Advancements in medical treatment for pancreatic neuroendocrine tumors:A beacon of hope

This editorial highlights the remarkable advancements in medical treatment strategies for pancreatic neuroendocrine tumors(pan-NETs),emphasizing tailored approaches for specific subtypes.Cytoreductive surgery and somatostatin analogs(SSAs)play pivotal roles in managing tumors,while palliative options such as molecular targeted therapy,peptide receptor radionuclide therapy,and chemotherapy are reserved for SSA-refractory patients.Gastrinomas,insul-inomas,glucagonomas,carcinoid tumors and VIPomas necessitate distinct thera-peutic strategies.Understanding the genetic basis of pan-NETs and exploring immunotherapies could lead to promising avenues for future research.This review underscores the evolving landscape of pan-NET treatment,offering renewed hope and improved outcomes for patients facing this complex disease.

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

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.

Pancreatic neuroendocrine tumors:Are tumors smaller than 2 cm truly indolent?

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.

Temozolomide and capecitabine regimen as first-line treatment in advanced gastroenteropancreatic neuroendocrine tumors at a Latin American reference center

BACKGROUND Numerous studies have indicated that the temozolomide and capecitabine regimen(TEMCAP)exhibits a certain level of efficacy in treating advanced,welldifferentiated gastroenteropancreatic neuroendocrine tumors(GEP-NET).However,published data from Peru are limited.We hypothesize that this regimen could be a viable therapeutic option for advanced GEP-NET in the Peruvian population.AIM To evaluate overall survival(OS)in patients diagnosed with advanced GEP-NET treated with TEMCAP at the Instituto Nacional de Enfermedades Neoplásicas(INEN)in Lima-Perú.METHODS A retrospective review was conducted to identify patients with GEP-NEN treated with the TEMCAP regimen between 2011 and 2021 at the INEN.A total of thirtyeight patients were included in the final analysis:Thirty-five received TEMCAP as a first-line treatment,and three as a second-line treatment.The primary objective was to evaluate OS.The efficacy and safety of TEMCAP were assessed until the occurrence of unacceptable toxicity or disease progression.Survival outcomes were estimated using the Kaplan-Meier method.RESULTS The median age of the patients was 52 years(range 24-77 years),and 53.3%were female.The most common symptoms at diagnosis were abdominal pain in 31 patients(81.6%).Primary tumors included 12 in the rectum(31.6%),11 in the pancreas(28.9%),3 in the ileum(7.9%),2 in the mesentery(5.3%),2 in the small intestine(5.3%),1 in the appendix(2.6%),1 in the stomach(2.6%)and 6 cases of liver metastasis of unknown primary(15.8%).Five were neuroendocrine tumors(NET)G1(13.2%),33 were NET G2(86.8%),five had Ki67<3%(13.2%),and 33 had Ki67 between 3%and 20%(86.8%).TEMCAP was administered to 35(92.1%)patients as first-line treatment.OS at 12,36,and 60 months was estimated in 80%,66%,and 42%,respectively,with a median OS of 49 months.CONCLUSION TEMCAP therapy is a viable first-line option regarding efficacy and tolerability in areas where standard therapy is inaccessible.

Mixed neuroendocrine non-neuroendocrine tumors:The quest for evidence

Mixed neuroendocrine non-neuroendocrine neoplasms(MiNENs)are rare mixed tumors containing both neuroendocrine and non-neuroendocrine components that occupy at least 30%of the whole tumor.Biologically,both components appear to derive from an identical cellular precursor undergoing early dual differentiation or late transdifferentiation.While our understanding of MiNENs has improved in recent years,many areas of uncertainty remain.In this context,setting diagnostic criteria capable of capturing the continuum of disease biology while providing clinically meaningful information in terms of prognosis and response to treatments appears vital to advance the field and improve patients’outcomes.Evidence is needed to generate robust classification schemes,and multi-institutional cooperation will likely play a crucial role in building adequately powered cohorts to address some of the most pressing questions discussed in this Editorial.What is the minimum representation for each component needed to define MiNENs?How can the epidemiology of MiNENs change according to different diagnostic definitions?How can we generate the clinical evidence nee-ded to optimize the management of MiNENs?

