Adverse effects of early-life stress:focus on the rodent neuroendocrine system

Early-life stress is associated with a high prevalence of mental illnesses such as post-traumatic stress disorders,attention-deficit/hyperactivity disorder,schizophrenia,and anxiety or depressive behavior,which constitute major public health problems.In the early stages of brain development after birth,events such as synaptogenesis,neuron maturation,and glial differentiation occur in a highly orchestrated manner,and external stress can cause adverse long-term effects throughout life.Our body utilizes multifaceted mechanisms,including neuroendocrine and neurotransmitter signaling pathways,to appropriately process external stress.Newborn individuals first exposed to early-life stress deploy neurogenesis as a stress-defense mechanism;however,in adulthood,early-life stress induces apoptosis of mature neurons,activation of immune responses,and reduction of neurotrophic factors,leading to anxiety,depression,and cognitive and memory dysfunction.This process involves the hypothalamus-pituitary-adrenal axis and neurotransmitters secreted by the central nervous system,including norepinephrine,dopamine,and serotonin.The rodent early-life stress model is generally used to experimentally assess the effects of stress during neurodevelopment.This paper reviews the use of the early-life stress model and stress response mechanisms of the body and discusses the experimental results regarding how early-life stress mediates stress-related pathways at a high vulnerability of psychiatric disorder in adulthood.

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.

Early adenocarcinoma mixed with a neuroendocrine carcinoma component arising in the gastroesophageal junction: A case report

BACKGROUND Early adenocarcinoma mixed with a neuroendocrine carcinoma(NEC)component arising in the gastroesophageal junctional(GEJ)region is rare and even rarer in young patients.Here,we report such a case in a 29-year-old Chinese man.CASE SUMMARY This patient presented to our hospital with a 3-mo history of dysphagia and regurgitation.Upper endoscopy revealed an elevated nodule in the distal esophagus 1.6 cm above the GEJ line,without Barrett’s esophagus or involvement of the gastric cardia.The nodule was completely resected by endoscopic submu-cosal dissection(ESD).Pathological examination confirmed diagnosis of intra-mucosal adenocarcinoma mixed with an NEC component,measuring 1.5 cm.Immunohistochemically,both adenocarcinoma and NEC components were positive for P53 with a Ki67 index of 90%;NEC was positive for synaptophysin and chromogranin.Next-generation sequencing of 196 genes demonstrated a novel germline mutation of the ERCC3 gene in the DNA repair pathway and a germline mutation of the RNF43 gene,a common gastric cancer driver gene,in addition to pathogenic somatic mutations in P53 and CHEK2 genes.The patient was alive without evidence of the disease 36 mo after ESD.CONCLUSION Early adenocarcinoma with an NEC component arising in the distal esophageal side of the GEJ region showed evidence of gastric origin.

Liver transplantation as an alternative for the treatment of neuroendocrine liver metastasis: Appraisal of the current evidence

Background:Liver transplantation(LT)for neuroendocrine liver metastases(NELM)is still in debate.Studies comparing LT with liver resection(LR)for NELM are scarce,as patient selection is heterogeneous and experience is limited.The goal of this review was to provide a critical analysis of the evidence on LT versus LR in the treatment of NELM.Data sources:A scoping literature search on LT and LR for NELM was performed with PubMed,including English articles up to March 2023.Results:International guidelines recommend LR for NELM in resectable,well-differentiated tumors in the absence of extrahepatic metastatic disease with superior results of LR compared to systemic or liver-directed therapies.Advanced liver surgery has extended resectability criteria whilst entailing increased perioperative risk and short disease-free survival.In highly selected patients(based on the Milan criteria)with unresectable NELM,oncologic results of LT are promising.Prognostic factors include tumor biology(G1/G2)and burden,waiting time for LT,patient age and extrahepatic spread.Based on low-level evi-dence,LT for low-grade NELM within the Milan criteria resulted in improved disease-free survival and overall survival compared to LR.The benefits of LT were lost in patients beyond the Milan NELM-criteria.Conclusions:With adherence to strict selection criteria especially tumor biology,LT for NELM is becoming a valuable option providing oncologic benefits compared to LR.Recent evidence suggests even stricter selection criteria with regard to tumor biology.

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.

