Mixed neuroendocrine non-neuroendocrine neoplasms(MiNENs)are a hetero-geneous group of malignant neoplasms that can settle in the gastroenteropan-creatic tract.They are composed of a neuroendocrine(NE)and a non-NE com...Mixed neuroendocrine non-neuroendocrine neoplasms(MiNENs)are a hetero-geneous group of malignant neoplasms that can settle in the gastroenteropan-creatic tract.They are composed of a neuroendocrine(NE)and a non-NE compo-nent in at least 30%of each tumour.The non-NE component can include different histological combinations of glandular,squamous,mucinous and sarcomatoid phenotypes,and one or both of the components can be low-or high grade malignant.Recent changes in the nomenclature of these neoplasms might lead to great deal of confusion,and the lack of specific clinical trials is the main reason why their management is difficult.The review aims to clarify the definition of MiNEN and analyze available evidence about their diagnosis and treatment options according to their location and extension through careful analysis of the available data.It would be important to reach a general consensus on their diagnosis in order to construct a classification that remains stable over time and facilitates the design of clinical trials that,due to their low incidence,will require long recruitment periods.展开更多
AIM To identify the type localization andmorphology of APUD endocrine cells in thegastroenteropancreatic(GEP)system ofstomach-containing teleosts,and study APUDendocrine system in the stomach,intestine andpancreas of ...AIM To identify the type localization andmorphology of APUD endocrine cells in thegastroenteropancreatic(GEP)system ofstomach-containing teleosts,and study APUDendocrine system in the stomach,intestine andpancreas of fish species.METHODS Two kinds of immunocytochemical(ICC)techniques of the streptavidin biotin-peroxidase complex(SABC)and streptavidin-peroxidase(S-P)method were used.Theidentification,localization and morphology ofAPUD endocrine cells scattered in the mucosa ofdigestive tract,intermuscular nerve plexus andglandular body of northern snakehead(Channaargus),ricefield eel(Monopterus albus),yellow catfish(Pelteobagrus fulvidraco),mandarinfish(Siniperca chuatsi),largemouthbass(Micropterus salmoides),orientalsheatfish(Silurus asotus),freshwater pomfret(Colossoma brachypomum)and nile tilapia(Tilapia nilotica)were investigated with 8 kindsof antisera.RESULTS The positive reaction of 5-hydroxytryptamine(5-HT)immunoreactiveendocrine(IRE)cells was found in the digestive tract and glandular body of 8 fish species indifferent degree.Only a few gastrin(GAS)-IREcells were seen in C.argus,M.albus and P.fulvidraco.Glucagon(GLU)-IRE cells were notfound in the digestive tract and glandular bodybut existed in pancreatic island of most fishspecies.The positive reaction of growthhormone(GH)-IRE cells was found only inpancreatic island of S.Chuatsi and S.Asotus,no positive reaction in the other 6 fish species.Somatostatin(SOM)-,calcitonin(CAL)-,neurofilament(NF)-and insulin(INS)-IRE cellsin the stomach,intestine and pancreas of 8 kindsof fish were different in distribution and types.The distribution of all 8 APUD cells was the mostin gastrointestinal epithelium mucosa and then indigestive glands.The positive reaction of SOM-and 5-HT-IRE cells was found in intermuscularnerve plexus of intestine of P.fulvidraco andS.chuatsi.Only GH-IRE cells were denselyscattered in the pancreatic islands of S.chuatsiand S.asotus,and odd distribution in thepancreas of S.asotus,SOM-IRE cells weredistributed in the pancreatic islands of S.asotus,C.Brachypomum and T.nilotica.There were INS-IRE cells in the pancreaticislands of S.chuatsi and S.asolus.Eightkinds of APUD cells had longer cell body andcytoplasmic process when they were located inthe gastrointestinal epithelium,and had shortercell body and cytoplasmic process in the gastricgland,and irregular shape in the esophagus andpancreatic island.CONCLUSION Eight kinds of IRE cells were identified in the GEP system of stomach-containing teleosts. These endocrine cells were scattered in gastrointestinal mucosa, intermuscular nerve plexus, gland body, pancreatic gland and islands under APUD system. CAL- and GH-IRE cells in the pancreatic islands of fishes showed functional diversity for these two hormones. Their morphological feature provides evidence of endocrine-paracrine and endocrine-exocrine acting mode. This research can morphologically prove that the GEP endocrine system of fish ( the lowest vertebrate) is almost the same as of mammal and human.展开更多
Background: Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs) are a heterogeneous group of rare tumors. Many issues in terms of epidemiologic features, pathogenesis, and treatment of GEP-NENs are still under d...Background: Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs) are a heterogeneous group of rare tumors. Many issues in terms of epidemiologic features, pathogenesis, and treatment of GEP-NENs are still under discussion. Our study aimed to analyze the clinicopathologic characteristics and prognosis of Chinese patients with GEP-NENs.Methods: Complete clinicopathologic data and survival information of 1183 patients with GEP-NENs treated between 2005 and 2015 were collected from five medical centers in Guangdong Province, China. Patient survival was estimated using the Kaplan–Meier method and analyzed using the log-rank test; prognostic factors were analyzed using the Cox proportional hazards model.Results: The most common tumor location was the rectum(37.4%), followed by the pancreas(28.1%), stomach(20.7%), small intestine(7.2%), appendix(3.4%), and colon(3.3%). After initial definitive diagnosis, 1016(85.9%) patients underwent surgery. The 1-, 3-, and 5-year overall survival(OS) rates for the entire cohort were 87.9%, 78.5%, and 72.8%, respectively. The 3-year OS rates of patients with G1, G2, and G3 tumors were 93.1%, 82.7%, and 43.1%, respectively(P < 0.001). The 3-year OS rates of patients with stage I, II, III, and IV tumors were 96.0%, 87.3%, 64.0%, and 46.8%, respectively(P < 0.001). Patients with distant metastasis who underwent palliative surgery had a longer survival than those who did not(P = 0.003). Similar survival benefits of palliative surgery were observed in patients with neuroendocrine tumor(P y, M category, and sur= 0.031) or neuroendocrine carcinoma(P gery were found to be independent prog= 0.046). In multivariate analysis, age, grade, N categornostic factors.Conclusions: Patients with GEP-NENs who are women, younger than 50 years old, have smaller tumor size, have lower tumor grade, have lower T/N/M category, and who undergo surgery can have potentially longer survival time. Our data showed that surgery can improve the prognosis of GEP-NEN patients with distant metastasis. However, randomized controlled trials need to be conducted to establish the optimal criteria for selecting patients to undergo surgery.展开更多
Neuroendocrine(NE) gastroenteropancreatic tumors are a heterogeneous group of neoplasias arising from neuroendocrine cells of the embryological gut. Their incidence have increased significantly over the past 3 decades...Neuroendocrine(NE) gastroenteropancreatic tumors are a heterogeneous group of neoplasias arising from neuroendocrine cells of the embryological gut. Their incidence have increased significantly over the past 3 decades probably due to the improvements in imaging and diagnosis. The recent advances in molecular biology have translated into an expansion of therapeutic approaches to these patients. Somatostatin analogs, which initially were approved for control of hormonal syndromes, have recently been proven to inhibit tumor growth. Several new drugs such as antiangiogenics and others targeting mammalian target of rapamycin pathways have been approved to treat progressive pancreatic neuroendocrine tumors(NETs) although their role in nonpancreatic is still controversial. The treatment of NETs requires a coordinated multidisciplinary approach. The management of localized NETs primarily involves surgical resection followed by surveillance. However, the treatment of unresectable and/or metastatic disease may involve a combination of surgical resection, systemic therapy, and liver-directed therapies with the goal of alleviating symptoms of peptide release and controlling tumor growth. This article will review the current therapeutic strategies for metastatic gastroenteropancreatic NETs and will take a glimpse into the future approaches.展开更多
Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)are rare epithelial neoplasms derived from pluripotent endocrine cells along the gastrointestinal tract and pancreas.GEP-NENs are classified into well-different...Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)are rare epithelial neoplasms derived from pluripotent endocrine cells along the gastrointestinal tract and pancreas.GEP-NENs are classified into well-differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas.Despite overlapping morphological features,GEP-NENs vary in molecular biology,epigenetic,clinical behavior,treatment response,and prognosis features and remain an unmet clinical challenge.In this review,we introduce recent updates on the histopathologic classification,including the tumor grading and staging system,molecular genetics,and systemic evaluation of the diagnosis and treatment of GEP-NENs at different anatomic sites,together with some insights into the diagnosis of challenging and unusual cases.We also discuss the application of novel therapeutic approaches for GEP-NENs,including peptide receptor radionuclide therapy,targeted therapy,and immunotherapy with immune checkpoint inhibitors.These findings will help improve patient care with precise diagnosis and individualized treatment of patients with GEP-NENs.展开更多
