Rectal neuroendocrine neoplasms pose significant challenges due to their varied presentations and prognoses.Traditional prognostic models,while useful,often fall short of accurately predicting clinical outcomes for th...Rectal neuroendocrine neoplasms pose significant challenges due to their varied presentations and prognoses.Traditional prognostic models,while useful,often fall short of accurately predicting clinical outcomes for these patients.This article discusses the development and implications of a novel prognostic tool,the GATIS score,which aims to enhance predictive accuracy and guide treatment strategies more effectively than current methods.Utilizing data from a large cohort and employing sophisticated statistical models,the GATIS score integrates clinical and pathological markers to provide a nuanced assessment of prognosis.We evaluate the potential of this score to transform clinical decision-making processes,its integration into current medical practices,and future directions for its develo-pment.The integration of genetic markers and other biomarkers could further refine its predictive power,highlighting the ongoing need for innovation in the management of rectal neuroendocrine neoplasms.展开更多
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 increasi...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.展开更多
BACKGROUND Gastric neuroendocrine tumors(G-NETs)are rare tumors originating from enterochromaffin-like cells,with an incidence of 0.4 per 100000 annually.There are three main types:(1)Type I,linked to chronic atrophic...BACKGROUND Gastric neuroendocrine tumors(G-NETs)are rare tumors originating from enterochromaffin-like cells,with an incidence of 0.4 per 100000 annually.There are three main types:(1)Type I,linked to chronic atrophic gastritis and hypergastrinemia,makes up 75%–80%of G-NETs;(2)Type II,associated with Zollinger-Ellison syndrome(ZES)and multiple endocrine neoplasia,comprises 5%;and(3)Type III,sporadic tumors with a higher metastatic potential,accounting for 15%–25%.Diagnosis involves endoscopy,biopsy,and histological examination.Additional methods include serum gastrin testing,immunohistochemistry,and imaging techniques such as computer tomography or magnetic resonance imaging for detecting metastasis.Type I treatment usually involves endoscopic resection(ER),with surgical resection for recurrence.Somatostatin analogs(SSAs)can reduce tumor size,and the prognosis is generally excellent.Type II treatment centers on surgical removal of the gastrinoma,with ER for smaller lesions and SSAs for symptom management.Type III requires surgical resection(partial or total gastrectomy)with lymph node dissection,and possibly chemotherapy.This type has a worse prognosis due to its aggressive nature.Emerging treatments like Peptide Receptor Radionuclide Therapy are promising for advanced cases,and ongoing research into immunotherapies is expanding future treatment options.Regular endoscopic follow-up is crucial to monitor for recurrence or metastasis across all types.Our literature review explores the current perspectives on G-NETs and highlights the importance of further research to improve diagnostic precision and treatment,particularly for those associated with less favorable cases.AIM To improve diagnostic precision and treatment,particularly for those associated with less favorable cases.METHODS A systematic search was conducted in PubMed,Scopus,and Web of Science until September 2024.Two independent reviewers screened titles,abstracts,and full texts for eligibility based on G-NET treatment in adults.Eligible studies included cohort studies,clinical trials,case series,and case reports,while in vitro,pediatric,and non-English studies were excluded.Relevant data were extracted independently,and disagreements were resolved through discussion.Study quality was assessed using appropriate tools.RESULTS G-NETs are rare,classified into three types:(1)Type I;(2)Type II;and(3)Type III.Type I G-NETs,often associated with chronic atrophic gastritis,are typically slow-growing and low-grade,with favorable outcomes following surgical resection.Type II G-NETs arise in hypergastrinemia conditions like multiple endocrine neoplasia and ZES,showing moderate malignancy risk.Type III G-NETs,the most aggressive and least common,present with distant metastases and poor prognosis.Diagnosis relies on endoscopy,imaging,and biomarkers like chromogranin A.Treatment varies by type,ranging from ER to aggressive surgery and chemotherapy for advanced cases.Regular follow-up is essential to monitor recurrence,particularly for type III G-NETs.CONCLUSION G-NETs require tailored diagnosis and treatment based on type and stage.Types I and II generally have better prognosis,while types III and IV are linked to poorer outcomes due to invasion and metastasis.Treatment strategies vary from ER for type I to extensive surgery for type III.Emerging therapies,like somatostatin analogs and peptide-receptor radionuclide therapies,show promise in advanced cases.Further research is essential to improve early diagnosis and treatment,particularly for high-risk lesions.展开更多
