Neoplasms of the small bowel occur infrequently and account for fewer than 2% of all GI neoplasms. Tumors of the small intestine present insidiously with vague, nonspecific symptoms. Most benign tumors are diagnosed incidentally; however, they can act as lead points in an intussusception. On the other hand, the majority of malignant tumors eventually present with weight loss, abdominal pain, obstruction, perforation, or hemorrhage.
A. Benign tumors
Benign tumors are much more common than malignant tumors.
Leiomyoma is the most common benign neoplasm of the small intestine and arises from the mesenchymal cells of the small bowel. These tumors grow submucosally and project into the lumen of the small bowel. On a small-bowel contrast study, they appear as a smooth, eccentric filling defect with intact, normal-appearing mucosa. Histopathologic examination is needed to distinguish benign from malignant stromal tumors. Treatment consists of a segmental small bowel resection.
Adenomas can occur sporadically as solitary lesions or in association with familial adenomatous polyposis syndrome (Gardner variant). When they are symptomatic, lesions can cause fluctuating pain secondary to intermittent obstruction, intussusception, or bleeding. The three types of small-bowel adenomas are simple tubular adenomas, Brunner gland adenomas, and villous adenomas. The duodenum is the most common site for all three types of adenomas. Tubular and Brunner gland adenomas have a low malignant potential and can be treated with complete endoscopic polypectomy. Villous adenomas have significant malignant potential. If complete endoscopic resection is not possible, transduodenal excision with adequate margins is appropriate. Villous adenomas of the jejunum or ileum should be resected with a segmental bowel resection.
Hamartomas arise in patients with Peutz-Jeghers syndrome. This is an autosomal dominant inherited syndrome of mucocutaneous melanotic pigmentation and multiple gastrointestinal polyps. Operative therapy is indicated only for symptoms. At operation, all polyps larger than 1 cm should be resected. Due to an increased risk for de novo adenocarcinoma (arising separately from the hamartomatous polyps), patients need to be screened closely by endoscopy.
Lipomas occur most often in the ileum and have no malignant potential. On CT, they show fatty attenuation. Hemangiomas may be associated with Osler-Weber-Rendu disease and present with bleeding. Diagnosis can be made with enteroscopy, capsule endoscopy, or angiography. Neurofibromas and fibromas, less common tumors, can cause intussusception. Endometriosis can implant on the bowel, appearing as puckered, bluish-red, serosally based nodules. They can cause gastrointestinal bleeding or obstruction.
B. Malignant tumors
Adenocarcinoma is the most common malignant small intestinal tumor. Forty percent of these occur in the duodenum, and their frequency decreases distally through the small bowel.
Risk factors for the development of adenocarcinoma include villous adenomas, polyposis syndromes, Crohn disease, and hereditary nonpolyposis colorectal cancer (HNPCC). Patients often remain asymptomatic for long periods of time, and most patients have distant metastases at diagnosis. The presenting symptoms depend on the location of the primary tumor. Periampullary tumors can present with painless jaundice, duodenal obstruction, or bleeding. More-distal tumors tend to present with abdominal pain and weight loss from progressive obstruction. Contrast studies, CT, and endoscopy with or without ERCP can be used to make the diagnosis.
Treatment consists of segmental resection of the small bowel and its adjacent lymph node–bearing mesentery. Any adherent structures should be resected en bloc if possible. Tumors of the terminal ileum should be resected along with the right colon. For carcinomas of the duodenum, a pancreaticoduodenectomy is usually required. In completely resected duodenal adenocarcinoma, the 5-year survival rate is 56% for node-positive and 83% for node-negative disease, respectively (Ann Surg Oncol 2004;11:380). Distal lesions tend to present at a later stage. Patients with metastatic disease at the time of diagnosis rarely survive past 6 months. 5-Fluorouracil–based chemotherapy regimens have been tried, but data on their efficacy are lacking.
Gastrointestinal stromal tumors (GISTs) arise from mesodermal-derived components of the small intestine. They are equally distributed along the length of the small bowel. These tumors grow extraluminally and cause symptoms late in their course. Because of their vascular nature, when these tumors outgrow their blood supply and necrose, they may hemorrhage into either the peritoneum or the lumen of the bowel. Mutations of c-kit (CD117; a tyrosine kinase responsible for neoplastic growth) allow diagnosis by immunohistochemistry. The treatment for GI stromal tumors is resection. Wide en bloc resection to obtain tumor-free margins must be performed for curative therapy. Extensive lymph node resection is unnecessary because these tumors have a low potential for lymphatic spread. Traditional chemotherapy and radiation therapy are not effective in the treatment of metastatic GISTs. However, imatinib mesylate (Gleevec) is a recently developed medicine that may substantially change treatment of the disease. Imatinib targets the overactive tyrosine receptor c-kit found on all GIST cells. Inhibition of this receptor has been shown to lead to radiographic and histologic regression of metastatic lesions (N Engl J Med 2001;344:1052). Clinical trials are ongoing to address the use of imatinib after GIST resection. The benefit of resection of isolated lmonary or hepatic lesions is unknown. Histologic grade and tumor size are the most important predictors of survival. After complete resection, the overall 5-year survival rate is 50%. In low-grade tumors [<10 mitotic figures/high power field (mf/hpf)], the survival rate is 60% to 80%, whereas in high-grade tumors (>10 mf/hpf), the survival rate is less than 20%. With local recurrence, the median length of survival is 9 to 12 months. With metastatic disease, the median length of survival is 20 months (Br J Surg 2003;90:1178). However, imatinib mesylate treatment extends the 2-year survival rate to 78% for patients with metastatic disease (Eur J Cancer 2004;40:689).