AIM To compare health-related quality of life(HRQoL),anxiety, depression, and impulsivity scores in patients with and without carcinoid syndrome(CS), and correlated them with serum 5-hydroxyindoleacetic acid(5-HIAA) l...AIM To compare health-related quality of life(HRQoL),anxiety, depression, and impulsivity scores in patients with and without carcinoid syndrome(CS), and correlated them with serum 5-hydroxyindoleacetic acid(5-HIAA) levels.METHODS Patients with advanced gastroenteropancreatic neuroendocrine tumours(GEPNET), with and without CS completed HRQoL QLQ-C30 and QLQ-GI.NET21, Hospital Anxiety and Depression Scale(HADS) and Barratt Impulsivity Scale(BIS) questionnaires. Twosample Wilcoxon test was applied to assess differences in serum 5-HIAA levels, two-sample Mann-Whitney U test for HRQoL and BIS, and proportion test for HADS, between those with and without CS.RESULTS Fifty patients were included; 25 each with and without CS. Median 5-HIAA in patients with and without CS was 367 nmol/L and 86 nmol/L, respectively(P = 0.003). Scores related to endocrine symptoms were significantly higher amongst patients with CS(P = 0.04) and scores for disease-related worries approached significance in the group without CS, but no other statistically-significant differences were reported between patients with and without CS in responses on QLQ-C30 or QLQ-GI.NET21. Fifteen patients(26%) scored ≥ 8/21 on anxiety scale, and 6(12%) scored ≥ 8/21 on depression scale. There was no difference in median 5-HIAA between those scoring < or ≥ 8/21 on anxiety scale(P = 0.53). There were no statistically significant differences between groups in first or second-order factors(BIS) or total sum(P = 0.23).CONCLUSION Excepting endocrine symptoms, there were no significant differences in HRQoL, anxiety, depression or impulsivity between patients with advanced GEPNET, with or without CS. Over one quarter of patients had high anxiety scores, unrelated to peripheral serotonin metabolism.展开更多
BACKGROUND Long non-coding RNAs(lncRNAs) are a kind of single-stranded RNA of more than 200 nucleotides in length and have no protein-coding function. Amounting studies have indicated that lncRNAs could play a vital r...BACKGROUND Long non-coding RNAs(lncRNAs) are a kind of single-stranded RNA of more than 200 nucleotides in length and have no protein-coding function. Amounting studies have indicated that lncRNAs could play a vital role in the initiation and development of cancers, including gastric cancer(GC). Considering the crucial functions of lncRNAs, the identification and exploration of novel lncRNAs in GC is necessary.AIM To identify independent prognostic markers for the whole gastroenteropancreatic neuroendocrine tumor(GEP-NET) group.METHODS Ninety-three patients diagnosed with GEP-NETs within a specified period were included in this study. Patient data were retrospectively analyzed. The relationships between all independent variables and 5-year survival status calculated during the follow-up period(months) were assessed. In addition, the relationships between the independent variables were investigated.RESULTS When 5-year survival rate was compared, a statistically significant relationship between the age at diagnosis, male gender, tumor size, tumor stage, liver and/or distant metastasis, and tumor grade determined by the Ki-67 level and mitotic count, and the level of C-reactive protein(CRP), was observed. The meansurvival(overall survival) of the study group was 102.5 ± 6.3(SD) mo. The percentages of 1, 3 and 5-year survival were 90%, 72%, and 61%, respectively. In63 of 93 patients, Ki-67 and the mitotic count determined the same grade. The Ki-67 levels in 29 patients and the mitotic count in only 1 patient were in the higher grade. The risk of death increased by 4% for every 1 year increase at the diagnosis age and was 2.0-fold higher for male patients, 3.0-fold higher for G3 according to the mitotic count, 3.7-fold higher for G3 according to the Ki-67 level, 12.7-fold higher for cases with tumor stage 3 or 4 by a 1 cm increase in the ratio of 9% in tumor size, and 6.1-fold higher for patients with liver metastasis for every 1 mg/dL increase in the ratio of 1.5% in CRP level. There was a significant difference between pancreatic and stomach NETs in favor of stomach tumors in terms of survival.CONCLUSION Tumor site, stage, grade and Ki-67 level affected patient survival, and it was observed that CRP affected disease progression(particularly if it was > 20 mg/dL). However, a relationship between surgical resection of the lesion and survival was not shown. Larger scale prospective studies are required to determine whether CRP level may be a poor prognostic factor for the entire GEPNET group.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
BACKGROUND Gastroenteropancreatic neuroendocrine tumours(GEP-NETs)are slow-growing cancers that arise from diffuse endocrine cells in the gastrointestinal tract(GINETs)or the pancreas(P-NETs).They are relatively uncom...BACKGROUND Gastroenteropancreatic neuroendocrine tumours(GEP-NETs)are slow-growing cancers that arise from diffuse endocrine cells in the gastrointestinal tract(GINETs)or the pancreas(P-NETs).They are relatively uncommon,accounting for 2%of all gastrointestinal malignancies.The usual treatment options in advanced GEP-NET patients with metastatic disease include chemotherapy,biological therapies,and peptide receptor radionuclide therapy.Understanding the impact of treatment on GEP-NET patients is paramount given the nature of the disease.Health-related quality of life(HRQoL)is increasingly important as a concept reflecting the patients’perspective in conjunction with the disease presentation,severity and treatment.AIM To conduct a systematic literature review to identify literature reporting HRQoL data in patients with GEP-NETs between January 1985 and November 2019.METHODS The PRISMA guiding principles were applied.MEDLINE,Embase and the Cochrane library were searched.Data extracted from the publications included type of study,patient population data(mid-gut/hind-gut/GI-NET/P-NET),sample size,intervention/comparators,HRQoL instruments,average and data spread of overall and sub-scores,and follow-up time for data collection.RESULTS Forty-three publications met the inclusion criteria.The heterogeneous nature of the different study populations was evident;the percentage of female participants ranged between 30%-60%,whilst average age ranged from 53.8 to 67.0 years.Eight studies investigated GI-NET patients only,six studies focused exclusively on P-NET patients and the remaining studies involved both patient populations or did not report the location of the primary tumour.The most commonly used instrument was the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30(n=28)with consistent results across studies;the GI-NET-specific module Quality of Life Questionnaire-GINET21 was used in six of these studies.A number of randomised trials demonstrated no HRQoL changes between active treatment and placebo arms.The Phase III NETTER-1 study provides the best data available for advanced GEP-NET patients;it shows that peptide receptor radionuclide therapy can significantly improve GEP-NET patients’HRQoL.CONCLUSION HRQoL instruments offer a means to monitor patients’general disease condition,disease progression and their physical and mental well-being.Instruments including the commonly used European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 and GINET21 lack,however,validation and a defined minimal clinical important difference specifically for GINET and P-NET patients.展开更多
Our understanding about the epidemiological aspects,pathogenesis,molecular diagnosis,and targeted therapies of neuroendocrine neoplasms(NENs)have drastically advanced in the past decade.Gastroenteropancreatic(GEP)NENs...Our understanding about the epidemiological aspects,pathogenesis,molecular diagnosis,and targeted therapies of neuroendocrine neoplasms(NENs)have drastically advanced in the past decade.Gastroenteropancreatic(GEP)NENs originate from the enteroendocrine cells of the embryonic gut which share common endocrine and neural differentiation factors.Most NENs are welldifferentiated,and slow growing.Specific neuroendocrine biomarkers that are used in the diagnosis of functional NENs include insulin,glucagon,vasoactive intestinal polypeptide,gastrin,somatostatin,adrenocorticotropin,growth hormone releasing hormone,parathyroid hormone-related peptide,serotonin,histamine,and 5-hydroxy indole acetic acid(5-HIAA).Biomarkers such as pancreatic polypeptide,human chorionic gonadotrophin subunits,neurotensin,ghrelin,and calcitonin are used in the diagnosis of non-functional NENs.5-HIAA levels correlate with tumour burden,prognosis and development of carcinoid heart disease and mesenteric fibrosis,however several diseases,medications and edible products can falsely elevate the 5-HIAA levels.Organ-specific transcription factors are useful in the differential diagnosis of metastasis from an unknown primary of well-differentiated NENs.Emerging novel biomarkers include circulating tumour cells,circulating tumour DNA,circulating micro-RNAs,and neuroendocrine neoplasms test(NETest)(simultaneous measurement of 51 neuroendocrine-specific marker genes in the peripheral blood).NETest has high sensitivity(85%-98%)and specificity(93%-97%)for the detection of gastrointestinal NENs,and is useful for monitoring treatment response,recurrence,and prognosis.In terms of management,surgery,radiofrequency ablation,symptom control with medications,chemotherapy and molecular targeted therapies are all considered as options.Surgery is the mainstay of treatment,but depends on factors including age of the individual,location,stage,grade,functional status,and the heredity of the tumour(sporadic vs inherited).Medical management is helpful to alleviate the symptoms,manage inoperable lesions,suppress postoperative tumour growth,and manage recurrences.Several molecular-targeted therapies are considered second line to somatostatin analogues.This review is a clinical update on the pathophysiological aspects,diagnostic algorithm,and management of GEP NENs.展开更多
