| Objective: Gastrointestinal stromal tumors(Gastric stromal tumor, GIST) belong to a common malignant potential of gastrointestinal mesenchymal tumors. Currently, it is universally recognized that almost all gastrointestinal stromal tumors have varying degrees of malignant potential, therefore their clinical manifestations are significantly different biological behavior from low-grade to high-grade. The middle-risk and high-risk patients of GIST were resulted from low-risk ones which further developed, without timely surgical intervention, these patients may occur tumor rupture, bleeding and recurrence, and usually require adjuvant therapy of Glivec after operation. With the spreading of EUS, the diagnosis rate of small gastrointestinal stromal tumor patients was significantly improved. Clinical researches on how to preferably choose treatments of small GIST has become a hot spot. According to Rossi Naming Standard and stromal tumor of the NIH risk grading standard the diameter(aliased as d)≤2cm GIST were defined as "little GIST", and those whose diameter>2cm were defined as "large GIST". Currently, the risk classification of GIST whose diameter more than 5cm is middle-risk and high-risk, which need for surgery and(or) imatinib adjuvant therapy. However, it is controversial for small gastrointestinal stromal tumor about if early surgical intervention necessary and when to intervene. The consensus of 2013 on diagnosis and treatment for gastrointestinal stromal tumor has defined diameter of 2cm or less as small GIST. For these small GIST positively early surgery or regular follow-up observation only when the tumor diameter grows more than 2cm surgical treatment chosen, and patients choosing which kind of treatment can benefit needs further study. This article contains a case-control study by tumors diameter of less than 2cm and diameter between 2cm and 5cm of gastrointestinal stromal tumors, and in order to discuss the importance of early surgical intervention of small GIST treatment. Moreover, we wish to provide a reference for the clinical treatment of small GIST.Methods: A retrospective analysis clinical data of 61 cases of small GIST whose tumor diameter less than 2cm and accepted surgery and confirmed by pathology in the Fourth Hospital of Hebei Medical University during January 2009 to November 2013. Accordingly, 48 cases of GIST whose tumor diameter between 2cm and 5cm were chosen to be control group.The cases were divided into test group by d≤2cm and control group by 2cm <d ≤5cm according to the different tumor diameter(including primary gastric GIST and primary extragastric GIST, which were further divided into sub-groups by primary duodenum, intestine, colon and rectum). We collected the data of the two groups of patients, respectively, including the clinical characteristics and pathological features, the positive rate of CD117 and DOG-1 in immunohistochemical results, the proportion of middle-risk and high-risk,genes mutation characteristics and postoperative recurrence for comparative analysis. We investigated the importance of early surgical treatment of small GIST. All datas involved in the research were analyzed and processed by SPSS17.0 software, measurement data was analyzed by t test, and enumeration data was analyzed by Chi-square test. Univariate analysis of the impact of each factor on the recurrence rate was realized by Log Rank test method and Chi-square test.Furthermore, we calculated the cumulative recurrence rate of 1-year, 2-year and 3-year. Multivariate analysis realized by COX model. The results of all data were considered statistically significant by P<0.05.Results: 1 General statistics. 1.1 Sex: The sex ratio of test group and the control group was approximate, and there were no significant gender differences. 1.2 Age: test group: The average age of the participants was 61.0 ± 7.78, ranging from 26 to 82; control group: the average age of the participants was 57.0 ± 4.24, ranging from 26 to 78. 2 Clinical manifestations: test group and control group had no specific clinical symptoms, some patients were found by physical examination. The symptoms include abdominal discomfort, abdominal pain, abdominal tympany, melena, heartburn, acid reflux, anemia, fatigue, etc. The proportion of asymptomatic cases of test group was higher than control group, but the difference was not statistically significant(P>0.05). 3 Preoperative examinations The relevant checks before surgery mainly contained endoscopy, endoscopic ultrasonography(EUS), CT, ultrasound. All the patients of the two groups selected were not suggested to other organs metastasis. 4 Surgical options There were 61 patients involved in the test group,14 cases received subtotal gastrectomy or total gastrectomy, 41 cases received gastric wedge resection(33 cases in which by open surgery and 8 cases by laparoscopic partial resection), 1 case received duodenum tumor resection, 2 cases received small bowel resection, 3 cases received colorectal tumor resection. There were 48 patients involved in the control group, 5 cases received subtotal gastrectomy or total gastrectomy, 26 cases received gastric wedge resection(12 cases in which by open surgery and 14 cases by laparoscopic partial resection), 7 cases received duodenal tumor resection, 7 cases received small bowel resection, 1 cases received rectal tumor resection, 2 cases received pancreaticoduodenectomy. 5 Pathological features 5.1 The average tumor diameter was 2.19 cm, ranging from 0.6cm to 5cm.There were 61 cases belonged to test group, and there were 48 patients belonged to control group. 5.2 They were divided into primary gastric GIST and primary extragastric GIST by tumor position. Primary extragastric GIST were further divided into sub-groups by primary duodenum, intestine, colon and rectum. The proportion of primary gastric GIST of test group was higher than control group, but the difference was not statistically significant(P>0.05). 