Clinical experience sharing on gastric microneuroendocrine tumors: A case report

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.

Mixed pancreatic ductal adenocarcinoma and well-differentiated neuroendocrine tumor:A case report

BACKGROUND Pancreatic mixed neuroendocrine-non-neuroendocrine neoplasms(MiNENs)are rare malignancies affecting the pancreas.The World Health Organization defines MiNENs as neoplasms composed of morphologically recognizable neuroendocrine and non-neuroendocrine components,each constituting 30%or more of the tumor volume.Adenocarcinoma-neuroendocrine carcinoma is the most frequent MiNEN combination.A well-differentiated neuroendocrine tumor(NET)component is rarely reported in MiNENs.CASE SUMMARY Here we report a rare case with intermingled components of ductal adenocarcinoma and grade 1 well-differentiated NET in the pancreas.The two tumors show distinct histology and significant differentiation discrepancy(poorly differentiated high grade adenocarcinoma and well-differentiated low grade NET),and also present as metastases in separate lymph nodes.Next generation sequencing of the two components demonstrates KRAS and TP53 mutations in the ductal adenocarcinoma,but no genetic alterations in the NET,suggesting divergent origins for these two components.Although tumors like this meet the diagnostic criteria for MiNEN,clinicians often find the diagnosis and staging confusing and impractical for clinical management.CONCLUSION Mixed NET/non-NET tumors with distinct histology and molecular profiles might be better classified as collision tumors rather than MiNENs.

Role of ablation therapy in conjunction with surgical resection for neuroendocrine tumors involving the liver

BACKGROUND Resection of hepatic metastasis from neuroendocrine tumors(NETs)improves quality of life and prolongs 5-year survival.Ablation can be utilized with surgery to achieve complete resection.Although several studies report long-term out-comes for patients undergoing ablation,none have explored perioperative effects of ablation in patients with metastatic NETs.AIM To determine if intra-operative ablation during hepatectomy increases risk of ad-verse outcomes such as surgical site infections(SSIs),bleeding,and bile leak.METHODS A retrospective analysis of the hepatectomy National Surgical Quality Impro-vement Program database from 2015-2019 was performed to determine the odds of SSIs,bile leaks,or bleeding in patients undergoing intraoperative ablation when compared to hepatectomy alone.RESULTS Of the 966 patients included in the study,298(30.9%)underwent ablation during hepatectomy.There were 78(11.7%)patients with SSIs in the hepatectomy alone group and 39(13.1%)patients with a SSIs in the hepatectomy with ablation group.Bile leak occurred in 41(6.2%)and 14(4.8%)patients in the two groups,respec-tively;bleeding occurred in 117(17.5%)and 33(11.1%),respectively.After con-trolling for confounding variables,ablation did not increase risk of SSI(P=0.63),bile leak(P=0.34)or bleeding(P=0.07)when compared to patients undergoing resection alone on multivariate analysis.CONCLUSION Intraoperative ablation with hepatic resection for NETs is safe in the perioperative period without significant increased risk of infection,bleeding,or bile leak.Surgeons should utilize this modality when appropriate to a-chieve optimal disease control and outcomes.

Cystic ductal adenocarcinoma of pancreas complicated with neuroendocrine tumor:A case report and review of literature

BACKGROUND Difficulties in making an accurate preoperative diagnosis of cystic pancreatic lesions pose a challenge for radiologists.It would be helpful to report rare cases and review the literature.CASE SUMMARY In the present report,a case of a patient with a pancreatic cystic lesion initially misdiagnosed as a pseudocyst by radiologist was documented,which was later pathologically confirmed as pancreatic ductal adenocarcinoma with neuroendocrine tumor.However,subsequent literature review yielded no previous reports of pancreatic ductal adenocarcinoma with neuroendocrine tumors and cystic lesions.Therefore,literature on the imaging diagnosis of pancreatic cystic lesions was instead reviewed and discussed.CONCLUSION Careful evaluation of the characteristics revealed by multimodal imaging techniques,medical history,laboratory examination data and follow-up observations,is critical to the diagnosis and treatment of pancreatic cystic disease.We provide valuable insights into the diagnosis of pancreatic cystic disease through a rare case report and literature review.

