# Small Bowel Tumors: Clinical Presentation, Prognosis, and Outcome in 33 Patients in a Tertiary Care Center

Authors: Mirna H. Farhat; Ali I. Shamseddine; Kassem A. Barada
Journal: Journal of Oncology
 (2008)

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## Abstract

Introduction. Small bowel cancers are rare. Accumulation of data regarding their clinical presentation, pathologic features, prognostic factors, treatment modalities, and outcome is difficult. Methods. This is a retrospective study of the medical records of 33 patients with small bowel cancers treated at the American University of Beirut-Medical Center over a 20-year period. Results. The study included 25 males (76%) and 8 females (24%). Median age at presentation was 56 years. Most common symptoms were abdominal pain (66.7%) and weight loss (57.6%). Thirteen patients presented with abdominal emergencies (39.3%). Lymphoma was the most common malignant tumor (36.4%), followed by adenocarcinoma (33.3%), leiomyosarcoma (15.2%), gastrointestinal stromal tumors (12.1%), and neuroendocrine tumors (3.0%). Tumors were located in the duodenum in 30% of patients, jejunum in 33%, and ileum in 36%. Resectability rate was 72.7% and curative R0 resection was achieved in 54.1% (13/24) of patients. 5-year survival of the 33 patients was 24.2%. Conclusion. Small bowel cancers are difficult to diagnose because of the nonspecific symptoms. Most patients present with advanced disease and have poor prognosis. Adenocarcinoma and duodenal location have the worst 5-year survival in contrast to stromal tumors and those with ileal location which have the best survival.


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## Body

## 1. Introduction

Small bowel cancers are uncommon tumors of the
gastrointestinal tract. As a result of their infrequency and variety, the
accumulation of data regarding their clinical presentation, pathologic
features, prognostic factors, treatment modalities, and outcome has been
difficult.This study was conducted to review the experience with small bowel tumors of 33 patients seen
at the American University of Beirut Medical Center.


## 2. Patients and Methods

During a 20-year period (1986–2006), 33
patients were treated for small bowel tumors at the American University of
Beirut Medical Center. Approval was obtained from the Institutional Research
Board. Data obtained from the medical
records were gathered regarding standard demographic data, presenting signs and
symptoms, comorbid medical illnesses, diagnostic workup, operative procedures,
pathologic diagnosis, and subsequent follow-up visits to document the
recurrence of previous or subsequent associated primary cancers. Recurrence was
defined as biopsy-proven tumor or radiologic evidence of obvious local or
distant recurrence.Periampullary tumors, secondary, and benign tumors of the
small bowel were excluded. Staging of patients was done according to the TNM
classification system and AJCC for small bowel tumors [1], except for lymphomas.Survival duration
was measured from the time of diagnosis to the last follow-up evaluation or
death. Follow-up data was obtained from patient medical records or from
telephone interviews with the patient or family members. Follow-up data was
available on 30 out of 33 patients.All data was coded and entered
using “SPSS 15.0” computer program.


## 3. Results

### 3.1. Demographic Data

This
study included 33 patients with histologically confirmed small bowel
malignancies. They were 25 males (76%) and 8 females (24%) patients. The male
to female ratio was 3.1:1 with a median age at presentation of 56 years (range:
23–77). Two-thirds of the patients were older than 50
years (Table1).Table 1
Patient characteristics and clinical presentation.
No. of patients
(%)
Age
<50
≥50
Gender
Male
Female
Symptom
Abdominal pain
Weight loss
Nausea/vomiting
Bowel obstruction
GI bleeding
Anemia
Bowel perforation
Acute abdomen
Jaundice
ConstipationThere was a
history of Crohn’s disease in one patient, ulcerative colitis in another one,
and celiac disease in a third one. One-third of the patients were smokers
(11/33). Three patients (9.1%) had a history of another primary malignancy
(mucinous cystadenocarcinoma of ovary, biopsy-proven cholangiocarcinoma, and
leiomyosarcoma of the thigh).Most complaints
were nonspecific and these included in decreasing order abdominal pain (66.7%),
weight loss (57.6%), followed by nausea and vomiting (27%) (see Table1). Thirteen patients presented with emergencies
such as bowel obstruction (n
=
8, 24%) and bowel perforation (n
=
4, 12%). Of the
four patients that had perforation, three had lymphomas and one had
leiomyosarcoma. Acute abdomen was the initial presentation in four patients
(12%).Endoscopy was
performed on 10 out of 33 patients. It detected the tumor in 7 only (6
duodenum, 1 ileum) and it failed to detect the disease in 3 patients, all of
which had ileal disease. Upper GI series was performed on 12 out of 33
patients. The disease was detected in 11 patients (4 jejunum, 6 duodenum, 1
ileum) and missed in one patient having a tumor in the ileum.Computed
tomography was used in 13/33 patients and emergent laparatomy in 4/33.


