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      Time-trend and recurrence analysis of pancreatic neuroendocrine tumors

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          Abstract

          This study aimed to evaluate the evolving trends in clinicopathological features of pancreatic neuroendocrine tumors and to analyze the predictors of recurrence after curative resection. Data collected retrospectively from a single center between January 1990 and December 2017 were analyzed. Patients were categorized chronologically into three groups for evolving time-trend analysis. Overall, 542 patients (300 female, 55.4%) underwent surgical resection for pancreatic neuroendocrine tumors, including 435 (80.3%) with non-functional tumors. Time-trend analysis revealed that the surgically resected pancreatic neuroendocrine tumor number increased consistently; however, the incidental non-functional pancreatic neuroendocrine tumor number also increased over time ( P < 0.001). The 5- and 10-year disease-free survival rates were 86.4 and 81.3%, respectively. The overall recurrence rate was 13.7%, and the most common site of recurrence was the liver. The median time to recurrence after primary surgery was 19.0 (range 0.8–236.3) months, and the median survival time after recurrence was 22.6 (range 0.4–126.9) months. On multivariate analysis, grade G3 pancreatic neuroendocrine tumors (hazard ratio 4.51; P < 0.001), lymph node metastasis (hazard ratio 2.46; P = 0.009), lymphovascular invasion (hazard ratio 3.62; P = 0.004), perineural invasion (hazard ratio 2.61; P = 0.004) and resection margin (hazard ratio 4.20; P = 0.003) were independent prognostic factors of disease-free survival. The surgically resected pancreatic neuroendocrine tumor number increased over time mainly because of an increase in incidentally discovered non-functional pancreatic neuroendocrine tumors. Grade G3 pancreatic neuroendocrine tumors, lymph node metastasis, lymphovascular invasion, perineural invasion and a positive resection margin were significant predictors of worse disease-free survival in patients with surgically resected pancreatic neuroendocrine tumors.

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          Most cited references18

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          Pancreatic endocrine tumors: improved TNM staging and histopathological grading permit a clinically efficient prognostic stratification of patients.

          Pancreatic endocrine tumors are rare diseases and devising a clinically effective prognostic stratification of patients is a major clinical challenge. This study aimed at assessing whether the tumor-node-metastasis (TNM)-based staging and proliferative activity-based grading recently proposed by the European NeuroEndocrine Tumors Society (ENETS) have clinical value. TNM was applied to 274 patients with histologically diagnosed pancreatic endocrine tumors operated from 1991 to 2005, with last follow-up at December 2007. According to World Health Organization (WHO) classification, 246 were well-differentiated neoplasms (51 benign, 56 uncertain behavior, 139 carcinomas) and 28 poorly differentiated carcinomas. Grading was based on Ki67 immunohistochemistry. Survival analysis not only ascertained the prognostic value of the TNM system but also highlighted that in the absence of nodal and distant metastasis, infiltration and tumor dimensions over 4 cm had prognostic significance. T parameters were then appropriately modified to reflect this weakness. The 5-year survival for modified TNM stages I, II, III and IV were 100, 93, 65 and 35%, respectively. Multivariate analysis identified TNM stages as independent predictors of death, in which stages II, III and IV showed a risk of death of 7, 29 and 58 times higher than stage I tumors (P<0.0001). Ki67-based grading resulted an independent predictor of survival with cut-offs at 5 and 20%. In conclusion, WHO classification assigns clinically significant diagnostic categories to pancreatic endocrine tumors that need prognostic stratification by applying a staging system. The ENETS-TNM provides the best option, but it requires some modifications to be fully functional. The modified TNM described in this study ameliorates the clinical applicability and prediction of outcome of the ENETS-TNM; it (i) assigns a risk of death proportional to the stage at the time of diagnosis, and (ii) allows a clinically based staging of patients, as the T parameters as modified permit their clinical-radiological recognition. Ki67-based grading discerns prognosis of patients with same stage diseases.
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            Incidental pancreatic cysts: clinicopathologic characteristics and comparison with symptomatic patients.