Endoscopic ultrasonography-related diagnostic accuracy and clinical significance on small rectal neuroendocrine neoplasms

This research aimed to examine the diagnostic accuracy and clinical significance of endoscopic ultrasonography(EUS)in the context of small rectal neuroendocrine neoplasms(NENs).A total of 108 patients with rectal subepithelial lesions(SELs)with a diameter of<20 mm were included in the analysis.The diagnosis and depth assessment of EUS was compared to the histology findings.The prevalence of NENs in rectal SELs was 78.7%(85/108).The sensitivity of EUS in detecting rectal NENs was 98.9%(84/85),while the specificity was 52.2%(12/23).Overall,the diagnostic accuracy of EUS in identifying rectal NENs was 88.9%(96/108).The overall accuracy rate for EUS in assessing the depth of invasion in rectal NENs was 92.9%(78/84).Therefore,EUS demonstrates reasonable diagnostic accuracy in detecting small rectal NENs,with good sensitivity but inferior specificity.EUS may also assist physicians in assessing the depth of invasion in small rectal NENs before endoscopic excision.

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.

Molecular features of gastroenteropancreatic neuroendocrine carcinoma: A comparative analysis with lung neuroendocrine carcinoma and digestive adenocarcinomas

Objective: There is an ongoing debate about whether the management of gastroenteropancreatic(GEP)neuroendocrine carcinoma(NEC) should follow the guidelines of small-cell lung cancer(SCLC). We aim to identify the genetic differences of GEPNEC and its counterpart.Methods: We recruited GEPNEC patients as the main cohort, with lung NEC and digestive adenocarcinomas as comparative cohorts. All patients undergone next-generation sequencing(NGS). Different gene alterations were compared and analyzed between GEPNEC and lung NEC(LNEC), GEPNEC and adenocarcinoma to yield the remarkable genes.Results: We recruited 257 patients, including 99 GEPNEC, 57 LNEC, and 101 digestive adenocarcinomas.Among the mutations, KRAS, RB1, TERT, IL7R, and CTNNB1 were found to have different gene alterations between GEPNEC and LNEC samples. Specific genes for each site were revealed: gastric NEC(TERT amplification),colorectal NEC(KRAS mutation), and bile tract NEC(ARID1A mutation). The gene disparities between small-cell NEC(SCNEC) and large-cell NEC(LCNEC) were KEAP1 and CDH1. Digestive adenocarcinoma was also compared with GEPNEC and suggested RB1, APC, and KRAS as significant genes. The TP53/RB1 mutation pattern was associated with first-line effectiveness. Putative targetable genes and biomarkers in GEPNEC were identified in22.2% of the patients, and they had longer progression-free survival(PFS) upon targetable treatment [12.5 months vs. 3.0 months, HR=0.40(0.21-0.75), P=0.006].Conclusions: This work demonstrated striking gene distinctions in GEPNEC compared with LNEC and adenocarcinoma and their clinical utility.

Clinical analysis of 12 cases of ovarian neuroendocrine carcinoma

BACKGROUND Neuroendocrine neoplasms of the female genital tract are rare.AIM To enhance our clinical understanding of neuroendocrine carcinoma(NEC)of the ovary.METHODS A retrospective review was conducted on 12 patients diagnosed with NEC of the ovary,analyzing clinicopathological characteristics,treatment modalities,and survival status.RESULTS The median age at diagnosis was 34.5 years(range:20 to 62 years).Among the 12 cases,9 were small cell carcinoma of the ovary and 3 were large cell NEC.Five cases were stage I tumors,one case was stage IV,and six cases were stage III.Eleven patients underwent surgery as part of their treatment.All patients received adjuvant chemotherapy.Among the 12 patients,one patient received radiotherapy,and one patient with a BRCA2 mutation was administered PARP inhibitor maintenance after chemotherapy.The median progression-free survival was 13 months,and the median overall survival was 19.5 months.Four cases remained disease-free,while eight cases experienced tumor recurrence,including three cases that resulted in death due to disease recurrence.CONCLUSION NEC of the ovary is a rare condition that is more common in women of childbearing age and is associated with aggressive behavior and poor clinical outcomes.Surgical resection remains the mainstay of treatment,with some patients benefiting from adjuvant chemoradiation therapy.

