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Metformin and pancreatic neuroendocrine tumors:A systematic review and meta-analysis

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World Journal of Gastroenterology 2024年第7期30卷 759-769页

作者： Maja Cigrovski Berkovic Alessandro Coppola Vibor Sesa Anna Mrzljak Quirino Lai Department for Sport and Exercise Medicine Faculty of Kinesiology University of ZagrebZagreb 10000Croatia Department of Surgery Sapienza University of RomeRome 00185Italy Department of Gastroenterology and Hepatology Liver Transplant CenterUniversity Hospital Centre ZagrebZagreb 10000Croatia Department of Medicine School of MedicineZagreb 10000Croatia General Surgery and Organ Transplantation Unit Department of SurgerySapienza University of RomeRome 00018Italy

BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor ***,identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is *** this perspective,metformin is emerging as a molecule of *** studies have described metformin,a widely used agent for the treatment of patients with type 2 diabetes mellitus(T2DM),to be effective in modulating different tumor-related events,including cancer incidence,recurrence and survival by inhibiting mTOR *** systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with *** To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and posttreatment outcomes of *** A systematic review of the published literature was undertaken,focusing on the role of T2DM and metformin in insurgence and prognosis of pNET,measured through outcomes of tumor-free survival(TFS),overall survival and progression free *** A total of 13 studies(5674 patients)were included in this *** of 809 pNET cases from five retrospective studies(low study heterogeneity with I^(2)=0%)confirms the correlation between T2DM and insurgence of pNET(OR=2.13,95%CI=1.56-4.55;P<0.001).The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients(hazard ratio=1.84,95%CI=0.78-2.90;P<0.001).The study heterogeneity was intermediate,with I^(2)=51%.A few studies limited the possibility of performing pooled analysis in the setting of metformin;therefore,results were heterogeneous,with no statistical relevance to the use of this drug in the diagnosis and prognosis of *** T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS

关键词： pancreatic neuroendocrine tumors Type 2 diabetes mellitus Prognosis Treatment Metformin

Consensus on the clinical diagnosis and treatment of grade 3 pancreatic neuroendocrine tumors

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胰腺病学杂志(英文) 2024年第2期07卷 97-105页

作者： Chen Jie Wu Wenming Bai Chunmei Chi Yihebali Huo Li Jiang Liming Ji Yuan Luo Jie Li Jie Li Jingnan Lou Wenhui Shao Chenghao Shen Lin Wang Feng Wang Yu Xue Ling Xu Jin Yuan Chunhui Yu Xianjun Yin Xiaoyu Zhao Hong Zhu Xiongzeng Zhao Yupei Centre for neuroendocrine tumors Fudan University Shanghai Cancer Center Shanghai China Department of General Surgery State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College Hospital Chinese Academy of Medical Science and Peking Union Medical College Beijing China Department of Medical Oncology Peking Union Medical College Hospital Chinese Academy of Medical Science &amp Peking Union Medical College Beijing China Department of Medical Oncology National Cancer Center/ National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China Department of Nuclear Medicine State Key Laboratory of Complex Severe and Rare Diseases Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine Peking Union Medical College Hospital Chinese Academy of Medical Sciences Beijing China Department of Diagnostic Radiology National Cancer Center/National Clinical Research Center for Cancer/ Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China Department of Pathology Zhongshan Hospital Fudan University Shanghai China Department of Pathology China-Japan Friendship Hospital Beijing China Department of Gastroenterological Oncology Beijing Cancer Hospital Peking University Cancer Hospital &amp Institute Beijing China Department of Gastroenterology Peking Union Medical College Hospital Peking Union Medical College Chinese Academy of Medical Sciences Beijing China Department of pancreatic Surgery Zhongshan Hospital Fudan University Shanghai China Department of pancreatic-Biliary Surgery Second Affiliated Hospital of Naval Medical University Shanghai China Department of Gastrointestinal Oncology Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Peking University Cancer Hospital &amp Department of Nuclear Medicine Nanjing First Hospital Nanjing Medical University Nanjing China Depar

