AUTHOR AND EDITOR INFORMATION

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INTRODUCTION

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Background

Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms of the gastrointestinal (GI) tract defined by the expression of c-KIT (CD117) in the tumor cells. Previously, these tumors were classified as gastric or intestinal smooth muscle tumors; however, this traditional classification was abandoned with the advent of immunohistochemical methods enabling the specific identification of c-KIT–positive tumors. GISTs are rare and constitute only 1% of all malignant tumors of the GI tract; nevertheless, they are the most common mesenchymal neoplasm of the GI tract. GISTs are found in the stomach in 47-60% of cases, yet they are the least prevalent malignant tumors of the stomach, constituting only 1-3% of all malignant gastric tumors. While GISTs can occur at any point along the GI tract, the focus of this article is on GISTs of the stomach.

Histologically, GISTs vary from cellular spindle cell tumors to epithelioid and pleomorphic ones. By definition, GISTs are CD117 positive, although positivity for nestin and CD34 is also common.

Characteristics of GISTs that are predictive of malignancy are mitotic rate greater than 5 per 10 high-power fields (HPFs) or size larger than 5 cm. However, tumors with low mitotic index can also metastasize, and gastric GISTs are commonly less aggressive than those of nongastric intestinal origin.

Pathophysiology

GISTs are typically diagnosed as solitary lesions, although in rare cases, multiple lesions can be found. These tumors can grow intraluminally or extraluminally toward adjacent structures. When the growth pattern is extraluminal, patients can harbor the disease symptom free for an extended period of time and present with very large exogastric masses.

Distant metastases tend to appear late in the course of the disease in most cases. In contrast to other soft tissue tumors, the common metastatic sites of GISTs are the liver and peritoneum. Lymph node involvement is rare, occurring in only 0-8% of cases.

Frequency

United States

An estimated 150 new cases are diagnosed each year, with an annual incidence of 0.07 cases per 100,000 population.

International

GISTs are rare, and data concerning its worldwide prevalence are lacking. In general, it constitutes 1-3% of all gastric malignancies.

Mortality/Morbidity

Long-term survival is typically correlated inversely with tumor size and histologic grade. In general, GISTs portend a much better prognosis than adenocarcinoma of the stomach.

Race

No racial predilection exists.

Sex

No gender predilection exists.

Age

Onset can occur at any age but occurs most commonly in the sixth and seventh decades of life.

CLINICAL

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History

• Upper GI bleeding is the most common clinical manifestation of gastrointestinal stromal tumors (GISTs), manifesting as hematemesis or melena in 40-65% of patients. Bleeding occurs because of an ulcer forming in the gastric mucosa overlying the tumor.
• Other symptoms may include abdominal pain, anorexia, nausea, vomiting, weight loss, epigastric fullness, and early satiety.
• Occasionally, GISTs can be found incidentally. In Japan, mass screening for gastric adenocarcinoma with upper endoscopy has led to an increase in incidental findings of asymptomatic GISTs.

Physical

Physical examination rarely demonstrates any significant findings. In some cases, examination may identify a palpable abdominal mass in the abdomen. Palpable masses are typically detected in patients with an exogastric tumor growth.

Causes

No risk factors have been identified.

DIFFERENTIALS

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Other Problems to be Considered

Gastric schwannoma
True smooth muscle tumor of the stomach (leiomyoma)
Gastric sarcoma
Gastric adenocarcinoma

The differential diagnosis for gastric stromal tumors includes benign lesions such as true leiomyoma, schwannoma, lipoma, ectopic pancreas, and sarcomas.

Other possible lesions include the much more common gastric adenocarcinoma and other rare submucosal malignant tumors such as lymphoma and carcinoid.

Not infrequently, patients with GISTs of the stomach present with a large mass in the epigastrium or left upper quadrant. In such cases, the differential diagnosis may include masses originating from other organs such as the liver, spleen, pancreas, left adrenal gland, or retroperitoneum.

WORKUP

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Lab Studies

• Laboratory studies are not diagnostic, and no identifiable tumor markers exist.