Treatment-induced neuroendocrine prostate cancer and de novo neuroendocrine prostate cancer:Identification,prognosis and survival,genetic and epigenetic factors

Neuroendocrine prostate cancer(NEPC)shows an aggressive behavior compared to prostate cancer(PCa),also known as prostate adenocarcinoma.Scanty foci in PCa can harbor genetic alternation that can arise in a heterogeneity of prostate cancer.NEPC may arise de novo or develop following androgen deprivation therapy(ADT).NEPC that arise following ADT has the nomenclature“treatmentemerging/induced NEPC(t-NEPC)”.t-NEPC would be anticipated in castration resistant prostate cancer(CRPC)and metastatic PCa.t-NEPC is characterized by low or absent androgen receptor(AR)expression,independence of AR signaling,and gain of neuroendocrine phenotype.t-NEPC is an aggressive metastatic tumor,develops from PCa in response to drug induced ADT,and shows very short response to conventional therapy.t-NEPC occurs in 10%-17%of patients with CRPC.De novo NEPC is rare and is accounting for less than 2%of all PCa.The molecular mechanisms underlying the trans-differentiation from CRPC to t-NEPC are not fully elucidated.Sphingosine kinase 1 plays a significant role in t-NEPC development.Although neuroendocrine markers:Synaptophysin,chromogranin A,and insulinoma associated protein 1(INSM1)are expressed in t-NEPC,they are non-specific for diagnosis,prognosis,and follow-up of therapy.t-NEPC shows enriched genomic alteration in tumor protein P53(TP53)and retinoblastoma 1(RB1).There are evidences suggest that t-NEPC might develop through epigenetic evolution.There are genomic,epigenetic,and transcriptional alterations that are reported to be involved in development of t-NEPC.Knock-outs of TP53 and RB1 were found to contribute in development of t-NEPC.PCa is resistant to immunotherapy,and at present there are running trials to approach immunotherapy for PCa,CRPC,and t-NEPC.

Mixed neuroendocrine and adenocarcinoma of gastrointestinal tract:A complex diagnosis and therapeutic challenge

In this editorial we comment on the manuscript describing a case of adenocarcinoma mixed with a neuroendocrine carcinoma of the gastroesophageal junction.Mixed neuroendocrine and non-neuroendocrine neoplasms of the gastrointestinal system are rare heterogeneous group of tumors characterized by a high malignant potential,rapid growth,and poor prognosis.Due to the rarity of these cancers,the standard therapy is poorly defined.The diagnosis of these tumors is based on combination of morphological features,immunohistochemical and neuroendocrine and epithelial cell markers.Both endocrine and epithelial cell components can act independently of each other and thus,careful grading of each component separately is required.These cancers are aggressive in nature and the potential of each component has paramount importance in the choice of treatment and response.Regardless of the organ of origin,these tumors portend poor prognosis with increased proportion of neuroendocrine component.Multidisciplinary services and strategies are required for the management of these mixed malignancies to provide the best oncological outcomes.The etiopathogenesis of these mixed tumors remains obscure but poses interesting question.We briefly discuss a few salient points in this editorial.

Clinical features and prognostic factors of duodenal neuroendocrine tumours:A comparative study of ampullary and nonampullary regions

