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Cancer Biology & Medicine 2022年第12期19卷 1649-1661页

作者： Rilan Bai Wenqian Li Jiuwei Cui Cancer Center the First Hospital of Jilin UniversityChangchun 130021China

neuroendocrine neoplasms(NENs)are a highly heterogeneous class of tumors arising from neuroendocrine cells and peptidergic *** failure of first-line treatment,patients have poor prognosis and limited treatment *** checkpoint inhibitors(ICIs)may be a powerful means of increasing therapeutic efficacy for such patients,but ICIs alone have low response rates and short disease control durations in most NENs and may be effective for only a portion of the *** combined with other immunotherapies,targeted therapies,or cytotoxic drugs have achieved some efficacy in patients with NENs and are worthy of further exploration to assess their benefits to the *** addition,accumulating experimental and clinical evidence supports that the interaction between neuroendocrine and immune systems is essential to maintain homeostasis,and assessment of this broad neuroendocrine-immune correlation is essential for NEN *** this review,we summarize the immune microenvironment characteristics,advances in immunotherapy,predictive biomarkers of ICI efficacy for NENs,and the effects of common endocrine hormones on the immune system,highlighting possible new application areas for this promising treatment in neglected NENs.

关键词： neuroendocrine neoplasms immunotherapy predictive biomarker hormones

Incidence and survival of neuroendocrine neoplasms in China with comparison to the United States

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Chinese Medical Journal 2023年第10期136卷 1216-1224页

作者： Rongshou Zheng Hong Zhao Lan An Siwei Zhang Ru Chen Shaoming Wang Kexin Sun Hongmei Zeng Wenqiang Wei Jie He National Central Cancer Registry National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Hepatobiliary Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Thoracic Surgery National Cancer Registry OfficeNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Background:neuroendocrine neoplasms(NENs)are rare tumors characterized by variable biology and delayed ***,the nationwide epidemiology of NENs has never been reported in *** aimed to estimate the incidence and survival statistics of NENs in China,in comparison to those in the United States during the same ***:Based on the data from 246 population-based cancer registries covering 272.5 million people of China,we calculated age-specific incidence on NENs in 2017 and multiplied by corresponding national population to estimate the nationwide incidence in *** data of 22 population-based cancer registries were used to estimate the trends of NENs incidence from 2000 to 2017 through the Joinpoint regression *** used the cohort approach to analyze the 5-year age-standardized relative survival by sex,age group,and urban-rural area between 2008 and 2013,based on data from 176 high-quality cancer *** used data from the Surveillance,Epidemiology,and End Results(SEER)18 program to estimate the comparable incidence and survival of NENs in the United ***:The overall age-standardized rate(ASR)of NENs incidence was lower in China(1.14 per 100,000)than in the United States(6.26 per 100,000).The most common primary sites were lungs,pancreas,stomach,and rectum in *** ASRs of NENs incidence increased by 9.8%and 3.6%per year in China and the United States,*** overall 5-year relative survival in China(36.2%)was lower than in the United States(63.9%).The 5-year relative survival was higher for female patients than male patients,and was higher in urban areas than in rural ***:The disparities in burden of NENs persist across sex,area,age group,and site in China and the United *** findings may provide a scientific basis on prevention and control of NENs in the two countries.

关键词： neuroendocrine neoplasms Incidence Survival Age factor Lung China The United States

Diagnosis, treatment, and current concepts in the endoscopic management of gastroenteropancreatic neuroendocrine neoplasms

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World Journal of Gastroenterology 2022年第34期28卷 4943-4958页

作者： Giuseppe Iabichino Milena Di Leo Monica Arena Giovanni Giuseppe Rubis Passoni Elisabetta Morandi Francesca Turpini Paolo Viaggi Carmelo Luigiano Luca De Luca Digestive Endoscopy Unit ASST Santi Paolo e CarloMilano 20144Italy Gastroenterology Section Grande Ospedale Metropolitano“Bianchi-Melacrino-Morelli”Reggio Calabria 89124Italy

Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)are rare tumors derived from the neuroendocrine cell system,which that have increased in incidence and prevalence in recent *** improvements in radiological and metabolic imaging,endoscopy still plays a pivotal role in the number of *** detection,characterization,and staging are essential in management and treatment *** and lower gastrointestinal(GI)endoscopy is essential for correct localization of the primary tumor site of GI *** ultrasonography(EUS)has an important role in the imaging and tissue acquisition of pancreatic NENs and locoregional staging of GI neuroendocrine *** staging and histological diagnosis have important prognostic *** operating techniques allow the removal of small GI NENs in the early stage of mucosal or submucosal invasion of the intestinal *** EUS-guided techniques may help the surgeon locate small and deep tumors,thus avoiding formal pancreatic resections in favor of parenchymal-sparing ***,locoregional ablative treatments have been proposed in recent studies with promising results in selected patients.