Imaging Studies

• Computed tomography scanning of the abdomen: Abdominal CT scanning with intravenous and oral contrast material is a necessary step in the evaluation of these patients. The gastric mass can be detected originating from the gastric wall (see Image 2). CT scanning can also be used to evaluate tumor invasion to adjacent structures and the presence of intra-abdominal metastasis. As mentioned, findings on CT scanning can often be confused with masses originating from adjacent structures.
• Endoscopic ultrasonography: Endoscopic ultrasonography (EUS) is a valuable tool in the diagnosis and preoperative assessment of gastric GISTs. It can demonstrate the submucosal location of the tumor and can define its size, borders, and echoic pattern. Ultrasonic features associated with increased risk of malignancy are large tumors, tumors with irregular extraluminal borders, and the presence of cystic spaces and echogenic foci. Diagnosis can often be made using ultrasonographic-guided biopsy. However, while the histology obtained may be able to demonstrate a spindle cell tumor, differentiating between benign and malignant forms is often difficult (see Histologic Findings).

Procedures

• Upper endoscopy: This usually is the first examination performed in the evaluation of patients with upper gastrointestinal symptoms. Gastroscopy may demonstrate a firm, smooth, yellowish submucosal mass, which can be ulcerated (see Image 1). Nevertheless, these tumors can be missed because of their frequent submucosal and extraluminal growth.
• Preoperative biopsy: Preoperative biopsy is not always indicated. Surgical resection is required for treatment and for definitive diagnosis in most cases. Biopsy is important when the submucosal nature of this tumor is in doubt or when tumor characteristics as demonstrated by upper endoscopy and endoscopic ultrasonography are not typical. In specific patients, such as high-risk operative patients with small benign-appearing lesions and minimal or no symptoms, tissue diagnosis may help in further decision-making. The 2 ways to obtain a preoperative histologic diagnosis are as follows:
• • Endoscopic biopsy: Preoperative endoscopic biopsy may be taken with or without EUS guidance. When taken without the help of EUS, endoscopic biopsy is not accurate and leads to a correct diagnosis in less than 50% of patients. Biopsies may miss the tumor and show only mucosal tissue. In addition, samples from the tumor itself often are too small to establish malignant nature. EUS-guided biopsy is more accurate. This technique can achieve a correct histologic diagnosis in more than 80% of cases and should be performed whenever preoperative histology seems necessary.
  • Percutaneous biopsy: Tumor biopsy can be obtained percutaneously under CT scanning or ultrasonographic guidance. Consider this procedure in selected patients when endoscopic biopsy is impossible to perform or the results are negative.

Histologic Findings

Cellular morphology as visualized by light microscopy can be variable. Most often, the tumors are highly cellular and composed of spindle-shaped cells that resemble smooth-muscle tissue (see Image 3). However, this histologic appearance is not uniform. A similar tumor with a predominant epithelioid component was historically diagnosed as leiomyoblastoma (see Image 4). This variant is occasionally associated with a well-defined condition called Carney syndrome.

Important histologic factors to consider in evaluating these tumors are mitotic index, cellularity, necrosis, nuclear atypia and nuclear-cytoplasmic ratio, cell shape, amount of stroma, and vascularity.

Investigations of GISTs by immunohistochemistry and electron microscopy (ultrastructural parameters) reveal phenotype variability that includes myoid, neural, and indeterminate characteristics. Study of GISTs by immunohistochemistry methods reveals expression of CD117 and other various antigens, such as nestin (90-100% positivity), CD34 (70% positivity), CD44, vimentin, desmin, muscle-specific actin, smooth-muscle actin, S-100 protein, neurofilament, neuron-specific enolase, and PGP9.5. CD117 plays an important role in the latest specific diagnostic criteria for GISTs. CD117 (c-kit protein) is a growth factor receptor with tyrosine kinase activity and is a product of the proto-oncogene c-kit. CD117, although not tumor specific, is expressed in all GISTs but not in true smooth muscle tumors and neural tumors.

CD117 has become a very important tool in the differentiation of GIST from other GI mesenchymal tumors. Positive CD117 staining in a spindle-shaped cell GI tumor is diagnostic for GIST (see Image 5). CD34 is another important diagnostic marker. It is detected in approximately 70% of GISTs, and its presence may indicate a higher probability for a malignant phenotype. CD44 is variably expressed by GISTs, but its expression has been demonstrated to correlate with a better prognosis.

