Mixed neuroendocrine-nonneuroendocrine neoplasms(Mi NENs)of the digestive tract are a rare heterogeneous group of tumors that present many challenges in terms of diagnosis and treatment.Over the years,the diagnostic c...Mixed neuroendocrine-nonneuroendocrine neoplasms(Mi NENs)of the digestive tract are a rare heterogeneous group of tumors that present many challenges in terms of diagnosis and treatment.Over the years,the diagnostic criteria,classification,and clinical behavior of these tumors have been the subjects of ongoing debate,and the various changes in their nomenclature have strengthened the challenges associated with Mi NENs.This review is performed to provide an understanding of the key factors involved in the evolution of the designation of these tumors as Mi NEN,highlight the current diagnostic criteria,summarize the latest data on pathogenesis and provide information on available treatments.Moreover,this work seeks to increase the awareness about these rare neoplasms by presenting the clinicopathological features and prognostic factors that play important roles in their behavior and discussing their different regions of origin in the gastrointestinal system(GIS).Currently,the Mi NEN category also includes tumors in the GIS with a nonneuroendocrine component and epithelial tumors other than adenocarcinoma,depending on the organ of origin.Diagnosis is based on the presence of both morphological components in more than 30%of the tumor.However,this value needs to be reconfirmed with further studies and may be a limiting factor in the diagnosis of Mi NEN by biopsy.Furthermore,available clinicopathological data suggest that the inclusion of amphicrine tumors in the definition of Mi NEN is not supportive and warrants further investigation.The diagnosis of these tumors is not solely based on immunohistochemical findings.They are not hybrid tumors and both components can act independently;thus,careful grading of each component separately is required.In addition to parameters such as the metastatic state of the tumor at the time of diagnosis and the feasibility of surgical resection,the aggressive potential of both components has paramount importance in the choice of treatment.Regardless of the organ of origin within the GIS,almost Mi NENs are tumors with poor prognosis and are frequently encountered in the elderly and men.They are most frequently reported in the colorectum,where data from molecular studies indicate a monoclonal origin;however,further studies are required to provide additional support for this origin.展开更多
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.Th...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.These tumors present many challenges concerning the molecular basis and genomic profile,pathophysiology,clinicopathological features,histopathologic classification,diagnosis and treatment.There has been an ongoing debate on diagnostic criteria and clinical behavior,and various changes have been made over the last few years.Neuroendocrine 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 decade.Emerging novel biomarkers and metabolic players in cancer cells are useful and promising new diagnostic tools.Progress 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 imaging.Promising results provide targeted therapies with biological agents,new drugs,chemotherapy and immunotherapy.However,the role of surgery is important,since it is the cornerstone of management.Simultaneous resection of small bowel NETs with synchronous liver metastases is a surgical challenge.Endoscopy offers novel options not only for diagnosis but also for interventional management.The therapeutic option should be individualized based on current multidisciplinary information.展开更多
Gastroenteropancreatic neuroendocrine neoplasms are a heterogenous group of rare neoplasms that are increasingly being discovered,often incidentally,throughout the gastrointestinal tract with varying degrees of activi...Gastroenteropancreatic neuroendocrine neoplasms are a heterogenous group of rare neoplasms that are increasingly being discovered,often incidentally,throughout the gastrointestinal tract with varying degrees of activity and malignant potential.Confusing nomenclature has added to the complexity of managing these lesions.The term carcinoid tumor and embryonic classification have been replaced with gastroenteropancreatic neuroendocrine neoplasm,which includes gastrointestinal neuroendocrine and pancreatic neuroendocrine neoplasms.A comprehensive multidisciplinary approach is important for clinicians to diagnose,stage and manage these lesions.While histological diagnosis is the gold standard,recent advancements in endoscopy,conventional imaging,functional imaging,and serum biomarkers complement histology for tailoring specific treatment options.In light of developing technology,our review sets out to characterize diagnostic and therapeutic advancements for managing gastroenteropancreatic neuroendocrine tumors,including innovations in radiolabeled peptide imaging,circulating biomarkers,and endoscopic treatment approaches adapted to different locations throughout the gastrointestinal system.展开更多
Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)are rare tumors derived from the neuroendocrine cell system,which that have increased in incidence and prevalence in recent years.Despite improvements in radiol...Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)are rare tumors derived from the neuroendocrine cell system,which that have increased in incidence and prevalence in recent years.Despite improvements in radiological and metabolic imaging,endoscopy still plays a pivotal role in the number of GEPNENs.Tumor detection,characterization,and staging are essential in management and treatment planning.Upper and lower gastrointestinal(GI)endoscopy is essential for correct localization of the primary tumor site of GI NENs.Endoscopic ultrasonography(EUS)has an important role in the imaging and tissue acquisition of pancreatic NENs and locoregional staging of GI neuroendocrine tumors.Correct staging and histological diagnosis have important prognostic implications.Endoscopic operating techniques allow the removal of small GI NENs in the early stage of mucosal or submucosal invasion of the intestinal wall.Preoperative EUS-guided techniques may help the surgeon locate small and deep tumors,thus avoiding formal pancreatic resections in favor of parenchymal-sparing surgery.Finally,locoregional ablative treatments have been proposed in recent studies with promising results in selected patients.展开更多
Mixed neuroendocrine non-neuroendocrine neoplasms constitute rare tumors that are located mainly in the gastrointestinal(GI)tract and have high degrees of malignancy,and the frequency of these tumors has been increasi...Mixed neuroendocrine non-neuroendocrine neoplasms constitute rare tumors that are located mainly in the gastrointestinal(GI)tract and have high degrees of malignancy,and the frequency of these tumors has been increasing.They consist of a neuroendocrine neoplastic component with another component of adenocarcinoma usually and have a dismal prognosis.The rare GI pure neuroendocrine carcinoma is highly aggressive and requires complex and extensive management since a genetic distinction exists between it and GI non-neuroendocrine neoplasms,which are generally slow-growing lesions.The most common GI-mixed neuroendocrine non-neuroendocrine neoplasms are colorectal,followed by gastric,mainly in the gastroesophageal junction.Current imaging modalities of nuclear medicine and radiology play important roles in the accuracy of diagnosis.Liquid biopsy may contribute to early detection and timely diagnosis.Ultrasonography,either endoscopic or abdominal,is a technique that contributes to a diagnosis;additionally,contrast-enhanced ultrasonography is very helpful in followup appointments.Histopathology establishes a definite diagnosis and stage by evaluating the cell differentiation grade and the cell proliferation index Ki67.The genetic profile can be valuable in diagnosis and gene therapy.Surgical resection with wide lymphadenectomy,whenever possible,and adjuvant chemotherapy constitute the main therapeutic management strategies.Targeted therapy and immunotherapy achieve encouraging results.展开更多
Neuroendocrine neoplasms(NENs)are rare heterogeneous tumors that can develop in almost any organ,with the digestive organs,including the gastrointestinal tract and pancreas being the most commonly affected sites.Despi...Neuroendocrine neoplasms(NENs)are rare heterogeneous tumors that can develop in almost any organ,with the digestive organs,including the gastrointestinal tract and pancreas being the most commonly affected sites.Despite the fact that advances in initial therapies have progressed,there is presently no recognized effective treatment for advanced NEN.Immune checkpoint inhibitors(ICIs)have shown superior efficacy in treating several types of solid tumors.Despite their successful role in the treatment of partial NENs,such as small cell lung cancer,and Merkel cell carcinoma,the role of ICIs in most of the NENs remains limited.Nevertheless,due to their specific anti-tumor mechanisms and acceptable safety profile,ICIs are a promising avenue for further study in NENs therapy.Recent clinical trials have illustrated that combination therapy with ICI is more efficient than monotherapy,and multiple clinical trials are constantly ongoing to evaluate the efficacy and safety of these combination therapies.Therefore,the purpose of this review is to provide a comprehensive summary of the clinical progress of immunotherapy in NENs affecting the digestive system,with a specific emphasis on the application of programmed cell death protein 1/programmed death receptor ligand 1 inhibitor.Furthermore,this review has an exploration of the potential beneficiary population and the inherent value of utilizing immunotherapy in the management of NENs.展开更多