关键词： neuroendocrine neoplasms Gastrointestinal endoscopy Endoscopic resection Endoscopic ultrasound Ablative technique Tissue acquisition

neuroendocrine neoplasms of liver-A 5-year retrospective clinico-pathological study applying World Health Organization 2010 classification

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World Journal of Gastroenterology 2016年第40期22卷 8956-8966页

作者： Deepak Kalyansingh Burad Thomas Alex Kodiatte Sayd Mohamed Rajeeb Ashish Goel Chundamannil Eapen Eapen Banumathi Ramakrishna Department of Pathology Christian Medical College Department of Hepatology Christian Medical College

AIM To study the clinicopathological characteristics of neuroendocrine neoplasms(NEN) on liver samples and apply World Health Organization(WHO) 2010 grading of gastroenteropancreatic(GEP) *** Clinicopathological features of 79 cases of NEN of the liver diagnosed between January 2011 to December 2015 were analyzed. WHO 2010 classification of GEP NEN was applied and the tumors were graded as G1, G2 or G3. Two more categories, D1/2(discordant 1/2) and D2/3(discordant 2/3) were also applied. The D1/2 grade tumors had a mitotic count of G1 and Ki-67 index of G2. The D2/3 tumors had a mitotic count of G2 and Ki-67 index of G3. The follow up details which were available till the end of the study period(December 2015) were *** Of the 79 tumors, 16 each were G1 and G2, and 18 were G3 tumors. Of the remaining 29 tumors, 13 were assigned to D1/2 and 16 were D2/3 grade. Male preponderance was noted in all tumors except for G2 neoplasms, which showed a slight female predilection. The median age at presentation was 47 years(range 10-82 years). The most common presentation was abdominal pain(81%). Pancreas(49%) was the most common site of primary followed by gastrointestinal tract(24.4%) and lungs(18%). Radiologically, 87% of the patients had multiple liver lesions. Histopathologically, necrosis was seen in only D2/3 and G3 tumors. Microvascular invasion was seen in all grades. Metastasis occurred in all grades of primary NEN and the grades of the metastatic tumors and their corresponding primary tumors were similar in 67% of the cases. Of the 79 patients, 36 had at least one follow up visit with a median duration of follow up of 8.5 mo(range: 1-50 mo). This study did not show any impact of the grade of tumor on the short term clinical outcome of these *** Liver biopsy is an important tool for clinicopathological characterization and grading of NEN, especially when the primary is not identified. Eighty-seven percent of the patients had multifo

关键词： Liver neuroendocrine neoplasms Ki-67 Gastroenteropancreatic neuroendocrine neoplasms Metastasis Microvascular invasion

Advances in the treatment of gastroenteropancreatic neuroendocrine neoplasms with somatostatin analogues

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Journal of Pancreatology 2022年第1期5卷 1-14页

作者： Ming Lu Panpan Zhang Jianwei Zhang Jie Li Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of GI OncologyPeking University Cancer Hospital&InstituteBeijing 100142China

neuroendocrine neoplasms(NENs)include well-differentiated neuroendocrine tumors(NETs)and poorly-differentiated neuroendocrine carcinomas(NECs).Somatostatin receptors(SSTRs)are highly expressed on NETs cells,and somatostatin analogs(SSAs)could bind to SSTRs with high affinities,regulating cell proliferation and hormone *** many clinical trials have demonstrated the antiproliferative efficacy and safety of SSAs in metastatic gastroenteropancreatic NETs(GEP-NETs),SSAs have been recommended by multiple NEN guidelines as the first-line therapy of *** recent years,more and more researches have been exploring new therapeutic possibilities of SSA in GEP-NETs,such as high-dose SSA as second-line therapy,SSA in metastatic GEP-NETs with Ki67>10%,SSA as adjuvant therapy for postoperative pancreatic NETs patients,and combinations of SSA with chemotherapy or targeted *** this review,we summarized the latest published or released researches and discussed new application attempts of SSA in GEP-NETs.