Recent studies suggest that GISTs may originate from the interstitial cells of Cajal. These cells are distributed along the GI tract and play a role in the control of gut motility. The interstitial cells of Cajal exhibit both myeloid and neural features and express the c-kit proto-oncogene receptor. However, the fact that GISTs are detected (although very rarely) outside of the GI tract (ie, omentum, mesentry, retroperitoneum) argues against this hypothesis.

Staging

No consensus has been reached regarding a uniform staging system, and none of the currently used classifications is fully satisfactory. Most staging systems employ the 3 most important survival predictors—tumor size, histologic grade, and presence or absence of distant metastatic disease.

Many studies have shown that tumor diameter greater than 5 cm is associated with increased risk for malignancy. However, relation of size to malignant potential may be gradual, with no clear cut-off point.

The number of mitotic figures is the most accepted index for grade classification, although other histologic parameters, such as cellularity, atypia, and necrosis, are also taken into consideration. A high mitotic index of more than 5 mitoses per 10 HPFs usually signifies highly malignant disease. However, a low mitotic index is not always associated with benign course. As many as 25% of tumors with mitotic index of less than 5 mitoses per 10 HPFs may manifest an aggressive biological behavior. Some authors have defined an intermediate-risk category applied for tumors with a mitotic index of 2-4 mitoses per 10 HPFs.

• Tumor size
• • T1- Tumor less than 5 cm, localized
  • T2 - Tumor greater than or equal to 5 cm, localized
  • T3 - Contiguous organ invasion or peritoneal implants
  • T4 - Tumor rupture
• Tumor grade
• • G1- Low grade
  • G2 - High grade
• Metastasis
• M0 - No metastasis
• M1 - Distant metastases

  Table 1. Proposed Staging System for Malignant Gastrointestinal Stromal Tumors

  Stage	Tumor Size	Tumor Grade	Metastasis
  Stage I	T1	G1	M0
  Stage II	T2	G1	M0
  Stage III	T1-2 T3	G2 Any G	M0 M0
  Stage IVa	…	…	M1 or residual disease after surgery
  Stage IVb	T4	…	…

TREATMENT

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Medical Care

No standard regimen for adjuvant therapy presently exists for malignant gastric stromal tumors.

• Data regarding the use of radiotherapy in an adjuvant setting failed to show a statistically significant benefit.
• Current data suggest a major role for the tyrosine kinase inhibitor, imatinib mesylate (STI-571, Gleevec), for patients with GISTs. Numerous trials have demonstrated substantial tumor response in patients with metastatic or advanced disease.
• • The Food and Drug Administration (FDA) approved imatinib mesylate for GIST on February 1, 2002, under accelerated approval regulations and under the orphan drug program, which provides financial incentives for drugs developed to treat rare diseases (ie, diseases that affect fewer than 200,000 patients). Imatinib had first been used in patients with chronic myeloid leukemia (CML), which is characterized by a balanced translocation between chromosomes 9 and 22 (the Philadelphia chromosome). This abnormality results in the production of the BCR-ABL fusion protein, which has uncontrolled tyrosine kinase activity. Imatinib has been found to induce a near-complete response in virtually all patients treated in the chronic phase of CML.
  • The initial approval of imatinib for the treatment of GIST was based upon a study of 147 patients with unresectable or metastatic GIST who received daily oral imatinib. While no patient had complete disappearance of tumor, 56 patients (38%) had reduction in tumor size by 50% or greater (partial response).
  • The subsequent development of imatinib mesylate has revolutionized the treatment of GISTs. After numerous clinical trials, 55-80% of patients with metastatic GIST achieve a partial response or stable disease while receiving imatinib. The adverse reactions of imatinib are manageable and include edema, rash, diarrhea, nausea, abdominal pain, and fatigue.
• Other agents with tyrosine kinase inhibitory activity are also showing significant promise for the treatment of GISTs, and especially in the treatment of GISTs with resistance to imatinib. Dasatinib (BMS-354825) is currently being studied in clinical trials. In January 2006, the FDA approved sunitinib malate (SU-11248, Sutent) for the treatment of patients with GISTs whose disease has progressed or who are unable to tolerate treatment with imatinib. While studying the treatment in patients, sunitinib was shown at interim analysis to delay the median time-to-tumor progression (TTP) of GISTs to 27 weeks as compared with 6 weeks for patients who did not receive the drug.

