BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor progression.Therefore,identifying new therapies with low toxicity and good tolerability to use concomitantly with the esta...BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor progression.Therefore,identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is relevant.In this perspective,metformin is emerging as a molecule of interest.Retrospective studies have described metformin,a widely used agent for the treatment of patients with type 2 diabetes mellitus(T2DM),to be effective in modulating different tumor-related events,including cancer incidence,recurrence and survival by inhibiting mTOR phosphorylation.This systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with pNET.AIM To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and posttreatment outcomes of pNET.METHODS A systematic review of the published literature was undertaken,focusing on the role of T2DM and metformin in insurgence and prognosis of pNET,measured through outcomes of tumor-free survival(TFS),overall survival and progression free survival.RESULTS A total of 13 studies(5674 patients)were included in this review.Analysis of 809 pNET cases from five retrospective studies(low study heterogeneity with I^(2)=0%)confirms the correlation between T2DM and insurgence of pNET(OR=2.13,95%CI=1.56-4.55;P<0.001).The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients(hazard ratio=1.84,95%CI=0.78-2.90;P<0.001).The study heterogeneity was intermediate,with I^(2)=51%.A few studies limited the possibility of performing pooled analysis in the setting of metformin;therefore,results were heterogeneous,with no statistical relevance to the use of this drug in the diagnosis and prognosis of pNET.CONCLUSION T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients.Unfortunately,a few studies with heterogeneous results limited the possibility of exploring the effect of metformin in the diagnosis and prognosis of pNET.展开更多
BACKGROUND Pancreatic neuroendocrine tumors(PNETs)are relatively rare but rank as the second most common pancreatic neoplasm.They can be functional,causing early metabolic disturbances due to hormone secretion,or non-...BACKGROUND Pancreatic neuroendocrine tumors(PNETs)are relatively rare but rank as the second most common pancreatic neoplasm.They can be functional,causing early metabolic disturbances due to hormone secretion,or non-functional and diagnosed later based on tumor size-related symptoms.Recent diagnoses of PNETs under 2 cm in size have sparked debates about their management;some practitioners advocate for surgical removal and others suggest observation due to the tumors’lower potential for malignancy.However,it is unclear whether managing these small tumors expectantly is truly safe.AIM To evaluate poor prognostic factors in PNETs based on tumor size(>2 cm or<2 cm)in surgically treated patients.METHODS This cohort study included 64 patients with PNETs who underwent surgical resection between 2006 and 2019 at a high-complexity reference hospital in Medellín,Colombia.To assess patient survival,quarterly follow-ups were conducted during the first year after surgery,followed by semi-annual con-sultations at the hospital's hepatobiliary surgery department.Qualitative variables were described using absolute and relative frequencies,and quantitative variables were expressed using measures of central tendency and their corresponding measures of dispersion.RESULTS The presence of lymph node involvement,neural involvement,and lymphovascular invasion were all associated with an increased risk of mortality,with hazard ratios of 5.68(95%CI:1.26–25.61,P=0.024),6.44(95%CI:1.43–28.93,P=0.015),and 24.87(95%CI:2.98–207.19,P=0.003),respectively.Neural involvement and lymphovascular invasion were present in tumors smaller than 2 cm in diameter and those larger than 2 cm in diameter.The recurrence rates between the two tumor groups were furthermore similar:18.2%for tumors smaller than 2 cm and 21.4%for tumors larger than 2 cm.Patient survival was additionally comparable between the two tumor groups.CONCLUSION Tumor size does not dictate prognosis;lymph node and lymphovascular involvement affect mortality,which high-lights that histopathological factors-rather than tumor size-may play a role in management.展开更多
BACKGROUND The majority of gastric neuroendocrine tumors(G-NENs)are present in various lesions under endoscopy,and they can be polypoid uplifts,submucosal tumors or papules,erosions,and ulcers.The lesions are mostly c...BACKGROUND The majority of gastric neuroendocrine tumors(G-NENs)are present in various lesions under endoscopy,and they can be polypoid uplifts,submucosal tumors or papules,erosions,and ulcers.The lesions are mostly confined to the mucosal or submucosal layer,usually less than 2 cm,and exclusively localized to the gastric body or fundus.In type 1 G-NENs,about 22%of cases have no visible lesions under an endoscope,and such lesions can only be detected via biopsies(microcar-cinoids).CONCLUSION In the case under study,the patient did not have any visible raised lesions under a gastroscope,and the lesions were found only after a random biopsy.This article combines the endoscopic manifestations and clinical features of the lesions in this case to improve the diagnosis of G-NENs.展开更多
Gastrointestinal neuroendocrine tumors are rare slow-growing tumors with distinct histological,biological,and clinical characteristics that have increased in incidence and prevalence within the last few decades.They c...Gastrointestinal neuroendocrine tumors are rare slow-growing tumors with distinct histological,biological,and clinical characteristics that have increased in incidence and prevalence within the last few decades.They contain chromogranin A,synaptophysin and neuron-specific enolase which are necessary for making a diagnosis of neuroendocrine tumor.Ki-67 index and mitotic index correlate with cellular proliferation.Serum chromogranin A is the most commonly used biomarker to assess the bulk of disease and monitor treatment and is raised in both functioning and non-functioning neuroendocrine tumors.Most of the gastrointestinal neuroendocrine tumors are non-functional.World Health Organization updated the classification of neuroendocrine tumors in 2017 and renamed mixed adenoneuroendocrine carcinoma into mixed neuroendocrine neoplasm.Gastric neuroendocrine tumors arise from enterochromaffin like cells.They are classified into 4 types.Only type I and type II are gastrin dependent.Small intestinal neuroendocrine tumor is the most common small bowel malignancy.More than two-third of them occur in the terminal ileum within 60 cm of ileocecal valve.Patients with small intestinal neuroendrocrine tumors frequently show clinical symptoms and develop distant metastases more often than those with neuroendocrine tumors of other organs.Duodenal and jejunoileal neuroendocrine tumors are distinct biologically and clinically.Carcinoid syndrome generally occurs when jejuno-ileal neuroendocrine tumors metastasize to the liver.Appendiceal neuroendocrine tumors are generally detected after appendectomy.Colonic neuroendocrine tumors generally present as a large tumor with local or distant metastasis at the time of diagnosis.Rectal neuroendocrine tumors are increasingly being diagnosed since the implementation of screening colonoscopy in 2000.Gastrointestinal neuroendocrine tumors are diagnosed and staged by endoscopy with biopsy,endoscopic ultrasound,serology of biomarkers,imaging studies and functional somatostatin scans.Various treatment options are available for curative and palliative treatment of gastrointestinal neuroendocrine tumors.展开更多