Primary small-bowel lymphomas are most common in the ileum because it has the largest amount of gut-associated lymphoid tissue. Virtually all small-bowel lymphomas are non-Hodgkin, B-cell lymphomas. Lymphomas can arise de novo or in association with a preexisting systemic condition such as celiac disease, Crohn disease, or immunosuppression (iatrogenic, HIV, etc.). The presentation of these patients is highly variable. Imaging can help make a diagnosis, but operation is frequently required for histologic confirmation. Treatment of lymphoma localized to the small bowel involves wide resection of the affected segment of intestine and its associated mesentery. To stage the tumor accurately, the liver should be biopsied and the periaortic lymph nodes sampled. For widespread disease, resection of the affected small bowel should be performed to prevent complications. The role of adjuvant chemotherapy and radiotherapy remains controversial. The 5-year survival rate for patients with fully resected disease approaches 80%, but individuals with more advanced disease usually die within 1 year of operation.
Carcinoid tumors arise from the Kulchitsky or enterochromaffin cells of the intestinal crypts. Most intestinal carcinoids occur within 2 ft of the ileocecal valve. Small-bowel carcinoid tumors tend to be much more aggressive than their appendiceal or rectal counterparts. Patients rarely manifest signs or symptoms of the tumor until late in the course. Symptoms include local complications (intestinal obstruction, pain, or bleeding) or systemic symptoms of the carcinoid syndrome. Metastases are rare in tumors smaller than 1 cm in size; half of tumors between 1 and 2 cm metastasize, and almost all tumors larger than 2 cm spread.
Carcinoid syndrome implies metastatic spread. Normally, hormones released by intestinal tumors are metabolized by the liver and produce no symptoms. However, hepatic metastases drain into the systemic circulation. Classic symptoms include diarrhea and transient flushing of the face, neck, and upper chest. Tachycardia, hypotension, bronchospasm, and even coma can also occur. In long-standing carcinoid syndrome, patients develop right heart endocardial and valvular fibrosis. The hormonal mediators responsible for carcinoid syndrome are not well understood. The diagnosis of carcinoid syndrome is confirmed by finding increased urinary excretion of 5-hydroxyindoleacetic acid, a metabolite of serotonin.
The treatment of carcinoid tumors is operative. The entire small bowel should be inspected because in 30% of cases synchronous lesions are present. Jejunal and ileal tumors should be treated with segmental resection including the adjacent mesentery. Small tumors (<1 cm) that are located in the third or fourth portions of the duodenum can be either locally excised or included in a segmental resection. For large duodenal tumors and periampullary tumors, a pancreaticoduodenectomy should be performed. In the presence of locally advanced disease with involvement of adjacent organs or peritoneum, aggressive resection should be undertaken. This can help to delay the occurrence of mesenteric desmoplastic reaction, hepatic metastases, and carcinoid syndrome. Solitary and accessible liver lesions should be resected. Adjuvant cytotoxic chemotherapy and radiotherapy are of little benefit. The somatostatin analog octreotide offers excellent palliation of carcinoid syndrome in patients with unresectable disease. Octreotide decreases the concentration of circulating serotonin and urinary 5-hydroxyindoleacetic acid and can relieve diarrhea and flushing in 90% of patients.Carcinoids are slow-growing tumors, and prognosis depends on the stage of the tumor. The overall 5-year survival rate is 60%. Patients with local disease that is completely resected have a normal life expectancy. For patients with resectable node-positive disease, the median length of survival is 15 years. The median length of survival drops to 5 years with unresectable intra-abdominal disease, and it is 3 years for patients with hepatic metastases. Of note, there are outliers who survive for many years with metastatic disease.
Carcinomatosis is diffuse studding of the peritoneal, mesenteric, and bowel surfaces by tumor nodules. Many tumors can cause peritoneal carcinomatosis, including cancer of the pancreas, stomach, ovaries, appendix, and colon. Carcinomatosis has an extremely poor prognosis, and surgical treatment is palliative, usually for obstruction. The only exception is pseudomyxoma peritonei; patients with this low-grade malignancy may benefit from resection and intraperitoneal chemotherapy.
Metastases can spread to the small bowel. Palliative resection is appropriate if needed for symptom relief.