Although gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)have always been considered rare tumors,their incidence has risen over the past few decades.They represent a highly heterogeneous group of neoplasms wi...Although gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)have always been considered rare tumors,their incidence has risen over the past few decades.They represent a highly heterogeneous group of neoplasms with several prognostic factors,including disease stage,proliferative index(Ki67),and tumor differentiation.Most of these neoplasms express somatostatin receptors on the cell surface,a feature that has important implications in terms of prognosis,diagnosis,and therapy.Although International Guidelines propose algorithms aimed at guiding therapeutic strategies,GEP-NEN patients are still very different from one another,and the need for personalized treatment continues to increase.Radical surgery is always the best option when feasible;however,up to 80%of cases are metastatic upon diagnosis.Regarding medical treatments,as GEP-NENs are characterized by relatively long overall survival,multiple therapy lines are adopted during the lifetime of these patients,but the optimum sequence to be followed has never been clearly defined.Furthermore,although new molecular markers aimed at predicting the response to therapy,as well as prognostic scores,are currently being studied,their application is still far from being part of daily clinical practice.As they represent a complex disease,with therapeutic protocols that are not completely standardized,GEP-NENs require a multidisciplinary approach.This review will provide an overview of the available therapeutic options for GEP-NENs and attempts to clarify the possible approaches for the management of these patients and to discuss future perspectives in this field.展开更多
Theranostics is the highly targeted molecular imaging and therapy of tumors.Targeted peptide receptor radionuclide therapy has taken the lead in demonstrating the safety and effectiveness of this molecular approach to...Theranostics is the highly targeted molecular imaging and therapy of tumors.Targeted peptide receptor radionuclide therapy has taken the lead in demonstrating the safety and effectiveness of this molecular approach to treating cancers.Metastatic,well-differentiated gastroenteropancreatic neuroendocrine tumors may be most effectively imaged and treated with DOTATATE ligands.We review the current practice,safety,advantages,and limitations of DOTATATE based theranostics.Finally,we briefly describe the exciting new areas of development and future directions of gastroenteropancreatic neuroendocrine tumor theranostics.展开更多
Gastroenteropancreatic neuroendocrine neoplasms comprise a heterogeneous group of tumors that differ in their pathogenesis,hormonal syndromes produced,biological behavior and consequently,in their requirement for and/...Gastroenteropancreatic neuroendocrine neoplasms comprise a heterogeneous group of tumors that differ in their pathogenesis,hormonal syndromes produced,biological behavior and consequently,in their requirement for and/or response to specific chemotherapeutic agents and molecular targeted therapies.Various imaging techniques are available for functional and morphological evaluation of these neoplasms and the selection of investigations performed in each patient should be customized to the clinical question.Also,with the increased availability of cross sectional imaging,these neoplasms are increasingly being detected incidentally in routine radiology practice.This article is a review of the various imaging modalities currently used in the evaluation of neuroendocrine neoplasms,along with a discussion of the role of advanced imaging techniques and a glimpse into the newer imaging horizons,mostly in the research stage.展开更多
Neuroendocrine neoplasms(NENs)of the gastroenteropancreatic system are rare and heterogeneous tumours,yet with increasing prevalence.The most frequent primary sites are the small intestine,rectum,pancreas,and stomach....Neuroendocrine neoplasms(NENs)of the gastroenteropancreatic system are rare and heterogeneous tumours,yet with increasing prevalence.The most frequent primary sites are the small intestine,rectum,pancreas,and stomach.For a localized disease,surgical resection with local lymph nodes is usually curative with good overall and disease free survival.More complex situation is the treatment of locally advanced lesions,liver metastases,and,surprisingly,small asymptomatic tumours of the rectum and pancreas.In this review,we focus on the current role of surgical management of gastroenteropancreatic NENs.We present surgical approach for the most frequent primary sites.We highlight the role of endoscopic surgery and the watch-and-wait strategy for selected cases.As liver metastases pose an important clinical challenge,we present current indications and contraindications for liver resection and a role of liver transplantation for metastatic NENs.展开更多
Over the last 40 years,the incidence and prevalence of gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)have continued to increase.Compared to other epithelial neoplasms in the same organ,GEP-NENs exhibit indo...Over the last 40 years,the incidence and prevalence of gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)have continued to increase.Compared to other epithelial neoplasms in the same organ,GEP-NENs exhibit indolent biological behavior,resulting in more chances to undergo surgery.However,the role of surgery in high-grade or advanced GEP-NENs is still controversial.Surgery is associated with survival improvement of well-differentiated highgrade GEP-NENs,whereas poorly differentiated GEP-NENs that may benefit from resection require careful selection based on Ki67 and other tissue biomarkers.Additionally,surgery also plays an important role in locally advanced and metastatic disease.For locally advanced GEP-NENs,isolated major vascular involvement is no longer an absolute contraindication.In the setting of metastatic GEP-NENs,radical intended surgery is recommended for patients with low-grade and resectable metastases.For unresectable metastatic disease,a variety of surgical approaches,including cytoreduction of liver metastasis,liver transplantation,and surgery after neoadjuvant treatment,show survival benefits.Primary tumor resection in GEP-NENs with unresectable metastatic disease is associated with symptom control,prolonged survival,and improved sensitivity toward systemic therapies.Although there is no established neoadjuvant or adjuvant strategy,increasing attention has been given to this emerging research area.Some studies have reported that neoadjuvant therapy effectively reduces tumor burden,improves the effectiveness of subsequent surgery,and decreases surgical complications.展开更多
Objective: To analyze the angiography appearance of liver metastases from gastroenteropancreatic neuroendocrine tumors(GEP-NETs),and evaluate the clinical efficacy and prognostic factors of interventional treatment fo...Objective: To analyze the angiography appearance of liver metastases from gastroenteropancreatic neuroendocrine tumors(GEP-NETs),and evaluate the clinical efficacy and prognostic factors of interventional treatment for hepatic metastases.Methods: Fifty GEP-NETs patients with hepatic metastases were treated from January 2012 to December 2016,and received transarterial embolization(TAE) in the hepatic tumor or hepatic arterial infusion chemotherapy(HAIC).All patients received 179 times of the intervention therapy in total.Results: Blood supplies were identified in the 50 cases with angiography,which showed that 35 cases had abundant vessels,while 15 cases had poor blood supply.Twenty-two cases were found either collateral blood supply,or portal vein invasion or arterial-portal vein fistula.The best curative efficacy was complete remission(CR)in 4 cases,partial remission(PR) in 28 cases and stable disease(SD) in 18 cases during the process of treatment.The angiography(P=0.047) and the frequency of intervention(P=0.037) showed significantly statistical difference with Kaplan-Meier analysis.The Cox analysis showed that more than 3 times of interventional therapy was an independent prognostic factor.Conclusions: Interventional treatment is safe and effective for GEP-NETs,and is beneficial to patients with main hepatic metastases after endocrine therapy.展开更多
Objective: To investigate the clinicopathological features, survival and prognostic factors for gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs) in a Chinese population.Methods: We investigated 154 consecutiv...Objective: To investigate the clinicopathological features, survival and prognostic factors for gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs) in a Chinese population.Methods: We investigated 154 consecutive patients(88 males, 66 females; median age 56 years, age range 9-86 years) diagnosed with GEP-NENs between 2001 and 2013 at The Affiliated Hospital of Qingdao University. Demographic, clinical and pathological variables and survival data were retrieved.Results: The pancreas was the most common site of involvement(63/154, 40.9%). Tumor size varied from 0.3 to 16.0 cm(median, 1.2 cm). The patients were followed up for a median period of 22 months(range, 1-157 months). The estimated 3- and 5-year overall survival(OS) rates for all patients were 84.0% and 81.9%, respectively. Multivariate analysis showed that larger tumor size, lymphatic metastases and distant metastases were significant predictors for poor survival outcome.Conclusions: Our data provide further information on the clinicopathological features of GEP-NENs in China. Additionally, we identified tumor size, lymphatic metastases and distant metastases as independent prognostic factors for long-term survival.展开更多
