Small Bowel Neoplasms

Malignant Tumors

1. Neuroendocrine Tumors (NETS, Carcinoids)
1. Tumor Characteristics
• most common malignancy of the small intestine
• arise from enterochromaffin cells (Kulchitsky cells)
• can occur anywhere along the GI tract
• 45% occur in the small intestine, most commonly the ileum
• capable of secreting a variety of biologically active substances
• most ileal and jejunal carcinoids secrete serotonin; duodenal carcinoids secrete gastrin or somatostatin
• have a variable malignant potential
• most occur sporadically
• synchronous or metachronous lesions occur in 29% of patients
• coexistence of a second primary cancer of different histologic type occurs in 10% - 20% of patients


2. Pathology
• low-grade (G1), intermediate-grade (G2), and high-grade (G3) is determined based on appearance, mitotic rates, behavior (local invasion, angioinvasion), and Ki-67 proliferation index
• malignant potential is related to location, size, depth of invasion, and growth pattern
• only 3% of appendiceal NETs metastasize; 35% of ileal NETs metastasize
• 75% of GI NETs are < 1 cm in size and have a 2% rate of metastasis
• NETs between 1 and 2 cm have a 50% rate of metastasis; NETS > 2 cm have a 80% - 90% rate of metastasis


1. Gross Appearance
• firm, submucosal nodules that are usually yellow on cut surface
• often associated with a larger mesenteric mass (nodal disease)
• intense desmoplastic reaction causes mesenteric fibrosis, intestinal kinking, and intermittent obstruction



3. Clinical Presentation
• most common symptom is abdominal pain
• obstructive symptoms may be caused by intussusception or by the desmoplastic reaction
• rarely, encasement of mesenteric vessels can lead to bowel ischemia
• duodenal carcinoids may obstruct the ampulla of Vater, resulting in jaundice


1. Carcinoid Syndrome
• flushing, abdominal pain, diarrhea, bronchoconstriction, right-sided heart valvular disease
• caused by the release of vasoactive amines into the systemic circulation
• because the amines causing carcinoid syndrome are degraded by the liver, liver metastases or extra-abdominal disease are required to develop the syndrome


4. Diagnosis
• many small bowel NETs are discovered at laparotomy, either incidentally or for exploration for bowel obstruction
• biochemical basis of carcinoid syndrome can be made by a 24-hour urine collection measuring for elevated levels of 5-HIAA
• serum chromogranin A (CgA) is elevated in 80% of patients with NETs
• octreotide scanning is useful for identifying extra-abdominal metastatic disease or occult primary tumors not identified by CT scan


5. Treatment
1. Surgery
• only potential curative therapy
• wide excision of bowel and mesentery is required
• small duodenal NETs can be excised locally; larger lesions will require pancreaticoduodenectomy
• abdomen must be carefully explored for multicentric lesions and metastatic disease
• surgical debulking of metastatic disease may provide symptomatic relief and prolong survival
• hepatic metastases may be managed with resection, hepatic artery embolization, cryotherapy, radiofrequency ablation


2. Medical Therapy
• long-acting somatostatin analogs are highly effective in controlling carcinoid syndrome symptoms
• may be given preoperatively to prevent carcinoid crisis
• aside from octreotide, no treatment has proven antitumor activity
• chemotherapy (streptozotocin) and interferon are of limited value
• targeted therapies against vascular endothelial growth factor, platelet-derived growth factor, angiogenesis factors, mammalian target of rapamycin (mTOR) are in active development


6. Prognosis
• NETs have the best prognosis of small bowel tumors
• 5-year survival rates are 65% with nodal disease and ~ 30% with metastatic disease
• when widespread metastatic disease precludes cure, extensive resection for palliation is indicated


2. Adenocarcinoma
1. Tumor Characteristics
• second most common cancer of the small intestine
• occurs most often in the duodenum, except in Crohn’s patients, where the ileum is the most common site
• may be associated with other diseases: celiac disease, familial adenomatous polyposis, hereditary nonpolyposis colon cancer, Peutz-Jegher’s syndrome







2. Presentation
• tumors of the duodenum present with jaundice and bleeding
• more distal tumors have nonspecific symptoms – vague abdominal pain, weight loss
• obstruction and bleeding can also occur in distal tumors
• distal tumors are often advanced at the time of diagnosis


