Incidence and Possible Causative Factors

Incidence and Possible Causative Factors for Gastro-Intestinal Stromal Tumor (GI Stromal Tumor) in Chinese Population

The objective of this work in writing is to examine the incidence and possible causative factors for Gastro-Intestinal Stromal Tumor (GI stromal tumor in the Chinese population. GI Stromal Tumors are a quite rare sarcoma in the United States. There is now a specific treatment available for targeting this disease.

GI stromal tumors (GISTs) are reported to be a subset of GI mesenchymal tumors of varying differentiation." (Hassan, et al., 2008) These tumors were classified as GI leiomyomas, leiomyosarcomas, leiomyoblastomas, or schwannomas "as a result of their histological findings and apparent origin in the muscularis propira layer of the intestinal wall. GISTs are acknowledged as a "distinct group of mesenchymal tumors which account for approximately 80% of GI mesechymal tumors." (Hassan, et al., 2008)

The work of Corless, Fletcher, and Heinrich (2004) states that gastrointestinal stromal tumor (GIST) while at one time being a "poorly defined pathological oddity…has emerged as a distinct ontogenetic entity that is now center stage in clinical trials of kinase-targeted therapies" (Corless, Fletcher, and Heinrich (2004).

Definition of a Stromal Tumor

The term stromal tumor is stated to have been first coined in 1983 in the work of Mazur and Clark which gave recognition to the growing body of evidence that "…these gastrointestinal tract neoplasms were a clinicopathologically distinct entity." (Corless, Fletcher, and Heinrich, 2004) it is related that this appellation for GIST was not adopted in a wide basis however, in the early 1990s it was discovered that the majority of stromal tumors that arise in the gastrointestinal tract are positive for CD34." (Miettinen, Virolainen and Maarit, 1995, and Mikhael, Bacchi, Zrbo, 1994, cited in: Corless, Fletcher, and Heinrich, 2004) in the 1980s there was an alternate diagnosis of "gastrointestinal autonomic nerve tumor… that e4xhibiteed significant neural differentiation. It is now established that gastrointestinal autonomic nerve tumor is a morphologic variant of GIST." (Corless, Fletcher, and Heinrich, 2004)

Curvilinear collections of extracellular collagen called skeinoid fibers may be seen in either spindle cell or epithelioid tumors. Approximately 5% of cases have prominent myxoid stroma. Occasional tumors have neuroendocrine-like features that resemble paraganglioma or carcinoid. A signet ring-like variant has also been described.

Only five percent of cases are found to have "prominent myxoid stroma. Occasional tumors have neuroendocrine-like features that resemble paraganglioma or carcinoid. A signet ring-like variant has also been described. Some GISTs have a marked lymphocytic infiltrate, but this is uncommon. Nuclear atypia and multinucleation are more common in epithelioid GISTs; when present, they are often accompanied by other malignant features." (Corless, Fletcher, and Heinrich 2004)

There are two tumors most frequently mistaken for GISTs which are those of:

(1) Fibromatosis; and (2) leiomyosarcoma. (Rubic, Heinrich, and Corless, 2007)

GISTS are stated to arise primarily in the stomach (60%) and small intestine (25%); in the rectum (5%), esophagus (5%); and a variety of other locations (5%), including appendix, gallbladder, pancreas, mesentery, omentum, and retroperitoneum. (Rubic, Heinrich, and Corless, 2007) Individuals who are GIST patients are stated to be ranging in age from the teens to ninety years of age with peak at approximately 60 years of age. The tumors are stated to be generally speaking "between 2 and 30 cm in diameter at the time of diagnosis. The tumors may also cause "…mass-related symptoms or anemia due to mucosal ulceration." (Rubic, Heinrich, and Corless, 2007)

Many times GISTs are discovered by accident in the course of radiologic imaging for another unrelated condition. The primary therapy for GIST is stated to be that of 'surgical resection' with outcomes stated as being 'relatively good' for low- and intermediate-risk tumors. Resection of high-risk tumors practically always results in recurrence and in those who are recurrent. (Rubic, Heinrich, and Corless, 2007)