### 3.2. Characteristics of the Tumors

Four
different histologic types of tumors were identified. Lymphoma was the most common tumor (36.4%),
followed by adenocarcinoma (33.3%), leiomyosarcoma (15.2%), gastrointestinal
stromal tumors (GISTs) (12.1%), or neuroendocrine tumors (3.0%)
(see Table2).Table 2
Distribution of small bowel tumors by pathology and anatomical distribution.
Duodenum
Jejunum
Ileum
No. (%)
Lymphoma
2
4
6
12 (36.4)
Adenocarcinoma
7
1
3
11 (33)
Leiomyosarcoma
0
3
2
5 (15.2)
GIST
*
1
3
0
4 (12.1)
Neuroendocrine
0
0
1
1 (3.0)
Total(%)
10
11
12
33Table2 shows
the anatomical distribution of the tumors with respect to histology. The tumor
was located in the duodenum in 30% of patients, jejunum in 33%, and ileum in
36%. Most adenocarcinomas were located
in the duodenum (7/10), in contrast to most lymphomas (10/12) and all
leiomyosarcomas (5/5) that were located in the jejunum and ileum.


### 3.3. Treatment

Surgical
resection was carried out in 24 out of 33 patients. Resectability rate was 72.7%
and R0 resection was achieved in 54.1% (13/24) of patients (see Table3). Two
patients underwent palliative double bypass surgery. Four patients were deemed
unresectable because of peritoneal metastasis, locally advanced disease, and
vascular invasion. The surgical procedures performed are listed in Table 4.
There were four cases of tumor recurrence.Table 3
Treatment modalities offered to 33 patients with small bowel tumors.
Modality
No.
(%)
No treatment
4
12.1
Complete resection
12
36.3
Complete resection + chemotherapy
6
18.1
Incomplete resection
4
12.1
Incomplete resection + chemotherapy
2
6.0
Chemotherapy (palliative)
5
15.1Table 4
Types of surgeries performed for small intestine tumors.
Surgery
No. of patients (26)
(%)
Whipple
5
(16.6)
Duodenal resection
2
(6.6)
Jejunal resection
9
(30)
Ileal resection
5
(16.6)
Right hemicolectomy
3
(10)
Bypass
2
(6.6)Reoperation was
performed in 5 patients for the following reasons: tumor recurrence,
metastasis, and postoperative complications. Emergent laparatomy was performed
in 4 patients (3 lymphoma and 1 leiomyosarcoma). Chemotherapy was administered
to 13 patients (39.3%).


### 3.4. Tumor Characteristics

Tumor size was
available on 27 patients. Sixteen patients (59%) had tumors greater than 5 cm,
8 patients (30%) had tumors less than 3 cm, and 3 patients (11%) had tumor
sizes between 3 and 5 cm.Tumor grade was available for 12 patients (36.4%). Among the 12 patients, 8 patients (66.7%) had well
or moderately differentiated tumors and 4 had poorly differentiated tumors (33.3%) (see Table5).Table 5
TNM staging of small bowel malignancies, excluding lymphoma. (Adapted from the AJCC Cancer Staging Manual, 6th Edition (2002), Springer New York).
Stage
Primarytumor
1
Regional lymphnodes
2
Distantmetastasis
3
I
T1/T2
N0
M0
II
T3/T4
N0
M0
III
Any T
N1
M0
IV
Any T
Any N
M1
Primary
1 tumor
T1: tumor invades lamina propria or submucosa;
T2: tumor invades muscularis propria;
T3: tumor invades through muscularis propria into the subserosa;
T4: tumor perforates the vascular peritoneum or directly invades other organs, including mesentery, abdominal wall, and pancreas.
Regional
2 lymph nodes
N0: no regional lymph nodes metastasis;
N1: regional lymph nodes metastasis.
Distant
3 metastasis
M0: no distant metastasis;
M1: distant metastasis.TNM staging was available on 26
patients (78.7%). According to AJCC staging of small bowel malignancies (Table5), tumors in our study were classified as stage I (n
=
2), stage II (n
=
9), stage
III (n
=
8), stage IV (n
=
7) (see Table 6). Almost half of the patients presented
with metastatic disease (stage III/IV). Lymph nodes (10/33) were the most
common site involved by metastasis followed by the liver (5/33), lung (3/33),
brain (1/33), bone (1/33), and omentum (1/33).Table 6
Stage and grade of small bowel tumors.
Grade
N
(%)
Well
3
(9)
Moderate
5
(15)
Poor
4
(12)
N/A
21
(64)
Stage
I
2
(6)
II
9
(27)
III
8
(24)
IV
7
(21)
N/A
7
(21)