BACKGROUND The molecular changes present in gastric neuroendocrine tumors(NETs)include a loss of heterozygosity or mutation of MEN1,CDKN1B gene mutation,P27 heterozygous mutation,and ATP4A gene missense mutation.We id...BACKGROUND The molecular changes present in gastric neuroendocrine tumors(NETs)include a loss of heterozygosity or mutation of MEN1,CDKN1B gene mutation,P27 heterozygous mutation,and ATP4A gene missense mutation.We identified and are the first to report a case of type 1 histamine-producing enterochromaffin-like cell NETs(ECL-cell NETs)with a BRCA2 gene germline mutation.CASE SUMMARY The patient had a history of iron-deficient anemia for 5 years,and gastroscopic examination indicated multiple gastric tumors.Then,the patient underwent distal gastrectomy.Microscopically,multifocal tumor cells were found in the mucosa and submucosa;tumor cells were organoid and arranged in nests and cords,and the stroma was rich in sinusoids.The surrounding gastric mucosa showed atrophy with mild intestinal metaplasia or pseudopyloric gland metaplasia.Neuroendocrine cells could be seen with diffuse linear,nodular,and adenomatous hyperplasia.Immunohistochemically,the tumor cells diffusely expressed cytokeratin,chromogranin,synaptophysin,and CD56.Whole-genome highthroughput molecular sequencing revealed a pathogenic germline mutation in the BRCA2 gene,a heterozygous germline frameshift mutation in exon 11,c.6443_6444del(p.S2148Yfs*2).The final diagnosis was gastric type 1 ECL-cell NETs with a BRCA2 gene germline mutation,accompanied by autoimmune gastritis.CONCLUSION This is the first report of a case of type 1 gastric ECL-cell NETs with a pathogenic germline mutation of the BRCA2 gene.The findings of this report will expand the germline mutation spectrum of gastric NETs and increase the understanding of the molecular changes present in these tumors for their improved diagnosis in the future.展开更多
Small intestinal neuroendocrine tumors(NETs)are a heterogeneous group of epithelial tumors with a predominant neuroendocrine differentiation.Although NETs are usually considered rare neoplasms,small intestinal NETs ar...Small intestinal neuroendocrine tumors(NETs)are a heterogeneous group of epithelial tumors with a predominant neuroendocrine differentiation.Although NETs are usually considered rare neoplasms,small intestinal NETs are the most common primary malignancy of the small bowel,with an increasing prevalence worldwide during the course of the past few decades.The indolent nature of these tumors often leads to a delayed diagnosis,resulting in over one-third of patients presenting with synchronous metastases.Primary tumor resection remains the only curative option for this type of tumor.In this review article,the various surgical aspects for the excision of small intestinal NETs are discussed.展开更多
Objective:Currently,pre-treatment prediction of patients with pancreatic neuroendocrine tumors with liver metastases(PNELM)receiving surufatinib treatment was unsatisfying.Our objective was to examine the association ...Objective:Currently,pre-treatment prediction of patients with pancreatic neuroendocrine tumors with liver metastases(PNELM)receiving surufatinib treatment was unsatisfying.Our objective was to examine the association between radiological characteristics and efficacy/prognosis.Methods:We enrolled patients with liver metastases in the phase III,SANET-p trial(NCT02589821)and obtained contrast-enhanced computed tomography(CECT)images.Qualitative and quantitative parameters including hepatic tumor margins,lesion volumes,enhancement pattern,localization types,and enhancement ratios were evaluated.The progression-free survival(PFS)and hazard ratio(HR)were calculated using Cox’s proportional hazard model.Efficacy was analyzed by logistic-regression models.Results:Among 152 patients who had baseline CECT assessments and were included in this analysis,the surufatinib group showed statistically superior efficacy in terms of median PFS compared to placebo across various qualitative and quantitative parameters.In the multivariable analysis of patients receiving surufatinib(N=100),those with higher arterial phase standardized enhancement ratio-peri-lesion(ASER-peri)exhibited longer PFS[HR=0.039;95%confidence interval(95%CI):0.003−0.483;P=0.012].Furthermore,patients with a high enhancement pattern experienced an improvement in the objective response ratio[31.3%vs.14.7%,odds ratio(OR)=3.488;95%CI:1.024−11.875;P=0.046],and well-defined tumor margins were associated with a higher disease control rate(DCR)(89.3%vs.68.2%,OR=4.535;95%CI:1.285−16.011;P=0.019)compared to poorlydefined margins.Conclusions:These pre-treatment radiological features,namely high ASER-peri,high enhancement pattern,and well-defined tumor margins,have the potential to serve as predictive markers of efficacy in patients with PNELM receiving surufatinib.展开更多
BACKGROUND Intrapancreatic accessory spleen(IPAS)shares similar imaging findings with hypervascular pancreatic neuroendocrine tumors(PNETs),which may lead to unnecessary surgery.AIM To investigate and compare the diag...BACKGROUND Intrapancreatic accessory spleen(IPAS)shares similar imaging findings with hypervascular pancreatic neuroendocrine tumors(PNETs),which may lead to unnecessary surgery.AIM To investigate and compare the diagnostic performance of absolute apparent diffusion coefficient(ADC)and normalized ADC(lesion-to-spleen ADC ratios)in the differential diagnosis of IPAS from PNETs.METHODS A retrospective study consisting of 29 patients(16 PNET patients vs 13 IPAS patients)who underwent preoperative contrast-enhanced magnetic resonance imaging together with diffusion-weighted imaging/ADC maps between January 2017 and July 2020 was performed.Two independent reviewers measured ADC on all lesions and spleens,and normalized ADC was calculated for further analysis.The receiver operating characteristics analysis was carried out for evaluating the diagnostic performance of both absolute ADC and normalized ADC values in the differential diagnosis between IPAS and PNETs by clarifying sensitivity,specificity,and accuracy.Inter-reader reliability for the two methods was evaluated.RESULTS IPAS had a significantly lower absolute ADC(0.931±0.773×10^(-3)mm^(2)/s vs 1.254±0.219×10^(-3)mm^(2)/s)and normalized ADC value(1.154±0.167 vs 1.591±0.364)compared to PNET.A cutoff value of 1.046×10^(-3)mm^(2)/s for absolute ADC was associated with 81.25%sensitivity,100%specificity,and 89.66%accuracy with an area under the curve of 0.94(95%confidence interval:0.8536-1.000)for the differential diagnosis of IPAS from PNET.Similarly,a cutoff value of 1.342 for normalized ADC was associated with 81.25%sensitivity,92.31%specificity,and 86.21%accuracy with an area under the curve of 0.91(95%confidence interval:0.8080-1.000)for the differential diagnosis of IPAS from PNET.Both methods showed excellent inter-reader reliability with intraclass correlation coefficients for absolute ADC and ADC ratio being 0.968 and 0.976,respectively.CONCLUSION Both absolute ADC and normalized ADC values can facilitate the differentiation between IPAS and PNET.展开更多
BACKGROUND The incidence of type I gastric neuroendocrine neoplasms(gNENs)has increased significantly over the past 50 years.Although autoimmune gastritis(AIG)increases the likelihood of developing gNENs,the exact inc...BACKGROUND The incidence of type I gastric neuroendocrine neoplasms(gNENs)has increased significantly over the past 50 years.Although autoimmune gastritis(AIG)increases the likelihood of developing gNENs,the exact incidence and prevalence of this association remain unclear.AIM To evaluate the incidence and prevalence of type I gNENs in a cohort of patients with a histological diagnosis of AIG.METHODS Patients with a histological diagnosis of AIG were enrolled between October 2020 and May 2022.Circulating levels of CgA and gastrin were assessed at enrollment.Included patients underwent regular endoscopic follow-up to detect gastric neoplastic lesions,enterochromaffin-like(ECL)cell hyperplasia,and the development of gNEN.RESULTS We included 176 patients[142 women(80.7%),median age 64 years,interquartile range(IQR)53–71 years]diagnosed with AIG between January 1990 and June 2022.At enrollment.One hundred and sixteen patients(65.9%)had ECL hyperplasia,of whom,29.5%had simple/linear,30.7%had micronodular,and 5.7%had macronodular type.The median follow-up time was 5(3–7.5)years.After 1032 person-years,33 patients developed a total of 50 type I gNENs,with an incidence rate of 0.057 person-years,corresponding to an annual cumulative incidence of 5.7%.Circulating CgA levels did not significantly differ between AIG patients who developed gNENs and those who did not.Conversely,gastrin levels were significantly higher in AIG patients who developed gNENs[median 992 pg/mL IQR=449–1500 vs 688 pg/mL IQR=423–1200,P=0.03].Calculated gastrin sensitivity and specificity were 90.9%and 1.4%,respectively,with an overall diagnostic accuracy of 30%and a calculated area under the gastrin receiver operating characteristic curve(AUROC or AUC)of 0.53.CONCLUSION Type I gNENs are a significant complication in AIG.Gastrin’s low diagnostic accuracy prevents it from serving as a marker for early diagnosis.Effective strategies for early detection and treatment are needed.展开更多