Neuroendocrine tumors(NETs), defined as epithelial tumors with predominant neuroendocrine differentiation, are among the most frequent types of small bowel neoplasm. They represent a rare, slow-growing neoplasm with s...Neuroendocrine tumors(NETs), defined as epithelial tumors with predominant neuroendocrine differentiation, are among the most frequent types of small bowel neoplasm. They represent a rare, slow-growing neoplasm with some characteristics common to all forms and others attributable to the organ of origin. The diagnosis of this subgroup of neoplasia is not usually straight-forward for several reasons. Being a rare form of neoplasm they are frequently not readily considered in the differential diagnosis. Also, clinical manifestations are nonspecific lending the clinician no clue that points directly to this entity. However, the annual incidence of NETs has risen in the last years to 40 to 50 cases per million probably not due to a real increase in incidence but rather due to better diagnostic tools that have become progressively available. Being a rare malignancy, investigation regarding its pathophysiology and efforts toward better understanding and classification of these tumors has been limited until recently. Clinical societies dedicated to this matter are emerging(NANETS, ENETS and UKINETS) and several guidelines were published in an effort to standardize the nomenclature, grading and staging systems as well as diagnosis and management of NETs. Also, some investigation on the genetic behavior of small bowel NETs has been recently released, shedding some light on the pathophysiology of these tumors, and pointing some new directions on the possible treating options. In this review we focus on the current status of the overall knowledge about small bowel NETs, focusing on recent breakthroughs and its potential application on clinical practice.展开更多
文摘Mixed neuroendocrine-nonneuroendocrine neoplasms(Mi NENs)of the digestive tract are a rare heterogeneous group of tumors that present many challenges in terms of diagnosis and treatment.Over the years,the diagnostic criteria,classification,and clinical behavior of these tumors have been the subjects of ongoing debate,and the various changes in their nomenclature have strengthened the challenges associated with Mi NENs.This review is performed to provide an understanding of the key factors involved in the evolution of the designation of these tumors as Mi NEN,highlight the current diagnostic criteria,summarize the latest data on pathogenesis and provide information on available treatments.Moreover,this work seeks to increase the awareness about these rare neoplasms by presenting the clinicopathological features and prognostic factors that play important roles in their behavior and discussing their different regions of origin in the gastrointestinal system(GIS).Currently,the Mi NEN category also includes tumors in the GIS with a nonneuroendocrine component and epithelial tumors other than adenocarcinoma,depending on the organ of origin.Diagnosis is based on the presence of both morphological components in more than 30%of the tumor.However,this value needs to be reconfirmed with further studies and may be a limiting factor in the diagnosis of Mi NEN by biopsy.Furthermore,available clinicopathological data suggest that the inclusion of amphicrine tumors in the definition of Mi NEN is not supportive and warrants further investigation.The diagnosis of these tumors is not solely based on immunohistochemical findings.They are not hybrid tumors and both components can act independently;thus,careful grading of each component separately is required.In addition to parameters such as the metastatic state of the tumor at the time of diagnosis and the feasibility of surgical resection,the aggressive potential of both components has paramount importance in the choice of treatment.Regardless of the organ of origin within the GIS,almost Mi NENs are tumors with poor prognosis and are frequently encountered in the elderly and men.They are most frequently reported in the colorectum,where data from molecular studies indicate a monoclonal origin;however,further studies are required to provide additional support for this origin.