The World Health Organization (WHO) 2017 classifications for neuroendocrine neoplasms (NENs) subdivided grade 3 pancreatic neuroendocrine neoplasms (pNENs) into G3 well-differentiated pancreatic neuroendocrine tumors (G3 pNETs) and poorly differentiated pancreatic neuroendocrine carcinomas (pNECs), according to the mitotic count, Ki-67 index, and cell differentiation. As a new category, G3 pNETs remain a challenging group of tumors to manage by lacking large randomized trials and consensus to support its clinical practice. Therefore, the Chinese pancreatic Surgery Association, Chinese Society of Surgery, Chinese Medical Association gathered experts in this field to formulate this consensus for the diagnosis and treatment of G3 pNETs.

关键词： Clinical diagnosis Grade 3 pancreatic neuroendocrine tumors Treatment

pancreatic neuroendocrine tumors: Therapeutic challenges and research limitations

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World Journal of Gastroenterology 2020年第28期26卷 4036-4054页

作者： Gabriel Benyomo Mpilla Philip Agop Philip Bassel El-Rayes Asfar Sohail Azmi Department of Oncology Wayne State University School of MedicineDetroitMI 48201United States Department of Hematology Oncology Emory Winship InstituteAtlantaGA 30322United States

pancreatic neuroendocrine tumors(PNETs)are known to be the second most common epithelial malignancy of the *** can be listed among the slowest growing as well as the fastest growing human *** prevalence of PNETs is deceptively low;however,its incidence has significantly increased over the past *** to the American Cancer Society’s estimate,about 4032(>7%of all pancreatic malignancies)individuals will be diagnosed with PNETs in *** often cause severe morbidity due to excessive secretion of hormones(such as serotonin)and/or overall tumor *** can live for many years(except for those patients with poorly differentiated G3 neuroendocrine tumors);thus,the prevalence of the tumors that is the number of patients actually dealing with the disease at any given time is fairly high because the survival is much longer than pancreatic ductal *** to significant heterogeneity,the management of PNETs is very complex and remains an unmet clinical *** terms of research studies,modest improvements have been made over the past decades in the identification of potential oncogenic drivers in order to enhance the quality of life and increase survival for this growing population of ***,the majority of systematic therapies approved for the management of advanced stage PNETs lack objective response or at most result in modest benefits in *** this review,we aim to discuss the broad challenges associated with the management and the study of PNETs.

关键词： pancreatic neuroendocrine tumors Gastroenteropancreatic neuroendocrine tumors Management Limitation Novel Agents Emerging targets

Genomic landscape of pancreatic neuroendocrine tumors

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World Journal of Gastroenterology 2014年第46期20卷 17498-17506页

作者： Niklas Gebauer Christian Schmidt-Werthern Veronica Bernard Alfred C Feller Tobias Keck Nehara Begum Dirk Rades Hendrik Lehnert Georg Brabant Christoph Thorns Department of Pathology University Hospital of Schleswig-Holstein23538 LuebeckGermany Department of Surgery University Hospital of Schleswig-Holstein23538 LuebeckGermany Department of Radiation Oncology University Hospital of Schleswig-Holstein 23538 LuebeckGermany Department of Internal Medicine I University Hospital of Schleswig-Holstein23538 LuebeckGermany

AIM: To investigate the prognostic role of genomic stability and copy number alterations (CNAs) pancreatic neuroendocrine tumors (PanNETs).