Objective: To determine the capability of dynamic enhanced computed tomography(CT) to differentiate liver metastases(LMs) of well-differentiated from poorly-differentiated gastroenteropancreatic neuroendocrine neoplas...Objective: To determine the capability of dynamic enhanced computed tomography(CT) to differentiate liver metastases(LMs) of well-differentiated from poorly-differentiated gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs).Methods: Patients with LMs of GEP-NENs who underwent dynamic enhanced CT examination in Peking University Cancer Hospital from January 2009 to October 2015 were included and data were retrospectively analyzed. We assessed the qualitative and quantitative CT features to identify the significant differentiating CT features of LMs of poorly-differentiated GEP-NENs from those of well-differentiated GEP-NENs using univariate analysis and a multivariate logistic regression model.Results: The study included 22 patients with LMs of well-differentiated GEP-NENs and 32 patients with LMs of poorly-differentiated GEP-NENs. Univariate analysis revealed statistically significant differences between the LMs of well-and poorly-differentiated GEP-NENs in terms of feeding arteries(36.4% vs. 75.0%, χ2=8.061,P=0.005), intratumoral neovascularity(18.2% vs. 59.4%, χ2=9.047, P=0.003), lymphadenopathy(27.3% vs. 81.2%,χ2=15.733, P<0.001), tumor-to-aortic ratio in the hepatic arterial and portal venous phase(T-A/AP: 0.297±0.080 vs.0.251±0.059, t=2.437, P=0.018; T-A/PVP: 0.639±0.138 vs. 0.529±0.117, t=3.163, P=0.003) and tumor-to-liver ratio in the hepatic arterial phase(T-L/AP: 1.108±0.267 vs. 0.907±0.240, t=2.882, P=0.006). The LMs of poorlydifferentiated GEP-NENs showed more feeding arteries, more intratumoral neovascularity, more lymphadenopathy and a lower tumor-to-aortic ratio. Multivariate analysis suggested that intratumoral neovascularity [P=0.015, OR=0.108, 95% confidence interval(95% CI), 0.018–0.646], lymphadenopathy(P=0.001,OR=0.055, 95% CI, 0.009–0.323) and T-A/PVP(P=0.004, OR=5.3 E–5, 95% CI, 0.000–0.044) were independent factors for differentiating LMs of poorly-differentiated from well-differentiated GEP-NENs.Conclusions: Dynamic enhanced CT features(intratumoral neovascularity, lymphadenopathy and T-A/PVP)are useful in the pathological classification of LMs of GEP-NENs.展开更多
Objective Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs) constitute a rare and heterogeneous group of tumors with varied biology and still constitute a diagnostic and therapeutic challenge for physicians of...Objective Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs) constitute a rare and heterogeneous group of tumors with varied biology and still constitute a diagnostic and therapeutic challenge for physicians of all specialties. In the present study, we aimed to review and study the clinicopathological characteristics of GEP-NENs applying the World Health Organization(WHO) 2010 grading criterion.Methods A total of 48 patients were enrolled in the study. The study included patients diagnosed with GEP-NENs who were treated and followed up at our Hospital from January 2013 to December 2017. Data regarding clinicopathological features of the patients were retrospectively evaluated. The expression of neuroendocrine markers was measured using the immunohistochemical Ultra Sensitive^(TM) S-P method of staining in 48 cases of primary GEP-NENs; and serum levels of neuron-specific enolase, carbohydrate an-tigen 19-9, and carcinoembryonic antigen in 36 GEP-NEN patients were measured using the electrochemiluminescence method.Results The median age at presentation was 59.3(range 48–82) years, and 39 cases(81.3%) were seen between the 5 th and 6 th decades. There was a male predilection(male: female=3:1). In 79.2% cases(38/48), tumors were hormonally nonfunctional. The most common presentation was abdominal pain, and the most frequent primary site of the tumor was the rectum, followed by the stomach(n = 15, 31.3%), colon(n = 5, 10.4%), and so on. Of the 48 tumors, 16(33.3%) were G1, 6(12.5%) cases were G2, 16(33.3%) were neuroendocrine carcinoma(NEC), and 10(20.8%) were mixed adenoneuroendocrine carcinoma(MANEC). According to the AJCC/UICC classification, 45.8%(n = 22) were diagnosed at low stage(stage I or II) while 54.2%(n = 26) were diagnosed at high stage(stage III or IV)(the majority of NEC, G3, and MANEC). A male preponderance was noted for all tumors except for G2 neoplasms, which showed no gender predilection. Thirty-nine patients underwent endoscopic biopsy. The lesions in 18.8%(n = 9) of the patients were indentified only radiologically. After the surgical procedures, 36 had at least one follow-up visit with a median follow-up duration of 5 months; the mean follow-up period was 28 ± 16 months. The oneyear and three-year survival rates were 72.2%(26/36) and 61.1%(22/36), respectively. This study did not find an effect of grade 3(G3) of tumor on the short-term clinical outcome of these patients. In the survival analysis, NEN G3, higher stage(stage III or IV) according to the AJCC/UICC classification(P < 0.05), and metastases at diagnosis(P < 0.05) were associated with poorer prognosis.Conclusion Most GEP-NENs are nonfunctional and nonspecific in presentation. The most frequent primary site of the tumor was the rectum and the commonest ages at diagnosis were the 5 th and 6 th decades. Endoscopic biopsy is the main diagnostic and histological grading method for GEP-NEN. In the survival analysis, NEN G3, a higher stage according to the AJCC/UICC classification, and metastases at diagnosis are associated with poorer prognosis.展开更多
BACKGROUND Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)are rare tumors,often diagnosed in an advanced stage when curative treatment is impossible and grueling symptoms related to vasoactive substance rele...BACKGROUND Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)are rare tumors,often diagnosed in an advanced stage when curative treatment is impossible and grueling symptoms related to vasoactive substance release by tumor cells affect patients’quality of life.Cardiovascular complications of GEP-NENs,primarily tricuspid and pulmonary valve disease,and right-sided heart failure,are the leading cause of death,even compared to metastatic disease.CASE SUMMARY We present a case of a 35-year-old patient with progressive dyspnea,back pain,polyneuropathic leg pain,and nocturnal diarrhea lasting for a decade before the diagnosis of neuroendocrine carcinoma of unknown primary with extensive liver metastases.During the initial presentation,serum biomarkers were not evaluated,and the patient received five cycles of doxorubicin,which he did not tolerate well,so he refused further therapy and was lost to follow-up.After 10 years,he presented to the emergency room with signs and symptoms of right-sided heart failure.Panneuroendocrine markers,serum chromogranin A,and urinary 5-hydroxyindoleacetic acid were extremely elevated(900 ng/mL and 2178µmol/L),and transabdominal ultrasound confirmed hepatic metastases.Computed tomo-graphy(CT)showed liver metastases up to 6 cm in diameter and metastases in mesenteric lymph nodes and pelvis.Furthermore,an Octreoscan showed lesions in the heart,thoracic spine,duodenum,and ascendent colon.A standard trans-thoracic echocardiogram confirmed findings of carcinoid heart disease.The patient was not a candidate for valve replacement.He started octreotide acetate treatment,and the dose escalated to 80 mg IM monthly.Although biochemical CONCLUSION Carcinoid heart disease occurs with carcinoid syndrome related to advanced neuroendocrine tumors,usually with liver metastases,which manifests as right-sided heart valve dysfunction leading to right-sided heart failure.Carcinoid heart disease and tumor burden are major prognostic factors of poor survival.Therefore,they must be actively sought by available biochemical markers and imaging techniques.Moreover,imaging techniques aiding tumor detection and staging,somatostatin receptor positron emission tomography/CT,and CT or magnetic resonance imaging,should be performed at the time of diagnosis and in 3-to 6-mo intervals to determine tumor growth rate and assess the possibility of locoregional therapy and/or palliative surgery.Valve replacement at the onset of symptoms or right ventricular dysfunction may be considered,while any delay can worsen right-sided ventricular failure.展开更多
文摘Mixed neuroendocrine non-neuroendocrine neoplasms(MiNENs)are a hetero-geneous group of malignant neoplasms that can settle in the gastroenteropan-creatic tract.They are composed of a neuroendocrine(NE)and a non-NE compo-nent in at least 30%of each tumour.The non-NE component can include different histological combinations of glandular,squamous,mucinous and sarcomatoid phenotypes,and one or both of the components can be low-or high grade malignant.Recent changes in the nomenclature of these neoplasms might lead to great deal of confusion,and the lack of specific clinical trials is the main reason why their management is difficult.The review aims to clarify the definition of MiNEN and analyze available evidence about their diagnosis and treatment options according to their location and extension through careful analysis of the available data.It would be important to reach a general consensus on their diagnosis in order to construct a classification that remains stable over time and facilitates the design of clinical trials that,due to their low incidence,will require long recruitment periods.