Surgical Care

Despite the proven success of imatinib and other newer tyrosine kinase inhibitors, surgical resection remains the treatment of choice and offers the only chance for cure from GIST. The main operative principle is resection of the tumor with clear margins, preferably about 2 cm wide.

• For small gastric tumors, wedge resection is adequate, if technically possible. Larger tumors necessitate subtotal or total gastrectomy. Enucleation should be avoided because predicting malignant potential preoperatively is difficult, even in benign-appearing lesions.
• For locally invasive tumors, en bloc resection of adjacent involved organs, such as colon, spleen, or liver, may be indicated.
• Routine lymphadenectomy is not indicated and has not been shown to yield any survival benefit.
• Recurrence and survival are not associated with the type of resection (wedge resection versus any type of gastrectomy) provided that a complete resection (R0) is performed.
• Direct every effort at avoiding tumor rupture during the operation. Tumor rupture is associated with a worse prognosis because of peritoneal seeding.
• In cases of disseminated disease, consider palliative resection because long-term survival has been reported in certain cases.
• Also consider resection in patients with recurrent disease, manifested as a solitary lesion in the liver or peritoneal cavity. Published reports of liver resection for hepatic metastasis from gastric and other GISTs suggest a survival benefit in selected patients.
• Because adequate resection for small malignant GISTs can be achieved by wedge resection, minimally invasive surgery techniques can be considered in selected cases. In recent years, numerous published reports of laparoscopic resection of gastric GISTs have demonstrated the feasibility and safety of this technique.

MEDICATION

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The goals of pharmacotherapy are to induce remission, reduce morbidity, and prevent complications.

Drug Category: Tyrosine kinase inhibitors

Agents with strong tyrosine kinase inhibition activity of the bcr-abl abnormality in all cell cycle phases of gastric tumor cells.

Drug Category: Multikinase inhibitors

Elicit actions via multiple tyrosine kinase inhibitors implicated in tumor growth, pathologic angiogenesis, and metastatic progression.

FOLLOW-UP

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Further Outpatient Care

• Follow-up care after curative operations is important because certain patients with recurrent disease may benefit from second surgical intervention and from systemic therapy with imatinib mesylate or sunitinib malate for unresectable and/or metastatic disease. Follow-up includes physical examination and periodical gastroscopies as well as CT scanning. Ideal time intervals for performing these studies have not been well established.

Prognosis

• In general, long-term survival for malignant GIST after a curative-intent surgery is strongly related to tumor size and histologic grade.
• Because no standardized staging system exists for stromal tumors of the GI tract and most series are small and heterogenous, comparison of the different published survival rates is difficult. However, various reports of 5-year survival rates after R0 resection for gastric stromal tumors range from 32-93%. In large series, this rate is about 60%. The median survival after palliative resection is about 10 months, with a 5-year survival rate as high as 10%. These rates improve with the addition of imatinib.
• Ng et al in 1992 have reported the long-term survival of 139 patients with gastrointestinal malignant stromal tumors from different sites—40% gastric tumors. The overall 5-year survival rates by stage for GI stromal tumors is as follows:
  • Stage I - 75%
  • Stage II - 52%
  • Stage III - 28%
  • Stage IVa - 12%
  • Stage IVb - 7%
• In another large series of patients after resection of malignant GISTs published by Koga et al in 1995, survival was studied according to a classification combining tumor size and mitotic index. A very high survival rate was found in patients with tumors smaller than 6 cm and low mitotic index (see Table 2).

  Table 2. Five-Year Survival According to Size and Number of Mitoses

  Size cm	Mitoses per 20 HPFs	5-Year Survival Rate
  <6	<4	97.5%
  >6	<4	91.5%
  <6	>4	80.0%
  >6	>4	17.7%

• Histologic grade alone is a strong prognostic factor. In 1982, Shiu et al reported a 5-year survival rate of 80% in patients after resection of low-grade tumors. The 5-year survival rate dropped to 32% in patients with high-grade tumors.
• Other factors found to have a negative impact on prognosis are tumor rupture during operation, involvement of histologic margins, and lymph node involvement.
• The liver and the peritoneal cavity represent the predominant sites of recurrence after attempted curative surgery. Extra-abdominal sites (eg, lungs) are less common. Evaluate patients with recurrent disease for possible second resection if feasible. Survival prolongation is reported for resected local recurrences and even for resected isolated hepatic or peritoneal recurrent lesions.

