregivers. The use of therapeutic
modalities such as surgery, chemotherapy, and radiation
therapy for maternal health and well-being has to be
weighed against the potential risk to the fetus.
7
The treatment of GI malignancies frequently involves a
combination of surgery, chemotherapy, and radiotherapy,
and therefore has a potential major impact on a womans
life, fertility, and pregnancy. Inevitably, given the rarity of
GI cancers, studies quantifying these potential adverse
outcomes are lacking. Our aim was therefore to review our
centres experience with pregnant patients with a prior or
current diagnosis of a GI cancer.
METHODS
We searched the Mount Sinai Hospital Maternal-Fetal
Medicine units database for women who had a diagnosis
before or during pregnancy of one of the following
conditions: colon cancer, rectal cancer, anal cancer,
small intestinal cancer, gastric cancer, duodenal cancer,
esophageal cancer, or oral cancer, and who were pregnant
between January 1998 and March 2013. In this unit,
pregnant women with cancer are typically managed by a
multidisciplinary team composed of representatives of
maternalfetal medicine, surgical and medical oncology,
gastroenterology, obstetric medicine, anaesthesiology,
psychiatry, nursing, and social work.
Patients who have previously received chemotherapy
undergo echocardiography, electrocardiography, and lung,
liver, and renal function tests in early pregnancy, but if
these are normal the patients typically receive the usual
pregnancy care.
We retrospectively reviewed all charts for information on
the diagnosis and management of the malignancies as
well as for maternal and infant outcomes. Tumour-related
characteristics included location, type, grade, stage, and
treatment. Maternal and infant characteristics included
gestational age at delivery, route of delivery, and eventual
obstetric or perinatal complications. Neonatal data
included birth weight, Apgar scores, need for admission
to the NICU and eventual neonatal complications before
discharge from hospital. Patients for whom data were
incomplete on chart review were contacted by telephone
for data completion.
Ethics approval for the study was provided by the Research
Ethics Board of Mount Sinai Hospital.
RESULTS
We identifed 18 pregnancies among 13 women with a
current or prior history of GI cancer. Details of the nine
patients with a diagnosis of GI malignancy during pregnancy
(group 1) are shown in Table 1. One of the patients had
a GI tumour diagnosed before pregnancy and managed
conservatively. The mean maternal age at diagnosis was
31 years (range 18 to 38). The gestational age at diagnosis
ranged from pre-gestational to 36 weeks of gestation.
The wide range of tumour types identifed is detailed in
Table 1. The commonest presenting tumour symptoms
were abdominal pain (44%), nausea (55%), vomiting (44%),
rectal bleeding (55%), and abdominal swelling (44%).
The time from presentation with symptoms to diagnosis
of malignancy was variable, and was diffcult to quantify
because many of the symptoms of GI malignancy were
also typically encountered during pregnancy. It was diffcult
to ascertain if there was signifcant delay in the diagnosis
of malignancy due to pregnancy. Five women underwent
diagnostic GI endoscopy and biopsy (4 colonoscopies and
1 upper GI endoscopy). Two women (22%) underwent
surgical resection of the tumour during pregnancy, and
one (11%) received capecitabine chemotherapy during
pregnancy. Cancer management was altered because of
pregnancy in all patients. The alteration ranged from delay
of surgery until the postpartum period to delay in initiation
of chemotherapy or radiotherapy. Pregnancy outcome was
directly affected by the malignancy in one patient who
presented with advanced metastatic gastric carcinoma.
The mean gestational age at delivery was 37 weeks
(range 30 to 41 weeks). Three women (33%) delivered
preterm; one of these preterm deliveries was of a twin
gestation with spontaneous preterm labour. The second
preterm delivery (at 32 weeks gestation) followed preterm
prelabour rupture of membranes at the time of upper
GI endoscopy. The third preterm delivery (at 35 weeks
36 l JANUARY JOGC JANVIER 2014
OBSTETRICS
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JANUARY JOGC JANVIER 2014 l 37
Pregnancy and Maternal Outcomes in Women With Prior or Current Gastrointestinal Malignancies
gestation) followed induction of labour because of poor
maternal general condition.