The work of Chan et al. (2006) entitled: "Gastrointestinal Stromal Tumors in a Cohort of Chinese Patients in Hong Kong" reports a study that had the aim of investigation the prevalence and clinical patterns of gastrointestinal stromal tumors or GISTs in Hong Kong Chinese and to assess the impact of introduction of CD117 on the incidence of the disease. It was concluded in the study that the incidence of GIST when comparing the U.S. And Hong Kong demonstrates that Hong Kong is comparable to the U.S. And lower than Finland. The true incidence of GISTs could be underestimated before the introduction of CD117. Incomplete resection, tumor size 5 cm or above, invasion to the adjacent organ or presence of metastasis are factors predicting tumor-related death or recurrence. (Rubic, Heinrich, and Corless, 2007)

Surgical resection was the only method available for treating GIST until 2001 and it is reported that a case study report in the New England Journal which used various degrees of success in the treatment of other such disease and found that this treatment was completely ineffective. (Rubic, Heinrich, and Corless, 2007) the following table labeled Figure of this study for 'Advanced Nonresectable Gastrointestinal Stromal Tumors" in the study reported by Rubic, Heinrich and Corless."

Figure One -- Studies for Advanced Unresectable Gastrointestinal Strong

Conclusions of the student state that the evolution of treatment for GIST and specifically that for metstatic and metastatic and unresectable GIST, has been remarkable -- from ineffective cytotoxic chemotherapy to oral tyrosine kinase inhibitors that are quite efficacious. In the course of 7 years, the prognosis, treatment, and understanding of this disease have rapidly escalated…" (Rubic, Heinrich and Corless, 2007) it is related that while there has been notable improvement viewed with imatrib, the truth is that "…primary and acquired resistance has limited the effectiveness of this agent, and alternative therapies remain of utmost importance.

Beyond resistance, intolerance to treatment is a realistic concern as well. With new trials being conducted to identify new therapeutic agents for GIST, further changes and challenges are likely to emerge. The role of sunitinib in the current management of patients with GIST needs further exploration. A phase III trial evaluation is planned to determine whether there is a role for first-line therapy with sunitinib instead of imatinib, and treatment based on genotype information and mutational status needs further exploration." (Rubic, Heinrich and Corless, 2007)

The work of Dong, et al. (2007) entitled: "Gastrointestinal stromal tumors of the rectum: Clinical, pathologic, immunohistochemical characteristics and prognostic analysis" reports a study that focused on description of the pathological and immunohistochemical characteristics of rectal gastrointestinal stromol tumors and the papers are not corrected to reflect this. Dong, at al (2007) report a study review of 29 patients. The objectives of the study is to "…describe the clinical, pathological and immunohistochemical characteristics of rectal gastrointestinal stromal tumors (GISTs) and to correlate them with clinical outcomes. Material and methods." (2007)

The work of Zhou, Zeng, and Liu (2009) entitled: "Aberrations of Chromosome 13q in Gastrointestinal Stromal Tumors: Analysis of 91 Cases by Fluorescence in Situ Hybridization (FISH)" reports that the clinical behavior of gastrointestinal stromal tumors (GISTS) range from benign to malignant. It has been reported recently that Studies who that a loss of 13q could be correlated with GIST progression. The study reported by Zhou, Zeng and Liu (2009) states that the objectives of the study reported were to:

(1) detect chromosome aberrations and determine the corresponding gene status in GISTs; and (2) to assess potential roles of 13q aberrations in GIST by correlating various 13q aberrations with various histologic parameters and disease-free survival in a group of GIST patients. (Zhou, Zeng, and Liu, 2009)

Zhou, Zeng, and Liu report that there was a loss of RP11-685I15 detected in 18.7% of cases and 13 observations of Chromosome 13 in 24.2% of cases. Additionally stated in the findings are those as follows: "The frequency of RP11-352N7 deletion, RP11-505F3 deletion, and chromosome 13 polysomy tended to be higher in the high-risk GISTs. Shorter disease-free survival was significantly associated with RP11-352N7 deletion (P=0.0361) and high-risk grade (P=0.0003). Chromosome 13 instability of GISTs may play a role in tumor progression. Loss of 13q, especially loss of Rb, RFP2, KCNRG, and KLF5 genes are frequent events in high-risk GISTs. Loss of 13q may be associated with tumor progression." (2009)