Gastric neuroendocrine neoplasms(gNENs)are a rare type of gastric neoplasm,even if their frequency is increasing according to the latest epidemiologic revisions of the main registries worldwide.They are divided into t...Gastric neuroendocrine neoplasms(gNENs)are a rare type of gastric neoplasm,even if their frequency is increasing according to the latest epidemiologic revisions of the main registries worldwide.They are divided into three main subtypes,with different pathogeneses,biological behaviors,and clinical characteristics.GNEN heterogeneity poses challenges,therefore these neoplasms require different management strategies.Update the knowledge on the endoscopic treatment options to manage g-NENs.This manuscript is a narrative review of the literature.In recent years,many advances have been made not only in the knowledge of both the pathogenesis and the molecular profiling of gNENs but also in the endoscopic expertise towards innovative treatment options,which proved to be less aggressive without losing the capa-bility of being radical.The endoscopic approach is increasingly applied in the field of gastrointestinal(GI)luminal neoplasms,and this is true not only for adenocarcinomas but also for gNENs.In particular,different techniques have been described for the endoscopic removal of suspected lesions,ranging from classical polypectomy(cold or hot snare)to endoscopic mucosal resection(both with“en bloc”or piecemeal technique),endoscopic submucosal dissection,and endoscopic full-thickness resection.GNENs comprise different subtypes of neoplasms with distinct management and prognosis.New endoscopic techniques offer a wide variety of approaches for GI localized neoplasms,which demonstrated to be appropriate and effective also in the case of gNENs.Correct evaluation of size,site,morphology,and clinical context allows the choice of tailored therapy in order to guarantee a definitive treatment.展开更多
BACKGROUND Significant correlation between lymphatic,microvascular,and perineural invasion(LMPI)and the prognosis of pancreatic neuroendocrine tumors(PENTs)was confirmed by previous studies.There was no previous study...BACKGROUND Significant correlation between lymphatic,microvascular,and perineural invasion(LMPI)and the prognosis of pancreatic neuroendocrine tumors(PENTs)was confirmed by previous studies.There was no previous study reported the relationship between magnetic resonance imaging(MRI)parameters and LMPI.AIM To determine the feasibility of using preoperative MRI of the pancreas to predict LMPI in patients with non-functioning PENTs(NFPNETs).METHODS A total of 61 patients with NFPNETs who underwent MRI scans and lymphadenectomy from May 2011 to June 2018 were included in this retrospective study.The patients were divided into group 1(n=34,LMPI negative)and group 2(n=27,LMPI positive).The clinical characteristics and qualitative MRI features were collected.In order to predict LMPI status in NF-PNETs,a multivariate logistic regression model was constructed.Diagnostic performance was evaluated by calculating the receiver operator characteristic(ROC)curve with area under ROC,sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV)and accuracy.RESULTS There were significant differences in the lymph node metastasis stage,tumor grade,neuron-specific enolase levels,tumor margin,main pancreatic ductal dilatation,common bile duct dilatation,enhancement pattern,vascular and adjacent tissue involvement,synchronous liver metastases,the long axis of the largest lymph node,the short axis of the largest lymph node,number of the lymph nodes with short axis>5 or 10 mm,and tumor volume between two groups(P<0.05).Multivariate analysis showed that tumor margin(odds ratio=11.523,P<0.001)was a predictive factor for LMPI of NF-PNETs.The area under the receiver value for the predictive performance of combined predictive factors was 0.855.The sensitivity,specificity,PPV,NPV and accuracy of the model were 48.1%(14/27),97.1%(33/34),97.1%(13/14),70.2%(33/47)and 0.754,respectively.CONCLUSION Using preoperative MRI,ill-defined tumor margins can effectively predict LMPI in patients with NF-PNETs.展开更多
Rectal neuroendocrine tumors(rNETs)measuring less than 10 mm in diameter are defined as small rNETs.Due to the low risk of distant invasion and metastasis,endoscopic treatments,including modified endoscopic mucosal re...Rectal neuroendocrine tumors(rNETs)measuring less than 10 mm in diameter are defined as small rNETs.Due to the low risk of distant invasion and metastasis,endoscopic treatments,including modified endoscopic mucosal resection,endoscopic submucosal dissection,and other transanal surgical procedures,are effective.This review article proposes a follow-up plan according to the size and histopathology of the tumor after operation.展开更多
BACKGROUND A rectal neuroendocrine tumor(rNET)is a malignant tumor originating from neuroendocrine cells.Currently,tumor size is the primary basis for assessing tumor risk.CASE SUMMARY This article reports the case of...BACKGROUND A rectal neuroendocrine tumor(rNET)is a malignant tumor originating from neuroendocrine cells.Currently,tumor size is the primary basis for assessing tumor risk.CASE SUMMARY This article reports the case of a 46-year-old male patient who underwent a colonoscopy that found a 3 mm rectal polypoid bulge.The pathological examination of a sample collected with biopsy forceps revealed a neuroendocrine tumor.Further endoscopic submucosal dissection rescue therapy was used.The presence of lymphatic vessels indicated that the tumor had infiltrated the negative resection margin.The lesion was located in the distal rectum near the anal canal.Therefore,to ensure the patient’s quality of life,follow-up observation was conducted after full communication with the patient.No tumor recurrence or distant metastasis has been found during the 13-mo follow-up after surgery.CONCLUSION Despite the presence of lymphatic invasion and extremely small diameter rNETs in our case,this phenomenon may not imply a higher risk of distant lymph node and organ metastasis.展开更多
BACKGROUND Endoscopic resection remains an effective method for the treatment of small rectal neuroendocrine tumors(NETs)(≤10 mm).Moreover,endoscopic mucosal resection(EMR)with double band ligation(EMR-dB),a simplifi...BACKGROUND Endoscopic resection remains an effective method for the treatment of small rectal neuroendocrine tumors(NETs)(≤10 mm).Moreover,endoscopic mucosal resection(EMR)with double band ligation(EMR-dB),a simplified modification of EMR with band ligation,is an alternative strategy to remove small rectal NETs.AIM To evaluate the feasibility and safety of EMR-dB for the treatment of small rectal NETs(≤10 mm).METHODS A total of 50 patients with small rectal NETs,without regional lymph node enlargement or distant metastasis confirmed by endoscopic ultrasound,computerized tomography scan,or magnetic resonance imaging,were enrolled in the study from March 2021 to June 2022.These patients were randomly assigned into the EMR-dB(n=25)group or endoscopic submucosal dissection(ESD)group(n=25).The characteristics of the patients and tumors,procedure time,devices cost,complete resection rate,complications,and recurrence outcomes were analyzed.RESULTS There were 25 patients(13 males,12 females;age range 28-68 years old)in the EMR-dB group,and the ESD group contained 25 patients(15 males,10 females;age range 25-70 years old).Both groups had similar lesion sizes(EMR-dB 4.53±1.02 mm,ESD 5.140±1.74 mm;P=0.141)and resected lesion sizes(1.32±0.52 cm vs 1.58±0.84 cm;P=0.269).Furthermore,the histological complete resection and en bloc resection rates were achieved in all patients(100%for each).In addition,there was no significant difference in the complication rate between the two groups.However,the procedure time was significantly shorter and the devices cost was significantly lower in the EMRdB group.Besides,there was no recurrence in both groups during the follow-up period.CONCLUSION The procedure time of EMR-dB was shorter compared with ESD,and both approaches showed a similar curative effect.Taken together,EMR-dB was a feasible and safe option for the treatment of small rectal NETs.展开更多
