Laparoscopic Gastric Wedge Resection for a GIST

The stomach is involved in multiple common ailments, including gastroesophageal reflux disease, gastric ulcers and cancer, the latter of which can take many forms. Originally, GISTs arise from the connective tissue, or stroma, of the stomach, rather than the lining, from which the more common and more deadly gastric adenocarcinoma finds its origin. However, over time, study revealed that GIST arises from a very specific cell, called the interstitial cells of Cajal, that are responsible for the timing of contraction in the stomach and small intestine. GIST masses generally behave more indolently than gastric adenocarcinoma, with distant or lymph node metastases a rare feature, although involvement of the liver and peritoneum has been described. Due to this indolent nature, certain masses, once they have been identified as GIST through endoscopic biopsy, are candidates for surveillance. However, larger masses (as identified through evidence of necrosis on imaging) and rapidly growing masses are treated primarily with surgical resection. While in the past surgical resection would have involved a large abdominal incision and a lengthy postoperative recovery, laparoscopic techniques have allowed gastric resection to become a short procedure necessitating only an overnight stay.

A 63-year-old female patient was admitted to our clinic with complaints of dull pain in the epigastric region. Contrast-enhanced CT, revealed a 6-cm well-defined exophytic mass in the posterior wall of the stomach. The mass had a heterogeneous appearance with areas of necrosis and enhancement. No evidence of lymphadenopathy or distant metastasis was observed. These features were suggestive of a gastrointestinal stromal tumor (GIST).

Upper gastrointestinal endoscopy demonstrated a submucosal mass with overlying mucosal ulceration in the posterior wall of the stomach. A biopsy was performed, and histopathology revealed spindle-shaped cells, consistent with a diagnosis of gastrointestinal stromal tumor (GIST). Due to the tumor’s location, a decision was made to perform a laparoscopic gastric wedge resection.

The patient’s surgical history includes a skin-preserving right mastectomy for multifocal breast cancer with TRAM flap reconstruction. Her past medical history includes controlled grade 2 hypertension (ACC/AHA classification). No known allergies and no family history of genetic diseases were reported.

Most patients presenting with GIST are symptomatic, with the common complaints being vague abdominal pain and evidence of gastrointestinal bleeding, either through melena, or stool with digested blood, or hematochezia. In situations where metastases exist at the time of presentation, signs of liver failure, although this is rare. GIST can also occur in the setting of endocrine syndromes such as von Hippel-Lindau disease or neurofibromatosis, but the majority are isolated findings. A small, but, due to the overall increase in imaging studies, an increasing number of patients are being diagnosed via abdominal imaging and are thus asymptomatic.

Patients with GIST have little in the way of physical findings, unless the tumor is markedly advanced, at which time a palpable abdominal mass overlying the stomach may be identified. Patients also may have pain to palpation of the abdomen, and, if the liver is involved, findings of jaundice.

The natural history of gastric GIST is variable, with some tumors behaving indolently while others exhibit local and distant metastasis. Two variables in particular have been identified as predictive of metastasis. The first is the size of the tumor, with greater than 10 centimeters in greatest dimension being a poor prognostic sign. Greater than 5 mitoses per high power field on histologic analysis of the tumor is also a harbinger of metastasis.

In masses less than 2 centimeters, that do not demonstrate increased mitotic activity on endoscopic biopsy, the natural history is uniformly benign and nothing further need to be done. In tumors that are either between 2 and 5 centimeters with no increased mitotic activity, or tumors less than 2 centimeters but with increased mitotic activity, a watchful waiting strategy with surveillance CT may be adopted. However, in larger tumors (>5 centimeters) that are accompanied with increased mitotic activity or signs of necrosis on imaging, resection of the mass is the mainstay of treatment.

In this particular patient, a stomach mass was discovered after an endoscopy was performed secondary to abdominal pain. Due to the small size and lack of mitotic activity on biopsy, surveillance was elected initially. However, the mass grew over the course of a year, and repeat biopsy showed increase in mitotic activity, as well as positive c-KIT staining. After discussion with the patient, the decision was made to proceed with resection of the mass.

While GIST is the most common sarcomatous tumor of the gastrointestinal tract, it is still a rare cancer, comprising only one percent of all GI tumors.¹  Due to this, effective screening strategies have proven elusive. Most patients with gastric GIST present with symptoms, most commonly abdominal pain, although an increasing number are discovered incidentally. Almost one-third of GIST masses carry high risk for malignant potential or are frankly malignant, and the poor state of adjuvant therapy associated with GIST is reflected in the high mortality rates associated with these high-risk and frankly malignant tumors.²
Diagnosis of gastric GIST is based on histologic analysis of tissue obtained at the time of endoscopy. This is due to two specific defects that have been identified as giving rise to GIST. The most common is found in the c-KIT gene of the affected cells. The c-KIT gene encodes for a transmembrane receptor, which is thought to play a crucial role in cellular apoptosis.³ In affected cells, the c-KIT tyrosine kinase is constitutively active, causing deregulation of cellular growth.¹ Another, and mutually exclusive, gene defect is the one found in the gene responsible for platelet-derived growth factor alpha(PDGFR-α).⁴

Presence of either of these mutations are diagnostic of GIST; however, they do not predict malignant potential of the mass. Rather, the combination of number of mitoses, or actively dividing cells, that are seen during histologic analysis, combined with the size of the tumor itself, is highly predictive of metastatic potential.⁵ In one large pathologic review of patients identified as having GIST, 86% of patients with greater than 5 mitoses per fifty high-powered field on microscopy, combined with a tumor mass of greater than 10 centimeters had eventual metastasis of GIST, while only two to three percent of patients who had neither finding.⁵

If a GIST is detected and found to have concerns for increased malignant potential, removal of the mass via surgical resection is the mainstay of treatment. With the advent of laparoscopy, in otherwise uncomplicated patients, resection of gastric masses has become a much less morbid procedure, with patients returning home within twenty-four hours, as well as returning to regular diets soon postoperatively. This is especially the case for tumors located on the greater curvature of the stomach, where the mass is relatively simple to access and may be removed simply by stapling across the base of the mass with an endoscopic gastrointestinal stapler.

In the setting of metastatic or unresectable disease,⁶ or patients with high risk for recurrence based on primary tumor characteristics,⁷ adjuvant therapy with imatinab, a tyrosine kinase inhibitor, may be considered. In fact, response to imatinib has been so positive that its continuous use in patients with GIST has been approved by the Federal Food and Drug Administration.⁸

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