BACKGROUND Neuroendocrine tumors(NETs)are rare malignancies arising from the diffuse neuroendocrine system,often in the gastroenteropancreatic(GEP)tract.GEP-NETs,primarily involving the intestines(50%)and pancreas(30%...BACKGROUND Neuroendocrine tumors(NETs)are rare malignancies arising from the diffuse neuroendocrine system,often in the gastroenteropancreatic(GEP)tract.GEP-NETs,primarily involving the intestines(50%)and pancreas(30%),may occa-sionally secrete hormones,causing syndromes.Diagnosis relies on markers like chromogranin A,synaptophysin,and Ki-67,along with imaging modalities.Ri-sing NETs incidence is attributed to advancements in diagnostic modalities,parti-cularly endoscopic ultrasonography(EUS).EUS demonstrates high accuracy in detecting small lesions,assessing tumor depth,and identifying locoregional lymph nodes.Despite its proven diagnostic utility,there is limited data on EUS's role in evaluating GEP-NETs in resource-constrained settings like Pakistan.AIM To evaluate the diagnostic role of EUS in characterizing GEP-NETs based on clinical,histopathological,tumor grading,and site-specific differences.METHODS This single-center retrospective descriptive study was conducted at Aga Khan University Hospital,Karachi,a tertiary care hospital,from January 2021 to December 2023.Fourteen adult patients(≥18 years)with suspected NETs who underwent EUS and were diagnosed via histopathology were included.Data on demographics,clinical features,radiological findings,and histopathological characteristics were collected.Descriptive analysis was performed using SPSS version 23,with descriptive statistics expressed as means±SD for continuous variables and frequencies/percentages for categorical data.RESULTS A total of 14 adult GEP-NETs patients who underwent EUS were included,with a mean age of 52±14 years and the majority being male(71.4%).Common clinical presentations included weight loss(85.7%)and abdominal pain(78.6%).Computed tomography scans were performed in 92.9%of cases,with pancreatic masses detected in 42.9%of patients.EUS-guided fine needle biopsy(FNB)had a 100%diagnostic yield.The pancreas was the most common tumor site(57.1%).Histopathology revealed 78.6%of cases as well-differentiated NETs with 42.9%being grade II.Metastases were seen in 57.1%of patients,with the liver being the most common site.Surgical interventions were performed in 28.6%of patients,and all patients were alive at the time of study analysis.CONCLUSION EUS,with accurate imaging and effective EUS-FNB,is the gold standard for GEP-NET diagnosis,aiding tumor assessment and prognosis.Larger studies are needed to validate its impact on management outcomes.展开更多
BACKGROUND Primary hepatic neuroendocrine tumors(PHNETs)are extremely rare tumors originating from neuroendocrine cells.Due to lack of neuroendocrine symptoms and specific radiographic characteristics,PHNETs are chall...BACKGROUND Primary hepatic neuroendocrine tumors(PHNETs)are extremely rare tumors originating from neuroendocrine cells.Due to lack of neuroendocrine symptoms and specific radiographic characteristics,PHNETs are challenging to differentiate from other liver tumors.CASE SUMMARY This case involved a 67-year-old male who was admitted with a discovered hepatic mass and a suspicious lung lesion.Primary hepatic carcinoma was initially speculated based on the characteristic magnetic resonance imaging findings.The patient underwent a laparoscopic right partial hepatectomy,and subsequent immunohistochemical examination revealed a HNET.To exclude other potential origins,a positron emission tomography-computed tomography scan and gastrointestinal endoscopy were performed,leading to a final diagnosis of PHNETs.Then we conducted a literature review using the PubMed database,identifying 99 articles and 317 cases related to PHNETs.The characteristics,diagnostic methods,and treatment of PHNETs have been described.Finally,we elaborate on the presumed origins,pathological grades,clinical features,diagnosed methods,and treatments associated with PHNETs.CONCLUSION The diagnosis of PHNETs was primarily an exclusionary process.A definitive diagnosis of PHNETs relied mainly on immunohistochemical markers(chromogranin A,synaptophysin,and cluster of differentiation 56)and exclusion of primary foci in other organs.Radical surgery was the preferred treatment for early-stage tumors.展开更多
