Tumours of the small bowel
Neoplasms of the small bowel are unusual. Although the small bowel comprises 75% of the length of the gastrointestinal tract, less than 2% of all malignant neoplasms arise there. Small bowel tumours generally manifest with non-specific symptoms and frequently can be missed in the usual screening tests of the gastrointestinal tract.
Small bowel cancers are more common in developed Western countries. The incidence of small bowel malignancy is about 1.5 cases per 100 000 population. There is no racial predilection for adenocarcinoma, although lymphoma is more common in Caucasians.
The peak incidence occurs in the 60–70 years age group. Small bowel neoplasms occur with equal frequency in men and women. They usually present insidiously with non-specific and intermittent symptoms (Table 24, “Clinical presentation of small bowel tumours”). Malignant neoplasms are less common than benign tumours, but are more likely to produce symptoms. Symptoms vary with site of origin and nature of the tumour. Diagnosis is often delayed until the disease is advanced.
|Small bowel obstruction||Yes||Yes|
|Obstructive jaundice||Periampullary tumour||No|
|Carcinoid syndrome||Carcinoid tumours||No|
Abdominal pain is the most common complaint and is related to underlying subacute bowel obstruction. The pain may be a dull ache or crampy in nature. More than 50% of patients present as emergencies with complications of the tumour. Small bowel obstruction and bleeding are the most common complications. Obstruction may be secondary to luminal narrowing, volvulus or occasionally intussusception, with the tumour acting as the lead point. When all causes are considered, small bowel tumour is an uncommon (<5%) cause of small bowel obstruction. Bleeding from small bowel tumours may be occult with symptoms due to anaemia, or occasionally overt with maroon-coloured stools. Massive haemorrhage is rare and is more likely with small bowel angioma and leiomyosarcoma. Abdominal masses are more likely with leiomyosarcoma and lymphoma than with adenocarcinoma.
When more common causes for small bowel obstruction, such as adhesion or external hernia, are absent a small bowel tumour should be considered. Plain abdominal radiograph will confirm a small bowel obstruction. In patients with partial or subacute small bowel obstruction, barium studies may be diagnostic. Enteroclysis or a barium small bowel enema is more sensitive than a standard barium small bowel series. An enteroclysis study is performed by first passing an intestinal tube through the stomach into the duodenum or jejunum. Dilute barium is then slowly and steadily infused. This technique provides excellent visualisation of the small bowel mucosa. Computed tomography (CT) with oral contrast may show the extraluminal extent and nodal or liver metastases, thereby aiding the pre-operative staging. Upper gastrointestinal endoscopy is diagnostic of duodenal neoplasms. Capsule enteroscopy provides excellent images of the stomach, duodenum and small bowel. It involves swallowing a small camera which relays digitised images to a computer recorder over an 8-hour duration. Push enteroscopy can visualise the proximal small bowel but is no more sensitive than a capsule endoscopy.
In patients with anaemia secondary to occult gastrointestinal bleeding, small bowel barium studies are the best way to diagnose a small bowel tumour. If bleeding is massive, mesenteric angiography will localise the bleeding site if the rate of bleeding is faster than 0.5 mL/min. Radiolabelled red blood cell scans are useful if the bleeding is less severe or is intermittent. Upper gastrointestinal endoscopy and colonoscopy are helpful to exclude gastroduodenal and colonic sources of haemorrhage. Despite these investigations, the diagnosis of small bowel tumour is made at operation in most patients.
The management of small bowel tumours is surgical. Details of management tend to depend on the pathology of the tumour.
Most benign tumours are relatively asymptomatic and are undiagnosed until autopsy. Benign tumours arise from any of the endothelial or mesenchymal cells within the bowel wall (Table 25, “Tumours of the small bowel, in order of frequency”). Leiomyomas, adenomas and lipomas are most common.
|Hamartoma (Peutz-Jeghers syndrome)||Leiomyosarcoma|
Leiomyoma occurs most frequently in the jejunum as a firm, grey-white lesion. Histologically, it contains welldifferentiated smooth muscle cells without mitoses. Radiographically, it appears as a smooth filling defect with intact mucosa. It enlarges extraluminally and may cause obstruction or intussusception. Treatment requires simple segmental resection.