基金the National Natural Science Foundation of China,No.39470554
文摘AIM To identify the type localization andmorphology of APUD endocrine cells in thegastroenteropancreatic(GEP)system ofstomach-containing teleosts,and study APUDendocrine system in the stomach,intestine andpancreas of fish species.METHODS Two kinds of immunocytochemical(ICC)techniques of the streptavidin biotin-peroxidase complex(SABC)and streptavidin-peroxidase(S-P)method were used.Theidentification,localization and morphology ofAPUD endocrine cells scattered in the mucosa ofdigestive tract,intermuscular nerve plexus andglandular body of northern snakehead(Channaargus),ricefield eel(Monopterus albus),yellow catfish(Pelteobagrus fulvidraco),mandarinfish(Siniperca chuatsi),largemouthbass(Micropterus salmoides),orientalsheatfish(Silurus asotus),freshwater pomfret(Colossoma brachypomum)and nile tilapia(Tilapia nilotica)were investigated with 8 kindsof antisera.RESULTS The positive reaction of 5-hydroxytryptamine(5-HT)immunoreactiveendocrine(IRE)cells was found in the digestive tract and glandular body of 8 fish species indifferent degree.Only a few gastrin(GAS)-IREcells were seen in C.argus,M.albus and P.fulvidraco.Glucagon(GLU)-IRE cells were notfound in the digestive tract and glandular bodybut existed in pancreatic island of most fishspecies.The positive reaction of growthhormone(GH)-IRE cells was found only inpancreatic island of S.Chuatsi and S.Asotus,no positive reaction in the other 6 fish species.Somatostatin(SOM)-,calcitonin(CAL)-,neurofilament(NF)-and insulin(INS)-IRE cellsin the stomach,intestine and pancreas of 8 kindsof fish were different in distribution and types.The distribution of all 8 APUD cells was the mostin gastrointestinal epithelium mucosa and then indigestive glands.The positive reaction of SOM-and 5-HT-IRE cells was found in intermuscularnerve plexus of intestine of P.fulvidraco andS.chuatsi.Only GH-IRE cells were denselyscattered in the pancreatic islands of S.chuatsiand S.asotus,and odd distribution in thepancreas of S.asotus,SOM-IRE cells weredistributed in the pancreatic islands of S.asotus,C.Brachypomum and T.nilotica.There were INS-IRE cells in the pancreaticislands of S.chuatsi and S.asolus.Eightkinds of APUD cells had longer cell body andcytoplasmic process when they were located inthe gastrointestinal epithelium,and had shortercell body and cytoplasmic process in the gastricgland,and irregular shape in the esophagus andpancreatic island.CONCLUSION Eight kinds of IRE cells were identified in the GEP system of stomach-containing teleosts. These endocrine cells were scattered in gastrointestinal mucosa, intermuscular nerve plexus, gland body, pancreatic gland and islands under APUD system. CAL- and GH-IRE cells in the pancreatic islands of fishes showed functional diversity for these two hormones. Their morphological feature provides evidence of endocrine-paracrine and endocrine-exocrine acting mode. This research can morphologically prove that the GEP endocrine system of fish ( the lowest vertebrate) is almost the same as of mammal and human.
基金supported by the Natural Science Foundation of Guangdong Province(No.2015A030313089)the Medical Science and Technology Research Foundation of Guangdong Province(No.B2014160)the Major Program of Collaborative Innovation of Guangzhou(No.201508030042)
文摘Background: Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs) are a heterogeneous group of rare tumors. Many issues in terms of epidemiologic features, pathogenesis, and treatment of GEP-NENs are still under discussion. Our study aimed to analyze the clinicopathologic characteristics and prognosis of Chinese patients with GEP-NENs.Methods: Complete clinicopathologic data and survival information of 1183 patients with GEP-NENs treated between 2005 and 2015 were collected from five medical centers in Guangdong Province, China. Patient survival was estimated using the Kaplan–Meier method and analyzed using the log-rank test; prognostic factors were analyzed using the Cox proportional hazards model.Results: The most common tumor location was the rectum(37.4%), followed by the pancreas(28.1%), stomach(20.7%), small intestine(7.2%), appendix(3.4%), and colon(3.3%). After initial definitive diagnosis, 1016(85.9%) patients underwent surgery. The 1-, 3-, and 5-year overall survival(OS) rates for the entire cohort were 87.9%, 78.5%, and 72.8%, respectively. The 3-year OS rates of patients with G1, G2, and G3 tumors were 93.1%, 82.7%, and 43.1%, respectively(P < 0.001). The 3-year OS rates of patients with stage I, II, III, and IV tumors were 96.0%, 87.3%, 64.0%, and 46.8%, respectively(P < 0.001). Patients with distant metastasis who underwent palliative surgery had a longer survival than those who did not(P = 0.003). Similar survival benefits of palliative surgery were observed in patients with neuroendocrine tumor(P y, M category, and sur= 0.031) or neuroendocrine carcinoma(P gery were found to be independent prog= 0.046). In multivariate analysis, age, grade, N categornostic factors.Conclusions: Patients with GEP-NENs who are women, younger than 50 years old, have smaller tumor size, have lower tumor grade, have lower T/N/M category, and who undergo surgery can have potentially longer survival time. Our data showed that surgery can improve the prognosis of GEP-NEN patients with distant metastasis. However, randomized controlled trials need to be conducted to establish the optimal criteria for selecting patients to undergo surgery.