MISCELLANEOUS

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Medical/Legal Pitfalls

• No consensus has been reached regarding a uniform staging system, and none of the currently used classifications is fully satisfactory.
• No standard regimen for adjuvant therapy presently exists for malignant gastric stromal tumors.
• Direct every effort at avoiding tumor rupture during surgical therapy. Tumor rupture is associated with a worse prognosis because of peritoneal seeding.
• Because malignant potential is difficult to determine preoperatively, a wide resection with clear margins is routinely indicated.
• Malignant behavior in low mitotic tumors is rare but is reported.

MULTIMEDIA

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Media file 1:  Shown here is a gastric gastrointestinal stromal tumor (GIST). This is a gross specimen following partial gastrectomy. Note the submucosal tumor mass with the classic features of central umbilication and ulceration.
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Media type:  Photo

Media file 2:  CT scan of the abdomen with oral contrast in a 60-year-old woman with a gastric gastrointestinal stromal tumor (GIST). A huge mass with central necrosis is observed originating from the gastric wall and narrowing its lumen. An ulcer crater can be identified within the mass (arrow).
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Media type:  CT

Media file 3:  Photomicrograph of gastrointestinal stromal tumor (GIST) stained with hematoxylin and eosin (H&E) and magnified 40X. Note the solid sheet of spindle cells.
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Media type:  Photo

Media file 4:  Photomicrograph of gastric gastrointestinal stromal tumor (GIST) stained with hematoxylin and eosin (H&E) and magnified 400X. This stromal tumor demonstrates spindle cells with epithelioid features.
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Media type:  Photo

Media file 5:  Photomicrograph of gastrointestinal stromal tumor (GIST) with immunohistochemical staining for CD117. Note the strong positive staining of tumor cells with negative staining of the adjacent vessel. Positive stain for CD117 is diagnostic of GIST.
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Media type:  Photo