文摘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.These tumors present many challenges concerning the molecular basis and genomic profile,pathophysiology,clinicopathological features,histopathologic classification,diagnosis and treatment.There has been an ongoing debate on diagnostic criteria and clinical behavior,and various changes have been made over the last few years.Neuroendocrine 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 decade.Emerging novel biomarkers and metabolic players in cancer cells are useful and promising new diagnostic tools.Progress 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 imaging.Promising results provide targeted therapies with biological agents,new drugs,chemotherapy and immunotherapy.However,the role of surgery is important,since it is the cornerstone of management.Simultaneous resection of small bowel NETs with synchronous liver metastases is a surgical challenge.Endoscopy offers novel options not only for diagnosis but also for interventional management.The therapeutic option should be individualized based on current multidisciplinary information.
文摘Gastroenteropancreatic neuroendocrine neoplasms are a heterogenous group of rare neoplasms that are increasingly being discovered,often incidentally,throughout the gastrointestinal tract with varying degrees of activity and malignant potential.Confusing nomenclature has added to the complexity of managing these lesions.The term carcinoid tumor and embryonic classification have been replaced with gastroenteropancreatic neuroendocrine neoplasm,which includes gastrointestinal neuroendocrine and pancreatic neuroendocrine neoplasms.A comprehensive multidisciplinary approach is important for clinicians to diagnose,stage and manage these lesions.While histological diagnosis is the gold standard,recent advancements in endoscopy,conventional imaging,functional imaging,and serum biomarkers complement histology for tailoring specific treatment options.In light of developing technology,our review sets out to characterize diagnostic and therapeutic advancements for managing gastroenteropancreatic neuroendocrine tumors,including innovations in radiolabeled peptide imaging,circulating biomarkers,and endoscopic treatment approaches adapted to different locations throughout the gastrointestinal system.
文摘Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)are rare tumors derived from the neuroendocrine cell system,which that have increased in incidence and prevalence in recent years.Despite improvements in radiological and metabolic imaging,endoscopy still plays a pivotal role in the number of GEPNENs.Tumor detection,characterization,and staging are essential in management and treatment planning.Upper and lower gastrointestinal(GI)endoscopy is essential for correct localization of the primary tumor site of GI NENs.Endoscopic ultrasonography(EUS)has an important role in the imaging and tissue acquisition of pancreatic NENs and locoregional staging of GI neuroendocrine tumors.Correct staging and histological diagnosis have important prognostic implications.Endoscopic operating techniques allow the removal of small GI NENs in the early stage of mucosal or submucosal invasion of the intestinal wall.Preoperative EUS-guided techniques may help the surgeon locate small and deep tumors,thus avoiding formal pancreatic resections in favor of parenchymal-sparing surgery.Finally,locoregional ablative treatments have been proposed in recent studies with promising results in selected patients.
文摘Mixed neuroendocrine non-neuroendocrine neoplasms constitute rare tumors that are located mainly in the gastrointestinal(GI)tract and have high degrees of malignancy,and the frequency of these tumors has been increasing.They consist of a neuroendocrine neoplastic component with another component of adenocarcinoma usually and have a dismal prognosis.The rare GI pure neuroendocrine carcinoma is highly aggressive and requires complex and extensive management since a genetic distinction exists between it and GI non-neuroendocrine neoplasms,which are generally slow-growing lesions.The most common GI-mixed neuroendocrine non-neuroendocrine neoplasms are colorectal,followed by gastric,mainly in the gastroesophageal junction.Current imaging modalities of nuclear medicine and radiology play important roles in the accuracy of diagnosis.Liquid biopsy may contribute to early detection and timely diagnosis.Ultrasonography,either endoscopic or abdominal,is a technique that contributes to a diagnosis;additionally,contrast-enhanced ultrasonography is very helpful in followup appointments.Histopathology establishes a definite diagnosis and stage by evaluating the cell differentiation grade and the cell proliferation index Ki67.The genetic profile can be valuable in diagnosis and gene therapy.Surgical resection with wide lymphadenectomy,whenever possible,and adjuvant chemotherapy constitute the main therapeutic management strategies.Targeted therapy and immunotherapy achieve encouraging results.