文摘Neuroendocrine(NE) gastroenteropancreatic tumors are a heterogeneous group of neoplasias arising from neuroendocrine cells of the embryological gut. Their incidence have increased significantly over the past 3 decades probably due to the improvements in imaging and diagnosis. The recent advances in molecular biology have translated into an expansion of therapeutic approaches to these patients. Somatostatin analogs, which initially were approved for control of hormonal syndromes, have recently been proven to inhibit tumor growth. Several new drugs such as antiangiogenics and others targeting mammalian target of rapamycin pathways have been approved to treat progressive pancreatic neuroendocrine tumors(NETs) although their role in nonpancreatic is still controversial. The treatment of NETs requires a coordinated multidisciplinary approach. The management of localized NETs primarily involves surgical resection followed by surveillance. However, the treatment of unresectable and/or metastatic disease may involve a combination of surgical resection, systemic therapy, and liver-directed therapies with the goal of alleviating symptoms of peptide release and controlling tumor growth. This article will review the current therapeutic strategies for metastatic gastroenteropancreatic NETs and will take a glimpse into the future approaches.
文摘Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)are rare epithelial neoplasms derived from pluripotent endocrine cells along the gastrointestinal tract and pancreas.GEP-NENs are classified into well-differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas.Despite overlapping morphological features,GEP-NENs vary in molecular biology,epigenetic,clinical behavior,treatment response,and prognosis features and remain an unmet clinical challenge.In this review,we introduce recent updates on the histopathologic classification,including the tumor grading and staging system,molecular genetics,and systemic evaluation of the diagnosis and treatment of GEP-NENs at different anatomic sites,together with some insights into the diagnosis of challenging and unusual cases.We also discuss the application of novel therapeutic approaches for GEP-NENs,including peptide receptor radionuclide therapy,targeted therapy,and immunotherapy with immune checkpoint inhibitors.These findings will help improve patient care with precise diagnosis and individualized treatment of patients with GEP-NENs.
文摘AIM To compare health-related quality of life(HRQoL),anxiety, depression, and impulsivity scores in patients with and without carcinoid syndrome(CS), and correlated them with serum 5-hydroxyindoleacetic acid(5-HIAA) levels.METHODS Patients with advanced gastroenteropancreatic neuroendocrine tumours(GEPNET), with and without CS completed HRQoL QLQ-C30 and QLQ-GI.NET21, Hospital Anxiety and Depression Scale(HADS) and Barratt Impulsivity Scale(BIS) questionnaires. Twosample Wilcoxon test was applied to assess differences in serum 5-HIAA levels, two-sample Mann-Whitney U test for HRQoL and BIS, and proportion test for HADS, between those with and without CS.RESULTS Fifty patients were included; 25 each with and without CS. Median 5-HIAA in patients with and without CS was 367 nmol/L and 86 nmol/L, respectively(P = 0.003). Scores related to endocrine symptoms were significantly higher amongst patients with CS(P = 0.04) and scores for disease-related worries approached significance in the group without CS, but no other statistically-significant differences were reported between patients with and without CS in responses on QLQ-C30 or QLQ-GI.NET21. Fifteen patients(26%) scored ≥ 8/21 on anxiety scale, and 6(12%) scored ≥ 8/21 on depression scale. There was no difference in median 5-HIAA between those scoring < or ≥ 8/21 on anxiety scale(P = 0.53). There were no statistically significant differences between groups in first or second-order factors(BIS) or total sum(P = 0.23).CONCLUSION Excepting endocrine symptoms, there were no significant differences in HRQoL, anxiety, depression or impulsivity between patients with advanced GEPNET, with or without CS. Over one quarter of patients had high anxiety scores, unrelated to peripheral serotonin metabolism.
文摘BACKGROUND Long non-coding RNAs(lncRNAs) are a kind of single-stranded RNA of more than 200 nucleotides in length and have no protein-coding function. Amounting studies have indicated that lncRNAs could play a vital role in the initiation and development of cancers, including gastric cancer(GC). Considering the crucial functions of lncRNAs, the identification and exploration of novel lncRNAs in GC is necessary.AIM To identify independent prognostic markers for the whole gastroenteropancreatic neuroendocrine tumor(GEP-NET) group.METHODS Ninety-three patients diagnosed with GEP-NETs within a specified period were included in this study. Patient data were retrospectively analyzed. The relationships between all independent variables and 5-year survival status calculated during the follow-up period(months) were assessed. In addition, the relationships between the independent variables were investigated.RESULTS When 5-year survival rate was compared, a statistically significant relationship between the age at diagnosis, male gender, tumor size, tumor stage, liver and/or distant metastasis, and tumor grade determined by the Ki-67 level and mitotic count, and the level of C-reactive protein(CRP), was observed. The meansurvival(overall survival) of the study group was 102.5 ± 6.3(SD) mo. The percentages of 1, 3 and 5-year survival were 90%, 72%, and 61%, respectively. In63 of 93 patients, Ki-67 and the mitotic count determined the same grade. The Ki-67 levels in 29 patients and the mitotic count in only 1 patient were in the higher grade. The risk of death increased by 4% for every 1 year increase at the diagnosis age and was 2.0-fold higher for male patients, 3.0-fold higher for G3 according to the mitotic count, 3.7-fold higher for G3 according to the Ki-67 level, 12.7-fold higher for cases with tumor stage 3 or 4 by a 1 cm increase in the ratio of 9% in tumor size, and 6.1-fold higher for patients with liver metastasis for every 1 mg/dL increase in the ratio of 1.5% in CRP level. There was a significant difference between pancreatic and stomach NETs in favor of stomach tumors in terms of survival.CONCLUSION Tumor site, stage, grade and Ki-67 level affected patient survival, and it was observed that CRP affected disease progression(particularly if it was > 20 mg/dL). However, a relationship between surgical resection of the lesion and survival was not shown. Larger scale prospective studies are required to determine whether CRP level may be a poor prognostic factor for the entire GEPNET group.
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BACKGROUND Gastroenteropancreatic neuroendocrine tumours(GEP-NETs)are slow-growing cancers that arise from diffuse endocrine cells in the gastrointestinal tract(GINETs)or the pancreas(P-NETs).They are relatively uncommon,accounting for 2%of all gastrointestinal malignancies.The usual treatment options in advanced GEP-NET patients with metastatic disease include chemotherapy,biological therapies,and peptide receptor radionuclide therapy.Understanding the impact of treatment on GEP-NET patients is paramount given the nature of the disease.Health-related quality of life(HRQoL)is increasingly important as a concept reflecting the patients’perspective in conjunction with the disease presentation,severity and treatment.AIM To conduct a systematic literature review to identify literature reporting HRQoL data in patients with GEP-NETs between January 1985 and November 2019.METHODS The PRISMA guiding principles were applied.MEDLINE,Embase and the Cochrane library were searched.Data extracted from the publications included type of study,patient population data(mid-gut/hind-gut/GI-NET/P-NET),sample size,intervention/comparators,HRQoL instruments,average and data spread of overall and sub-scores,and follow-up time for data collection.RESULTS Forty-three publications met the inclusion criteria.The heterogeneous nature of the different study populations was evident;the percentage of female participants ranged between 30%-60%,whilst average age ranged from 53.8 to 67.0 years.Eight studies investigated GI-NET patients only,six studies focused exclusively on P-NET patients and the remaining studies involved both patient populations or did not report the location of the primary tumour.The most commonly used instrument was the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30(n=28)with consistent results across studies;the GI-NET-specific module Quality of Life Questionnaire-GINET21 was used in six of these studies.A number of randomised trials demonstrated no HRQoL changes between active treatment and placebo arms.The Phase III NETTER-1 study provides the best data available for advanced GEP-NET patients;it shows that peptide receptor radionuclide therapy can significantly improve GEP-NET patients’HRQoL.CONCLUSION HRQoL instruments offer a means to monitor patients’general disease condition,disease progression and their physical and mental well-being.Instruments including the commonly used European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 and GINET21 lack,however,validation and a defined minimal clinical important difference specifically for GINET and P-NET patients.