Pancreatic neuroendocrine tumors(PNETs)are known to be the second most common epithelial malignancy of the pancreas.PNETs can be listed among the slowest growing as well as the fastest growing human cancers.The preval...Pancreatic neuroendocrine tumors(PNETs)are known to be the second most common epithelial malignancy of the pancreas.PNETs can be listed among the slowest growing as well as the fastest growing human cancers.The prevalence of PNETs is deceptively low;however,its incidence has significantly increased over the past decades.According to the American Cancer Society’s estimate,about 4032(>7%of all pancreatic malignancies)individuals will be diagnosed with PNETs in 2020.PNETs often cause severe morbidity due to excessive secretion of hormones(such as serotonin)and/or overall tumor mass.Patients can live for many years(except for those patients with poorly differentiated G3 neuroendocrine tumors);thus,the prevalence of the tumors that is the number of patients actually dealing with the disease at any given time is fairly high because the survival is much longer than pancreatic ductal adenocarcinoma.Due to significant heterogeneity,the management of PNETs is very complex and remains an unmet clinical challenge.In terms of research studies,modest improvements have been made over the past decades in the identification of potential oncogenic drivers in order to enhance the quality of life and increase survival for this growing population of patients.Unfortunately,the majority of systematic therapies approved for the management of advanced stage PNETs lack objective response or at most result in modest benefits in survival.In this review,we aim to discuss the broad challenges associated with the management and the study of PNETs.展开更多
BACKGROUND Primary hepatic neuroendocrine tumors(PHNETs),a group of neuroendocrine neoplasms,are extremely rare.There are only few case reports about PHNETs in the literature.The lack of large samples and multicenter ...BACKGROUND Primary hepatic neuroendocrine tumors(PHNETs),a group of neuroendocrine neoplasms,are extremely rare.There are only few case reports about PHNETs in the literature.The lack of large samples and multicenter research results in poor diagnostic and therapeutic approaches.AIM To discuss the clinical characteristics,diagnosis,and treatment of PHNETs and risk factors related to survival.METHODS We retrospectively analyzed the clinical data,imaging features,immunohistochemistry data,and treatment efficacy of 40 patients who were pathologically diagnosed with PHNETs and admitted to The First Affiliated Hospital of Zhengzhou University from January 1,2014 to November 15,2019.Finally,survival analysis was performed to identify the risk factors for survival.RESULTS The main symptoms and signs included intermittent abdominal pain(19 patients,47.5%)and bloating(8 patients,20.0%).The positive rates of tested tumor markers were recorded as follows:Carbohydrate antigen 19-9(CA19-9)(6 patients,15.0%),CA72-4(3 patients,7.5%),carcinoembryonic antigen(7 patients,17.5%),and alpha-fetoprotein(6 patients,15.0%).Immunohistochemical staining results showed positivity for Syn in 38(97.4%)of 39 patients,for chromogranin A in 17(65.4%)of 26 patients,for CD56 in 35(94.6%)of 37 patients,for AE1/AE3 in 28(87.5%)of 32 patients,and for Ki-67 in all 40(100.0%)patients.The overall survival rate was significantly related to the tumor grade,AE1/AE3,and Ki-67.tumor number,tumor size,metastasis,and treatment)and overall survival.CONCLUSION Higher grade,negative AE1/AE3,and higher Ki-67 are associated with a worse survival rate.Kinds of treatment and other parameters have no significant influence on overall survival.展开更多
Somatostatin analogs were initially developed for the control of hormonal syndromes associated with neuro-endocrine tumors (NETs). In recent years, accumul ating data has supported their role as antiproliferative agen...Somatostatin analogs were initially developed for the control of hormonal syndromes associated with neuro-endocrine tumors (NETs). In recent years, accumul ating data has supported their role as antiproliferative agents, capable of stabilizing tumor growth in patients with metastatic neuroendocrine malignancies, including carci-noid and pancreatic endocrine tumors. A phase Ⅲ, ran-domized, placebo-controlled trial has now demonstrated that octreotide long-acting repeatable (LAR) 30 mg can significantly prolong time to tumor progression among patients with metastatic midgut NETs regardless of functional status, chromogranin A level or age. In addition to signif icantly lengthening time to tumor pro-gression in the overall study population, subset analysis suggests that patients with low tumor burden are most likely to experience disease stabilization with octreotide LAR 30 mg, supporting the early use of octreotide LAR in patients with metastatic disease. Further research efforts are underway to evaluate the use of somatostatin analogs as antiproliferative agents in other types of gastroenteropancreatic-NETs. Ongoing studies are also evaluating novel somatostatin analogs and somatostatin analogs in combination with other anti-tumor therapies.展开更多
Colorectal neuroendocrine tumors (NETs) originate from neuroendocrine cells in the intestinal tract, and represent a small area within oncology, but one which has provided increasing new data during the past years. Al...Colorectal neuroendocrine tumors (NETs) originate from neuroendocrine cells in the intestinal tract, and represent a small area within oncology, but one which has provided increasing new data during the past years. Although the World Health Organization has determined clinical and histological features to predict prognosis for such tumors, they may not be valid on an individual basis. We aim to give an overview of the recent findings with regard to pathology, molecular genetics and diagnosis of NETs.展开更多
Rectal neuroendocrine neoplasms(r-NENs)are considered among the most frequent digestive NENs,together with small bowel NENs.Their incidence has increased over the past few years,and this is probably due to the widespr...Rectal neuroendocrine neoplasms(r-NENs)are considered among the most frequent digestive NENs,together with small bowel NENs.Their incidence has increased over the past few years,and this is probably due to the widespread use of endoscopic screening for colorectal cancer and the advanced endoscopic procedures available nowadays.According to the current European Neuroendocrine Tumor Society(ENETS)guidelines,well-differentiated r-NENs smaller than 10 mm should be endoscopically removed in view of their low risk of local and distant invasion.R-NENs larger than 20 mm are candidates for surgical resection because of their high risk of distant spreading and the involvement of the muscularis propria.There is an area of uncertainty regarding tumors between 10 and 20 mm,in which the metastatic risk is intermediate and the endoscopic treatment can be challenging.Once removed,the indications for surveillance are scarce and poorly codified by international guidelines,therefore in this paper,a possible algorithm is proposed.展开更多
