Surgical treatment and prognostic analysis for gastrointestinal stromal tumors (GISTs) of the small intestine: before the era of imatinib mesylate

BACKGROUND: Gastrointestinal stromal tumors (GISTs), the most common type of mesenchymal tumors of the gastrointestinal (GI) tract, demonstrate positive kit staining. We report our surgical experience with 100 small intestine GIST patients and identify predictors for long-term disease-free survival (DFS) and overall survival (OS) to clarify the difference between high- and low-risk patients. METHODS: The clinicopathologic and follow-up records of 100 small intestine GIST patients who were treated at Chung Gung Memorial Hospital between 1983 and 2002 were retrospectively reviewed. Clinical and pathological factors were assessed for long-term DFS and OS by using a univariate log-rank test and a multivariate Cox proportional hazard model. RESULTS: The patients included 52 men and 48 women. Their ages ranged from 27 to 82 years. Among the 85 patients who underwent curative resection, 44 (51.8%) developed disease recurrence (liver metastasis was the most common form of recurrence). The follow-up period ranged from 5 to 202 months (median: 33.2 months). The 1-, 3-, and 5-year DFS and OS rates were 85.2%, 53.8%, and 43.7%, and 91.5%, 66.6%, and 50.5%, respectively. Using multivariate analysis, it was found that high tumor cellularity, mitotic count >5/50 high-power field, and a Ki-67 index ≧10% were three independent factors that were inversely associated with DFS. However, absence of tumor perforation, mitotic count < 5/50 high power field, and tumor with low cellularity were predictors of long-term favorable OS. CONCLUSION: Tumors with low cellularity, low mitotic count, and low Ki-67 index, which indicate low risk, predict a more favorable DFS for small intestine GIST patients undergoing curative resection. Absence of tumor perforation with low mitotic count and low cellularity, which indicates low risk, can predict long-term OS for small intestine GIST patients who have undergone curative resection

Gastrointestinal Stromal Tumors (GIST)

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract, occurring predominantly in the stomach and small intestine. These tumors account for up to 3% of all gastrointestinal malignancies, with a reported annual incidence of 10–15 cases per million population. GISTs are thought to originate from interstitial cells of Cajal (ICC) or ICC precursor cells, and are characterized by activating mutations in the KIT (CD117) and platelet-derived growth factor receptor alpha (PDGFRα) proto-oncogenes in 85–95% of all cases. The clinical presentation and tumor biology of GISTs are widely variable, with several advances being made over the past two decades in the understanding of GIST tumor biology and pathophysiology. This has led to a paradigm shift in management from the purely surgical approach of the past, to a multi-modality treatment strategy with a greater role for targeted therapies in the form of tyrosine kinase inhibitors, resulting in significantly improved patient outcomes

Gastrointestinal stromal tumors: A clinicopathologic and risk stratification study of 255 cases from Pakistan and Review of Literature

Purpose: To describe the clinicopathological features of gastrointestinal stromal tumors (GIST) diagnosed in our section and to perform risk stratification of our cases by assigning them to specific risk categories and groups for disease progression based on proposals by Fletcher et al and Miettinen and Lasota. Material and Results: We retrieved 255 cases of GIST diagnosed between 2003 and 2014. Over 59% were male. The age range was 16 to 83 years with a mean of 51 years. Over 70% occurred between 40 and 70 years of age. Average diameter of tumors was 10 cms. The stomach was the most common site accounting for about 40%. EGISTs constituted about 16%. On histologic examination, spindle cell morphology was seen in almost of 85% cases. CD117 was the most useful immunohistochemical antibody, positive in 98%. Risk stratification was possible for 220 cases. Based on Fletcher\u27s consensus proposal, 62.3 gastric, 81.8% duodenal, 68% small intestinal, 72% colorectal and 89% EGISTs were assigned to the high risk category; while based on Miettinen and Lasota\u27s algorithm, about 48% gastric, 100% duodenal, 76% small intestinal, 100% colorectal and 100% EGISTs in our study were associated with high risk for disease progression, tumor metastasis and tumor related death. Follow up was available in 95 patients; 26 were dead and 69 alive at follow up. Most of the patients who died had high risk disease and on average death occurred just a few months to a maximum of one to two years after initial surgical resection. Conculsion: Epidemiological and morphologic findings in our study were similar to international published data. The majority of cases in our study belonged to the high risk category

SMALL BOWEL NEOPLASM CHARACTERIZATION AND INFLAMMATORY-RELATED AND SPORADIC SMALL BOWEL ADENOCARCINOMA COMPARISON OF CLINICAL FEATURES