文摘Our understanding about the epidemiological aspects,pathogenesis,molecular diagnosis,and targeted therapies of neuroendocrine neoplasms(NENs)have drastically advanced in the past decade.Gastroenteropancreatic(GEP)NENs originate from the enteroendocrine cells of the embryonic gut which share common endocrine and neural differentiation factors.Most NENs are welldifferentiated,and slow growing.Specific neuroendocrine biomarkers that are used in the diagnosis of functional NENs include insulin,glucagon,vasoactive intestinal polypeptide,gastrin,somatostatin,adrenocorticotropin,growth hormone releasing hormone,parathyroid hormone-related peptide,serotonin,histamine,and 5-hydroxy indole acetic acid(5-HIAA).Biomarkers such as pancreatic polypeptide,human chorionic gonadotrophin subunits,neurotensin,ghrelin,and calcitonin are used in the diagnosis of non-functional NENs.5-HIAA levels correlate with tumour burden,prognosis and development of carcinoid heart disease and mesenteric fibrosis,however several diseases,medications and edible products can falsely elevate the 5-HIAA levels.Organ-specific transcription factors are useful in the differential diagnosis of metastasis from an unknown primary of well-differentiated NENs.Emerging novel biomarkers include circulating tumour cells,circulating tumour DNA,circulating micro-RNAs,and neuroendocrine neoplasms test(NETest)(simultaneous measurement of 51 neuroendocrine-specific marker genes in the peripheral blood).NETest has high sensitivity(85%-98%)and specificity(93%-97%)for the detection of gastrointestinal NENs,and is useful for monitoring treatment response,recurrence,and prognosis.In terms of management,surgery,radiofrequency ablation,symptom control with medications,chemotherapy and molecular targeted therapies are all considered as options.Surgery is the mainstay of treatment,but depends on factors including age of the individual,location,stage,grade,functional status,and the heredity of the tumour(sporadic vs inherited).Medical management is helpful to alleviate the symptoms,manage inoperable lesions,suppress postoperative tumour growth,and manage recurrences.Several molecular-targeted therapies are considered second line to somatostatin analogues.This review is a clinical update on the pathophysiological aspects,diagnostic algorithm,and management of GEP NENs.
文摘Although gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)have always been considered rare tumors,their incidence has risen over the past few decades.They represent a highly heterogeneous group of neoplasms with several prognostic factors,including disease stage,proliferative index(Ki67),and tumor differentiation.Most of these neoplasms express somatostatin receptors on the cell surface,a feature that has important implications in terms of prognosis,diagnosis,and therapy.Although International Guidelines propose algorithms aimed at guiding therapeutic strategies,GEP-NEN patients are still very different from one another,and the need for personalized treatment continues to increase.Radical surgery is always the best option when feasible;however,up to 80%of cases are metastatic upon diagnosis.Regarding medical treatments,as GEP-NENs are characterized by relatively long overall survival,multiple therapy lines are adopted during the lifetime of these patients,but the optimum sequence to be followed has never been clearly defined.Furthermore,although new molecular markers aimed at predicting the response to therapy,as well as prognostic scores,are currently being studied,their application is still far from being part of daily clinical practice.As they represent a complex disease,with therapeutic protocols that are not completely standardized,GEP-NENs require a multidisciplinary approach.This review will provide an overview of the available therapeutic options for GEP-NENs and attempts to clarify the possible approaches for the management of these patients and to discuss future perspectives in this field.
文摘Theranostics is the highly targeted molecular imaging and therapy of tumors.Targeted peptide receptor radionuclide therapy has taken the lead in demonstrating the safety and effectiveness of this molecular approach to treating cancers.Metastatic,well-differentiated gastroenteropancreatic neuroendocrine tumors may be most effectively imaged and treated with DOTATATE ligands.We review the current practice,safety,advantages,and limitations of DOTATATE based theranostics.Finally,we briefly describe the exciting new areas of development and future directions of gastroenteropancreatic neuroendocrine tumor theranostics.
文摘Gastroenteropancreatic neuroendocrine neoplasms comprise a heterogeneous group of tumors that differ in their pathogenesis,hormonal syndromes produced,biological behavior and consequently,in their requirement for and/or response to specific chemotherapeutic agents and molecular targeted therapies.Various imaging techniques are available for functional and morphological evaluation of these neoplasms and the selection of investigations performed in each patient should be customized to the clinical question.Also,with the increased availability of cross sectional imaging,these neoplasms are increasingly being detected incidentally in routine radiology practice.This article is a review of the various imaging modalities currently used in the evaluation of neuroendocrine neoplasms,along with a discussion of the role of advanced imaging techniques and a glimpse into the newer imaging horizons,mostly in the research stage.
文摘Neuroendocrine neoplasms(NENs)of the gastroenteropancreatic system are rare and heterogeneous tumours,yet with increasing prevalence.The most frequent primary sites are the small intestine,rectum,pancreas,and stomach.For a localized disease,surgical resection with local lymph nodes is usually curative with good overall and disease free survival.More complex situation is the treatment of locally advanced lesions,liver metastases,and,surprisingly,small asymptomatic tumours of the rectum and pancreas.In this review,we focus on the current role of surgical management of gastroenteropancreatic NENs.We present surgical approach for the most frequent primary sites.We highlight the role of endoscopic surgery and the watch-and-wait strategy for selected cases.As liver metastases pose an important clinical challenge,we present current indications and contraindications for liver resection and a role of liver transplantation for metastatic NENs.
基金Supported by State Key Program of National Natural Science Foundation of China,No.81930016Zhejiang Provincial Natural Science Foundation of China,No.LY21H160026。
文摘Over the last 40 years,the incidence and prevalence of gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)have continued to increase.Compared to other epithelial neoplasms in the same organ,GEP-NENs exhibit indolent biological behavior,resulting in more chances to undergo surgery.However,the role of surgery in high-grade or advanced GEP-NENs is still controversial.Surgery is associated with survival improvement of well-differentiated highgrade GEP-NENs,whereas poorly differentiated GEP-NENs that may benefit from resection require careful selection based on Ki67 and other tissue biomarkers.Additionally,surgery also plays an important role in locally advanced and metastatic disease.For locally advanced GEP-NENs,isolated major vascular involvement is no longer an absolute contraindication.In the setting of metastatic GEP-NENs,radical intended surgery is recommended for patients with low-grade and resectable metastases.For unresectable metastatic disease,a variety of surgical approaches,including cytoreduction of liver metastasis,liver transplantation,and surgery after neoadjuvant treatment,show survival benefits.Primary tumor resection in GEP-NENs with unresectable metastatic disease is associated with symptom control,prolonged survival,and improved sensitivity toward systemic therapies.Although there is no established neoadjuvant or adjuvant strategy,increasing attention has been given to this emerging research area.Some studies have reported that neoadjuvant therapy effectively reduces tumor burden,improves the effectiveness of subsequent surgery,and decreases surgical complications.
基金supported by the National Natural Science Foundation of China(No.81571781)
文摘Objective: To analyze the angiography appearance of liver metastases from gastroenteropancreatic neuroendocrine tumors(GEP-NETs),and evaluate the clinical efficacy and prognostic factors of interventional treatment for hepatic metastases.Methods: Fifty GEP-NETs patients with hepatic metastases were treated from January 2012 to December 2016,and received transarterial embolization(TAE) in the hepatic tumor or hepatic arterial infusion chemotherapy(HAIC).All patients received 179 times of the intervention therapy in total.Results: Blood supplies were identified in the 50 cases with angiography,which showed that 35 cases had abundant vessels,while 15 cases had poor blood supply.Twenty-two cases were found either collateral blood supply,or portal vein invasion or arterial-portal vein fistula.The best curative efficacy was complete remission(CR)in 4 cases,partial remission(PR) in 28 cases and stable disease(SD) in 18 cases during the process of treatment.The angiography(P=0.047) and the frequency of intervention(P=0.037) showed significantly statistical difference with Kaplan-Meier analysis.The Cox analysis showed that more than 3 times of interventional therapy was an independent prognostic factor.Conclusions: Interventional treatment is safe and effective for GEP-NETs,and is beneficial to patients with main hepatic metastases after endocrine therapy.
文摘Objective: To investigate the clinicopathological features, survival and prognostic factors for gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs) in a Chinese population.Methods: We investigated 154 consecutive patients(88 males, 66 females; median age 56 years, age range 9-86 years) diagnosed with GEP-NENs between 2001 and 2013 at The Affiliated Hospital of Qingdao University. Demographic, clinical and pathological variables and survival data were retrieved.Results: The pancreas was the most common site of involvement(63/154, 40.9%). Tumor size varied from 0.3 to 16.0 cm(median, 1.2 cm). The patients were followed up for a median period of 22 months(range, 1-157 months). The estimated 3- and 5-year overall survival(OS) rates for all patients were 84.0% and 81.9%, respectively. Multivariate analysis showed that larger tumor size, lymphatic metastases and distant metastases were significant predictors for poor survival outcome.Conclusions: Our data provide further information on the clinicopathological features of GEP-NENs in China. Additionally, we identified tumor size, lymphatic metastases and distant metastases as independent prognostic factors for long-term survival.
