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Gastrointestinal Stromal Tumors: updating.

Romeo Giuli MD, resident.
School of General and Emergency Surgery.
University of Siena.   Italy.

February 2002.     Review Article.

To Previous Article about GIST
To the first updating
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Small bowel sarcomas ( SBS ) are rare, accounting for 10% of small bowel cancers. As a result, few studies of SBS have had enough patients to accurately define their natural history and to determine the factors that have an impact on patient survival. Data from the NCDB has demonstrated that adenocarcinomas are the most common malignant tumors of the small bowell, followed by carcinoid tumors, lymphomas, and sarcomas.
The objective of the Howe's study was to examine patient and tumor factors in SBS and to determine prognostic factors for disease-specific survival ( DSS ) using the National Cancer Data Base.

The NCDB collects data from a broad spectrum of hospitals in the USA on a voluntary basis and is a joint project of the American College of Surgeons Commission on Cancer and the American Cancer Society. These data are provided from cancer registries in a standardized format using coding schema from the Data Acquisition Manual, the American Joint Commission on Cancer ( AJCC ) Manual for Staging of Cancer and the World Health Organization's International Classification of Disease for Oncology ( ICD-O2 ) system for coding site and histologic type. An algorithm based on patient and disease characteristics ( including patient sex, site date of birth, and zip code ) was used to identify and remove duplicate records to ensure that patients seen at multiple institutions for the same cancer were not included within the database more than once.
The principal limitations of the cancer registry data are that they are collected retrospectively, do not contain specific details on presenting symptoms or the specific of the treatments received and are entered by cancer registrars. In fact the data in the NCDB did not include whether surgery was performed with curative or palliative intent, nor was there information regarding the completeness of resection. Specific details regarding the amount of radiation received or the agents and dosage used for chemotherapeutic regimens were also not available in the NCDB.
Also, unlike single-institution studies that pay attention to detail and can perform pathologic review when needed, the accuracy of staging and pathologic diagnosis within a national registry may vary widely across the institutions that submit data.
The advantages of the NCDB data are large numbers, representation from a broad spectrum of hospitals, and reduced selection bias for accrual of cases.

Of the 14,253 small bowel tumors diagnosed between 1985 and 1995, sarcomas represented 10,1%, ( 35% were adenocarcinomas, 28% were carcinoids, 21% were lymphomas ). Overall 5 year DSS was 38,9%, with a median survival of 34,1 months (n= 590).

Small bowel sarcomas are tumors that are challenging in terms of their histopathologic classification, grading and staging.

Most pathologists now refer to SBS as either GIST (previously referred to as leiomyosarcoma ) or GANT. GIST are much more common than GANT, and the latter are clearly of neural origin. Some have suggested subclassification of GI mesenchymal tumors into smooth muscle neoplasms (spindle, epithelioid, and mixed leiomyosarcomas), GANT, mixed leiomyosarcoma/neural tumors, and GIST-NOS (not otherwise specified). The data in the older literature describing GI leiomyomas and leimyosarcomas are still relevant in light of this new classification, for the majority of these tumors are GIST, and it is not clear whether CD117 positivity ( that suggests the origin from the interstitial cells of Cajal, a pacemaker cell in the lamina propria) has an influence on prognosis. However it has been shown that STI 571, a compound used to treat chronic myelogenous leukemia, can inhibit the tyrosine kinase activity of c-kit and seems to have activity in suppressing the proliferation of c-kit positive tumors.

The literature is further confused by grouping stromal tumors from all GI sites, despite evidence that tumors arising in the esophagus differ significantly in their behavior from those arising in the stomach, which differ from those arising in the small bowel.

Two other areas that present difficult diagnostic challenges for pathologists are distinguishing benign from malignant mesenchymal tumors and the grading of these tumors. Invasion into surrounding structures or metastases are unequivocal features of malignancy, but these are only evident in a subset of these tumors. For these reason, some have suggested that these tumors be described as having either low or high malignant potential. Characteristics such as tumor size, cellularity, mitotic rate, and necrosis dominate the criteria used for grading and malignant potential, but there is incomplete agreement on specific details, such as the critical size or mitotic rate ( 1 ).

The Howe's study used the general summary stage classification, which groups patients into those with localized tumors, those with regional extension, or those with distant metastases. But the authors proposed another staging system.
Ng et al defined T1 tumors as being localized and < 5cm in size, T2 as localized and > 5 cm, T3 as invading contiguous organs or with peritoneal implants, and T4 as tumor rupture.
G1 refers to low-grade tumors, G2 to high-grade tumors; M0 to no metastases, and M1 to the presence of metastases.
Patients with stage I lesions (T1, G1, M0) had a 75% 5 year overall survival, stage II (T2,G1,M0) a 52% 5 year overall survival, stage III (T1-2, G2, M0 or T3,G any, M0) a 28% 5 year overall survival, stage IV A a 12% 5 year overall survival, and stage IV B (any T4 tumor) a 7% 5 year overall survival ( 1, 2 ).

Significant differences in survival were determined using the Wilcoxon statistic for univariate analyses and by Cox regression in multivariate analyses.
By univariate analysis, patient age, sex, tumor size, tumor grade, histologic type, general summary stage, nodal status, and whether cancer-directed surgery was performed were significantly correlated with DSS. In multivariate analysis, tumor size <5 cm, leiomyosarcoma histology, and localized disease were found to be significant favorable prognostic factors for DSS.

When compared with other small bowel tumor types from the NCDB during this same period, the overall 5 year DSS for SBS (38,9%) was improved compared with adenocarcinomas ( 5year DSS of 30,5%) However, patients with carcinoid tumors ( 5year DSS of 72,7%) and lymphomas ( 5 year DSS of 56,4%) of the small bowel had even higher survival than those with SBS ( 1 ).

Shen et al. underline that submucosal lesions in the upper gastrointestinal tract are often difficult to evaluate.
EUS can assist in the accurate diagnosis of suspected submucoal lesions, frequently yelding previously unsuspected findings and providing supporting information about the nature of lesions, the likely need for endoscopic or surgical resection, and the need for further endoscoic follow-up.
This information may allay patient anxiety, increase physician certainty and reduce the need for further intervention.

Whether submucosal tumors can be distinguished as benign or malignant by EUS is still controversial. However, certain features on EUS may be more suggestive of malignancy. These include size greater than 3-4 cm, poorly defined or irregular margins, presence of internal echogenic foci of cystic spaces, adjacent lymphadenopathy and rapid growth rate at follow-up EUS ( 3 ).


1) James R Howe, Lucy H Karnell, and Carol Scott-Conner. Small Bowel Sarcoma: analysis of survival from the national cancer data base. Annals of surgical Oncology 2001, 8 ( 6 ): 496-508.

2) Ng EH, Pollock RE et al. Prognostic factors influencing survival in gastrointestinal leiomyosarcomas: implications for surgical management and staging. Ann Surg 1992; 215: 68-77.

3) EF Shen, et al. Endoscopic ultrasonography in the diagnosis and management of suspected upper gastrointestinal submucosal tumors. British Journal of Surgery 2002, 89, 231-235.

4) Leah Strickland et al. Gastrointestinal stromal tumors. Cancer Control, May/June 2001, vol.8, n3.

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