Villous adenoma of the small bowel occurs most frequently in the duodenum, especially in the periampullary region. It has the same malignant potential as villous adenoma of the colon. There is an association with familial adenomatous polyposis (see Colorectal cancer and adenoma). A large periampullary villous adenoma may bleed or cause duodenal or biliary obstruction. The diagnosis is confirmed by gastroduodenoscopy and biopsy. If the pre-operative evaluation suggests that the lesion is benign, a duodenotomy is made and a local submucosal excision is performed. With more extensive tumours, a formal pancreaticoduodenectomy (Whipple's operation) may be required. Lesions in the third or fourth part of the duodenum are treated with segmental resection.
Tubular adenoma is also most common in the duodenum. It is usually asymptomatic and is amenable to endoscopic polypectomy. It has a very low malignant potential. Brunner's gland adenoma is hyperplasia of the exocrine glands of the first portion of the duodenum. Most are asymptomatic and are found incidentally.
Lipoma arises from submucosal fat and usually occurs in the distal ileum. Computed tomography can confirm the diagnosis by defining the density of the lesion. Lipoma has no predisposition to malignancy. Excision is performed only if the lesion is symptomatic.
This condition is discussed in Chapter 24.
There are four major types of malignant small bowel tumour: adenocarcinoma, carcinoid tumour, lymphoma and leiomyosarcoma (Table 26, “Malignant tumours of the small bowel”). Tumours metastatic to small bowel may also mimic primary small bowel tumours.
|Tumour type||Overall (%)||Duodenum (%)||Jejunum (%)||Ileum (%)|
This neoplasm occurs with decreasing frequency from duodenum to ileum.Within the duodenum, two-thirds occur in the periampullary region. By contrast, adenocarcinoma associated with Crohn's disease is most common in distal ileum.
Adenocarcinoma of the small bowel may be associated with Crohn's disease, familial adenomatous polyposis and adult coeliac disease. It occurs in patients in the sixth or seventh decade. On gastrointestinal contrast study, the lesion may appear as an apple-core defect with mucosal ulceration. Sometimes, the diagnosis is made only at laparotomy for small bowel obstruction of unknown cause.
Adenocarcinoma of the duodenum is diagnosed by endoscopic examination with biopsy. As surgical treatment for duodenal lesions may be extensive, pre-operative staging with CT is performed. In periampullary lesions, endoscopic retrograde cholangiopancreatography to delineate biliary and pancreatic involvement is helpful.
Surgical management is determined by the location of the tumour. Unless the disease is extensive and disseminated, surgical exploration is indicated in most patients. The extent of the disease is evaluated intraoperatively. Wide segmental small bowel resection including the draining of the mesenteric lymph nodes is performed. However, resection of involved mesenteric lymph nodes should not be unduly extensive as it may jeopardise the viability of the remaining normal small bowel. Extensive lymph node metastases are associated with a poor outcome. Distal ileal lesions are managed by a right hemicolectomy and ileotransverse anastomosis. Even in advanced disease with hepatic metastases, palliative small bowel resection is performed to prevent bleeding or obstruction. If the disease is locally advanced and unresectable, a side-to-side enteroenteric bypass is performed.
For most duodenal lesions, pancreaticoduodenectomy (Whipple's operation) is the treatment of choice. Presence of lymph node metastases in the field of surgery is not a contraindication for resection. For small lesions affecting the first or fourth portions of the duodenum, segmental resection may be performed. In patients with unresectable duodenal adenocarcinoma, gastrojejunostomy and biliary stenting or bypass will provide palliation.
There is no proven value for radiotherapy or chemotherapy in the adjuvant or palliative setting.
Overall prognosis is poor because of the advanced state of presentation. Overall 5-year survival averages 20%. Without nodal metastases, survival improves to 60%.