BACKGROUND Duodenal neuroendocrine tumours(DNETs)are rare neoplasms.However,the incidence of DNETs has been increasing in recent years,especially as an incidental finding during endoscopic studies.Regrettably,there is no consensus regarding the ideal treatment of DNETs.Even there are few studies on the clinical features and survival analysis of DNETs.AIM To analyze the clinical characteristics and prognostic factors of patients with duodenal neuroendocrine tumours.METHODS The clinical data of DNETs diagnosed in the First Affiliated Hospital of Air Force Military Medical University from June 2011 to July 2022 were collected.Neuroen-docrine tumours located in the ampulla area of the duodenum were divided into the ampullary region group;neuroendocrine tumours in any part of the duo-denum outside the ampullary area were divided into the nonampullary region group.Using a retrospective study,the clinical characteristics of the two groups and risk factors affecting the survival of DNET patients were analysed.RESULTS Twenty-nine DNET patients were screened.The male to female ratio was 1:1.9,and females comprised the majority.The ampullary region group accounted for 24.1%(7/29),while the nonampullary region group accounted for 75.9%(22/29).When diagnosed,the clinical symptoms of the ampullary region group were mainly abdominal pain(85.7%),while those of the nonampullary region groups were mainly abdominal distension(59.1%).There were differences in the composition of staging of tumours between the two groups(Fisher's exact probability method,P=0.001),with nonampullary stage II tumours(68.2%)being the main stage(P<0.05).After the diagnosis of DNETs,the survival rate of the ampullary region group was 14.3%(1/7),which was lower than that of 72.7%(16/22)in the nonampullary region group(Fisher's exact probability method,P=0.011).The survival time of the ampullary region group was shorter than that of the nonampullary region group(P<0.000).The median survival time of the ampullary region group was 10.0 months and that of the nonampullary region group was 451.0 months.Multivariate analysis showed that tumours in the ampulla region and no surgical treatment after diagnosis were independent risk factors for the survival of DNET patients(HR=0.029,95%CI 0.004-0.199,P<0.000;HR=12.609,95%CI:2.889-55.037,P=0.001).Further analysis of nonampullary DNET patients showed that the survival time of patients with a tumour diameter<2 cm was longer than that of patients with a tumour diameter≥2 cm(t=7.243,P=0.048).As of follow-up,6 patients who died of nonampullary DNETs had a tumour diameter that was≥2 cm,and 3 patients in stage IV had liver metastasis.Patients with a tumour diameter<2 cm underwent surgical treatment,and all survived after surgery.CONCLUSION Surgical treatment is a protective factor for prolonging the survival of DNET patients.Compared to DNETs in the ampullary region,patients in the nonampullary region group had a longer survival period.The liver is the organ most susceptible to distant metastasis of nonampullary DNETs.

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.

GATIS score for predicting the prognosis of rectal neuroendocrine neoplasms:A Chinese multicenter study of 12-year experience

BACKGROUND There is currently a shortage of accurate,efficient,and precise predictive instruments for rectal neuroendocrine neoplasms(NENs).AIM To develop a predictive model for individuals with rectal NENs(R-NENs)using data from a large cohort.METHODS Data from patients with primary R-NENs were retrospectively collected from 17 large-scale referral medical centers in China.Random forest and Cox proportional hazard models were used to identify the risk factors for overall survival and progression-free survival,and two nomograms were constructed.RESULTS A total of 1408 patients with R-NENs were included.Tumor grade,T stage,tumor size,age,and a prognostic nutritional index were important risk factors for prognosis.The GATIS score was calculated based on these five indicators.For overall survival prediction,the respective C-indexes in the training set were 0.915(95%confidence interval:0.866-0.964)for overall survival prediction and 0.908(95%confidence interval:0.872-0.944)for progression-free survival prediction.According to decision curve analysis,net benefit of the GATIS score was higher than that of a single factor.The time-dependent area under the receiver operating characteristic curve showed that the predictive power of the GATIS score was higher than that of the TNM stage and pathological grade at all time periods.CONCLUSION The GATIS score had a good predictive effect on the prognosis of patients with R-NENs,with efficacy superior to that of the World Health Organization grade and TNM stage.

Small Cell Neuroendocrine Carcinoma of the Vulva: Case Report and Literature Review

Background: Neuroendocrine neoplasms are those that develop from a neuroendocrine cell. They most commonly affect the lungs, gastrointestinal tract, and pancreas, being rare conditions in the female genital tract. When present, these neoplasms often manifest with nonspecific signs and symptoms such as pain, itching, swelling, single-focus lesions, bleeding, and enlargement of inguinal lymph nodes, in addition to the presence of progressively enlarging vulvar nodules. Consequently, the diagnostic investigation involves histopathological examination and confirmation through immunohistochemistry. Objective: To present a comprehensive understanding of this rarely studied pathology. The primary objective is to provide valuable insights that could aid in the future development of universally applicable treatment guidelines. Case Presentation: A 57-year-old female, with no prior comorbidities, menopause at 36, who presented with a left vulvar nodule accompanied by intense pain and swelling, later diagnosed with small cell neuroendocrine carcinoma in the vulva. Conclusion: This case report highlights the importance of enhancing our knowledge regarding small cell neuroendocrine carcinoma in the vulva, given its scarcity in medical literature. The information presented here underscores the need for standardized diagnostic and treatment approaches, paving the way for future consensus on managing this uncommon but challenging neoplasm.

