Diagnosis, Management And Survival Analysis Of Gastrointestinal Stromal Tumors

BACKGROUND:Gastrointestinal stromal tumors (GIST) represent the most common mesenchymal tumors of the digestive tract. Most gastrointestinal soft tissue neoplasms, previously classified as leiomyomas, schwannomas, leiomyoblastomas or leiomyosarcomas, are today classified as GIST on the basis of molecular and immunohistological features. GIST express a protooncogene protein called CD₁17 (c-kit protein, tyrosin kinase receptor), which can be detected by immunohistochemistry. They grossly appear to arise from the muscular layer of hollow organs of which the stomach and small bowel are the most common sites. We started to formally diagnose such gastrointestinal mesenchymal tumors as GISTs since 2002 in our hospital. The histogenesis, classification, diagnostic criteria, and biological behavior of GISTs have been the subject of much controversy to our surgeons. Moreover, because GISTs were previously regarded as being generally resistant to conventional chemotherapy, it is a major breakthrough that it has been a 40-69% partial response of inoperable and metastatic GISTs to targeted therapy using imatinib mesylate (Glivec, Novartis). So it is valuable to make it clear about diagnosis, management and survival of GISTs in our hospital.OBJECTIVE:To select GISTs from fifteen years'mesenchymal tumours of gastrointestinal tract in Nanfang Hospital. The clinical presentation, diagnostic methods, surgicaltreatment, prognostic factors and survival are analyzed retrospectively and proposals are present to guide future clinical management. MATERIALS AND METHODS:1, Case MaterialTo select the cases from January 1990 to October 2004 in Nanfang Hospital's medical database department based on diagnosis of leiomyomas, schwannomas, leiomyoblastomas. Only cases with pathology diagnosis are collected and name, age, gender, address, telephone number, symptom, examination result (such as gastroscopy, B-ultrasonic, CT scan, MRI, Barium meal), operation data, tumor location, maximum tumor size, and immunohistochemistry are record. The data was input in statistic software SPSS 10.0 and middle amount cases were chosen with stratified sampling method according to location.2, Analysis of Histological and Immunohistochemistry Parameters Reviewing all the sections of chosen cases by a gastrointestinal pathologist andpicked up the most typical section representing GIST morphology of each case and paraffin block to the section from pathology department.Immunohistochemical analysis was performed on all 68 tumors sections by means of following steps. First, sections were deparaffinized with xylene and ethanol. Second, endogenous peroxidase activity was quenched by exposure to 3 percent hydrogen peroxide. Third, nonspecific binding sites were blocked by normal animal serum. Forth, antibodies to CDn7, CD34, Actin and S-100 were applied. Fifth, sections were incubated with biotinylated antibody. Sixth, visualization was achieved using commercial SP (VltraSensitive SP) and DAB reagents with Streptavidin-peroxidase method. The sections of control groups were done according to such steps except adding PBS during the forth steps. The section is regarded as positivity if more than 10% of tumors cells colored.GIST diagnosis is defined as the tumor section is positivity for immunohistochemistry of CDm- The patents clinical characteristics, such as sexual ratio, age, symptom, pathology and radiographic reports (gastroscopy, colonoscopy, B-ultrasonic, CT scan, MRI, Barium meal), tumor location, and maximum tumor sizeare record and analyzed. The mitotic count of H-E stains section of each GIST was collected and morphology of GIST was described under light microscopy.3, Follow-up ProceduresThe follow-up procedure included investigating the GIST patients' survival by letters and telephone communication and the survival who had metastatic gastrointestinal mesenchymal tumors are collected too. GISTs were divided into four groups: mitotic count <5/50HPF (high-power field), mitotic count>5/50 HPF (high-power field), maximum tumor size <5cm and maximum tumor size.4,Statistical analysisUnivariate survival analysis was carried out using Kaplan-Meier plots and the log rank test. Ratio and amounts analysis were carried out using crosstabs' chi-square and independence t test by SPSS 10.0. P<0.05 was considered statistically significant. RESULT: 1, Demographics220 gastrointestinal mesenchymal neoplasm patients were chosen in recent fifteen years from medical database and 133 cases that had confidently pathology diagnosis were qualified for our intention. 