BACKGROUND Neuroendocrine tumors(NETs)frequently occur in the gastrointestinal tract,lung,and pancreas,and the rectum and appendix are the sites with the highest incidence.Epidemiology statistics show that an estimate...BACKGROUND Neuroendocrine tumors(NETs)frequently occur in the gastrointestinal tract,lung,and pancreas,and the rectum and appendix are the sites with the highest incidence.Epidemiology statistics show that an estimated 8000 people every year in the United States are diagnosed with NETs occurring in the gastrointestinal tract,including the stomach,intestine,appendix,colon,and rectum.The pathological changes and clinical symptoms of NETs are not specific,and therefore they are frequently misdiagnosed.AIM To investigate the clinical symptoms,pathological characteristics,treatment,and prognosis of rectal neuroendocrine tumors(RNETs)by analyzing the clinical and pathological data of 132 RNET cases at our hospital.METHODS All RNETs were graded according to Ki-67 positivity and mitotic events.The tumors were staged as clinical stages I,II,III,and IV according to infiltrative depth and tumor size.COX proportional hazard model was used to assess the main risk factors for survival.RESULTS These 132 RNETs included 83 cases of G1,21 cases of G2,and 28 cases of G3(neuroendocrine carcinoma)disease.Immunohistochemical staining showed that 89.4%of RNETs were positive for synaptophysin and 39.4%positive for chromogranin A.There were 19,85,23,and 5 cases of clinical stages I,II,III,and IV,respectively.The median patient age was 52.96 years.The diameter of tumor,depth of invasion,and pathological grade were the main reference factors for the treatment of RNETs.The survival rates at 6,12,36,and 60 mo after operation were 98.5%,94.6%,90.2%,and 85.6%,respectively.Gender,tumor size,tumor grade,lymph node or distant organ metastasis,and radical resection were the main factors associated with prognosis of RNETs.Multivariate analysis showed that tumor size and grade were independent prognostic factors.CONCLUSION The clinical symptoms of RNETs are not specific,and they are easy to misdiagnose.Surgery is the main treatment method.The grade and stage of RNETs are the main indices to evaluate prognosis.展开更多
文摘BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor progression.Therefore,identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is relevant.In this perspective,metformin is emerging as a molecule of interest.Retrospective studies have described metformin,a widely used agent for the treatment of patients with type 2 diabetes mellitus(T2DM),to be effective in modulating different tumor-related events,including cancer incidence,recurrence and survival by inhibiting mTOR phosphorylation.This systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with pNET.AIM To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and posttreatment outcomes of pNET.METHODS A systematic review of the published literature was undertaken,focusing on the role of T2DM and metformin in insurgence and prognosis of pNET,measured through outcomes of tumor-free survival(TFS),overall survival and progression free survival.RESULTS A total of 13 studies(5674 patients)were included in this review.Analysis of 809 pNET cases from five retrospective studies(low study heterogeneity with I^(2)=0%)confirms the correlation between T2DM and insurgence of pNET(OR=2.13,95%CI=1.56-4.55;P<0.001).The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients(hazard ratio=1.84,95%CI=0.78-2.90;P<0.001).The study heterogeneity was intermediate,with I^(2)=51%.A few studies limited the possibility of performing pooled analysis in the setting of metformin;therefore,results were heterogeneous,with no statistical relevance to the use of this drug in the diagnosis and prognosis of pNET.CONCLUSION T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients.Unfortunately,a few studies with heterogeneous results limited the possibility of exploring the effect of metformin in the diagnosis and prognosis of pNET.
基金reviewed and approved by the Hospital Pablo Tobón Uribe Institutional Review Board(Approval No.PG-DMD-046-F1).
文摘BACKGROUND Pancreatic neuroendocrine tumors(PNETs)are relatively rare but rank as the second most common pancreatic neoplasm.They can be functional,causing early metabolic disturbances due to hormone secretion,or non-functional and diagnosed later based on tumor size-related symptoms.Recent diagnoses of PNETs under 2 cm in size have sparked debates about their management;some practitioners advocate for surgical removal and others suggest observation due to the tumors’lower potential for malignancy.However,it is unclear whether managing these small tumors expectantly is truly safe.AIM To evaluate poor prognostic factors in PNETs based on tumor size(>2 cm or<2 cm)in surgically treated patients.METHODS This cohort study included 64 patients with PNETs who underwent surgical resection between 2006 and 2019 at a high-complexity reference hospital in Medellín,Colombia.To assess patient survival,quarterly follow-ups were conducted during the first year after surgery,followed by semi-annual con-sultations at the hospital's hepatobiliary surgery department.Qualitative variables were described using absolute and relative frequencies,and quantitative variables were expressed using measures of central tendency and their corresponding measures of dispersion.RESULTS The presence of lymph node involvement,neural involvement,and lymphovascular invasion were all associated with an increased risk of mortality,with hazard ratios of 5.68(95%CI:1.26–25.61,P=0.024),6.44(95%CI:1.43–28.93,P=0.015),and 24.87(95%CI:2.98–207.19,P=0.003),respectively.Neural involvement and lymphovascular invasion were present in tumors smaller than 2 cm in diameter and those larger than 2 cm in diameter.The recurrence rates between the two tumor groups were furthermore similar:18.2%for tumors smaller than 2 cm and 21.4%for tumors larger than 2 cm.Patient survival was additionally comparable between the two tumor groups.CONCLUSION Tumor size does not dictate prognosis;lymph node and lymphovascular involvement affect mortality,which high-lights that histopathological factors-rather than tumor size-may play a role in management.
文摘BACKGROUND The majority of gastric neuroendocrine tumors(G-NENs)are present in various lesions under endoscopy,and they can be polypoid uplifts,submucosal tumors or papules,erosions,and ulcers.The lesions are mostly confined to the mucosal or submucosal layer,usually less than 2 cm,and exclusively localized to the gastric body or fundus.In type 1 G-NENs,about 22%of cases have no visible lesions under an endoscope,and such lesions can only be detected via biopsies(microcar-cinoids).CONCLUSION In the case under study,the patient did not have any visible raised lesions under a gastroscope,and the lesions were found only after a random biopsy.This article combines the endoscopic manifestations and clinical features of the lesions in this case to improve the diagnosis of G-NENs.
文摘Gastrointestinal neuroendocrine tumors are rare slow-growing tumors with distinct histological,biological,and clinical characteristics that have increased in incidence and prevalence within the last few decades.They contain chromogranin A,synaptophysin and neuron-specific enolase which are necessary for making a diagnosis of neuroendocrine tumor.Ki-67 index and mitotic index correlate with cellular proliferation.Serum chromogranin A is the most commonly used biomarker to assess the bulk of disease and monitor treatment and is raised in both functioning and non-functioning neuroendocrine tumors.Most of the gastrointestinal neuroendocrine tumors are non-functional.World Health Organization updated the classification of neuroendocrine tumors in 2017 and renamed mixed adenoneuroendocrine carcinoma into mixed neuroendocrine neoplasm.Gastric neuroendocrine tumors arise from enterochromaffin like cells.They are classified into 4 types.Only type I and type II are gastrin dependent.Small intestinal neuroendocrine tumor is the most common small bowel malignancy.More than two-third of them occur in the terminal ileum within 60 cm of ileocecal valve.Patients with small intestinal neuroendrocrine tumors frequently show clinical symptoms and develop distant metastases more often than those with neuroendocrine tumors of other organs.Duodenal and jejunoileal neuroendocrine tumors are distinct biologically and clinically.Carcinoid syndrome generally occurs when jejuno-ileal neuroendocrine tumors metastasize to the liver.Appendiceal neuroendocrine tumors are generally detected after appendectomy.Colonic neuroendocrine tumors generally present as a large tumor with local or distant metastasis at the time of diagnosis.Rectal neuroendocrine tumors are increasingly being diagnosed since the implementation of screening colonoscopy in 2000.Gastrointestinal neuroendocrine tumors are diagnosed and staged by endoscopy with biopsy,endoscopic ultrasound,serology of biomarkers,imaging studies and functional somatostatin scans.Various treatment options are available for curative and palliative treatment of gastrointestinal neuroendocrine tumors.