基金funding by the National Natural Science Foundation of China (No. 61520106004 and No. 81471640)
文摘Objective: To determine the capability of dynamic enhanced computed tomography(CT) to differentiate liver metastases(LMs) of well-differentiated from poorly-differentiated gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs).Methods: Patients with LMs of GEP-NENs who underwent dynamic enhanced CT examination in Peking University Cancer Hospital from January 2009 to October 2015 were included and data were retrospectively analyzed. We assessed the qualitative and quantitative CT features to identify the significant differentiating CT features of LMs of poorly-differentiated GEP-NENs from those of well-differentiated GEP-NENs using univariate analysis and a multivariate logistic regression model.Results: The study included 22 patients with LMs of well-differentiated GEP-NENs and 32 patients with LMs of poorly-differentiated GEP-NENs. Univariate analysis revealed statistically significant differences between the LMs of well-and poorly-differentiated GEP-NENs in terms of feeding arteries(36.4% vs. 75.0%, χ2=8.061,P=0.005), intratumoral neovascularity(18.2% vs. 59.4%, χ2=9.047, P=0.003), lymphadenopathy(27.3% vs. 81.2%,χ2=15.733, P<0.001), tumor-to-aortic ratio in the hepatic arterial and portal venous phase(T-A/AP: 0.297±0.080 vs.0.251±0.059, t=2.437, P=0.018; T-A/PVP: 0.639±0.138 vs. 0.529±0.117, t=3.163, P=0.003) and tumor-to-liver ratio in the hepatic arterial phase(T-L/AP: 1.108±0.267 vs. 0.907±0.240, t=2.882, P=0.006). The LMs of poorlydifferentiated GEP-NENs showed more feeding arteries, more intratumoral neovascularity, more lymphadenopathy and a lower tumor-to-aortic ratio. Multivariate analysis suggested that intratumoral neovascularity [P=0.015, OR=0.108, 95% confidence interval(95% CI), 0.018–0.646], lymphadenopathy(P=0.001,OR=0.055, 95% CI, 0.009–0.323) and T-A/PVP(P=0.004, OR=5.3 E–5, 95% CI, 0.000–0.044) were independent factors for differentiating LMs of poorly-differentiated from well-differentiated GEP-NENs.Conclusions: Dynamic enhanced CT features(intratumoral neovascularity, lymphadenopathy and T-A/PVP)are useful in the pathological classification of LMs of GEP-NENs.
基金Supported by a grant from the Jining Medical University Teacher’s Research Support Fund(No.2018)
文摘Objective Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs) constitute a rare and heterogeneous group of tumors with varied biology and still constitute a diagnostic and therapeutic challenge for physicians of all specialties. In the present study, we aimed to review and study the clinicopathological characteristics of GEP-NENs applying the World Health Organization(WHO) 2010 grading criterion.Methods A total of 48 patients were enrolled in the study. The study included patients diagnosed with GEP-NENs who were treated and followed up at our Hospital from January 2013 to December 2017. Data regarding clinicopathological features of the patients were retrospectively evaluated. The expression of neuroendocrine markers was measured using the immunohistochemical Ultra Sensitive^(TM) S-P method of staining in 48 cases of primary GEP-NENs; and serum levels of neuron-specific enolase, carbohydrate an-tigen 19-9, and carcinoembryonic antigen in 36 GEP-NEN patients were measured using the electrochemiluminescence method.Results The median age at presentation was 59.3(range 48–82) years, and 39 cases(81.3%) were seen between the 5 th and 6 th decades. There was a male predilection(male: female=3:1). In 79.2% cases(38/48), tumors were hormonally nonfunctional. The most common presentation was abdominal pain, and the most frequent primary site of the tumor was the rectum, followed by the stomach(n = 15, 31.3%), colon(n = 5, 10.4%), and so on. Of the 48 tumors, 16(33.3%) were G1, 6(12.5%) cases were G2, 16(33.3%) were neuroendocrine carcinoma(NEC), and 10(20.8%) were mixed adenoneuroendocrine carcinoma(MANEC). According to the AJCC/UICC classification, 45.8%(n = 22) were diagnosed at low stage(stage I or II) while 54.2%(n = 26) were diagnosed at high stage(stage III or IV)(the majority of NEC, G3, and MANEC). A male preponderance was noted for all tumors except for G2 neoplasms, which showed no gender predilection. Thirty-nine patients underwent endoscopic biopsy. The lesions in 18.8%(n = 9) of the patients were indentified only radiologically. After the surgical procedures, 36 had at least one follow-up visit with a median follow-up duration of 5 months; the mean follow-up period was 28 ± 16 months. The oneyear and three-year survival rates were 72.2%(26/36) and 61.1%(22/36), respectively. This study did not find an effect of grade 3(G3) of tumor on the short-term clinical outcome of these patients. In the survival analysis, NEN G3, higher stage(stage III or IV) according to the AJCC/UICC classification(P < 0.05), and metastases at diagnosis(P < 0.05) were associated with poorer prognosis.Conclusion Most GEP-NENs are nonfunctional and nonspecific in presentation. The most frequent primary site of the tumor was the rectum and the commonest ages at diagnosis were the 5 th and 6 th decades. Endoscopic biopsy is the main diagnostic and histological grading method for GEP-NEN. In the survival analysis, NEN G3, a higher stage according to the AJCC/UICC classification, and metastases at diagnosis are associated with poorer prognosis.
文摘BACKGROUND Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)are rare tumors,often diagnosed in an advanced stage when curative treatment is impossible and grueling symptoms related to vasoactive substance release by tumor cells affect patients’quality of life.Cardiovascular complications of GEP-NENs,primarily tricuspid and pulmonary valve disease,and right-sided heart failure,are the leading cause of death,even compared to metastatic disease.CASE SUMMARY We present a case of a 35-year-old patient with progressive dyspnea,back pain,polyneuropathic leg pain,and nocturnal diarrhea lasting for a decade before the diagnosis of neuroendocrine carcinoma of unknown primary with extensive liver metastases.During the initial presentation,serum biomarkers were not evaluated,and the patient received five cycles of doxorubicin,which he did not tolerate well,so he refused further therapy and was lost to follow-up.After 10 years,he presented to the emergency room with signs and symptoms of right-sided heart failure.Panneuroendocrine markers,serum chromogranin A,and urinary 5-hydroxyindoleacetic acid were extremely elevated(900 ng/mL and 2178µmol/L),and transabdominal ultrasound confirmed hepatic metastases.Computed tomo-graphy(CT)showed liver metastases up to 6 cm in diameter and metastases in mesenteric lymph nodes and pelvis.Furthermore,an Octreoscan showed lesions in the heart,thoracic spine,duodenum,and ascendent colon.A standard trans-thoracic echocardiogram confirmed findings of carcinoid heart disease.The patient was not a candidate for valve replacement.He started octreotide acetate treatment,and the dose escalated to 80 mg IM monthly.Although biochemical CONCLUSION Carcinoid heart disease occurs with carcinoid syndrome related to advanced neuroendocrine tumors,usually with liver metastases,which manifests as right-sided heart valve dysfunction leading to right-sided heart failure.Carcinoid heart disease and tumor burden are major prognostic factors of poor survival.Therefore,they must be actively sought by available biochemical markers and imaging techniques.Moreover,imaging techniques aiding tumor detection and staging,somatostatin receptor positron emission tomography/CT,and CT or magnetic resonance imaging,should be performed at the time of diagnosis and in 3-to 6-mo intervals to determine tumor growth rate and assess the possibility of locoregional therapy and/or palliative surgery.Valve replacement at the onset of symptoms or right ventricular dysfunction may be considered,while any delay can worsen right-sided ventricular failure.