关键词： neuroendocrine neoplasms neuroendocrine tumors Somatostatin analogs combination therapy clinical trials

Diagnostic accuracy of endoscopic ultrasonography for rectal neuroendocrine neoplasms

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World Journal of Gastroenterology 2014年第30期20卷 10470-10477页

作者： Hong-Tan Chen Guo-Qiang Xu Xiao-Dong Teng Yi-Peng Chen Li-Hua Chen You-Ming Li Department of Gastroenterology The First Affiliated Hospital of Zhejiang University School of Medicine Department of Pathology The First Affiliated Hospital of Zhejiang University School of Medicine

AIM: To investigate the diagnostic accuracy of endoscopic ultrasonography (EUS) for rectal neuroendocrine neoplasms (NENs) and the differential diagnosis of rectal NENs from other subepithelial lesions (SELs).

关键词： Rectum neuroendocrine neoplasms Endoscopic ultrasonography Diagnosis

Liver-directed therapies for liver metastases from neuroendocrine neoplasms:Can laser ablation play any role?

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World Journal of Gastroenterology 2020年第23期26卷 3118-3125页

作者： Sergio Sartori Lara Bianchi Francesca Di Vece Paola Tombesi Department of Internal Medicine Section of Interventional UltrasoundSt.Anna HospitalFerrara 44100Italy

Aggressive cytoreduction can prolong survival in patients with unresectable liver metastases(LM)from neuroendocrine neoplasms(NEN),and minimally invasive,liver-directed therapies are gaining increasing ***-based treatments are used in disseminated disease,whereas ablation techniques are usually indicated when the number of LM is *** radiofrequency ablation(RFA)is by far the most used ablative technique,the goal of this opinion review is to explore the potential role of laser ablation(LA)in the treatment of LM from *** uses thinner needles than RFA,and this is an advantage when the tumors are in at-risk ***,the multi-fiber technique enables the use of one to four laser fibers at once,and each fiber provides an almost spherical thermal lesion of 12-15 mm in *** a characteristic enables to tailor the size of each thermal lesion to the size of each tumor,sparing the liver parenchyma more than any other liver-directed therapy,and allowing for repeated treatments with low risk of liver failure.A recent retrospective study reporting the largest series of LM treated with LA documents both safety and effectiveness of LA,that can play a useful role in the multimodality approach to LM from NEN.

关键词： neuroendocrine neoplasms Liver metastases Liver-directed therapies Ablation techniques Laser ablation Radiofrequency ablation

Review of recent advances in medical treatment for neuroendocrine neoplasms:somatostatin analogs and chemotherapy

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Journal of Cancer Metastasis and Treatment 2016年第1期2卷 313-320页

作者： Francesca Spada Monica Valente Gastrointestinal Medical Oncology and neuroendocrine Tumors Unit European Institute of Oncology Via Ripamonti 43520141 MilanItaly Medical Oncology and Immunotherapy Division University Hospital of Sienaviale Bracci 1453100 SienaItaly

neuroendocrine neoplasms(NENs)are a heterogeneous group of rare tumours often producing high levels of hormones and causing *** are a number of different types of *** usually arise as advanced and low/intermediate grade only in a minority of cases,as high *** depends on which type and may include surgery,interventional radiology,and systemic treatment,including chemotherapy,somatostatin analogs,interferonα2b,peptide receptor radionuclide therapy,and only for pancreatic neuroendocrine tumors,molecular targeted agents,including everolimus and *** aim of the article is to review the medical approaches with somatostatin analogs and *** treatment of NENs is mainly based on their biological characteristics of aggressiveness and functional features,such as symptoms and endocrine markers.