Three women (33%) delivered by Caesarean section:
the indication for the frst was non-vertex twins in
preterm labour, for the second it was poor maternal
general condition, and for the third it was cephalopelvic
disproportion diagnosed during labour.
One indirect maternal death occurred at 15 days
postpartum and was due to advanced metastatic gastric
carcinoma. The birth weight of the infants ranged from
1270 g to 3400 g with a mean of 2520 g. Three infants
were admitted to the NICU because of prematurity. These
infants were discharged from the NICU in good condition
with no long-term complications.
Patients whose GI malignancies were diagnosed and
managed before pregnancy (group 2) and their pregnancy
outcomes are shown in Table 2. Three of these are also
listed in group 1 and are indicated by the same letter with
the pregnancy number. As in group 1, patients in this
heterogeneous cohort underwent a wide range of surgical
procedures and received several forms of chemotherapy.
None had radiotherapy before pregnancy. There were no
tumour recurrences during these pregnancies, and only
one patient had a tumour-related complication (bowel
obstruction after previous extensive intestinal surgery for
colorectal cancer). Two patients are currently pregnant and
healthy. Seven women had no obstetric complications and
delivered at term (mean gestational age 38 weeks, range
38 to 41 weeks). Mean birth weight was 3060 g (range
2380 to 3260 g). There were no neonatal complications.
Six Caesarean sections were performed, four of which
were for obstetric indications, and two of which were the
consequence of the previous cancer surgery (ileo-anal
pouch).
DISCUSSION
In this series we have shown the heterogeneity of GI
malignancies presenting during pregnancy and the range
of possible consequences of surgery and chemotherapy
for GI malignancy before pregnancy. Most patients had
uncomplicated pregnancies and deliveries, although
preterm delivery was planned for one woman to optimize
maternal therapy and was probably precipitated in another
woman by endoscopy. However, all neonates recovered
well after short stays in the NICU. The only maternal death
was related to metastatic disease.
GI malignancies are very rare, and the types of tumours
encountered are heterogeneous.
The incidence of colorectal cancer during pregnancy is
reported to be 0.002%.
2
Gastric cancer in pregnancy is very
rare
8
and often not diagnosed until a very late stage.
9
Gastric
carcinoma coincident with pregnancy and lactation is very
rare except in the Japanese population, in which the incidence
is estimated at 0.1%.
46
Pancreatic cancer is also extremely
unusual in women of childbearing age.
3
The patient in our
cohort with pseudopapillary tumour of the pancreas during
pregnancy is the seventh to be reported,
1012
and the patient
in our cohort with gastrointestinal stromal tumour is the
ffth such patient to be reported.
13
There have been fewer
than 40 reported cases of hepatocellular carcinoma during
pregnancy,
14
and our patient B1 is the frst patient presenting
with anal melanoma during pregnancy to be reported.
The diagnosis and management of GI malignancies during
pregnancy is very challenging. Many of the symptoms
and signs of GI malignancies can be masked by the
symptoms of pregnancy.
1517
Symptoms of pregnancy and
GI malignancies encountered in this cohort are listed and
compared in Table 3.
18
When symptoms persist suffciently during pregnancy to cause
a high level of suspicion, the investigation of the pregnant
patient with a GI malignancy poses a signifcant challenge.
16
In the non-pregnant population, a CT scan is commonly
performed for the investigation of GI malignancy. The
radiation exposure to the fetus from an abdominopelvic CT
scan is estimated to be 8 mGy, which is below the 50 mGy
considered to be the threshold for safety during pregnancy.
1921

MRI avoids exposure of the mother and fetus to ionizing
radiation and often does not require intravenous contrast
material during pregnancy.
16
It is important to use the most
effcient diagnostic modality for the disease suspected, be it
CT scan or MRI, and pregnancy should not mandate the use
of an inferior modality for fear of radiation exposure.