Enhancing prognostic accuracy in predicting rectal neuroendocrine neoplasms

The recently published retrospective study introduces the GATIS score,a new predictive model for rectal neuroendocrine neoplasms.By analyzing data from a large Chinese multicenter cohort,the study shows that the GATIS score,incor-porating tumor grade,T stage,tumor size,age,and prognostic nutritional index,demonstrates superior predictive power for overall survival and progression-free survival compared to traditional World Health Organization grade and tumor,nodes and metastases staging systems.This editorial aims to discuss the impor-tance of the GATIS score,its potential impact on clinical practice,and the strengths and limitations of the study.Finally,it explores the significance,methodology,and clinical implications of these findings.

Correlation between the neuroendocrine axis,microbial species,inflammatory response,and gastrointestinal symptoms in irritable bowel syndrome

BACKGROUND This study examines the complex relationships among the neuroendocrine axis,gut microbiome,inflammatory responses,and gastrointestinal symptoms in patients with irritable bowel syndrome(IBS).The findings provide new insights into the pathophysiology of IBS and suggest potential therapeutic targets for improving patient outcomes.AIM To investigate the interactions between the neuroendocrine axis,gut microbiome,inflammation,and gastrointestinal symptoms in patients with IBS.METHODS Patients diagnosed with IBS between January 2022 and January 2023 were selected for the study.Healthy individuals undergoing routine check-ups during the same period served as the control group.Data were collected on neuroendocrine hormone levels,gut microbiome profiles,inflammatory biomarkers,and gastrointestinal symptomatology to analyze their interrelations and their potential roles in IBS pathogenesis.RESULTS IBS patients exhibited significant dysregulation of the neuroendocrine axis,with altered levels of cortisol,serotonin,and neuropeptides compared to healthy controls.The gut microbiome of IBS patients showed reduced diversity and specific alterations in bacterial genera,including Bifidobacterium,Lactobacillus,and Faecalibacterium,which were associated with neuroendocrine disturbances.Additionally,elevated levels of inflammatory markers,such as C-reactive protein,interleukin-6,and tumor necrosis factor-α,were observed and correlated with the severity of gastrointestinal symptoms like abdominal pain,bloating,and altered bowel habits.CONCLUSION The findings suggest that targeting the neuroendocrine axis,gut microbiome,and inflammatory pathways may offer novel therapeutic strategies to alleviate symptoms and improve the quality of life in IBS patients.

Primary large cell neuroendocrine carcinoma of the bladder:A case report

BACKGROUND Large cell neuroendocrine carcinoma(LCNEC)of the bladder is a rare nonurothelial tumor of the bladder.The treatment of LCNEC of the bladder is different from that of urothelial carcinoma(UC);therefore,early and accurate diagnosis is particularly important.As LCNEC of the bladder is rare and its clinical symptoms and radiographic features are similar to those of urothelial tumors,the clinical diagnosis of the disease remains challenging.CASE SUMMARY We report a 72-year-old female patient who presented with gross hematuria for 3 mo.A solitary tumor located in the anterior wall of the bladder was found by cystoscopy.Pathological examination after biopsy suggested UC of the bladder in the absence of immunohistochemical assessment.The patient underwent partial cystectomy and was finally diagnosed with LCNEC(pT2bN0M0)based on the results of postoperative immunohistochemical examination.During the 10-mo follow-up,no signs of tumor recurrence or metastasis were found.CONCLUSION Immunohistochemical examination is essential for diagnosing LCNEC of the bladder.Accurate diagnosis and multidisciplinary treatment in the early stage of the disease are crucial for improving the prognosis.

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.

Mixed neuroendocrine non-neuroendocrine neoplasms in gastroenteropancreatic tract

Mixed neuroendocrine non-neuroendocrine neoplasms(MiNENs)are a hetero-geneous group of malignant neoplasms that can settle in the gastroenteropan-creatic tract.They are composed of a neuroendocrine(NE)and a non-NE compo-nent in at least 30%of each tumour.The non-NE component can include different histological combinations of glandular,squamous,mucinous and sarcomatoid phenotypes,and one or both of the components can be low-or high grade malignant.Recent changes in the nomenclature of these neoplasms might lead to great deal of confusion,and the lack of specific clinical trials is the main reason why their management is difficult.The review aims to clarify the definition of MiNEN and analyze available evidence about their diagnosis and treatment options according to their location and extension through careful analysis of the available data.It would be important to reach a general consensus on their diagnosis in order to construct a classification that remains stable over time and facilitates the design of clinical trials that,due to their low incidence,will require long recruitment periods.