基金Supported by Natural Science Foundation of Zhejiang Province,No.LQ20H1600036 (to Wen X).
文摘BACKGROUND The molecular changes present in gastric neuroendocrine tumors(NETs)include a loss of heterozygosity or mutation of MEN1,CDKN1B gene mutation,P27 heterozygous mutation,and ATP4A gene missense mutation.We identified and are the first to report a case of type 1 histamine-producing enterochromaffin-like cell NETs(ECL-cell NETs)with a BRCA2 gene germline mutation.CASE SUMMARY The patient had a history of iron-deficient anemia for 5 years,and gastroscopic examination indicated multiple gastric tumors.Then,the patient underwent distal gastrectomy.Microscopically,multifocal tumor cells were found in the mucosa and submucosa;tumor cells were organoid and arranged in nests and cords,and the stroma was rich in sinusoids.The surrounding gastric mucosa showed atrophy with mild intestinal metaplasia or pseudopyloric gland metaplasia.Neuroendocrine cells could be seen with diffuse linear,nodular,and adenomatous hyperplasia.Immunohistochemically,the tumor cells diffusely expressed cytokeratin,chromogranin,synaptophysin,and CD56.Whole-genome highthroughput molecular sequencing revealed a pathogenic germline mutation in the BRCA2 gene,a heterozygous germline frameshift mutation in exon 11,c.6443_6444del(p.S2148Yfs*2).The final diagnosis was gastric type 1 ECL-cell NETs with a BRCA2 gene germline mutation,accompanied by autoimmune gastritis.CONCLUSION This is the first report of a case of type 1 gastric ECL-cell NETs with a pathogenic germline mutation of the BRCA2 gene.The findings of this report will expand the germline mutation spectrum of gastric NETs and increase the understanding of the molecular changes present in these tumors for their improved diagnosis in the future.
文摘Small intestinal neuroendocrine tumors(NETs)are a heterogeneous group of epithelial tumors with a predominant neuroendocrine differentiation.Although NETs are usually considered rare neoplasms,small intestinal NETs are the most common primary malignancy of the small bowel,with an increasing prevalence worldwide during the course of the past few decades.The indolent nature of these tumors often leads to a delayed diagnosis,resulting in over one-third of patients presenting with synchronous metastases.Primary tumor resection remains the only curative option for this type of tumor.In this review article,the various surgical aspects for the excision of small intestinal NETs are discussed.
文摘Objective:Currently,pre-treatment prediction of patients with pancreatic neuroendocrine tumors with liver metastases(PNELM)receiving surufatinib treatment was unsatisfying.Our objective was to examine the association between radiological characteristics and efficacy/prognosis.Methods:We enrolled patients with liver metastases in the phase III,SANET-p trial(NCT02589821)and obtained contrast-enhanced computed tomography(CECT)images.Qualitative and quantitative parameters including hepatic tumor margins,lesion volumes,enhancement pattern,localization types,and enhancement ratios were evaluated.The progression-free survival(PFS)and hazard ratio(HR)were calculated using Cox’s proportional hazard model.Efficacy was analyzed by logistic-regression models.Results:Among 152 patients who had baseline CECT assessments and were included in this analysis,the surufatinib group showed statistically superior efficacy in terms of median PFS compared to placebo across various qualitative and quantitative parameters.In the multivariable analysis of patients receiving surufatinib(N=100),those with higher arterial phase standardized enhancement ratio-peri-lesion(ASER-peri)exhibited longer PFS[HR=0.039;95%confidence interval(95%CI):0.003−0.483;P=0.012].Furthermore,patients with a high enhancement pattern experienced an improvement in the objective response ratio[31.3%vs.14.7%,odds ratio(OR)=3.488;95%CI:1.024−11.875;P=0.046],and well-defined tumor margins were associated with a higher disease control rate(DCR)(89.3%vs.68.2%,OR=4.535;95%CI:1.285−16.011;P=0.019)compared to poorlydefined margins.Conclusions:These pre-treatment radiological features,namely high ASER-peri,high enhancement pattern,and well-defined tumor margins,have the potential to serve as predictive markers of efficacy in patients with PNELM receiving surufatinib.
基金Supported by the National Natural Science foundation of China,No. 82202135, and No. 82171925Foundation of Excellent Young Doctor of Jiangsu Province Hospital of Chinese Medicine,No. 2023QB0112+1 种基金Innovative Development Foundation of Department in Jiangsu Hospital of Chinese Medicine,No. Y2021CX19Developing Program for High-level Academic Talent in Jiangsu Hospital of TCM,No. y2021rc03
文摘BACKGROUND Intrapancreatic accessory spleen(IPAS)shares similar imaging findings with hypervascular pancreatic neuroendocrine tumors(PNETs),which may lead to unnecessary surgery.AIM To investigate and compare the diagnostic performance of absolute apparent diffusion coefficient(ADC)and normalized ADC(lesion-to-spleen ADC ratios)in the differential diagnosis of IPAS from PNETs.METHODS A retrospective study consisting of 29 patients(16 PNET patients vs 13 IPAS patients)who underwent preoperative contrast-enhanced magnetic resonance imaging together with diffusion-weighted imaging/ADC maps between January 2017 and July 2020 was performed.Two independent reviewers measured ADC on all lesions and spleens,and normalized ADC was calculated for further analysis.The receiver operating characteristics analysis was carried out for evaluating the diagnostic performance of both absolute ADC and normalized ADC values in the differential diagnosis between IPAS and PNETs by clarifying sensitivity,specificity,and accuracy.Inter-reader reliability for the two methods was evaluated.RESULTS IPAS had a significantly lower absolute ADC(0.931±0.773×10^(-3)mm^(2)/s vs 1.254±0.219×10^(-3)mm^(2)/s)and normalized ADC value(1.154±0.167 vs 1.591±0.364)compared to PNET.A cutoff value of 1.046×10^(-3)mm^(2)/s for absolute ADC was associated with 81.25%sensitivity,100%specificity,and 89.66%accuracy with an area under the curve of 0.94(95%confidence interval:0.8536-1.000)for the differential diagnosis of IPAS from PNET.Similarly,a cutoff value of 1.342 for normalized ADC was associated with 81.25%sensitivity,92.31%specificity,and 86.21%accuracy with an area under the curve of 0.91(95%confidence interval:0.8080-1.000)for the differential diagnosis of IPAS from PNET.Both methods showed excellent inter-reader reliability with intraclass correlation coefficients for absolute ADC and ADC ratio being 0.968 and 0.976,respectively.CONCLUSION Both absolute ADC and normalized ADC values can facilitate the differentiation between IPAS and PNET.