Periampullary duodenal neuroendocrine tumor in a patient with neurofibromatosis-1:A case report

BACKGROUND Patients with neurofibromatosis type 1(NF1)are exposed to a higher risk of developing neuroendocrine tumors(NETs).Periampullary neuroendocrine neoplasms(NENs)in NF1 patients primarily affect the duodenum and periampullary region.CASE SUMMARY A 50-year-old male patient was admitted to our hospital due to progressive skin and scleral yellowing for over 6 months.An abdominal contrast-enhanced computed tomography scan revealed a tumor in the periampullary region,which measured 1.2 cm×1.4 cm in size and showed a progressive enhancement.Magnetic resonance cholangiopancreatography indicated the dilation of intrahepatic and extrahepatic bile ducts.The patient was diagnosed with an ampullary tumor with the possibility of malignancy.A Whipple procedure was performed.Microscopically,the duodenum tumor was found to invade the mucosa,sphincter,and muscular layer of the duodenal papilla.Histologic hematoxylin and eosin staining confirmed the presence of duodenal G1 NET.Subsequently,a bibliometric analysis was performed to evaluate the state of NEN research.Publications about periampullary NENs showed an annual increase,with most of them focusing on the treatment and diagnosis of NENs.CONCLUSION This article reported a case of periampullary duodenal NET in a patient with NF1,and a bibliometric analysis was conducted.

Incidence and prevalence of gastric neuroendocrine tumors in patients with chronic atrophic autoimmune gastritis

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.

Baseline radiologic features as predictors of efficacy in patients with pancreatic neuroendocrine tumors with liver metastases receiving surufatinib

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.

Diagnostic accuracy of apparent diffusion coefficient to differentiate intrapancreatic accessory spleen from pancreatic neuroendocrine tumors

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.

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

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.

Primary coexisting adenocarcinoma of the colon and neuroendocrine tumor of the duodenum: A case report and review of the literature

BACKGROUND Neuroendocrine tumors(NETs)arise from the body’s diffuse endocrine system.Coexisting primary adenocarcinoma of the colon and NETs of the duodenum(D-NETs)is a rare occurrence in clinical practice.The classification and treatment criteria for D-NETs combined with a second primary cancer have not yet been determined.CASE SUMMARY We report the details of a case involving female patient with coexisting primary adenocarcinoma of the colon and a D-NET diagnosed by imaging and surgical specimens.The tumors were treated by surgery and four courses of chemothe-rapy.The patient achieved a favorable clinical prognosis.CONCLUSION Coexisting primary adenocarcinoma of the colon and D-NET were diagnosed by imaging,laboratory indicators,and surgical specimens.Surgical resection com-bined with chemotherapy was a safe,clinically effective,and cost-effective treat-ment.

Surgical aspects of small intestinal neuroendocrine tumors

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.

Endoscopic treatment and management of rectal neuroendocrine tumors less than 10 mm in diameter

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.

Gastric neuroendocrine tumors in a BRCA2 germline mutation carrier:A case report

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.

Recent research hotspots in sequencing and the pancreatic neuroendocrine tumor microenvironment

Multiple endocrine neoplasia 1(MEN1)syndrome,a disease arising from a genetic predisposition to tumor development caused by MEN1 loss-of-function mutations,is characterized by the combined occurrence of neuroendocrine tumors in multiple human organs.With advances in diagnostic technologies and improvements in living standards.

Is lymphatic invasion of microrectal neuroendocrine tumors an incidental event?:A case report

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.