Small bowel cancer (SBC) represents 1 to 5 % of all gastrointestinal cancer and is a rare cancer with a bad prognosis often arising in a Crohn's disease context. Histopathologic types of small bowel cancer comprehend adenocarcinomas, gastrointestinal stromal tumors (GISTs), neuroendocrine tumors (NET), and lymphoma. This study first aims to assess if there are prognostic and clinical criteria to distinguish between adenocarcinoma, Net and Gist to create a possible algorithm for the diagnostic exams in patients with undefined small bowel neoplasm. This study second aims to assess the burden of small bowel cancer (SBC) in patients with Crohn's disease (CD) and in those without IBD, and to identify possible factors associated with morbidity and with a poor prognosis.Small bowel cancer (SBC) represents 1 to 5 % of all gastrointestinal cancer and is a rare cancer with a bad prognosis often arising in a Crohn's disease context. Histopathologic types of small bowel cancer comprehend adenocarcinomas, gastrointestinal stromal tumors (GISTs), neuroendocrine tumors (NET), and lymphoma. This study first aims to assess if there are prognostic and clinical criteria to distinguish between adenocarcinoma, Net and Gist to create a possible algorithm for the diagnostic exams in patients with undefined small bowel neoplasm. This study second aims to assess the burden of small bowel cancer (SBC) in patients with Crohn's disease (CD) and in those without IBD, and to identify possible factors associated with morbidity and with a poor prognosis

Recent advances in the management of gastrointestinal stromal tumor.

Gastrointestinal stromal tumor (GIST) is a rare but an important clinical entity seen in our clinical practice. It is the most common mesenchymal tumor of the gastrointestinal tract and most common malignancy of the small intestine. Although the exact prevalence of GIST is not known, the incidence of GIST has been increasing. GISTs arise from interstitial cells of Cajal. Most of the GISTs occur due to mutation in c-kit gene or platelet derived growth factor receptor alpha gene. 15% of GISTs do not have these mutations and they are called wild-type GISTs. Almost all GISTs express KIT receptor tyrosine kinase. Histologically, GISTs look like spindle cell tumors most of the time but they can be epitheloid or mixed type. The median size of GISTs varies from 2.7 cm to 8.9 cm. Clinically, patients with small GISTs remain asymptomatic but as the GIST size increases, patients present with various symptoms depending on the location of the GIST. Most of GISTs are located in the stomach or small bowel. Diagnosis is suspected on imaging and endoscopic studies, and confirmed by tissue acquisition with immunohistochemical staining. The aggressiveness of GISTs depends on the size, mitotic index and location. Surgical resection is the treatment of choice. But various endoscopic modalities of resection are increasingly being tried. Tyrosine kinase inhibitors are extremely useful in the management of large GISTs, unresectable GISTs and metastatic GISTs. Treatment options for metastatic GISTs also include radiotherapy, chemotherapy, hepatic artery embolization, chemoembolization and radiofrequency ablation

Clinical Practice Guideline for Accurate Diagnosis and Effective Treatment of Gastrointestinal Stromal Tumor in Korea

Despite the rarity in incidence and prevalence, gastrointestinal stromal tumor (GIST) has emerged as a distinct pathogenetic entity. And the clinical management of GIST has been evolving very rapidly due to the recent recognition of its oncogenic signal transduction pathway and the introduction of new molecular-targeted therapy. Successful management of GIST requires a multidisciplinary approach firmly based on accurate histopathologic diagnosis. However, there was no standardized guideline for the management of Korean GIST patients. In 2007, the Korean GIST study group (KGSG) published the first guideline for optimal diagnosis and treatment of GIST in Korea. As the second version of the guideline, we herein have updated recent clinical recommendations and reflected changes in diagnosis, surgical and medical treatments for more optimal clinical practice for GIST in Korea. We hope the guideline can be of help in enhancing the quality of diagnosis by members of the Korean associate of physicians involving in GIST patients's care and subsequently in achieving optimal efficacy of treatment

Deletions of Chromosome 1p and 15q are Associated with Aggressiveness of Gastrointestinal Stromal Tumors

Background/PurposeSite-dependent profiles of chromosome imbalances (CIs) have been reported in gastrointestinal stromal tumors (GISTs). However, the role of specific CIs in association with metastasis is not clear.MethodsThirteen resected liver metastatic GISTs, including seven from the stomach and six from the small intestine, were analyzed using comparative genomic hybridization (CGH). The CIs associated with metastatic risk were assessed by comparing them with those identified in our previous study of 25 primary GISTs, including 14 from the stomach and 11 from the small intestine.ResultsSynchronous detection of liver metastasis was found more often in patients with intestinal than gastric GIST (5/6 vs. 2/7, p = 0.048). When compared with the primary tumors, the CI profile of liver metastases was similar in the intestinal group, but became more complex in the gastric group. Deletions of chromosomes 1p and 15q were very common (> 80%) in primary and metastatic tumors of the intestinal group, and exhibited a trend towards increase in the metastatic tumors of the gastric group. Both groups had a doubling in the frequency of 22q deletion in the liver metastases, which was not significantly different. Other CIs, including 9p deletion, increased significantly in the liver metastases of the gastric group, but not in the intestinal group.ConclusionOur results, together with clinical findings, indicated a CGH profile associated with the intrinsic aggressiveness of the GISTs. Deletion of 1p and 15q play a critical role in the acquisition of aggressiveness during early GIST development