文摘BACKGROUND The incidence of type I gastric neuroendocrine neoplasms(gNENs)has increased significantly over the past 50 years.Although autoimmune gastritis(AIG)increases the likelihood of developing gNENs,the exact incidence and prevalence of this association remain unclear.AIM To evaluate the incidence and prevalence of type I gNENs in a cohort of patients with a histological diagnosis of AIG.METHODS Patients with a histological diagnosis of AIG were enrolled between October 2020 and May 2022.Circulating levels of CgA and gastrin were assessed at enrollment.Included patients underwent regular endoscopic follow-up to detect gastric neoplastic lesions,enterochromaffin-like(ECL)cell hyperplasia,and the development of gNEN.RESULTS We included 176 patients[142 women(80.7%),median age 64 years,interquartile range(IQR)53–71 years]diagnosed with AIG between January 1990 and June 2022.At enrollment.One hundred and sixteen patients(65.9%)had ECL hyperplasia,of whom,29.5%had simple/linear,30.7%had micronodular,and 5.7%had macronodular type.The median follow-up time was 5(3–7.5)years.After 1032 person-years,33 patients developed a total of 50 type I gNENs,with an incidence rate of 0.057 person-years,corresponding to an annual cumulative incidence of 5.7%.Circulating CgA levels did not significantly differ between AIG patients who developed gNENs and those who did not.Conversely,gastrin levels were significantly higher in AIG patients who developed gNENs[median 992 pg/mL IQR=449–1500 vs 688 pg/mL IQR=423–1200,P=0.03].Calculated gastrin sensitivity and specificity were 90.9%and 1.4%,respectively,with an overall diagnostic accuracy of 30%and a calculated area under the gastrin receiver operating characteristic curve(AUROC or AUC)of 0.53.CONCLUSION Type I gNENs are a significant complication in AIG.Gastrin’s low diagnostic accuracy prevents it from serving as a marker for early diagnosis.Effective strategies for early detection and treatment are needed.
基金AMAF Monza ONLUS and AIRCS for the unrestricted research funding
文摘Gastric neuroendocrine neoplasms(gNENs)are a rare type of gastric neoplasm,even if their frequency is increasing according to the latest epidemiologic revisions of the main registries worldwide.They are divided into three main subtypes,with different pathogeneses,biological behaviors,and clinical characteristics.GNEN heterogeneity poses challenges,therefore these neoplasms require different management strategies.Update the knowledge on the endoscopic treatment options to manage g-NENs.This manuscript is a narrative review of the literature.In recent years,many advances have been made not only in the knowledge of both the pathogenesis and the molecular profiling of gNENs but also in the endoscopic expertise towards innovative treatment options,which proved to be less aggressive without losing the capa-bility of being radical.The endoscopic approach is increasingly applied in the field of gastrointestinal(GI)luminal neoplasms,and this is true not only for adenocarcinomas but also for gNENs.In particular,different techniques have been described for the endoscopic removal of suspected lesions,ranging from classical polypectomy(cold or hot snare)to endoscopic mucosal resection(both with“en bloc”or piecemeal technique),endoscopic submucosal dissection,and endoscopic full-thickness resection.GNENs comprise different subtypes of neoplasms with distinct management and prognosis.New endoscopic techniques offer a wide variety of approaches for GI localized neoplasms,which demonstrated to be appropriate and effective also in the case of gNENs.Correct evaluation of size,site,morphology,and clinical context allows the choice of tailored therapy in order to guarantee a definitive treatment.
基金Supported by Beijing Hospitals Authority Youth Program,No.QML20231103.
文摘BACKGROUND Significant correlation between lymphatic,microvascular,and perineural invasion(LMPI)and the prognosis of pancreatic neuroendocrine tumors(PENTs)was confirmed by previous studies.There was no previous study reported the relationship between magnetic resonance imaging(MRI)parameters and LMPI.AIM To determine the feasibility of using preoperative MRI of the pancreas to predict LMPI in patients with non-functioning PENTs(NFPNETs).METHODS A total of 61 patients with NFPNETs who underwent MRI scans and lymphadenectomy from May 2011 to June 2018 were included in this retrospective study.The patients were divided into group 1(n=34,LMPI negative)and group 2(n=27,LMPI positive).The clinical characteristics and qualitative MRI features were collected.In order to predict LMPI status in NF-PNETs,a multivariate logistic regression model was constructed.Diagnostic performance was evaluated by calculating the receiver operator characteristic(ROC)curve with area under ROC,sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV)and accuracy.RESULTS There were significant differences in the lymph node metastasis stage,tumor grade,neuron-specific enolase levels,tumor margin,main pancreatic ductal dilatation,common bile duct dilatation,enhancement pattern,vascular and adjacent tissue involvement,synchronous liver metastases,the long axis of the largest lymph node,the short axis of the largest lymph node,number of the lymph nodes with short axis>5 or 10 mm,and tumor volume between two groups(P<0.05).Multivariate analysis showed that tumor margin(odds ratio=11.523,P<0.001)was a predictive factor for LMPI of NF-PNETs.The area under the receiver value for the predictive performance of combined predictive factors was 0.855.The sensitivity,specificity,PPV,NPV and accuracy of the model were 48.1%(14/27),97.1%(33/34),97.1%(13/14),70.2%(33/47)and 0.754,respectively.CONCLUSION Using preoperative MRI,ill-defined tumor margins can effectively predict LMPI in patients with NF-PNETs.
文摘Rectal neuroendocrine tumors(rNETs)measuring less than 10 mm in diameter are defined as small rNETs.Due to the low risk of distant invasion and metastasis,endoscopic treatments,including modified endoscopic mucosal resection,endoscopic submucosal dissection,and other transanal surgical procedures,are effective.This review article proposes a follow-up plan according to the size and histopathology of the tumor after operation.
基金Supported by Guizhou Science and Technology Plan Project,No.ZK2022-General-443Science and Technology Fund of Guizhou Provincial Health and Health Commission,No.gzwkj2023-135。
文摘BACKGROUND A rectal neuroendocrine tumor(rNET)is a malignant tumor originating from neuroendocrine cells.Currently,tumor size is the primary basis for assessing tumor risk.CASE SUMMARY This article reports the case of a 46-year-old male patient who underwent a colonoscopy that found a 3 mm rectal polypoid bulge.The pathological examination of a sample collected with biopsy forceps revealed a neuroendocrine tumor.Further endoscopic submucosal dissection rescue therapy was used.The presence of lymphatic vessels indicated that the tumor had infiltrated the negative resection margin.The lesion was located in the distal rectum near the anal canal.Therefore,to ensure the patient’s quality of life,follow-up observation was conducted after full communication with the patient.No tumor recurrence or distant metastasis has been found during the 13-mo follow-up after surgery.CONCLUSION Despite the presence of lymphatic invasion and extremely small diameter rNETs in our case,this phenomenon may not imply a higher risk of distant lymph node and organ metastasis.
基金Supported by Technical Research and Development Project of Shenzhen,No.JCYJ20210324113215040.
文摘BACKGROUND Endoscopic resection remains an effective method for the treatment of small rectal neuroendocrine tumors(NETs)(≤10 mm).Moreover,endoscopic mucosal resection(EMR)with double band ligation(EMR-dB),a simplified modification of EMR with band ligation,is an alternative strategy to remove small rectal NETs.AIM To evaluate the feasibility and safety of EMR-dB for the treatment of small rectal NETs(≤10 mm).METHODS A total of 50 patients with small rectal NETs,without regional lymph node enlargement or distant metastasis confirmed by endoscopic ultrasound,computerized tomography scan,or magnetic resonance imaging,were enrolled in the study from March 2021 to June 2022.These patients were randomly assigned into the EMR-dB(n=25)group or endoscopic submucosal dissection(ESD)group(n=25).The characteristics of the patients and tumors,procedure time,devices cost,complete resection rate,complications,and recurrence outcomes were analyzed.RESULTS There were 25 patients(13 males,12 females;age range 28-68 years old)in the EMR-dB group,and the ESD group contained 25 patients(15 males,10 females;age range 25-70 years old).Both groups had similar lesion sizes(EMR-dB 4.53±1.02 mm,ESD 5.140±1.74 mm;P=0.141)and resected lesion sizes(1.32±0.52 cm vs 1.58±0.84 cm;P=0.269).Furthermore,the histological complete resection and en bloc resection rates were achieved in all patients(100%for each).In addition,there was no significant difference in the complication rate between the two groups.However,the procedure time was significantly shorter and the devices cost was significantly lower in the EMRdB group.Besides,there was no recurrence in both groups during the follow-up period.CONCLUSION The procedure time of EMR-dB was shorter compared with ESD,and both approaches showed a similar curative effect.Taken together,EMR-dB was a feasible and safe option for the treatment of small rectal NETs.
