Figure 51-1. These Kaplan–Meier curves illustrate disease-specific survival stratified by (A) disease stage, (B) subsite in the small

bowel for stage I and II diseases, and (C) subsite in the small bowel for stage III disease. Codes for the duodenum (C17.0),

jejunum, (C17.1), and ileum (C17.2) are from the International Classification of Diseases for Oncology and Related Health

Problems 10th Revision. (Overman MJ, Hu CY, Wolff RA, et al. Prognostic value of lymph node evaluation in small bowel

adenocarcinoma: Analysis of the surveillance, epidemiology, and end results database. Cancer 2010;116(23):5374–5382.)

The typical clinical presentation of small bowel lymphoma is nausea, vomiting, abdominal pain, and

weight loss. Severe symptoms, such as obstruction, intussusceptions, or perforation are rare.12

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Figure 51-2. These Kaplan–Meier curves illustrate disease-specific survival stratified by (A) the total number of lymph nodes

assessed (TLN) in patients with stage I and II diseases and (B) the TLNs assessed in patients with stage III disease. (Overman MJ,

Hu CY, Wolff RA, et al. Prognostic value of lymph node evaluation in small bowel adenocarcinoma: Analysis of the surveillance,

epidemiology, and end results database. Cancer 2010;116(23):5374–5382.)

Several types of lymphoma can occur in the small bowel. However, the most commonly encountered

lymphoma is diffuse large B-cell lymphoma. Despite the incidence of lymphoma in the small intestine,

surgery is typically not the method for management. These patients should undergo resection in

situations of obstruction or bleeding, and should still receive chemotherapy.12 Immunoproliferative

small intestinal disease occurs in patients who are chronically immunosuppressed as a result of infection

by Helicobacter pylori and Campylobacter jejuni. Antibiotic therapy for these bacteria usually results in

regression of immunoproliferative small intestinal disease. Most of these patients relapse and will need

radiation and chemotherapy with nutritional support.70,71

Gastrointestinal Stromal Tumor

9 GISTs are the most mesenchymal tumors of the small bowel. GISTs are found in the stomach (60% to

70%), small intestine (20% to 30%), and in the duodenum (4% to 5%).72 GISTs are known to arise from

the interstitial cells of Cajal, which are described as the gastrointestinal pacemakers.73 Coincidentally,

that same year GISTs were termed gastrointestinal pacemaker cell tumors, Hirota et al.74 recognized the

c-kit proto-oncogene which codes for a tyrosine kinase inhibitor, as the genetic mutation leading to

GISTs. As a result, there has been a dramatic shift in the way GISTs are managed.

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Figure 51-3. These Kaplan–Meier curves illustrate disease-specific survival stratified by (A) the number of positive lymph nodes

(PLN) and (B) the lymph node ratio (LNR) in tertiles. (Overman MJ, Hu CY, Wolff RA, et al. Prognostic value of lymph node

evaluation in small bowel adenocarcinoma: Analysis of the surveillance, epidemiology, and end results database. Cancer

2010;116(23):5374–5382.)

The diagnosis of small bowel GISTs is similar to that of other small bowel tumors; however, the GIST

is unique with regard to the submucosal origin and its likelihood to grow in size away from the lumen

of the small bowel. This also makes it difficult to make a diagnosis with intraluminal biopsy. A study by

Bümming et al. in 2006 demonstrated that only one-third of diagnoses are made with biopsies, and that

the most common method of detection was endoscopy and CT scan.75 Most commonly, patients with

GISTs present with vague abdominal symptoms, pain, GI bleeding from a mucosal erosion, or an

abdominal mass.76

GISTs do not have the malignant pattern predicted in other types of cancers based on histopathology

alone. Several factors influence malignant behavior including tumor size, mitotic rate, tumor location,

kinase mutational status, and occurrence of tumor rupture. Mitotic rate and tumor size are the most

commonly acceptable indices for prognosis.72

Tumor size and location dictate the type of treatment. Complete surgical resection remains the only

method for curative treatment, and simple negative margins are needed, as wide margins have not

shown significant benefit.72 Small segmental resection of the small bowel is adequate because GISTs

rarely metastasize to lymph nodes. Lymph node dissection is not warranted. En bloc resection should be

done for locally advanced GISTs.72 Overall 5-year survival rate for patients with complete resection of

GISTs is 50% to 65%.72,76–78

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Algorithm 51-2. Algorithm showing the management of patients with small bowel adenocarcinomas. The treatment strategy

depends on disease stage and involves en bloc resection for locoregional disease and systemic chemotherapy for metastatic disease.

All current recommendations are based on case series, retrospective reviews or nonrandomized prospective trials because of an

absence of any randomized data. 5-FU, 5-fluorouracil; CAPOX, capecitabine and oxaliplatin; FOLFIRI, 5-FU, leucovorin and

irinotecan; FOLFOX, 5-FU, leucovorin and oxaliplatin; KRAS-WT, KRAS wild-type; PS, performance status; XRT, radiation therapy.

(Elias D, Lefevre JH, Duvillard P, et al. Hepatic metastases from neuroendocrine tumors with a “thin slice” pathological

examination: they are many more than you think. Ann Surg 2010;251(2):307–310.)

Patients have a defined risk for recurrence and may benefit from adjuvant therapy. The Modified

NIH–Fletcher GIST Risk Assessment Criteria is presented in Table 51-7. Other risk assessment tools are

available such as Armed Forces Institute of Pathology Classification and the Memorial Sloan-Kettering

Cancer Center Prognostic Nomogram. Adjuvant therapy utilizes imatinib (Gleevec). This drug is used in

the treatment algorithms for patients with advanced or metastatic GIST or with resectable GIST.

Algorithm 51-3A shows these algorithms. Imatinib is a competitive inhibitor for multiple tyrosine kinase

inhibitors and was originally recommended for chronic myelogenous leukemia treatment. It became

first-line treatment for GIST once it was recognized to disrupt the KIT oncogene in GISTs.79 Shortly after

that, imatinib was approved for use in unresectable or metastatic disease shown in Algorithm 51-3B.80,81

A randomized prospective study was done in 2009 to evaluate imatinib for the use in adjuvant therapy,

showing significant improvement in 5-year recurrence-free survival, 98% versus 83%, respectively, in

the treatment group over placebo.82 The NCCN guidelines in the management of GISTs provide a

standard algorithm.83

Table 51-7 Modified NIH–Fletcher GIST Risk Assessment Criteria

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Algorithm 51-3. Treatment algorithms for patients with (A) advanced/metastatic GIST and (B) resectable GIST. GIST indicates

gastrointestinal stromal tumor. (Mullady DK, Tan BR. A multidisciplinary approach to the diagnosis and treatment of

gastrointestinal stromal tumor. J Clin Gastroenterol 2013;47(7):578–585.)

METASTATIC TUMORS TO THE SMALL BOWEL

10 Metastasis to the small bowel occurs in two different ways, either from distant spread or direct

invasion from a nearby organ malignancy. The most common are from breast cancer and melanoma.

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

bowel (Fig. 51-4).84 Patients with metastatic melanoma to the small bowel often present with other

extraintestinal metastasis.85 Primary tumors of intraperitoneal organs such as colon, ovary, uterus, and

stomach metastasize to the small bowel.84

Figure 51-4. Metastatic melanoma to small bowel resecting en bloc.

Patients with small bowel metastasis are usually offered palliative systemic chemotherapy. Other

palliative measures can be considered on a case-by-case basis including surgical resection, internal

bypass, or usage of an endoscopically placed stent.9

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