Serum carcinoembryonic antigen measurement can be
helpful for prognostication and for detecting recurrences,
and its level is not affected by pregnancy.
16
Serum alpha-
fetoprotein is normally elevated in pregnancy and is not
useful for detecting and monitoring GI malignancies during
pregnancy unless it suddenly increases in the second and
third trimester.
16
Upper and lower GI endoscopy is not contraindicated in
pregnancy and should be performed whenever there is a
clear clinical indication.
16,2225
Delay in the diagnosis of GI malignancies in pregnant
women due to the masking symptoms of pregnancy and
underutilization of MRI and endoscopy signifcantly
affects the survival of these patients. Most patients in our
38 l JANUARY JOGC JANVIER 2014
OBSTETRICS
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JANUARY JOGC JANVIER 2014 l 39
Pregnancy and Maternal Outcomes in Women With Prior or Current Gastrointestinal Malignancies
cohort were thoroughly investigated during pregnancy, but
the stages of their malignancies at the time of diagnosis
indicate a possible delay. This delay is very diffcult to
quantify because of the masking effect of pregnancy
symptoms and the occult nature of GI malignancies.
Judging from the stages of each malignancy encountered,
it is also likely that most of these malignancies existed
before conception.
The management of GI malignancies in pregnant women
should be tailored to each individual patient. Pregnancy can
lead to delays in cancer management because of concerns
about surgery, chemotherapy, or radiotherapy during
pregnancy. On the other hand, cancer can affect pregnancy
outcome because of its debilitating effect on the mother or
because of ongoing investigations or interventions during
pregnancy. A multidisciplinary team with representatives
from maternalfetal medicine, obstetric medicine, medical
and surgical oncology, gastroenterology, anaesthesiology,
mental health, nursing, and social work is paramount in
the management of these complex patients.
Non-obstetric surgical procedures during pregnancy
should not be delayed if this will affect maternal health
and outcome. The American College of Obstetrics and
Gynecology recommends that a pregnant woman should
never be denied indicated surgery, regardless of trimester.
26
If delay is possible, surgery during the second trimester
carries the least risk of pregnancy loss. The need for general
or regional anaesthesia for non-obstetric surgery occurs
in up to 2% of all pregnancies. Safe perioperative care is
a challenge to anaesthetists because of physiologic changes
during pregnancy. Profound knowledge of physiological
and pathophysiological changes during pregnancy and the
possible effects of different drugs and anaesthesia techniques
on mother and fetus is necessary. Although evidence from
randomized controlled trials is missing, anaesthesia during
pregnancy has been well-documented as safe for most open
or minimally invasive operative procedures.
27,28
Chemotherapy can be given during pregnancy in
selected cases after careful counselling, as increasing
evidence is being published about the safety of
several chemotherapeutic agents during gestation.
29,30

Chemotherapeutic agents used in cancer treatment may
cross the placenta and may adversely affect embryogenesis
by affecting cell division. Exposure to such agents after
the frst trimester of pregnancy has not been associated
with increased risk of malformations but is associated with
increased risk of stillbirth, intrauterine growth restriction,
and fetal toxicities.
29,30
Published series of GI cancers have been mostly divided
into specifc malignancy types. Approximately 275 cases
of colon cancer associated with pregnancy have been
reported,
18
in addition to a population-based survey from
California.
31
In this population survey, the survival of
women who were found to have colorectal cancer during
pregnancy was not different from the control group. On
the other hand, Chan et al. reported these women having
a poor prognosis; the median survival in a review of 42
pregnant patients with colorectal carcinoma was less than
fve months and more than one half of them (56%) had
died by the time of the report.
32
Our knowledge about gastric cancer in pregnancy is limited
to less than 200 reported patients, of whom 136 are from
Japan.
33
Gastric cancer is often not diagnosed in pregnancy
until the very late stages, which explains the poor reported
rates of survival.