基金Capital Health Development Research Program,No.2022-2-7081Science and Technology Program of Tongzhou,Beijing,No.KJ2022CX016Beijing Natural Science Foundation,No.7234377。
文摘Neuroendocrine neoplasms(NENs)are rare heterogeneous tumors that can develop in almost any organ,with the digestive organs,including the gastrointestinal tract and pancreas being the most commonly affected sites.Despite the fact that advances in initial therapies have progressed,there is presently no recognized effective treatment for advanced NEN.Immune checkpoint inhibitors(ICIs)have shown superior efficacy in treating several types of solid tumors.Despite their successful role in the treatment of partial NENs,such as small cell lung cancer,and Merkel cell carcinoma,the role of ICIs in most of the NENs remains limited.Nevertheless,due to their specific anti-tumor mechanisms and acceptable safety profile,ICIs are a promising avenue for further study in NENs therapy.Recent clinical trials have illustrated that combination therapy with ICI is more efficient than monotherapy,and multiple clinical trials are constantly ongoing to evaluate the efficacy and safety of these combination therapies.Therefore,the purpose of this review is to provide a comprehensive summary of the clinical progress of immunotherapy in NENs affecting the digestive system,with a specific emphasis on the application of programmed cell death protein 1/programmed death receptor ligand 1 inhibitor.Furthermore,this review has an exploration of the potential beneficiary population and the inherent value of utilizing immunotherapy in the management of NENs.
文摘Neuroendocrine tumors(NETs), defined as epithelial tumors with predominant neuroendocrine differentiation, are among the most frequent types of small bowel neoplasm. They represent a rare, slow-growing neoplasm with some characteristics common to all forms and others attributable to the organ of origin. The diagnosis of this subgroup of neoplasia is not usually straight-forward for several reasons. Being a rare form of neoplasm they are frequently not readily considered in the differential diagnosis. Also, clinical manifestations are nonspecific lending the clinician no clue that points directly to this entity. However, the annual incidence of NETs has risen in the last years to 40 to 50 cases per million probably not due to a real increase in incidence but rather due to better diagnostic tools that have become progressively available. Being a rare malignancy, investigation regarding its pathophysiology and efforts toward better understanding and classification of these tumors has been limited until recently. Clinical societies dedicated to this matter are emerging(NANETS, ENETS and UKINETS) and several guidelines were published in an effort to standardize the nomenclature, grading and staging systems as well as diagnosis and management of NETs. Also, some investigation on the genetic behavior of small bowel NETs has been recently released, shedding some light on the pathophysiology of these tumors, and pointing some new directions on the possible treating options. In this review we focus on the current status of the overall knowledge about small bowel NETs, focusing on recent breakthroughs and its potential application on clinical practice.
文摘背景胃肠神经内分泌肿瘤(gastrointestinal neuroendocrine neoplasms,GI-NENs)临床表现多样,部分具有高侵袭性及转移性,预后差.收集我院诊治的GI-NENs患者的临床病理资料,免疫组化检测CD155、T细胞免疫球蛋白和ITIM结构域蛋白(T cell immunoreceptor with Ig and ITIM domains,TIGIT)的表达量,探讨其与临床病理和预后的关系,为患者的治疗提供一个新的方向.目的探讨CD155、TIGIT在GI-NENs中的表达量与临床病理特征的关系.方法收集2016-11/2020-08经我院诊治的168例GI-NENs患者的临床病理资料.免疫组化检测CD155、TIGIT的表达量,探讨其与临床病理和预后的关系.结果CD155和TIGIT在病理分级高的GI-NENs组织中,表达量也较高,差异有统计学意义(P<0.05);CD155表达量与年龄、肿瘤位置、肿瘤最大直径、病理分级、T分期、淋巴结转移、远处转移、TNM分期、Ki-67指数有关(P<0.05);TIGIT表达量与肿瘤最大直径、病理分级、T分期、淋巴结转移、TNM分期、Ki-67指数有关(P<0.05);CD155和TIGIT表达量高的患者预后较表达量低者差,差异有统计学意义(P<0.05).结论CD155和TIGIT表达量在不同分级、分期的GI-NENs患者存在差异,可能参与了GI-NENs的发生及进展的调控过程,高表达可能提示预后不佳.