REFERENCES

Section 11 of 11

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• Aogi K, Hirai T, Mukaida H, et al. Laparoscopic resection of submucosal gastric tumors. Surg Today. 1999;29(2):102-6. [Medline].
• Aparicio T, Boige V, Sabourin JC, et al. Prognostic factors after surgery of primary resectable gastrointestinal stromal tumours. Eur J Surg Oncol. Dec 2004;30(10):1098-103.
• Bandoh T, Isoyama T, Toyoshima H. Submucosal tumors of the stomach: a study of 100 operative cases. Surgery. May 1993;113(5):498-506. [Medline].
• Bauer S, Lang H, Schutte J, Hartmann JT. Complete remission with imatinib in metastastic gastrointestinal stromal tumors. J Clin Oncol. Sep 20 2005;23(27):6800-1; author reply 6801-2.
• Bedard EL, Mamazza J, Schlachta CM, Poulin EC. Laparoscopic resection of gastrointestinal stromal tumors: not all tumors are created equal. Surg Endosc. Mar 2006;20(3):500-3.
• Benjamin RS, Blanke CD, Blay JY, et al. Management of gastrointestinal stromal tumors in the imatinib era: selected case studies. Oncologist. Jan 2006;11(1):9-20.
• Blanke C, Eisenberg BL, Heinrich M. Epidemiology of GIST. Am J Gastroenterol. Oct 2005;100(10):2366.
• Blay JY, Bonvalot S, Casali P, et al. Consensus meeting for the management of gastrointestinal stromal tumors. Report of the GIST Consensus Conference of 20-21 March 2004, under the auspices of ESMO. Ann Oncol. Apr 2005;16(4):566-78.
• Boni L, Benevento A, Dionigi G, et al. Surgical resection for gastrointestinal stromal tumors (GIST): experience on 25 patients. World J Surg Oncol. 2005;3:78.
• Bucher P, Egger JF, Gervaz P, et al. An audit of surgical management of gastrointestinal stromal tumours (GIST). Eur J Surg Oncol. Apr 2006;32(3):310-4.
• Carson W, Karakousis C, Douglass H, et al. Results of aggressive treatment of gastric sarcoma. Ann Surg Oncol. May 1994;1(3):244-51. [Medline].
• Chak A, Canto MI, Rosch T, et al. Endosonographic differentiation of benign and malignant stromal cell tumors. Gastrointest Endosc. Jun 1997;45(6):468-73. [Medline].
• Chen H, Pruitt A, Nicol TL, et al. Complete hepatic resection of metastases from leiomyosarcoma prolongs survival. J Gastrointest Surg. Mar-Apr 1998;2(2):151-5. [Medline].
• Corless CL, Fletcher JA, Heinrich MC. Biology of gastrointestinal stromal tumors. J Clin Oncol. Sep 15 2004;22(18):3813-25.
• Cypriano MS, Jenkins JJ, Pappo AS, et al. Pediatric gastrointestinal stromal tumors and leiomyosarcoma. Cancer. Jul 1 2004;101(1):39-50.
• Darnell A, Dalmau E, Pericay C, et al. Gastrointestinal stromal tumors. Abdom Imaging. Feb 7 2006.
• Durham MM, Gow KW, Shehata BM, et al. Gastrointestinal stromal tumors arising from the stomach: a report of three children. J Pediatr Surg. Oct 2004;39(10):1495-9.
• Efron DT, Lillemoe KD. The current management of gastrointestinal stromal tumors. Adv Surg. 2005;39:193-221.
• Eisenberg BL, Judson I. Surgery and imatinib in the management of GIST: emerging approaches to adjuvant and neoadjuvant therapy. Ann Surg Oncol. May 2004;11(5):465-75.
• Fields S, Libson E. CT-guided aspiration core needle biopsy of gastrointestinal wall lesions. J Comput Assist Tomogr. Mar-Apr 2000;24(2):224-8. [Medline].
• Franquemont DW. Differentiation and risk assessment of gastrointestinal stromal tumors. Am J Clin Pathol. Jan 1995;103(1):41-7. [Medline].
• Graadt van Roggen JF, van Velthuysen ML, Hogendoorn PC. The histopathological differential diagnosis of gastrointestinal stromal tumours. J Clin Pathol. Feb 2001;54(2):96-102. [Medline].
• Grant CS, Kim CH, Farrugia G, et al. Gastric leiomyosarcoma. Prognostic factors and surgical management. Arch Surg. Aug 1991;126(8):985-9; discussion 989-90. [Medline].
• Haider N, Kader M, Mc Dermott M, et al. Gastric stromal tumors in children. Pediatr Blood Cancer. Feb 2004;42(2):186-9.
• Hepworth CC, Menzies D, Motson RW. Minimally invasive surgery for posterior gastric stromal tumors. Surg Endosc. Apr 2000;14(4):349-53. [Medline].