文摘Pancreatic neuroendocrine tumors(PNETs)are known to be the second most common epithelial malignancy of the pancreas.PNETs can be listed among the slowest growing as well as the fastest growing human cancers.The prevalence of PNETs is deceptively low;however,its incidence has significantly increased over the past decades.According to the American Cancer Society’s estimate,about 4032(>7%of all pancreatic malignancies)individuals will be diagnosed with PNETs in 2020.PNETs often cause severe morbidity due to excessive secretion of hormones(such as serotonin)and/or overall tumor mass.Patients can live for many years(except for those patients with poorly differentiated G3 neuroendocrine tumors);thus,the prevalence of the tumors that is the number of patients actually dealing with the disease at any given time is fairly high because the survival is much longer than pancreatic ductal adenocarcinoma.Due to significant heterogeneity,the management of PNETs is very complex and remains an unmet clinical challenge.In terms of research studies,modest improvements have been made over the past decades in the identification of potential oncogenic drivers in order to enhance the quality of life and increase survival for this growing population of patients.Unfortunately,the majority of systematic therapies approved for the management of advanced stage PNETs lack objective response or at most result in modest benefits in survival.In this review,we aim to discuss the broad challenges associated with the management and the study of PNETs.
文摘BACKGROUND Primary hepatic neuroendocrine tumors(PHNETs),a group of neuroendocrine neoplasms,are extremely rare.There are only few case reports about PHNETs in the literature.The lack of large samples and multicenter research results in poor diagnostic and therapeutic approaches.AIM To discuss the clinical characteristics,diagnosis,and treatment of PHNETs and risk factors related to survival.METHODS We retrospectively analyzed the clinical data,imaging features,immunohistochemistry data,and treatment efficacy of 40 patients who were pathologically diagnosed with PHNETs and admitted to The First Affiliated Hospital of Zhengzhou University from January 1,2014 to November 15,2019.Finally,survival analysis was performed to identify the risk factors for survival.RESULTS The main symptoms and signs included intermittent abdominal pain(19 patients,47.5%)and bloating(8 patients,20.0%).The positive rates of tested tumor markers were recorded as follows:Carbohydrate antigen 19-9(CA19-9)(6 patients,15.0%),CA72-4(3 patients,7.5%),carcinoembryonic antigen(7 patients,17.5%),and alpha-fetoprotein(6 patients,15.0%).Immunohistochemical staining results showed positivity for Syn in 38(97.4%)of 39 patients,for chromogranin A in 17(65.4%)of 26 patients,for CD56 in 35(94.6%)of 37 patients,for AE1/AE3 in 28(87.5%)of 32 patients,and for Ki-67 in all 40(100.0%)patients.The overall survival rate was significantly related to the tumor grade,AE1/AE3,and Ki-67.tumor number,tumor size,metastasis,and treatment)and overall survival.CONCLUSION Higher grade,negative AE1/AE3,and higher Ki-67 are associated with a worse survival rate.Kinds of treatment and other parameters have no significant influence on overall survival.
文摘Somatostatin analogs were initially developed for the control of hormonal syndromes associated with neuro-endocrine tumors (NETs). In recent years, accumul ating data has supported their role as antiproliferative agents, capable of stabilizing tumor growth in patients with metastatic neuroendocrine malignancies, including carci-noid and pancreatic endocrine tumors. A phase Ⅲ, ran-domized, placebo-controlled trial has now demonstrated that octreotide long-acting repeatable (LAR) 30 mg can significantly prolong time to tumor progression among patients with metastatic midgut NETs regardless of functional status, chromogranin A level or age. In addition to signif icantly lengthening time to tumor pro-gression in the overall study population, subset analysis suggests that patients with low tumor burden are most likely to experience disease stabilization with octreotide LAR 30 mg, supporting the early use of octreotide LAR in patients with metastatic disease. Further research efforts are underway to evaluate the use of somatostatin analogs as antiproliferative agents in other types of gastroenteropancreatic-NETs. Ongoing studies are also evaluating novel somatostatin analogs and somatostatin analogs in combination with other anti-tumor therapies.
基金Supported by The Science and Technology Commission of Shanghai Municipality
文摘Colorectal neuroendocrine tumors (NETs) originate from neuroendocrine cells in the intestinal tract, and represent a small area within oncology, but one which has provided increasing new data during the past years. Although the World Health Organization has determined clinical and histological features to predict prognosis for such tumors, they may not be valid on an individual basis. We aim to give an overview of the recent findings with regard to pathology, molecular genetics and diagnosis of NETs.
文摘Rectal neuroendocrine neoplasms(r-NENs)are considered among the most frequent digestive NENs,together with small bowel NENs.Their incidence has increased over the past few years,and this is probably due to the widespread use of endoscopic screening for colorectal cancer and the advanced endoscopic procedures available nowadays.According to the current European Neuroendocrine Tumor Society(ENETS)guidelines,well-differentiated r-NENs smaller than 10 mm should be endoscopically removed in view of their low risk of local and distant invasion.R-NENs larger than 20 mm are candidates for surgical resection because of their high risk of distant spreading and the involvement of the muscularis propria.There is an area of uncertainty regarding tumors between 10 and 20 mm,in which the metastatic risk is intermediate and the endoscopic treatment can be challenging.Once removed,the indications for surveillance are scarce and poorly codified by international guidelines,therefore in this paper,a possible algorithm is proposed.
文摘BACKGROUND Neuroendocrine tumors(NETs)frequently occur in the gastrointestinal tract,lung,and pancreas,and the rectum and appendix are the sites with the highest incidence.Epidemiology statistics show that an estimated 8000 people every year in the United States are diagnosed with NETs occurring in the gastrointestinal tract,including the stomach,intestine,appendix,colon,and rectum.The pathological changes and clinical symptoms of NETs are not specific,and therefore they are frequently misdiagnosed.AIM To investigate the clinical symptoms,pathological characteristics,treatment,and prognosis of rectal neuroendocrine tumors(RNETs)by analyzing the clinical and pathological data of 132 RNET cases at our hospital.METHODS All RNETs were graded according to Ki-67 positivity and mitotic events.The tumors were staged as clinical stages I,II,III,and IV according to infiltrative depth and tumor size.COX proportional hazard model was used to assess the main risk factors for survival.RESULTS These 132 RNETs included 83 cases of G1,21 cases of G2,and 28 cases of G3(neuroendocrine carcinoma)disease.Immunohistochemical staining showed that 89.4%of RNETs were positive for synaptophysin and 39.4%positive for chromogranin A.There were 19,85,23,and 5 cases of clinical stages I,II,III,and IV,respectively.The median patient age was 52.96 years.The diameter of tumor,depth of invasion,and pathological grade were the main reference factors for the treatment of RNETs.The survival rates at 6,12,36,and 60 mo after operation were 98.5%,94.6%,90.2%,and 85.6%,respectively.Gender,tumor size,tumor grade,lymph node or distant organ metastasis,and radical resection were the main factors associated with prognosis of RNETs.Multivariate analysis showed that tumor size and grade were independent prognostic factors.CONCLUSION The clinical symptoms of RNETs are not specific,and they are easy to misdiagnose.Surgery is the main treatment method.The grade and stage of RNETs are the main indices to evaluate prognosis.