关键词： Array comparative genomic hybridization Copy number alterations Chromosomal aberrations pancreatic neuroendocrine tumors Prognosis

Prediction of the lymphatic,microvascular,and perineural invasion of pancreatic neuroendocrine tumors using preoperative magnetic resonance imaging

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World Journal of Gastrointestinal Surgery 2023年第12期15卷 2809-2819页

作者： Yu-Liang Liu Hai-Bin Zhu Mai-Lin Chen Wei Sun Xiao-Ting Li Ying-Shi Sun Department of Radiology Peking University Cancer Hospital and InstituteBeijing 100142China Department of Pathology Peking University Cancer Hospital and InstituteBeijing 100142China

BACKGROUND Significant correlation between lymphatic,microvascular,and perineural invasion(LMPI)and the prognosis of pancreatic neuroendocrine tumors(PENTs)was confirmed by previous *** was no previous study reported the relationship between magnetic resonance imaging(MRI)parameters and *** To determine the feasibility of using preoperative MRI of the pancreas to predict LMPI in patients with non-functioning PENTs(NFPNETs).METHODS A total of 61 patients with NFPNETs who underwent MRI scans and lymphadenectomy from May 2011 to June 2018 were included in this retrospective *** patients were divided into group 1(n=34,LMPI negative)and group 2(n=27,LMPI positive).The clinical characteristics and qualitative MRI features were *** order to predict LMPI status in NF-PNETs,a multivariate logistic regression model was *** performance was evaluated by calculating the receiver operator characteristic(ROC)curve with area under ROC,sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV)and *** There were significant differences in the lymph node metastasis stage,tumor grade,neuron-specific enolase levels,tumor margin,main pancreatic ductal dilatation,common bile duct dilatation,enhancement pattern,vascular and adjacent tissue involvement,synchronous liver metastases,the long axis of the largest lymph node,the short axis of the largest lymph node,number of the lymph nodes with short axis>5 or 10 mm,and tumor volume between two groups(P<0.05).Multivariate analysis showed that tumor margin(odds ratio=11.523,P<0.001)was a predictive factor for LMPI of *** area under the receiver value for the predictive performance of combined predictive factors was *** sensitivity,specificity,PPV,NPV and accuracy of the model were 48.1%(14/27),97.1%(33/34),97.1%(13/14),70.2%(33/47)and 0.754,*** Using preoperative MRI,ill-defined tumor margins can effectively predict LMPI in

关键词： pancreatic neuroendocrine tumors Magnetic resonance imaging Lymphatic invasion Microvascular invasion Perineural invasion

Analysis of risk factors affecting the prognosis of pancreatic neuroendocrine tumors

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Chinese Medical Journal 2014年第16期127卷 2924-2928页

作者： Tao Ming Yuan Chunhui Xiu Dianrong Shi Xueying Tao Liyuan Ma Zhaolai Jiang Bin Zhang Zhipeng Zhang Lingfu Wang Hangyan Department of General Surgery Peking University Third HospitalBeijing 100191 China Department of Pathology Peking University Health Science CenterBeijing 100191 China Peking University Third Hospital Research Center of Clinical Epidemiology Beijing 100191 China

Background pancreatic neuroendocrine tumors （pNETs） are a type of tumors with the characteristics of easy metastasis and *** date,the risk factors affecting the prognosis are still in the *** this study,several risk factors will be discussed combined with our cases and *** Thirty-three patients diagnosed as pNETs were enrolled and the clinical features,blood tests,pathological features,surgical treatment,and follow-up data of these patients were collected and *** In this study,operation time of G3 cases was longer than G1/G2 cases （P=0.017）.The elevated level of tumor markers such as AFP,CEA,Ca125,and Ca19-9 may predict easier metastasis,earlier recurrence,and poor prognosis （P=0.007）.The presence of cancer embolus and nerve invasion increases along with the TNM stage （P=0.037 and P=0.040）,and the incidence of positive surgical margin increased （P=0.007）.When the presence of nerve invasion occurs,the chance of cancer embolus and lymph node metastasis also increases （P=0.016 and P=0.026）.Conclusions pNETs were tumors with the features of easy recurrence and metastasis and many risk factors could affect its prognosis such as the elevated levels of tumor markers and the presence of nerve invasion,except some recognized risk *** one or more of these factors existed,postoperative treatments may be needed to improve prognosis.

关键词： tumor marker risk factors nerve invasion prognosis pancreatic neuroendocrine tumors

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Non-functioning pancreatic neuroendocrine tumors: Surgery or observation?