9
Table 3. Symptoms and signs of pregnancy and GI malignancies in this cohort
Signs and symptoms Normal pregnancy Pregnancy with GI malignancy
Nausea and vomiting Most common symptoms of pregnancy, usually frst
trimester but can persist. Hyperemesis gravidarum not
uncommon.
Delay in the diagnosis of gastric or advanced colorectal
malignancy.
Rectal bleeding Common in pregnancy due to the high incidence of
hemorrhoids during pregnancy
Delay in the diagnosis of colorectal and anal
malignancies.
Constipation Very common in pregnancy Delay in the diagnosis of colorectal and anal
malignancies
Abdominal mass Uterus increasing in size throughout gestation Palpable masses obscured by the gravid uterus
Anemia Physiologic anemia due to hemodilution in pregnancy Delay in the diagnosis of all malignancies
Weight loss Not uncommon in early pregnancy with hyperemesis
gravidarum but normally signifcant gains
Weight gain can mask the usual weight loss seen with
malignancies
Abdominal pain Non-specifc abdominal pain and discomfort not
uncommon during pregnancy
Delay in the diagnosis of stomach and colorectal
malignancies
Adapted from Cappell MS.
18

40 l JANUARY JOGC JANVIER 2014
OBSTETRICS
The very small number of cases of pseudopapillary
tumour of the pancreas and gastrointestinal stromal
tumour reported and the limited experience with these
tumours hinders the analysis of outcomes and our ability
to draw any conclusions.
1013
The same can be said for
hepatocellular carcinoma, considering that it is usually seen
in conjunction with liver cirrhosis, which complicates and
worsens pregnancy outcomes.
14,34
Pregnancy in women with a previous GI malignancy can be
complicated by the long-term consequences of previous
surgical procedures, radiotherapy, and chemotherapy.
These women should optimally be seen before pregnancy
for counselling. We generally tailor our investigations
for these patients according to the primary disease, the
presence of a stoma or ileal pouch, and end-organ damage.
Different chemotherapeutic agents used in the management
of GI malignancies can lead to cardiomyopathy, pulmonary
fbrosis, and renal and liver impairment. A multidisciplinary
approach should be taken when end-organ damage is
detected.
Monitoring for disease recurrence during pregnancy can
be diffcult, as not all tumour markers have been validated
during pregnancy and many normally have elevated levels
during pregnancy.
Most patients with GI malignancies will have some form
of bowel resection and anastomosis, as seen in our group
2 patients. There is no indication for mandatory Caesarean
section in a woman who has had resection and primary
small bowel or large bowel anastomosis.
Remzi et al. surveyed 110 women who had at least one
delivery following an ileal pouch-anal anastomosis.
35

Eighty-two women responded to the questionnaire: 62
had had a Caesarean section, and 20 had had a vaginal
delivery. The risk of sphincter injury and quality of life
measured by time trade-off method were signifcantly
worse after vaginal delivery than after Caesarean section
in these women. In the short term, this does not seem to
substantially infuence pouch function or quality of life;
however, the long-term effects remain unknown, and thus
obstetric concern may not be the only factor dictating the
type of delivery in this group. Remzi et al. concluded that
planned Caesarean section may eliminate these potential
and factual concerns in patients who have had an ileal
pouch-anal anastomosis.
35
Because of these fndings,
we generally recommend elective Caesarean section if a
woman has an ileal pouch-anal anastomosis. In general, the
majority of patients conceiving after GI cancer treatment
are expected to do well.
CONCLUSION
This study shows the heterogeneity of GI malignancies
that can precede or complicate ongoing pregnancies, as
well as the complexity of management of each individual
patient and the value of a multidisciplinary approach to
management. One of the most important limitations of
analysis is the diffculty in distinguishing between pregnancy
symptoms and tumour symptoms, so the time when
symptoms due to disease begin is diffcult or impossible to
determine in many cases. With the increasing number of
cancer registries around the world and improved reporting
we should soon have a better understanding of and
clearer guidelines for the management of these complex
conditions during pregnancy.
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