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≤2 Cm), Non-Functioning Pancreatic Neuroendocrine Tumors: a Consensus Statement by the Chinese Study Group for Neuroendocrine Tumors (CSNET

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≤2 Cm), Non-Functioning Pancreatic Neuroendocrine Tumors: a Consensus Statement by the Chinese Study Group for Neuroendocrine Tumors (CSNET INTERNATIONAL JOURNAL OF ONCOLOGY 50: 567-574, 2017 Surgery management for sporadic small (≤2 cm), non-functioning pancreatic neuroendocrine tumors: A consensus statement by the Chinese Study Group for Neuroendocrine Tumors (CSNET) GUANG YANG1*, MENG JI1*, JIE CHEN2, RUFU CHEN3, YE CHEN4, DELIANG FU5, BAOHUA HOU6, HEGUANG HUANG7, LIMING JIANG8, KAIZHOU JIN9, NENGWEN KE10, YING LI11, YONG LI6, HOUJIE LIANG12, AN'AN LIU1, JIE LUO13, QUANXING NI9, CHENGWEI SHAO14, BOYONG SHEN15, WEIQI SHENG16, BIN SONG17, JIAN SUN3, CHUNLU TAN10, HUANGYING TAN18, QIYUN TANG19, YINGMEI TANG20, XIAODONG TIAN21, JIAN Wang22, JIE Wang23, WEI Wang24, WEI Wang25, ZHENG WU26, JIN XU9, QIANG YAN27, NING YANG28, YINMO YANG21, XIAOYU YIN29, XIANJUN YU9, CHUNHUI YUAN30, SHAN ZENG31, GUOCHAO ZHANG32, RENCHAO ZHANG33, ZHIWEI ZHOU25, ZHAOHUI ZHU34 and CHENGHAO SHAO1 1Department of General Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai; 2Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong; 3Department of Hepatopancreatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong; 4Department of Gastroenterology, Nanfang Hospial, Southern Medical University, Guangzhou, Guangdong; 5Department of Pancreatic Surgery, Pancreatic Disease Institute, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai; 6Department of General Surgery, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong; 7Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian; 8Department of Radiology, Cancer Hospital/Institute, Chinese Academy of Medical Sciences, Beijing; 9Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University; Pancreatic Cancer Institute, Fudan University, Shanghai; 10Department of Hepatobiliary and Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan; 11Department of Radiology, Peking University Cancer Hospital and Institute, Beijing; 12Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing; 13Department of Pathology, China-Japan Friendship Hospital, Beijing; 14Department of Radiology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai; 15Department of General Surgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai; 16Department of Pathology, Shanghai Cancer Center, Fudan University, Shanghai; 17Department of Pancreatic Surgery, Shanghai Changhai Hospital, Second Military Medical University, Shanghai; 18Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing; 19Department of Gastroenterology, Jiangsu People's Hospital, Nanjing Medical University, Nanjing, Jiangsu; 20Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University, Yunnan Research Center for Liver Diseases, Kunming, Yunnan; 21Department of General Surgery, Peking University First Hospital, Beijing; 22Department of Biliary and Pancreatic Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai; 23Department of General Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong; 24Department of General Surgery, Huadong Hospital, Shanghai Medical College, Fudan University, Shanghai; 25Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong; 26Department of Hepatobiliary Surgery, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi; 27Department of Surgery, Huzhou Central Hospital, Huzhou, Zhejiang; 28Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai; 29Department of Biliary and Pancreatic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong; Correspondence to: Dr Chenghao Shao, Department of General Surgery, Shanghai Changzheng Hospital, Second Military Medical University, No. 415 Fengyang Road, Shanghai 200003, P.R. China E-mail: [email protected] *Contributed equally Key words: surgical management, non-functioning pancreatic neuroendocrine tumors, 2 cm, consensus, Chinese Study Group for Neuroendocrine Tumors (CSNET) 568 YANG et al: A CONSENSUS STATEMENT ON SURGERY MANAGEMENT FOR SMALL NF-pNET PATIENTS BY CSNET 30Department of General Surgery, Peking University Third Hospital, Peking University, Beijing; 31Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan; 32Department of General Surgery, China-Japan Friendship Hospital, Beijing; 33Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang; 34Department of Nuclear Medicine, Peiking Union Medical College Hospital, Beijing, P.R. China Received October 14, 2016; Accepted December 12, 2016 