15 (11.3%) patients had metastasis during operations and among which 10 spread to the liver, 5 to perioneum, mesentery, lung, adrenal gland and pancreas. The size of such tumor was 12.27±6.352 cm and the patient's age was 54.00±11.05 years. We used stratified sampling method according to locations to choose 68 cases from 133 cases. The group consists of 58.8% male and 41.2% female, average age was 49.118 years; average size of GIST was 7.40±6.923 cm. Based on the stated location in pathology or operative report, 10.3% tumors were in esophagus, 44.1% in stomach, 10.3% in duodenum, 20.6% in jejunum, 7.4% in ileum, 1.5% in colon and rectum and 5.9% in other place of abdomen. 33.8% patients were diagnosed as leiomyomas, 17.6% as leiomyosarcomas, 14.7% as schwannomas, 2.9% as malignant schwannomas and 30.9% as GIST. A total of 51 patients were diagnosed as GIST. Of the GISTs, 56.9(29/51) were male and 43.1(22/51) were female. The patient age range 10 to 76 years (average, 48.9 years). The GISTs size range 1.0 to 35.0cm(average, 7.0cm). 43.1% tumors were smaller than 5cm. 7.8%tumors were in esophagus, 47.1% in stomach, 5.9% in duodenum, 25.5% in jejunum, 7.8% in ileum, 2.0% in colon and rectum and 3.9% in mesentery and peritonum.No metastasis GISTs and metastatic gastrointestinal mesenchymal tumors are compared with age and tumor size. The age of latter is older than GISTs'; there is no statistic significance. The size of latter is larger than GISTs', P=0.007.2, Clinical PresentationA major of GIST patients (56.9%) presented with GI bleeding as melena and hematemesis, 43.1% with upper abdominal discomfort as pain and distention, 5.9% and 7.8% with ileus and palpable mass respectively.3, Examination resultEndoscopic examination was engaged in 68.6% of GISTs and positivity is 77.1%, and biopsy positivity is less than 10%. Endoscopic ultrasonograpy (EUS) was employed in 31.4% of GISTs and positivity is 93.8%. CT was performed in 25.5% of GISTs and positivity is 92.3%. Barium meal was performed in 47.1% of GISTs and positivity is 91.7%. DSA was performed in 15.7% of GISTs and positivity is 87.5%. PET was performed in 3.9% of GISTs and positivity is 50%. Though the positivity of endoscopy is lower than those of EUS, DSA and CT, P>0.05, there is no statistic significance.4, Surgical Procedures43(84.3%) GISTs were operated by routine laparotomy, and only one case was found to invasive adjacent organs, 6 cases had distance metastasis during operation, 5 primary location was in small intestinal and one in stomach. Metastatic locations included liver, lung, spleen and mesentery. 8(15.7%) GISTs were performed in laparoscopic operation, 3 in stomach, 4 in jejunum and 1 in mesentery. The maximum size of GISTs in this group is 10cm. 18(13.5%) of 133 gastrointestinal mesenchymal tumors were treated through endoscopic therapy with resection, burn and knot.5, Histologic and Immunohistochemical Features75% of GISTs histologic pattern is spindle cells, 20% is epithelioid cells and 5% is mixture of spindle and epithelioid cells. 75.0%(51/68) is CDm positive, 64.7%(44/68) is CD34 positive, 17.6%(12/68) is S-100 positive and 63.2%(43/68) isSMA positive. GIST is defined as CDn7 positive, and positivity of CD34 is 76.5%, S-100 is 15.7% and SMA is 62.7%.6, Follow-upTotal 14 GISTs were lost to follow-up till April 2005, Ratio of lost to follow-up is 27.5%. Average survival time of GIST patients with tumor size no more than 5cm is 108.92 months. The medium survival time is unclear for the survival curve has no interface with 0.5. Average survival time of GIST patients with tumor size more than 5cm is 57,78 months, the medium survival time is 54.00 months, P=0.0020 (Log Rank). Average survival time of GIST patients with tumor mitotic count no more than 5/50HFP is 88.64 months. The medium survival time is unclear for the survival curve has no interface with 0.5. Average survival time of GIST patients with tumor mitotic count more than 5/50HFP is 76.12 months, the medium survival time is 54.00 months, P=0.0276(Log Rank).15 metastatic gastrointestinal mesenchymal tumor patients were investigated too, 2 patients were alive, 5 patients were dead and 8 were lost to follow-up. The ratio of lost to follow-up is 53.3%.CONCLUSION:1, The patients has poor prognosis with metastatic gastrointestinal mesenchymal tumor in the operation.2, EUS and CT are best diagnostic modalities before GIST operation.3, The result of laparoscopy and endoscopy therapy GIST needs further evaluation.4, The GISTs with size more than 5cm and mitotic count more than 5/50HFP have poor prognosis and should be performed regular follow-up after operation.