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Chapter 51

Small Bowel Tumors

Steven G. Leeds and James W. Fleshman

Key Points

1 The main types of primary small bowel tumors include adenoma, adenocarcinoma, neuroendocrine

(carcinoid), lymphoma, and sarcoma (GIST). Surgical resection remains the treatment of choice for

all except lymphoma (only needed for symptomatic lesions causing obstruction or bleeding).

2 There is a rising incidence of small bowel tumors, directly caused by a relative increase in the

incidence of carcinoid tumors over adenocarcinoma of the small bowel. This trend is occurring

globally.

3 Research is now focused on the molecular cause of the discrepancy between the number of small

bowel and colorectal adenocarcinomas.

4 Size and location influence the symptoms caused by tumors within the small bowel. The majority of

tumors found incidentally are asymptomatic.

5 Capsule endoscopy (CE) is helpful for diagnosis but lack of spatial orientation, inability to biopsy,

and capsule retention causing obstruction limit its usefulness. Small bowel enteroscopy, deviceassisted enteroscopy (DAE), or deep enteroscopy (DE), are excellent alternative modalities.

6 Even though small neuroendocrine tumors (NETs) can metastasize, the risk of metastasis correlates

with the size of the primary tumor.

7 There are three common radiographic modalities used to diagnose small bowel tumors which include

CT scan, MRI and CT, or MR enterography. NETs also benefit from octreotide scanning as a

functional scan to detect metastasis.

8 Chromogranin A tends to be the most sensitive indicator of recurrence during surveillance of NET,

and sensitivity and specificity depends on the functionality of the tumor.

9 Gastrointestinal stromal tumors (GISTs) arise from pacemaker cells (Interstitial cells of Cajal) of the

small intestine and, based on mutations in the c-kit proto-oncogene region of the tyrosine kinase

gene, respond to imitanib (tyrosine kinase inhibitor) monoclonal antibody. Surgical resection

remains the only curative method of treatment.

10 Melanoma is the most common extraintestinal malignancy with predilection to metastasize to the

small bowel.

INTRODUCTION

1 The small bowel can give rise to both malignant and benign neoplasms. It comprises about 75% of the

entire length of the gastrointestinal tract and provides about 90% of its mucosal surface area, but

surprisingly these neoplasms represent less than 5% of the cancer affecting the entire gastrointestinal

tract.1 Even so, small bowel cancer causes significant morbidity and mortality because of its potential to

metastasize and to invade critical structures in the abdomen and retroperitoneum. The main types of

malignancy include adenocarcinoma, neuroendocrine (carcinoid), lymphoma, and sarcoma (GIST).

Several benign neoplasms such as lipomas, hamartomas, leiomyomas, and desmoid tumors are found in

the small intestines. Recent large database queries have demonstrated that the most common

malignancy is now carcinoid. Adenocarcinoma formerly was the most common, but the rising incidence

of carcinoid tumors has recently surpassed it.2,3 The relative inaccessibility of the small bowel

endoscopically presents several difficulties in diagnosis, results in a delay in diagnosis, and yields

advanced disease or metastatic disease at the time of treatment. There is some utility for upper

endoscopy (EGD), but the progress in Pillcam endoscopy and small bowel enteroscopy has improved the

ability to diagnose, and possibly treat, these neoplasms. Exploratory laparoscopy can also be utilized for

diagnosis and in the treatment of these tumors. Once diagnosed, management varies based on the type

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of neoplasm. Metastatic tumors to the small bowel are rare, but direct invasion, and carcinomatosis

tends to be the common presentation for nonprimary tumors. Operative treatment with extended

resection is not possible with the small bowel like the extent of resection that can be performed in the

colon. Now, treatment modalities and multidisciplinary approaches may offer improved survival.

EPIDEMIOLOGY

2 The American Cancer Society estimates that 6,900 new cases of small bowel cancer will be seen in

2015 with an estimated 1,100 deaths.4 The incidences increased from the 2008 query estimating 6,110

new cases of small bowel cancer and about the same number of deaths, approximately 1,110.5 These

reports indicate a rising incidence of small bowel cancers, and are directly caused by the increasing

incidence of carcinoid tumors of the small bowel.2 This trend is occurring not only in the United States,

but across the world. A recent review of cancer incidence showed a rising incidence of small bowel

carcinoid tumors in England. The same rising incidence is demonstrated in the United States, along with

a change in the distribution of the carcinoid tumors along the length of the small bowel.3

In the population below the age of 40, the incidence of small bowel neoplasms is low. The incidence

for males and females is essentially the same. Sporadic, nonfamilial cancer occurs rarely in young

patients.

PATHOGENESIS

With respect to the entire gastrointestinal tract, small bowel cancers are relatively rare. This raises the

question as to why the region of the GI tract with the largest surface area has the lowest rate of cancer.

Several factors have been identified as potential explanations; (1) the small bowel has liquid contents

with an alkaline pH exposing the mucosa to a decrease in mechanical and chemical inflammation, (2)

transit through the small bowel is rapid, thus shortening the time carcinogens are in contact with the

mucosal surface, (3) there is a rapid turnover in epithelial cells in the mucosa outpacing the potential

growth and development of neoplastic cells, (4) there is lower luminal bacterial load, particularly of

anaerobes, which results in less total production of potential carcinogens, (5) the small bowel mucosa

has an apparent enhanced ability to metabolize and/or detoxify certain dietary components or

breakdown products that may be carcinogenic, and (6) the elaborate lymphoid tissue network

surrounding the small bowel, and in particular, its ability to secrete immunoglobulin A, which might

confer an increased immunologic-related tumor control.1

3 The discrepancy between the number of small bowel adenocarcinomas and colorectal

adenocarcinomas has pushed the research to a molecular level. There is substantial effort toward

identifying the pathways for the mutation resulting in these cancers. These pathways include K-ras, Ecadherin, β-catenin, and p-53. The largest study of small bowel adenocarcinomas, n = 21, analyzed a

variety of genes known to be involved with tumor mutagenesis in nonhereditary and nonperiampullary

small bowel adenocarcinomas. The outcomes showed that all tumors presented with the hMLH1 and

hMSH2 (usually absent in mismatch repair defective inherited tumors) genes in the tumor nuclei. No

APC gene mutations were detected. One specimen had a replication error (RER). β-Catenin was

expressed in 17 specimens, 8 specimens had decreased or no expression of E-cadherin, and 5 specimens

had overexpression of p-53.6 This finding illustrates that the pathway to cancer that small bowel

adenocarcinoma follows is different from the colorectal pathway.

PREDISPOSITION TO SMALL BOWEL CANCER

There are several predisposing risk factors for development of small bowel cancers. These include

genetic and environmental factors.

Familial Adenomatous Polyposis

These patients have hundreds, and even thousands, of adenomas in their gastrointestinal tract, and have

a 100% transformation rate to colorectal cancer if untreated. Interestingly, the leading cause of death

for patients with familial adenomatous polyposis (FAP) is not the progression of colorectal cancer, due

to the fact that most of the patients undergo a total colectomy. It is actually the malignant

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