关键词： neuroendocrine neoplasms somatostatin analogs chemotherapy peptide receptor radionuclide therapy molecular targeted agents

High frequency of alternative splicing variants of the oncogene Focal Adhesion Kinase in neuroendocrine tumors of the pancreas and breast

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Frontiers of Medicine 2023年第5期17卷 907-923页

作者： Dawei Xie Zheng Wang Beibei Sun Liwei Qu Musheng Zeng Lin Feng Mingzhou Guo Guizhen Wang Jihui Hao Guangbiao Zhou 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 CollegeBeijing100021China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of Sciences&University of Chinese Academy of SciencesBeijing100101China State Key Laboratory of Oncology in South China Sun Yat-sen University Cancer CenterGuangzhou510060China Department of Gastroenterology&Hepatology and Department of Pathology Chinese People’s Liberation Army General HospitalBeijing100853China Department of Pancreatic Cancer Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin’s Clinical Research Center for CancerTianjin300060China

The characteristic genetic abnormality of neuroendocrine neoplasms(NENs),a heterogeneous group of tumors found in various organs,remains to be ***,based on the analysis of the splicing variants of an oncogene Focal Adhesion Kinase(FAK)in The Cancer Genome Atlas datasets that contain 9193 patients of 33 cancer subtypes,we found that Box 6/Box 7-containing FAK variants(FAK^(6/7))were observed in 7(87.5%)of 8 pancreatic neuroendocrine carcinomas and 20(11.76%)of 170 pancreatic ductal adenocarcinomas(PDACs).We tested FAK variants in 157 tumor samples collected from Chinese patients with pancreatic tumors,and found that FAK^(6/7)was positive in 34(75.6%)of 45 pancreatic NENs,19(47.5%)of 40 pancreatic solid pseudopapillary neoplasms,and 2(2.9%)of 69 *** further tested FAK splicing variants in breast neuroendocrine carcinoma(BrNECs),and found that FAK^(6/7)was positive in 14(93.3%)of 15 BrNECs but 0 in 23 non-NEC breast *** explored the underlying mechanisms and found that a splicing factor serine/arginine repetitive matrix protein 4(SRRM4)was overexpressed in FAK^(6/7)-positive pancreatic tumors and breast tumors,which promoted the formation of FAK^(6/7)in *** results suggested that FAK^(6/7)could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.

关键词： FAKFAK^(6/7) SRRM4 neuroendocrine neoplasms pancreas breast SRRM4 neuroendocrine neoplasms pancreas breast

Molecular factors,diagnosis and management of gastrointestinal tract neuroendocrine tumors:An update

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World Journal of Clinical Cases 2022年第27期10卷 9573-9587页

作者： Efstathios Theodoros Pavlidis Theodoros Efstathios Pavlidis Department of 2^(nd) Surgical Propedeutic Hippocration HospitalAristotle University of ThessalonikiSchool of MedicineThessaloniki 54642Greece Department of 2^(nd) Surgical Propedeutic Aristotle University of ThessalonikiSchool of MedicineThessaloniki 54642Greece

The prevalence of gastrointestinal neuroendocrine tumors(GI-NETs) is increasing,and despite recent advances in their therapy,it remains inadequate in patients with advanced well-differentiated neuroendocrine *** tumors present many challenges concerning the molecular basis and genomic profile,pathophysiology,clinicopathological features,histopathologic classification,diagnosis and *** has been an ongoing debate on diagnostic criteria and clinical behavior,and various changes have been made over the last few *** carcinoma of the gastrointestinal system is a rare but highly malignant neoplasm that is genetically distinct from gastrointestinal system neuroendocrine tumors(NETs).The diagnosis and management have changed over the past *** novel biomarkers and metabolic players in cancer cells are useful and promising new diagnostic *** in positron emission tomography-computerized tomography and scintigraphy with new radioactive agents(^(64)Cu-DOTATATE or ^(68)Ga-DOTATATE) replacing enough octreoscan,has improved further the current diagnostic *** results provide targeted therapies with biological agents,new drugs,chemotherapy and ***,the role of surgery is important,since it is the cornerstone of *** resection of small bowel NETs with synchronous liver metastases is a surgical *** offers novel options not only for diagnosis but also for interventional *** therapeutic option should be individualized based on current multidisciplinary information.

关键词： Gastrointestinal neuroendocrine tumors neuroendocrine neoplasms Mixed NEN neuroendocrine carcinoma APUD cells Carcinoids Somatostatin analogs