            Widespread use of computed tomography and ultrasound has led to the identification of increasing numbers of patients with asymptomatic cystic lesions of the pancreas. Retrospective case series of patients with pancreatic cystic lesions. University-affiliated tertiary care referral center. Two hundred twelve patients with pancreatic cystic lesions seen in our surgical practice during 5 years (April 1997-March 2002). Presence or absence of symptoms, cyst size and location, cytologic or pathologic diagnosis, surgical treatment, and outcome. Seventy-eight (36.7%) of 212 patients were asymptomatic. Incidental cysts were smaller (3.3 +/- 1.9 vs 4.6 +/- 2.7 cm; P<.001) and were found in older patients (65 +/- 13 vs 56 +/- 15 years; P<.001). Seventy-eight percent of the asymptomatic patients and 87% of those with symptoms underwent surgery, with a single operative death in the entire group (0.5%). Seventeen percent of asymptomatic cysts were serous cystadenomas; 28%, mucinous cystic neoplasms; 27%, intraductal papillary mucinous neoplasms; and 2.5%, ductal adenocarcinomas. The respective numbers for symptomatic cysts were 7%, 16%, 40%, and 9%. Ten percent of asymptomatic patients had a variety of other cystic lesions, and in 12%, no definitive cytologic or pathologic diagnosis was obtained. Overall, 17% of asymptomatic patients had in situ or invasive cancer, and 42% had a premalignant lesion. When evaluated as a function of size, only 1 (3.5%) of 28 asymptomatic cysts smaller than 2 cm had cancer compared with 13 (26%) of 50 cysts larger than 2 cm (P =.04). The proportion of premalignant lesions, however, remained high in both groups (46% and 38%, respectively). Pseudocysts comprised only 3.8% of asymptomatic cysts compared with 19.4% of symptomatic cysts (P =.003). Incidental pancreatic cysts are common, occur in older patients, are smaller than symptomatic cysts, and are unlikely to be pseudocysts. More than half of them are either malignant or premalignant lesions and therefore cannot be dismissed.
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              Liver, gallbladder, extrahepatic bile ducts, and pancreas.

              The liver, gallbladder, bile ducts, and pancreas have a common embryologic origin; cancers that arise from these sites therefore are expected to share a similar spectrum of histologic types. These cancers are known for their extremely poor prognoses. Data from the Surveillance, Epidemiology, and End Results Program regarding the incidence, distribution of histologic types, stage of disease, and survival for cancers of the gallbladder (n = 4412), extrahepatic bile ducts (n = 3486), pancreas (n = 23,116), and liver (n = 6,391) were reviewed. The most common histologic types are discussed, and the frequency of rare types is reported. The incidence of biliary cancer decreased, while the incidence of hepatic and pancreatic cancer rose slightly over the 15-year period from 1973 to 1987. Age and sex distributions varied by histologic type. Greater than 98% of pancreatic and biliary cancers were carcinomas, and adenocarcinoma (not otherwise specified) was the most common histologic type recorded. In the liver, hepatocellular carcinoma was the most common type, followed by intrahepatic cholangiocarcinoma. The overall 5-year relative survival rates for these cancers were very low: gallbladder, 12.3%; extrahepatic bile duct, 12.7%; liver 3.1%; and pancreas 2.5% (all stages combined, 1978-1986). This review confirmed that these carcinomas are associated with a very poor outcome; however, survival was influenced by stage of disease and histologic type. In the gallbladder and extrahepatic bile ducts, papillary adenocarcinoma was associated with the best outcome of all histologic types, and in the exocrine pancreas, mucinous cystadenocarcinoma was associated with the best prognosis.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                July 2019
                27 June 2019
                : 8
                : 7
                : 1052-1060
                Affiliations
                [1 ]Department of Surgery , Hallym University College of Medicine, Chuncheon, Republic of Korea
                [2 ]Division of Hepatobilliary and Pancreatic Surgery , Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea
                [3 ]Department of Surgery , College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
                Author notes
                Correspondence should be addressed to S C Kim: drksc@ 123456amc.seoul.kr
                Article
                EC-19-0282
                10.1530/EC-19-0282
                6652240
                31252400
                2a13e99e-200e-4cd5-b33b-ed42329f71e0
                © 2019 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 11 June 2019
                : 27 June 2019
                Categories
                Research

                pancreatic net,recurrence,time-trend,predictor
                pancreatic net, recurrence, time-trend, predictor

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