GI Cancer

Gastrointestinal cancer

Signs and symptoms

Patients present with trouble swallowing, gastrointestinal hemorrhage or metastases (mainly in the liver). Intestinal obstruction is rare, due to the tumor’s outward pattern of growth. Often, there is a history of vague abdominal pain or discomfort, and the tumor has become rather large by time the diagnosis is made.

Generally, the definitive diagnosis is made with a biopsy, which can be obtained endoscopically, percutaneously with CT or ultrasound guidance or at the time of surgery.

Causes

Most (50-80%) GISTs arise because of a mutation in a gene called c-kit. This gene encodes a transmembrane receptor for a growth factor termed scf (stem cell factor). The c-kit/CD117 receptor is expressed on ICCs and a large number of other cells, mainly bone marrow cells, mast cells, melanocytes and several others. In the gut, however, a mass staining positive for CD117 is likely to be a GIST, arising from ICC cells.

Diagnosis

As part of the analysis, blood tests and CT scanning are often undertaken.
A biopsy sample will be investigated under the microscope. The histopathologist identifies the characteristics of GISTs (spindle cells in 70-80%, epitheloid aspect in 20-30%). Smaller tumors can usually be found to the muscularis propria layer of the intestinal wall. Large ones grow, mainly outward, from the bowel wall until the point where they outstrip their blood supply and necrose (die) on the inside, forming a cavity that may eventually come to communicate with the bowel lumen.
Radiology
Barium fluoroscopic examinations (upper GI series and small bowel series (small bowel follow-through)) and CT are commonly used to evaluate the patient with upper abdominal pain. Both are adequate to make the diagnosis of GIST, although small tumors may be missed, especially in cases of a suboptimal examination.
Pathophysiology
GISTs are tumors of connective tissue, i.e. sarcomas; unlike most gastrointestinal tumors, they are non-epithelial. 70% occur in the stomach, 20% in the small intestine and less than 10% in the esophagus. Small tumors are generally benign, especially when cell division rate is slow, but large tumors disseminate to the liver, omentum and peritoneal cavity. They rarely occur in other abdominal organs.

Treatment

Therapy
Tumor size, mitotic rate, and location can be used to predict the risk of recurrence in GIST patients. Tumors
Surgery is the mainstay of therapy for non-metastatic GISTs. Lymph node metastases are rare and routine removal of lymph nodes is typically not necessary. Wide margins are not necessary. Laparoscopic surgery, a minimally invasive type of abdominal surgery using telescopes and specialized instruments, has been shown to be effective for removal of these tumors without needing large incisions.

Until recently, GISTs were notorious for being resistant to chemotherapy, with a success rate of <5%. Recently, the c-kit tyrosine kinase inhibitor imatinib, a drug initially marketed for chronic myelogenous leukemia, was found to be useful in treating GISTs, leading to a 40-70% response rate in metastatic or inoperable cases. Data presented at the 2007 ASCO meeting showed that adjuvant treatment with imatinib following surgical resection of GIST tumors can significantly reduce the risk of disease recurrence (6% recurrence on imatinib vs. 17% without therapy at 12 months). The optimal duration of adjuvant therapy is currently unknown; trials are ongoing evaluating treatment durations of 1, 2, and 3 years.

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