• Hindmarsh A, Koo B, Lewis MP, Rhodes M. Laparoscopic resection of gastric gastrointestinal stromal tumors. Surg Endosc. Aug 2005;19(8):1109-12. [Medline].
• Hirota S, Isozaki K. Pathology of gastrointestinal stromal tumors. Pathol Int. Jan 2006;56(1):1-9. [Medline].
• Iwahashi M, Takifuji K, Ojima T, et al. Surgical management of small gastrointestinal stromal tumors of the stomach. World J Surg. Jan 2006;30(1):28-35. [Medline].
• Joensuu H, Roberts PJ, Sarlomo-Rikala M, et al. Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med. Apr 5 2001;344(14):1052-6. [Medline].
• Kang HJ, Koh KH, Yang E, et al. Differentially expressed proteins in gastrointestinal stromal tumors with KIT and PDGFRA mutations. Proteomics. Feb 2006;6(4):1151-7.
• Katai H, Sasako M, Sano T. Wedge resection of the stomach for gastric leiomyosarcoma. Br J Surg. Apr 1997;84(4):560-1. [Medline].
• Kikuchi H, Yamashita K, Kawabata T, et al. Immunohistochemical and genetic features of gastric and metastatic liver gastrointestinal stromal tumors: sequential analyses. Cancer Sci. Feb 2006;97(2):127-32.
• King DM. The radiology of gastrointestinal stromal tumours (GIST). Cancer Imaging. 2005;5:150-6.
• Kitano S, Shiraishi N. Minimally invasive surgery for gastric tumors. Surg Clin North Am. Feb 2005;85(1):151-64, xi.
• Knoop M, St Friedrichs K, Dierschke J. Surgical management of gastrointestinal stromal tumors of the stomach. Langenbecks Arch Surg. Apr 2000;385(3):194-8. [Medline].
• Koga H, Ochiai A, Nakanishi Y, et al. Reevaluation of prognostic factors in gastric leiomyosarcoma. Am J Gastroenterol. Aug 1995;90(8):1307-12. [Medline].
• Koh JS, Trent J, Chen L, et al. Gastrointestinal stromal tumors: overview of pathologic features, molecular biology, and therapy with imatinib mesylate. Histol Histopathol. Apr 2004;19(2):565-74. [Medline].
• Kosmadakis N, Visvardis EE, Kartsaklis P, et al. The role of surgery in the management of gastrointestinal stromal tumors (GISTs) in the era of imatinib mesylate effectiveness. Surg Oncol. Aug 2005;14(2):75-84.
• Lehnert T, Sinn HP, Waldherr R, Herfarth C. Surgical treatment of soft tissue tumors of the stomach. Eur J Surg Oncol. Aug 1990;16(4):352-9. [Medline].
• Ludwig DJ, Traverso LW. Gut stromal tumors and their clinical behavior. Am J Surg. May 1997;173(5):390-4. [Medline].
• Maki RG. Gastrointestinal Stromal Tumors Respond to Tyrosine Kinase-targeted Therapy. Curr Treat Options Gastroenterol. Feb 2004;7(1):13-17.
• Matsui M, Goto H, Niwa Y, et al. Preliminary results of fine needle aspiration biopsy histology in upper gastrointestinal submucosal tumors. Endoscopy. Nov 1998;30(9):750-5. [Medline].
• Medeiros F, Corless CL, Duensing A, et al. KIT-negative gastrointestinal stromal tumors: proof of concept and therapeutic implications. Am J Surg Pathol. Jul 2004;28(7):889-94.
• Melichar B, Voboril Z, Nozicka J, et al. Pathological complete response in advanced gastrointestinal stromal tumor after imatinib therapy. Intern Med. Nov 2005;44(11):1163-8.
• Miettinen M, Sobin LH, Sarlomo-Rikala M. Immunohistochemical spectrum of GISTs at different sites and their differential diagnosis with a reference to CD117 (KIT). Mod Pathol. Oct 2000;13(10):1134-42. [Medline].
• Miettinen M, Lasota J. Gastrointestinal stromal tumors--definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Arch. Jan 2001;438(1):1-12. [Medline].
• Montgomery E, Abraham SC, Fisher C, et al. CD44 loss in gastric stromal tumors as a prognostic marker. Am J Surg Pathol. Feb 2004;28(2):168-77. [Medline].
• Ng EH, Pollock RE, Munsell MF, et al. Prognostic factors influencing survival in gastrointestinal leiomyosarcomas. Implications for surgical management and staging. Ann Surg. Jan 1992;215(1):68-77. [Medline].
• Ng EH, Pollock RE, Romsdahl MM. Prognostic implications of patterns of failure for gastrointestinal leiomyosarcomas. Cancer. Mar 15 1992;69(6):1334-41. [Medline].
• Nguyen SQ, Divino CM, Wang JL, Dikman SH. Laparoscopic management of gastrointestinal stromal tumors. Surg Endosc. May 2006;20(5):713-6. [Medline].
