Critical considerations for the management of gastrointestinal mixed neuroendocrine non-neuroendocrine neoplasms and pure neuroendocrine carcinomas

Mixed neuroendocrine non-neuroendocrine neoplasms constitute rare tumors that are located mainly in the gastrointestinal(GI)tract and have high degrees of malignancy,and the frequency of these tumors has been increasing.They consist of a neuroendocrine neoplastic component with another component of adenocarcinoma usually and have a dismal prognosis.The rare GI pure neuroendocrine carcinoma is highly aggressive and requires complex and extensive management since a genetic distinction exists between it and GI non-neuroendocrine neoplasms,which are generally slow-growing lesions.The most common GI-mixed neuroendocrine non-neuroendocrine neoplasms are colorectal,followed by gastric,mainly in the gastroesophageal junction.Current imaging modalities of nuclear medicine and radiology play important roles in the accuracy of diagnosis.Liquid biopsy may contribute to early detection and timely diagnosis.Ultrasonography,either endoscopic or abdominal,is a technique that contributes to a diagnosis;additionally,contrast-enhanced ultrasonography is very helpful in followup appointments.Histopathology establishes a definite diagnosis and stage by evaluating the cell differentiation grade and the cell proliferation index Ki67.The genetic profile can be valuable in diagnosis and gene therapy.Surgical resection with wide lymphadenectomy,whenever possible,and adjuvant chemotherapy constitute the main therapeutic management strategies.Targeted therapy and immunotherapy achieve encouraging results.

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?

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.

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.

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.

Practical hints for the diagnosis of mixed neuroendocrine-nonneuroendocrine neoplasms of the digestive system

In this editorial,a comment on the article by Díaz-López et al published in the recent issue of the 2024 is provided.We focus on the practical implications critical for providing a correct and complete diagnosis of mixed neuroendocrine-nonneuroendocrine neoplasm(MiNEN)in the gastrointestinal system.The diagnosis of MiNEN begins with the recognition of neuroendocrine features in one component of a biphasic tumor.The non-neuroendocrine counterpart can be virtually represented by any neoplastic type,even though the most frequent histologies are glandular and squamous.However,qualification of the neuroendocrine component requires histological and immunohistochemical confirmation.Neuroendocrine tumors are characterized by a peculiar architectural organization and bland nuclei with granular“salt and pepper”chromatin.Although neuroendocrine carcinomas have multiple and variable presentations,they typically show a solid or organoid architecture.The histological aspect needs to be confirmed by immunohistochemistry,and a diagnosis is confirmed whenever the expression of keratin and neuroendocrine markers is observed.Once both histopathological and immunohistochemical features of neuroendocrine neoplasms are identified,it is important to consider the three major pitfalls of MiNEN diagnostics:(1)Entrapment of neuroendocrine non-neoplastic cells within the tumor mass;(2)Differential diagnosis with amphicrine neoplasms;and(3)Differential diagnosis of tumors that partially express neuroendocrine markers.According to the current guidelines for diagnosing digestive MiNEN,each component must represent at least 30%of the entire neoplastic mass.Although the high-grade histopathological subtype frequently determines disease prognosis,both components can significantly affect prognosis.Thus,if one of the components,either neuroendocrine or non-neuroendocrine,does not fulfill the volumetric criteria,the guidelines still encourage reporting it.These strict criteria are essential for correctly recognizing and characterizing digestive MiNENs.This task is essential because it has prognostic relevance and substantial potential value for guiding further studies in this field.In the future,systematic analyses should be performed to validate or reconsider the current 30%cutoff value.

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.

Neuroendocrine carcinoma of the common hepatic duct coexisting with distal cholangiocarcinoma:A case report and review of literature

BACKGROUND Neuroendocrine carcinoma(NEC)of the extrahepatic bile duct is very rare,and the treatment and prognosis are unclear.Herein,we report the case of a middleaged female with primary large cell NEC(LCNEC)of the common hepatic duct combined with distal cholangiocarcinoma(dCCA).Additionally,after a review of the relevant literature,we summarize and compare mixed neuroendocrine-nonneuroendocrine neoplasm(MiNEN)and pure NEC to provide a reference for selecting the appropriate treatment and predicting the prognosis of this rare disease.CASE SUMMARY A 62-year-old female presented to the hospital due to recurrent abdominal pain for 2 months.Physical examination showed mild tenderness in the upper abdomen and a positive Courvoisier sign.Blood tests showed elevated liver transaminase and carbohydrate antigen 199 levels.Imaging examination revealed node dissection was performed,and hepatic duct tumours were unexpectedly found during surgery.Pathology suggested poorly differentiated LCNEC(approximately 0.5 cm×0.5 cm×0.4 cm),Ki-67(50%),synaptophysin+,and chromogranin A+.dCCA pathology suggested moderately differentiated adenocarcinoma.The patient eventually developed lymph node metastasis in the liver,bone,peritoneum,and abdominal cavity and died 24 months after surgery.Gene sequencing methods were used to compare gene mutations in the two primary bile duct tumours.CONCLUSION The prognosis of MiNEN and pure NEC alone is different,and the selection of treatment options needs to be differentiated.

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.

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.

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.

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.

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.

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.

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.

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.

User-friendly prognostic model for rectal neuroendocrine tumours: In the era of precision management

In this letter,we explore into the potential role of the recent study by Zeng et al.Rectal neuroendocrine tumours(rNETs)are rare,originate from peptidergic neurons and neuroendocrine cells,and express corresponding markers.Although most rNETs patients have a favourable prognosis,the median survival period significantly decreases when high-risk factors,such as larger tumours,poorer differentiation,and lymph node metastasis exist,are present.Clinical prediction models play a vital role in guiding diagnosis and prognosis in health care,but their complex calculation formulae limit clinical use.Moreover,the prognostic models that have been developed for rNETs to date still have several limitations,such as insufficient sample sizes and the lack of external validation.A high-quality prognostic model for rNETs would guide treatment and follow-up,enabling the precise formulation of individual patient treatment and follow-up plans.The future development of models for rNETs should involve closer collab-oration with statistical experts,which would allow the construction of clinical prediction models to be standardized and robust,accurate,and highly general-izable prediction models to be created,ultimately achieving the goal of precision medicine.