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World Journal of Gastrointestinal Endoscopy 2017年第4期9卷 153-161页

作者： Yehonatan Bar-Moshe Haggi Mazeh Simona Grozinsky-Glasberg Department of Surgery Hadassah-Hebrew University Medical CenterMount Scopus neuroendocrine Tumor Unit Hadassah-Hebrew University Medical Center

Incidentally detected, sporadic, nonfunctional pancreatic neuroendocrine tumors are increasingly diagnosed on imaging studies performed for unrelated purposes. Although their resection is usually recommended, controversy still exists regarding their optimal management, due to their highly variable and difficult to predict biologic behavior. Recently, several studies and guidelines advocated an expectant management approach in small size, low grade, incidentally diagnosed nonfunctional pancreatic neuroendocrine tumors. The aim of this study is to review and summarize the available literature addressing nonfunctional pancreatic neuroendocrine tumors, with an emphasis on surgical management controversies.

关键词： pancreatic neuroendocrine tumors Nonfunctional Incidental Surgery Observation

Molecular alterations and therapeutic targets in pancreatic neuroendocrine tumors

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Journal of Pancreatology 2023年第3期6卷 119-126页

作者： Yarui Ma Xiaoyue Wang Hong Zhao Yuchen Jiao State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Center for Bioinformatics School of Basic Medicine Peking Union Medical CollegeInstitute of Basic Medical Sciences Chinese Academy of Medical SciencesBeijingChina Department of Hepatobiliary Surgery State Key Laboratory of Molecular OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Human pancreatic neuroendocrine tumors(PanNETs)are a rare,deadly tumor type that is sporadic or arises in the background of a hereditary syndrome.A critical genetic event in sporadic tumors is inactivation of the gene menin 1(MEN1)on chromosome 11,and indeed,PanNETs occur in patients with the hereditary syndrome multiple endocrine neoplasia type 1(MEN1)due to germline mutations in the ***,we review the recent progress in the field of molecular genetics and therapeutic targets of *** key genomic alterations,including MEN1,ATRX/DAXX,mammalian target of rapamycin(mTOR),DNA damage and repair associated genes,vascular endothelial growth factor receptor(VEGFR)and SSTRs,and epigenetic aberrations in PanNETs are *** addition,the commonly used preclinical models for PanNETs are enumerated.

关键词： Multiple endocrine neoplasia type 1 pancreatic neuroendocrine tumors Therapeutic targets

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Perspective of neo-adjuvant/conversion and adjuvant therapy for pancreatic neuroendocrine tumors

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Journal of Pancreatology 2019年第3期2卷 91-99页

作者： Chen Luohai Chen Jie Department of Gastroenterology The First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080GuangdongChina

The incidence rate of pancreatic neuroendocrine tumors(panNET)is increasing *** resection was the primary treatment choice for ***,till now,there were few studies concerning neo-adjuvant/conversion and adjuvant therapy for *** this article,we reviewed the currently widely used medical treatments for advanced *** seemed that peptide receptor radionuclide therapy(PRRT),chemotherapy(temozolomide-based or streptozocin-based)and sunitinib might be more effective to induce tumor shrinkage in panNET and therefore,these treatments could be tried in panNET when neo-adjuvant/conversion therapy was *** for adjuvant therapy,it was of great importance to identify patients with high risks of recurrence after curative surgery and previous studies found that high ki-67 index,large tumor size,lymphatic metastasis and perineural/vascular invasion,and so on,were correlated with early recurrence of *** PRRT and chemotherapy were more cytotoxic,these two kinds of therapies might be worth trying as adjuvant therapies in patients with high risks of recurrence after curative resection of ***,no studies discussed in this review directly investigated neo-adjuvant/conversion and adjuvant therapy for ***,more prospective studies were still warranted.

关键词： Adjuvant therapy Neo-adjuvant therapy pancreatic neuroendocrine tumors

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