• Otani Y, Kitajima M. Laparoscopic surgery for GIST: too soon to decide. Gastric Cancer. 2005;8(3):135-6.
• Palazzo L, Landi B, Cellier C, et al. Endosonographic features predictive of benign and malignant gastrointestinal stromal cell tumours. Gut. Jan 2000;46(1):88-92. [Medline].
• Peiper M, Schroder S, Zornig C. Stromal sarcoma of the stomach--a report of 20 surgically treated patients. Langenbecks Arch Surg. Dec 1998;383(6):442-6. [Medline].
• Pidhorecky I, Cheney RT, Kraybill WG, Gibbs JF. Gastrointestinal stromal tumors: current diagnosis, biologic behavior, and management. Ann Surg Oncol. Oct 2000;7(9):705-12. [Medline].
• Rosen MJ, Heniford BT. Endoluminal gastric surgery: the modern era of minimally invasive surgery. Surg Clin North Am. Oct 2005;85(5):989-1007, vii. [Medline].
• Rubin BP. Gastrointestinal stromal tumours: an update. Histopathology. Jan 2006;48(1):83-96.
• Ruiz AR Jr, Nassar AJ, Fromm H. Multiple malignant gastric stromal tumors presenting with GI bleeding: a case report and a review of the literature. Gastrointest Endosc. Feb 2000;51(2):225-8. [Medline].
• Rutkowski P, Nowecki Z, Nyckowski P, et al. Surgical treatment of patients with initially inoperable and/or metastatic gastrointestinal stromal tumors (GIST) during therapy with imatinib mesylate. J Surg Oncol. Mar 15 2006;93(4):304-11.
• Schittenhelm MM, Shiraga S, Schroeder A, et al. Dasatinib (BMS-354825), a dual SRC/ABL kinase inhibitor, inhibits the kinase activity of wild-type, juxtamembrane, and activation loop mutant KIT isoforms associated with human malignancies. Cancer Res. Jan 1 2006;66(1):473-81.
• Shah JN, Sun W, Seethala RR, et al. Neoadjuvant therapy with imatinib mesylate for locally advanced GI stromal tumor. Gastrointest Endosc. Apr 2005;61(4):625-7.
• Shinomura Y, Kinoshita K, Tsutsui S, Hirota S. Pathophysiology, diagnosis, and treatment of gastrointestinal stromal tumors. J Gastroenterol. Aug 2005;40(8):775-80.
• Shiu MH, Farr GH, Papachristou DN, Hajdu SI. Myosarcomas of the stomach: natural history, prognostic factors and management. Cancer. Jan 1 1982;49(1):177-87. [Medline].
• Stewart AE, Heslin MH, Arch J, et al. Cyclooxygenase-2 expression and clinical outcome in gastrointestinal stromal tumors. J Gastrointest Surg. Feb 2006;10(2):315-9.
• Sugar I, Forgacs B, Istvan G, et al. Gastrointestinal stromal tumors (GIST). Hepatogastroenterology. Mar-Apr 2005;52(62):409-13.
• Tuveson DA, Willis NA, Jacks T, et al. STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: biological and clinical implications. Oncogene. Aug 16 2001;20(36):5054-8. [Medline].
• Tzen CY, Mau BL. Analysis of CD117-negative gastrointestinal stromal tumors. World J Gastroenterol. Feb 21 2005;11(7):1052-5.
• Van Oosterom AT, Judson I, Verweij J, et al. STI 571, an active drug in metastatic gastrointestinal tumors (GIST), AN EORTC phase I study. Plenary Presentation. The American Society of Clinical Oncology, 37th Annual Meeting. 2001.
• Verweij J, Casali PG, Zalcberg J, et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet. Sep 25-Oct 1 2004;364(9440):1127-34.
• Wang L, Vargas H, French SW. Cellular origin of gastrointestinal stromal tumors: a study of 27 cases. Arch Pathol Lab Med. Oct 2000;124(10):1471-5. [Medline].
• Warakaulle DR, Gleeson F. MDCT appearance of gastrointestinal stromal tumors after therapy with imatinib mesylate. AJR Am J Roentgenol. Feb 2006;186(2):510-5.
• Wong NA, Young R, Malcomson RD, et al. Prognostic indicators for gastrointestinal stromal tumours: a clinicopathological and immunohistochemical study of 108 resected cases of the stomach. Histopathology. Aug 2003;43(2):118-26. [Medline].
• de Mestier P, des Guetz G. Treatment of gastrointestinal stromal tumors with imatinib mesylate: a major breakthrough in the understanding of tumor-specific molecular characteristics. World J Surg. Mar 2005;29(3):357-61; discussion 362.
• van der Zwan SM, DeMatteo RP. Gastrointestinal stromal tumor: 5 years later. Cancer. Nov 1 2005;104(9):1781-8.

Article Last Updated: Jun 30, 2006