### 3.5. Survival

Survival
analysis of the 33 patients showed that 51.5%, 33.3%, and 24.2% were alive at 1,
3, and 5 years, respectively. Three patients were lost to follow-up. Mean
survival rates for the different malignancies were 22.03 months for
adenocarcinomas, 52.85 months for lymphomas, 47.6 months for leiomyosarcoma,
and 64.9 months for GIST.1-, 3-, and 5-year survivals for the different tumor locations and histologies are listed in
Tables7 and 8, respectively. However, the number of patients in some
categories was small which could have affected the significance of some of
these rates.Table 7
Survival of small intestine tumors at 1, 3, and 5 years by location.
1 year (%)
3 years (%)
5 years (%)
Duodenum
50%
40%
10%
Jejunum
50%
20%
20%
Ileum
62.5%
37.5%
37.5
%Table 8
Survival of small intestine tumors at 1, 3, and 5 years by histology.
1 year (%)
3 years (%)
5 years (%)
Adenocarcinoma
30%
20%
10%
Lymphoma
36.4%
27.3%
18.2%
Leiomyosarcoma
60%
20%
20%
GIST
100%
75%
50
%


## 3.1. Demographic Data

This
study included 33 patients with histologically confirmed small bowel
malignancies. They were 25 males (76%) and 8 females (24%) patients. The male
to female ratio was 3.1:1 with a median age at presentation of 56 years (range:
23–77). Two-thirds of the patients were older than 50
years (Table1).Table 1
Patient characteristics and clinical presentation.
No. of patients
(%)
Age
<50
≥50
Gender
Male
Female
Symptom
Abdominal pain
Weight loss
Nausea/vomiting
Bowel obstruction
GI bleeding
Anemia
Bowel perforation
Acute abdomen
Jaundice
ConstipationThere was a
history of Crohn’s disease in one patient, ulcerative colitis in another one,
and celiac disease in a third one. One-third of the patients were smokers
(11/33). Three patients (9.1%) had a history of another primary malignancy
(mucinous cystadenocarcinoma of ovary, biopsy-proven cholangiocarcinoma, and
leiomyosarcoma of the thigh).Most complaints
were nonspecific and these included in decreasing order abdominal pain (66.7%),
weight loss (57.6%), followed by nausea and vomiting (27%) (see Table1). Thirteen patients presented with emergencies
such as bowel obstruction (n
=
8, 24%) and bowel perforation (n
=
4, 12%). Of the
four patients that had perforation, three had lymphomas and one had
leiomyosarcoma. Acute abdomen was the initial presentation in four patients
(12%).Endoscopy was
performed on 10 out of 33 patients. It detected the tumor in 7 only (6
duodenum, 1 ileum) and it failed to detect the disease in 3 patients, all of
which had ileal disease. Upper GI series was performed on 12 out of 33
patients. The disease was detected in 11 patients (4 jejunum, 6 duodenum, 1
ileum) and missed in one patient having a tumor in the ileum.Computed
tomography was used in 13/33 patients and emergent laparatomy in 4/33.


## 3.2. Characteristics of the Tumors

Four
different histologic types of tumors were identified. Lymphoma was the most common tumor (36.4%),
followed by adenocarcinoma (33.3%), leiomyosarcoma (15.2%), gastrointestinal
stromal tumors (GISTs) (12.1%), or neuroendocrine tumors (3.0%)
(see Table2).Table 2
Distribution of small bowel tumors by pathology and anatomical distribution.
Duodenum
Jejunum
Ileum
No. (%)
Lymphoma
2
4
6
12 (36.4)
Adenocarcinoma
7
1
3
11 (33)
Leiomyosarcoma
0
3
2
5 (15.2)
GIST
*
1
3
0
4 (12.1)
Neuroendocrine
0
0
1
1 (3.0)
Total(%)
10
11
12
33Table2 shows
the anatomical distribution of the tumors with respect to histology. The tumor
was located in the duodenum in 30% of patients, jejunum in 33%, and ileum in
36%. Most adenocarcinomas were located
in the duodenum (7/10), in contrast to most lymphomas (10/12) and all
leiomyosarcomas (5/5) that were located in the jejunum and ileum.