Carcinoid tumours arise from enterochromaffin cells of the gastrointestinal tract. These pleuripotential, neuroendocrine cells are part of the amine precursor uptake and decarboxylation (APUD) system and can synthesise vasoactive amines and regulatory peptides. The majority (85%) of all carcinoids occur in the appendix. The small bowel (usually distal ileum) is the next most common site and, overall, 30% are multicentric.
The tumours have a characteristic yellow-orange colour and are usually small (<2 cm) and submucosal. These tumours have a variable malignant potential. They may cause an intense desmoplastic reaction in the mesentery, probably from local release of serotonin, with secondary mesenteric ischaemia and infarction or kinking of small bowel with subsequent obstruction.
Most appendiceal and many small bowel carcinoids remain asymptomatic. Appendiceal carcinoid tumours follow a very benign clinical course and are usually diagnosed following appendicectomy. Appendiceal carcinoids less than 2 cm in size require no therapy other than appendicectomy. Tumours larger than 2 cm require a right hemicolectomy to resect the draining lymph nodes.
Some small bowel carcinoids are more aggressive. Symptoms arise from the primary tumour itself or from the metastatic disease (anorexia, weight loss, lethargy or carcinoid syndrome). Diagnosis of carcinoid tumours necessitates a high index of suspicion. Barium small bowel series may show tethering of distal ileal loops without visualising the tumour itself. Computed tomography may show mesenteric nodal metastases or hepatic metastases. The operative management includes a segmental resection of the small bowel, en bloc mesenteric resection and primary anastomosis. Careful inspection for synchronous lesions should be performed because 30% are multicentric. Even with extensive disease, palliative resection will help to debulk the disease and often delay the occurrence of carcinoid syndrome. Lymphadenectomy will also prevent the desmoplastic reaction in the mesentery. Solitary or isolated liver metastases are resected if, technically, it is simple to perform and there are no contraindicating co-morbid factors.
Carcinoid syndrome is thought to be caused by the release of vasoactive substances into the systemic circulation. The pharmacology of the mediators remains uncertain. Bradykinin, serotonin, tachykinins (substance P, neuromedin A), histamine, dopamine and prostaglandins may act in concert. For carcinoid syndrome to occur from gastrointestinal primary tumours, hepatic metastases must be present. The carcinoid syndrome may also be seen in carcinoid tumours of the lung, testis and ovary, where venous drainage allows systemic circulation of the vasoactive substances directly.
Classic clinical features include diarrhoea, flushing of the face and upper trunk, which lasts seconds or a few minutes, and bronchospasm. Symptoms may be precipitated by foods, alcohol or emotional stress. Venous telangiectasias, pellagra (dementia, dermatitis, diarrhoea) and right-sided endocardial valvular fibrosis may develop in reaction to circulating vasoactive amines. Progress to tricuspid insufficiency, pulmonary stenosis and, ultimately, right-sided heart failure may occur. The carcinoid crisis is a rare life-threatening event involving intense flushing, severe diarrhoea, cardiovascular abnormalities (tachycardia, arrhythmias, hypertension or hypotension) and central nervous system problems that range from dizziness to coma.
Treatment of carcinoid syndrome is aimed at symptomatic relief. The synthetic somatostatin analogue, sandostatin, is the most effective therapy. It improves cutaneous flushing and diarrhoea. Improvement is sustained in 30% of patients for up to 2.5 years. Chemotherapy may also be used. Modest responses to doxorubicin, 5-fluorouracil or streptozotocin are obtained in 20% of patients. Chemotherapy is more effective if combined with hepatic artery ligation. Debulking of hepatic metastases has a short-lived response. Liver transplantation is still experimental.
Carcinoid tumours are slow growing. Many patients live for prolonged periods despite distant metastases. After curative resection of localised intestinal carcinoid tumour, survival is equivalent to that for the the general population. Following resectable nodal metastases, median survival is 15 years.With non-resectable intestinal disease or liver metastases, survivals are 5 and 3 years, respectively.