5.3 Nuclear division counts Test group was lower than the control group, when it comes to the percentage of patients whose nuclear division counts > 5/50 HPF,and the difference was statistically significant(P<0.05). 5.4 Risk classification The high-risk ratio of test group is lower than control group, and the difference was statistically significant(P<0.05). The high-risk ratio of primary gastric little GIST is less than large GIST group, and the difference was statistically significant(P<0.05). The high-risk ratio of primary extragastric little GIST is less than large GIST group, but the difference was not statistically significant(P>0.05). 6 Immunohistochemical results The positive rate of CD117 and DOG-1 is one of the standard of GIST diagnosis. The positive rate of CD117, CD34, DOG-1 in the test group was 100%(61/61), 93.44%(57/61), 100%(30/30), and respectively was 97.83%(46/48), 85.42%(41/48), 92.86%(13/14) in the control group. 7 Gene mutation detection The detection of genes including tyrosine kinase growth factor receptor(aliased as C-kit) and platelet-derived growth factor receptor α(aliased as PDGFRα). Either of the two kinds of genes mutated could be considered mutation group. The rate of gene mutation of test group 83.61% was lower than control group 89.58%, but the difference was not statistically significant(P>0.05). The rate of gene mutation of primary gastric little GIST patients 83.02% less than large GIST group 83.87%, and the difference was statistically significant(P<0.05). The rate of gene mutation of primary extragastric little GIST patients 87.5% less than large GIST group 100%, but the difference was not statistically significant(P>0.05). 8 Adjuvant therapy The proportion of patients required oral imatinib is lower than control group, and the difference was statistically significant(P<0.05). The proportion of patients of primary gastric little GIST group required adjuvant therapy is less than large GIST group, and the difference was statistically significant(P<0.05). The proportion of patients of primary extragastric little GIST group required adjuvant therapy is less than large GIST group, but the difference was not statistically significant(P>0.05). 9 Analysis of prognosis 9.1 Correlation analysis of relapse and metastasis Until January 2015, there weren’t lost cases. The cumulative recurrence rate of 1-year、2-year and 3-year in test group was 1.64%, 6.58%, 6.58% and 6.25%, 14.58%, 14.58% in control group. The recurrence rate of test group and control group was no significant difference(P>0.05). Analyzed the recurrence rate by different tumor positions of primary gastric GIST and primary extragastric GIST by d≤2cm and 2cm<d≤5cm was no significant difference(P>0.05,both of the two groups). 9.2 Univariate analysis 9.2.1 The recurrence rate of test group was less than control group, but the difference was not statistically significant(P>0.05). The recurrence rate of patients of primary gastric GIST in d≤2cm group was less than2cm<d≤5cm group, but the difference was not statistically significant(P>0.05). The recurrence rate of patients of primary extragastric GIST in d≤2cm group was less than 2cm<d≤5cm group, but the difference was not statistically significant(P>0.05). 9.2.2 Nuclear division counts The recurrence rate of nuclear division counts ≤5/50 HPF group was lower than >5/50 HPF group, and the difference was statistically significant(P<0.05). The recurrence rate of gastric GIST’s nuclear division counts≤5/50 HPF group was lower than nuclear division counts>5/50 HPF group, and the difference was statistically significant(P<0.05). The recurrence rate of primary extragastric GIST’s nuclear division counts≤5/50 HPF group was lower than nuclear division counts >5/50 HPF group, but the difference was not statistically significant(P>0.05). 9.2.3 Risk classification The recurrence rate of(very) low risk group was less than high risk group, and the difference was statistically significant(P<0.05). Respectively analyze by tumor positions of primary gastric GIST and primary extragastric GIST, the recurrence rate of(very) low risk group were less than high risk group, but the difference was not statistically significant(P>0.05). 9.2.4 Gene mutation The recurrence rate of mutation group is higher than non-mutated group, but the difference was not statistically significant(P> 0.05). The recurrence rate of primary gastric GIST’s mutation group was lower than non-mutated group, and the difference was statistically significant(P<0.05). The recurrence rate of primary extragastric GIST’s mutation group was higher than non-mutated group, but the difference was not statistically significant(P>0.05). 9.3 Multivariate analysis Tumor position and nuclear division counts were factors independently associated with the recurrence and metastasis of GIST. COX regression model results include tumor position and nuclear division counts. Just for the position, P<0.05, and the relative risk was 0.275, the recurrence rate of primary extragastric GIST patients was 3.64 times as primary gastric GIST. As far as nuclear division counts, P<0.05, and the relative risk was 0.258, the recurrence rate of nuclear division counts >5/50 HPF group was 3.88 times as nuclear division counts ≤5/50 HPF group.Conclusions:1 All the little GIST patients performed endoscopy, CT and EUS before surgery, and postoperative diagnose by CD117 and DOG-1 positive result. C-kit and PDGFRα genes testing can be supplement diagnosis.2 Compared with large GIST group, the percentage of nuclear division counts>5/50 HPF group of little GIST patients was lower, medium-risk and high-risk ratio according to NIH classification is relatively low, as long as lower potential malignant.3 Little primary extragastric GIST is relatively high malignant than primary gastric GIST.4 Early detection and timely intervention could decrease the postoperative recurrence rate, which benefit patients greatly, and reduce the probability of adjuvant therapy by oral targeted imatinib. Moreover, the suffering to patients and the burden of the society and the family will be greatly reduced. |
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