3. Diagnosis
• duodenal tumors often diagnosed by EGD or ERCP
• more distal tumors are diagnosed by capsule endoscopy, small bowel contrast studies, CT scan, or operative exploration


4. Treatment
• tumors of the first and second portion of the duodenum require pancreaticoduodenectomy
• for tumors of the third and fourth portions of the duodenum, segmental resection is preferred over pancreaticoduodenectomy as long as a negative margin can be obtained
• jejunal and ileal tumors require segmental resection with a wide mesenteric resection
• tumors of the distal ileum require a right hemicolectomy
• metastatic or locally advanced tumors may benefit from palliative resection to alleviate bowel obstruction or bleeding
• unresectable duodenal tumors may require a gastrojejunostomy, duodenal stent, or biliary stent for palliation


5. Prognosis
• duodenal adenocarcinoma has a 5-year survival of 50%; distal cancers have a 5-year survival of 14% - 33%
• lymph node involvement is the most important prognostic factor
• number of nodes assessed (<8) and number of nodes involved (>3) are also poor prognostic factors


3. Gastrointestinal Stromal Tumors (GISTs)
1. Tumor Characteristics
• originate from the interstitial cells of Cajal
• 30% occur in the small intestine, primarily in the jejunum
• most arise sporadically
• >90% of GISTs express the CD117 antigen, which is part of the KIT transmembrane tyrosine receptor kinase
• mutation in the KIT gene leads to an abnormally activated KIT protein
• GISTs that lack KIT mutations usually have mutations in PDGFA
• effective systemic therapies (imatinib) were developed in the form of tyrosine kinase inhibitors that block oncogenic signaling from KIT and PDGFA


2. Presentation
• intraluminal bleeding and obstruction are the most common symptoms
• abdominal pain, early satiety, distention may also be present
• occasionally, a GIST tumor may rupture intraperitoneally


3. Diagnosis
• median tumor size is 7.5 cm at presentation
• duodenal GISTs may be identified at EGD as a submucosal mass with smooth margins
• tumors of the jejunum and ileum may be identified by CT scan or contrast studies
• occasionally, a GIST may be identified at laparotomy



4. Clinical Behavior
• spread locally by direct extension
• hematogenous spread is commonly to liver, lungs, bone
• lymphatic spread is unusual
• large tumor size and higher mitotic rate are the major predictors of malignant behavior


5. Treatment
1. Surgery
• goal is R0 resection
• periampullary tumors may require pancreaticoduodenectomy
• local invasion will require en bloc resection
• routine lymphadenectomy is not required
• must avoid tumor rupture at the time of surgery since it is associated with a poorer prognosis
• marginally resectable tumors may benefit from neoadjuvant treatment with imatinib


2. Medical Therapy
• GISTs > 3 cm benefit from at least 3 years of adjuvant imatinib
• other indications for imatinib include incomplete resection, recurrent disease, and metastatic disease


6. Prognosis
• 5-year survival of resected small bowel GISTs is ~ 40%


4. Lymphoma
1. Tumor Characteristics
• may involve the small bowel primarily or as a manifestation of systemic disease
• accounts for ~ 25% of small bowel tumors in adults
• most common intestinal neoplasm in children < 10 years old
• most common in the ileum, which contains the greatest amount of gut-associated lymphoid tissue
• increased incidence in patients with celiac disease and AIDS


2. Clinical Characteristics
• abdominal pain is the most frequent symptom
• bleeding, obstruction, or a palpable abdominal mass may occur
• perforation may occur in 25% of patients


3. Treatment
• diagnosis requires a tissue biopsy for immunohistochemistry, flow cytometry, cytogenetic, and molecular genetic studies
• primary mode of treatment is chemotherapy
• surgery is reserved for complications such as bleeding, obstruction, perforation
• in some cases, surgery will be performed to avoid the risk of perforation during chemotherapy


5. Metastatic Tumors
1. Tumor Characteristics
• much more common than primary neoplasms
• may occur by direct extension from other abdominal primaries, intraperitoneal seeding (ovarian, gastric cancers), or hematogenous or lymphatic spread (melanoma, breast, lung)







2. Clinical Presentation
• obstruction is the most common presentation
• ascites, perforation, bleeding, mesenteric ischemia can also be seen


3. Treatment
• bowel obstructions are usually initially managed conservatively
• failure of conservative management mandates palliative resection or bypass
• stents can be used to palliate duodenal obstructions
• gastrostomy tubes or proximal ostomies can decompress patients with extensive disease