## 3.3. Treatment

Surgical
resection was carried out in 24 out of 33 patients. Resectability rate was 72.7%
and R0 resection was achieved in 54.1% (13/24) of patients (see Table3). Two
patients underwent palliative double bypass surgery. Four patients were deemed
unresectable because of peritoneal metastasis, locally advanced disease, and
vascular invasion. The surgical procedures performed are listed in Table 4.
There were four cases of tumor recurrence.Table 3
Treatment modalities offered to 33 patients with small bowel tumors.
Modality
No.
(%)
No treatment
4
12.1
Complete resection
12
36.3
Complete resection + chemotherapy
6
18.1
Incomplete resection
4
12.1
Incomplete resection + chemotherapy
2
6.0
Chemotherapy (palliative)
5
15.1Table 4
Types of surgeries performed for small intestine tumors.
Surgery
No. of patients (26)
(%)
Whipple
5
(16.6)
Duodenal resection
2
(6.6)
Jejunal resection
9
(30)
Ileal resection
5
(16.6)
Right hemicolectomy
3
(10)
Bypass
2
(6.6)Reoperation was
performed in 5 patients for the following reasons: tumor recurrence,
metastasis, and postoperative complications. Emergent laparatomy was performed
in 4 patients (3 lymphoma and 1 leiomyosarcoma). Chemotherapy was administered
to 13 patients (39.3%).


## 3.4. Tumor Characteristics

Tumor size was
available on 27 patients. Sixteen patients (59%) had tumors greater than 5 cm,
8 patients (30%) had tumors less than 3 cm, and 3 patients (11%) had tumor
sizes between 3 and 5 cm.Tumor grade was available for 12 patients (36.4%). Among the 12 patients, 8 patients (66.7%) had well
or moderately differentiated tumors and 4 had poorly differentiated tumors (33.3%) (see Table5).Table 5
TNM staging of small bowel malignancies, excluding lymphoma. (Adapted from the AJCC Cancer Staging Manual, 6th Edition (2002), Springer New York).
Stage
Primarytumor
1
Regional lymphnodes
2
Distantmetastasis
3
I
T1/T2
N0
M0
II
T3/T4
N0
M0
III
Any T
N1
M0
IV
Any T
Any N
M1
Primary
1 tumor
T1: tumor invades lamina propria or submucosa;
T2: tumor invades muscularis propria;
T3: tumor invades through muscularis propria into the subserosa;
T4: tumor perforates the vascular peritoneum or directly invades other organs, including mesentery, abdominal wall, and pancreas.
Regional
2 lymph nodes
N0: no regional lymph nodes metastasis;
N1: regional lymph nodes metastasis.
Distant
3 metastasis
M0: no distant metastasis;
M1: distant metastasis.TNM staging was available on 26
patients (78.7%). According to AJCC staging of small bowel malignancies (Table5), tumors in our study were classified as stage I (n
=
2), stage II (n
=
9), stage
III (n
=
8), stage IV (n
=
7) (see Table 6). Almost half of the patients presented
with metastatic disease (stage III/IV). Lymph nodes (10/33) were the most
common site involved by metastasis followed by the liver (5/33), lung (3/33),
brain (1/33), bone (1/33), and omentum (1/33).Table 6
Stage and grade of small bowel tumors.
Grade
N
(%)
Well
3
(9)
Moderate
5
(15)
Poor
4
(12)
N/A
21
(64)
Stage
I
2
(6)
II
9
(27)
III
8
(24)
IV
7
(21)
N/A
7
(21)


## 3.5. Survival

Survival
analysis of the 33 patients showed that 51.5%, 33.3%, and 24.2% were alive at 1,
3, and 5 years, respectively. Three patients were lost to follow-up. Mean
survival rates for the different malignancies were 22.03 months for
adenocarcinomas, 52.85 months for lymphomas, 47.6 months for leiomyosarcoma,
and 64.9 months for GIST.1-, 3-, and 5-year survivals for the different tumor locations and histologies are listed in
Tables7 and 8, respectively. However, the number of patients in some
categories was small which could have affected the significance of some of
these rates.Table 7
Survival of small intestine tumors at 1, 3, and 5 years by location.
1 year (%)
3 years (%)
5 years (%)
Duodenum
50%
40%
10%
Jejunum
50%
20%
20%
Ileum
62.5%
37.5%
37.5
%Table 8
Survival of small intestine tumors at 1, 3, and 5 years by histology.
1 year (%)
3 years (%)
5 years (%)
Adenocarcinoma
30%
20%
10%
Lymphoma
36.4%
27.3%
18.2%
Leiomyosarcoma
60%
20%
20%
GIST
100%
75%
50
%