Lymphoma of the small bowel arises either as a primary gastrointestinal tumour or as a manifestation of generalised lymphomatous disease. With primary gastrointestinal lymphoma, mesenteric lymph node involvement is limited to the area of involved bowel, white blood cell count is normal and there is no peripheral or mediastinal lymphadenopathy or splenomegaly. In Western countries, gastric lymphomas are most common, followed by small bowel lymphomas.
Small bowel lymphoma usually presents in the fifth decade and is multifocal in 15% of cases. Patients with Crohn's disease, coeliac disease or immunosuppressive diseases such as AIDS are susceptible to gastrointestinal lymphomas. Small bowel lymphomas predominate in the ileum. Most are intermediate or high-grade non-Hodgkin's B-cell lymphomas. T-cell varieties occur sporadically or with coeliac disease.
An abdominal mass is common. Obstruction, perforation, intussusception or haemorrhage occurs in 25% of patients. Malabsorption from diffuse mucosal involvement occurs occasionally. Small bowel contrast studies may suggest the presence of a tumour mass and CT may reveal bulky mesenteric nodes associated with thickened bowel or a large mass. Percutaneous cytology is not adequate for characterising the lymphoma, although core biopsies are more helpful.
Management includes diagnosis, staging, resection or debulking, and treatment of complications. Liver biopsy and sampling of nodes outside the field of resection are important, although splenectomy is not indicated. In patients with localised disease, resection of the involved bowel with a wide margin of adjacent mesentery is performed. Resection of primary duodenal lymphomas is controversial; Whipple resections have a high morbidity and mortality rate. Without surgery, perforation and bleeding occur in 20% of patients during combined radiation and chemotherapy. Adjuvant multi-drug chemotherapy regimens containing adriamycin are often offered after curative resection, on the premise that lymphomas are systemic diseases. With advanced disease, debulking or palliative resection is performed to prevent complications of bleeding or perforation, provided excessive removal of normal small bowel is avoided. If resection is not possible, tissue is obtained for histological diagnosis and classification, the extent of tumour is staged and an enteric bypass is performed to prevent obstruction. Responses to chemotherapy and radiotherapy are variable and short-lived but are dramatic in some patients.
Outcome depends on the stage of disease. With ‘curative’ resection for localised disease, 5-year survival is 80%. With more advanced disease, the prognosis is much less favourable and depends on response to chemotherapy.
Leiomyosarcoma arise from the smooth muscle cells of the small bowel. They are often encapsulated and subserosal in location. They often grow to a large size before causing symptoms.
An abdominal mass is evident in 50% of patients. As these highly vascular tumours reach a large size, necrosis within the tumour may cause haemorrhage or, less commonly, perforation. Small bowel obstruction may result from intussusception or from extramural and mural compression. Barium small bowel studies often show extrinsic compression of the small bowel and CT shows a large, extraluminal mass with central necrosis.
Surgical resection is the key treatment. Frozen section is unreliable in determining the malignancy of these tumours. Thus, all tumours of smooth muscle origin, whether they are thought to be benign or malignant, should be treated similarly with adequate surgical resection. In tumours of the distal duodenum and the remainder of the small bowel, segmental resection with primary anastomosis is the treatment of choice. As leiomyosarcoma tends to spread haematogenously, an extended lymphadenectomy is not necessary. Fifteen per cent of patients do have metastatic involvement of mesenteric lymph nodes. Resection of duodenal lesions requires pancreaticoduodenectomy because of the bulky tumour size. Both radiotherapy and chemotherapy are of little benefit.
Prognosis depends on the stage of the disease and histological grade. Histological grade is determined by cellularity, nuclear atypia and number of mitoses. Survival at 5 years after curative resection for low-grade tumour approaches 60%, but with high-grade lesions survival is less than 20%. Distant metastases (lung, liver, bone) are present in 30% of patients at presentation. Palliative resection of small bowel leiomyosarcoma in this situation is worthwhile and may be associated with 5 years' survival in as many as 20%.
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