Management and Survival Analysis of Patients with Duodenal Gastrointestinal Stromal Tumors

Among human gastrointestinal tumors, duodenal Gastrointestinal Stromal Tumors (GISTs) occur infrequently with a lack of lymphatic and submucosal dissemination and a location adjacent to the bile duct and pancreas, leaving the optimal surgical approach underexplored. Options aiming at a R0 resection include Limited Resection (LR) and Pancreaticoduodenectomy (PD). Fifteen patients with duodenal GIST were retrospectively reviewed who underwent surgical resection in our department from January 2008 to December 2012 and were separated into two groups (pancreaticoduodenectomy, PD, n=5 versus limited resection, LR, n=10). A total of 15 patients (seven males/eight females) with a median age of 57 years (range: 33 years to 76 years) were treated. Ten of the patients underwent limited resection: four went for wedge resections with primary closures and six went for segmental resections with end-to-end anastomosis. Patients undergoing PD were more likely to present with a larger tumor (median size: PD, 7.8 cm vs. LR, 5.1 cm; p=0.021) and longer operation time (median time: PD, 274 mins vs. LR, 196 mins; p=0.000). Duodenal GISTs treated by PD had more Mitotic number (median No.: PD, 9.2 vs. LR 4.3; p=0.006) and higher risk compared to LR group. In survival analysis of these patients, OS and DFS rates for the 10 duodenal GIST patients undergoing limited resection were 100% and 93.7% at 1 year and 75% and 67.8 % at 3 years respectively. Additionally, compared with patients undergoing LR, those treated with PD also tended to have a worse OS (p=0.04). And a worse disease-free survival and overall survival was also found associated with tumor size >5 cm and NIH high-risk classification, both with P<0.05. As a result, we recommended LR be performed whenever technically feasible. Jia-Jun Lu, Ya-Yun Zhu, Yang Gao, Yun-Tao Shi, Xin-Yu Huang and Zhou Yuan* Department of General Surgery, Shanghai Jiao Tong University, China Introduction Gastrointestinal Stromal Tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal tract, the main mechanism involved in the pathogenesis process is the mutation in one of two receptor tyrosine kinase genes (KIT and PDGF) [1-4]. While GISTs can arise anywhere along the gastrointestinal tract and most commonly originate from the stomach (60% to 70%), followed by small bowel (20% to 25%), of which, 3% to 5% are from the duodenum [5-7]. GISTs can arise in any part of the duodenum but most commonly arise from the second portion, which accounts for 30% of primary duodenal neoplasms [8]. There are so few studies centering on medical and surgical management of duodenal GISTs, and reports are limited by small sample size. Most of the patients with duodenum GISTs present with abdominal pain caused by obstruction, anemia, or gastrointestinal bleeding from a central ulceration [9]. Nevertheless, obstructive jaundice is rarely found even the tumor is located at the periampullary. Additionally, the special anatomic features of GISTs in the duodenum pose particular challenges for diagnosis and management. Tumor size, mitotic activity and anatomic site are currently used to predict malignant courses according to the modified Miettinen classification [10]. Furthermore, the results of mutation analysis of the KIT and PDGFRA gene and Comparative Genomic Hybridization (CGH) are employed as additional prognostic factors with impact on diagnosis and therapy [11,12]. A complete surgical resection remains the only curative treatment for localized GISTs despite of progression in systemic therapy in question [2,5,7,13,14]. But, unlike carcinomas, GISTs rarely develop lymph node infiltration although they can also develop liver and peritoneal metastases [15]. An extensive lymphadenectomy is unnecessary if no evidence showing lymph node metastases. Generally, local wedge resection, segmental duodenectomy and Pancreaticoduodenectomy (PD) are the most commonly used surgical procedures for duodenal GISTs [2,16-18]. The optimal surgical technique for duodenum GISTs, however, remains to be determined due to the anatomic and biological characteristics. The purpose of this study was to compare the efficacy of different surgical Zhou Yuan, et al., Clinics in Surgery General Surgery Remedy Publications LLC. , | http://clinicsinsurgery.com/ 2019 | Volume 4 | Article 2361 2 procedures in primary non-metastatic duodenal GISTs with regard to recurrence and survival at our institution. Material and Methods Fifteen patients with histology-assured diagnosis of duodenal GIST undergoing surgical resection from January 2008 to December 2012 in our department were retrospectively reviewed and were divided into two groups (pancreaticoduodenectomy, PD, n=5 versus limited resection, LR, n=10). Pathological diagnosis of GIST was achieved postoperatively by the biopsy and was confirmed by immunohistochemical staining for CD117. Data concerning age, gender, presentation, location of tumor, tumor size, surgical procedure and disease status were obtained from the patients information, including operation notes, pathology reports, and follow-up data. Tumor size and mitotic index were used for risk classification according to the NIH score [2,16,17]. Surgical procedures other than Pancreaticoduodenectomy (PD) were defined as Limited Resection (LR) which includes local, wedge and segmental resection of the duodenum [4,15,19]. The duodenal defect was primarily closed using absorbable suture after wedge resection. End-to-end anastomosis was performed after segmental duodenectomy. Whether a patient should be subject to a LR or PD procedure was determined by size and location of tumor. Nasogastric tube was put into the proximal end of the jejunum for better drainage of duodenal content during wedge or segmental resection. Surgical complications were classified as follows: abdominal bleeding, abdominal infection, pancreatic fistula, biliary leak and delayed gastric empting and so on. Octreotide was routinely used after surgery and was withdrawn when amylase of abdominal drainage was normal. Follow-up was carried out through routine visits for clinical assessment at outpatient clinic every 6 months during the first 2 years after surgery and 1 year thereafter. Yearly chest and abdominal Computed Tomography (CT) upper gastrointestinal endoscopy were performed in all patients. Disease relapse was defined as local recurrence or distant metastases. Statistical Analysis The study endpoints were Overall Survival (OS) and Disease Free Survival (DFS). OS was calculated from the date of operation to last follow-up or death. DFS was determined as the time from operation to either biopsy-proven or radiologically-evidenced disease recurrence, or to death. All of the data was analyzed by SPSS software, version 19 (StatSoft, Hamburg, Germany). Comparisons of clinical characteristics between surgical groups were assessed using the t-test (continuous variables) and chi-square test (dichotomous variables). Figure 1: Disease-free survival rate of patients who went through limited resection was 93.3% at the first year and 67.8% at the third year. Figure 2: Overall survival of 15 patients after resection of duodenal GIST: stratified by surgical procedure, PD (green line): 26.2 months vs. LR (purple line): 40.7 months (P=0.04). Variables LR(n=10) PD (n=5) P value Female 4(40%) 3(60%) 0.427 Median age(years) 59.5(33-76) 55.6(43-70) 0.59 Tumor size(cm ) 5.1(3-8) 7.8(6-10) 0.021 Mitotic No (mitosis/50 HPF) <5 mitosis/50 HPF 6(60%) 2(40%) 6-10 mitosis/50 HPF 3(30%) 2(40%) 0.006 >10 mitosis/50 HPF 1(10%) 1(20%)