## 4. Discussion

Neoplasms of the small intestine are unusual and
constitute less than 3% of all gastrointestinal tract cancers [2–4]. These tumors
are known for their rarity, variability, nonspecific symptomatology, diagnostic
difficulties, delayed presentation, and overall poor prognosis [2].Over 90% of cases occur in people over the age of 40 [5]
with a median age at diagnosis of 55 years [6, 7] and men tend to be more
affected by the tumors than women [5, 8], which is in agreement with our
results.Abdominal pain, weight loss, nausea, and vomiting were the
most common presenting symptoms for small bowel tumors in this study, which is
similar to findings reported in previous studies [7, 9]. Bleeding is more
common with carcinomas; perforation is more common with lymphomas, while
obstruction is common to all enteric malignancies [10]. No distinct
presentation by pathology was evident in our study.The lack of symptom specificity in patients suffering from
small intestinal malignancies and failure to evaluate the small bowel, which is
a blind spot to routine endoscopic and radiological diagnostic tests, have been
considered as a contributing factor to the late presentations of the disease
and eventually the delay in diagnosis [11].Histologically, small bowel tumors are of different
subtypes, with adenocarcinoma being the most frequent (47%) followed by
carcinoid tumors (28%), GI lymphomas (12%), and GI sarcomas (12%) [2, 3, 7, 12].
In this study, lymphomas were the most common type, followed by
adenocarcinomas, sarcomas, and stromal tumors.On average, adenocarcinomas are distributed more
proximally in the small intestine, most frequently in the duodenum followed by
the jejunum and ileum, whereas lymphomas are more common distally, with nearly
equal distribution between the jejunum and the ileum [5, 7, 8, 13]. Carcinoid
tumors are distributed throughout the small intestines, but are located
preponderantly in the ileum. Sarcomas are found most often in the jejunum [7].
In our study, adenocarcinomas were mostly located in the duodenum, while
sarcomas and lymphomas were mostly located in the more distal parts of the
small bowel.Small bowel tumors were noticed to be associated with an
increased incidence of second malignancies [2, 4, 13]. Treadwell and White reported second tumor occurrence in 43% of patients with primary small bowel
tumors [4], whereas Ripley and Weinerman noted an 8-fold increase in second
malignancies with small bowel carcinoma with 73% of the tumors occurring before
the diagnosis of the small bowel malignancy [13]. The incidence of a second malignancy
approached 9% in our series.Surgical resection remains the cornerstone of therapy for
these malignancies [11]. Cunningham et al. showed a significantly longer median
survival for the resected group (26 months versus 11 months) [14]. Much of the information on the effectiveness
of surgery for early GI lymphoma is based on limited, retrospective reviews
that do not specifically compare primary surgical therapy with primary medical management are either chemotherapy, radiotherapy, or radiochemotherapy.Regardless of surgical resection, the overall 5-year survival rate for small
bowel cancers ranges between 20 and 50% [2, 6, 7, 14, 15]. Their disappointing
course seems to be related to the delay in diagnosis because of the nonspecific
symptoms [8]. In our study, the 5-year survival rates of GIST (50%) were higher
than those of adenocarcinomas and lymphomas and are close to the 67% 5-year
survival reported by Egberts et al. [16]. Therefore, early surgical
intervention with a high index of suspicion is required to improve survival
[17].Given the low prevalence of this disease, few clinical
trials of chemotherapy have been conducted and despite a variety of
chemotherapeutic agents used to treat adenocarcinoma of the small bowel, no
standard chemotherapy regimen exists for this disease. Many oncologists
extrapolate information from trials of large bowel carcinomas or upper
gastrointestinal tumors, and apply similar chemotherapy regimens in the
treatment of advanced small bowel adenocarcinoma. In one of the largest
retrospective reviews conducted, the M. D. Anderson Cancer Center (Tex, USA) reviewed
217 patients with small bowel adenocarcinoma and showed that the use of
adjuvant chemotherapy administered to 59 patients had no survival benefit [6].The most
important limitation in our study is the small number of patients. This has
limited our ability to determine the significance of the difference in survival
among the various groups.In
summary, small bowel tumors are uncommon. They are difficult to diagnose
because of the nonspecific symptoms. They also have a poor prognosis because
most patients present with advanced disease. In our report, adenocarcinoma and
duodenal location showed the worst 5-year survival, while stromal tumors and
ileal location had the best 5-year survival.



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