DOI: 10.3892/ijo.2016.3826 Abstract. The incidence of small (≤2 cm), non-functioning that in 2005 and the number of the new incidences of non- pancreatic neuroendocrine tumors (NF-pNETs) increased functioning pNETs in 2010 was ~1.7-times that in 2005 (9). in the last decades. Before making appropriate strategy for Likewise, based on the first population-level analysis to patients with NF-pNETs ≤2 cm, pathological confirmation exclusively characterize NF-pNETs ≤2 cm in a surgical popu- is vital. Incidentally diagnosed, sporadic small NF-pNETs lation, the incidence of NF-pNETs ≤2 cm in the United States may bring aggressive behavior and poor prognosis, such as has increased by 710.4% over the 22-year study period with extrapancreatic extension, lymph nodal metastasis, distant annual percentage change 12.8%; while the NF-pNETs ≤2 cm metastasis and recurrence, even causing disease-related death. accounted for 20.2% of total pNET diagnoses in 2009, in Understanding and formulating an appropriate strategy for contrast to 12.3% of that in 1988, which nearly doubled over the the patients with sporadic small, non-functioning pancreatic last 22 years (10). Whether this is the result of a true increase neuroendocrine tumors have been controversial for some in incidence of the disease or result of increased detection is time. Although several studies have reported that patients still speculative. However, we have reasons to believe that the with NF-pNETs ≤2 cm had less rate of malignant behavior more frequent use of cross-sectional imaging, especially the compared with larger ones (>2 cm); and the surgery approach multiphasic computed tomography (CT) or magnetic reso- may leading to surgery-related pancreatic complications; but nance imaging (MRI) and endoscopic ultrasound (EUS) have there is still a lack of level I evidence to convince surgeons to played some important roles in this (2,3,10). abandon all cases with sporadic small NF-pNETs. Based on As for determining the appropriate management for an updated literature search and review, the members of the NF-pNETs ≤2 cm, surgery or surveillance, which one should Chinese Study Group for Neuroendocrine Tumors (CSNET) be taken into consideration remained controversial. In 2012, the from high-volume centers have reached a consensus on the European Neuroendocrine Tumor Society (ENETS) Guideline issue of the management strategy for the sporadic small suggested that a non-operative approach could be advocated NF-pNETs. We recommend that, except for some selected in selected cases for NF-pNETs ≤2 cm that are discovered patients with NF-pNETs <1 cm, incidentally discovered and incidentally (6); for the reasons that most of NF-pNETs unacceptable surgical risks, all others with NF-pNETs ≤2 cm ≤2 cm are likely benign or intermediate-risk lesions and only should undergo tumor resection with lymph node dissection 6% of NF-pNETs ≤2 cm are malignant when incidentally or at least lymph node sampling and careful postoperative discovered (11). However, in 2016, the latest ENETS Guideline surveillance. updated their views that patients with NF-pNETs ≤2 cm have two options: i) It is recommended to have surveillance approach Introduction for the patients with G1 or low G2, asymptomatic, mainly with head lesion, no radiological signs suspicious for malignancy, Pancreatic neuroendocrine tumors (pNETs), also named as as well as patient factors such as personal wishes, age, or with islet cell tumors, are relatively rare, accounting for 1-2% of all comorbidities; ii) while for the patients with G2, symptoms and pancreatic neoplasms (1,2). According to the hormonal symp- patient wishes, surgery is recommended (8). Moreover, during toms, they are broadly divided into functioning (F-pNETs) and the surveillance time, if the tumor size increase >0.5 cm or to non-functioning pNETs (NF-pNETs). An estimated 66-91% of a size of >2 cm, surgery is necessary (8). However, according the pNETs were non-functioning and patients with NF-pNETs to the National Comprehensive Cancer Network (NCCN) have been reported to have poorer outcomes than those with Guideline Version 2.2016, patients with NF-pNETs ≤2 cm F-pNETs (3,4). With respect to recent studies and consensus should undergo surgery (12). Observation can be considered in statements, in F-pNETs and symptomatic or large (>2 cm) cases as follows: tumors <1 cm, incidentally discovered; while NF-pNETs, radical pancreatic resection is the only treatment decision should be made based on estimated surgical risk, site capable of prolonging survival (5-7). However, in patients
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