Neuroendocrine neoplasms are a group of tumors with heterogenous malignancy that evolve from neuroendocrine cells,most frequently in the gastrointestinal tract and in the lung.The latest 2021 World Health Organization...Neuroendocrine neoplasms are a group of tumors with heterogenous malignancy that evolve from neuroendocrine cells,most frequently in the gastrointestinal tract and in the lung.The latest 2021 World Health Organization(WHO)classification of lung tumors defines neuroendocrine neoplasms of the lung as an independent group of tumors,including typical and atypical neuroendocrine tumors and small cell and large cell neuroendocrine carcinomas.Although the overall nomenclature is essentially unchanged from the fourth WHO classification,there are several clinically relevant updates.In this review article,we discuss the epidemiological,clinical,diagnostic,therapeutic and prognostic features of these fascinating neoplasms,including the latest insights,current challenges and future perspectives.展开更多
Neuroendocrine neoplasms(NENs)are highly heterogeneous and potentially malignant tumors arising from secretory cells of the neuroendocrine system.Gastroenteropancreatic NENs(GEP-NENs)are the most common subtype of NEN...Neuroendocrine neoplasms(NENs)are highly heterogeneous and potentially malignant tumors arising from secretory cells of the neuroendocrine system.Gastroenteropancreatic NENs(GEP-NENs)are the most common subtype of NENs.Historically,GEP-NENs have been regarded as infrequent and slow-growing malignancies;however,recent data have demonstrated that the worldwide prevalence and incidence of GEP-NENs have increased exponentially over the last three decades.In addition,an increasing number of studies have proven that GEP-NENs result in a limited life expectancy.These findings suggested that the natural biology of GEP-NENs is more aggressive than commonly assumed.Therefore,there is an urgent need for advanced researches focusing on the diagnosis and management of patients with GEP-NENs.In this review,we have summarized the limitations and recent advancements in our comprehension of the epidemiology,clinical presentations,pathology,molecular biology,diagnosis,and treatment of GEP-NETs to identify factors contributing to delays in diagnosis and timely treatment of these patients.展开更多
BACKGROUND Recently,several endoscopic techniques have been used to improve the R0 resection rate of rectal neuroendocrine neoplasms(R-NENs).However,none of these methods can achieve 100%complete resection(CR),particu...BACKGROUND Recently,several endoscopic techniques have been used to improve the R0 resection rate of rectal neuroendocrine neoplasms(R-NENs).However,none of these methods can achieve 100%complete resection(CR),particularly in the vertical direction.Endoscopic full-thickness resection(EFTR)has proven to be an effective method for the treatment of submucosal tumors but is seldom utilized in the eradication of R-NENs.AIM To review cases of R-NENs removed using EFTR and to evaluate the safety and efficacy of this technique.METHODS This retrospective cohort study enrolled 160 patients with pathologically confirmed R-NENs,including 132 who underwent endoscopic submucosal dissection(ESD)and 28 who underwent EFTR.Lesions were categorized as<1 cm,1-2 cm,and>2 cm in size.CR rate,en bloc resection rate,operation time,and complications were evaluated.Subgroup analyses and follow-up were also performed.RESULTS EFTR achieved 100%CR rates for lesions<1 cm and 1-2 cm,compared with 67.0%and 50.0%,respectively,in the ESD group.En bloc resection and successful removal of the R-NENs were achieved in all patients.Meanwhile,EFTR showed performance comparable to ESD in terms of operation time,hospitalization cost,and postoperative adverse events,except for a one-day longer hospital stay.We also analyzed the invasion depth of R-NENs based on full-thickness specimens.The data showed that 80%of lesions(<1 cm)and 85.7%of lesions(1-2 cm)had invaded the SM3 level or deeper at the time of resection.For ESD specimens,46.6%(<1 cm)and 89.3%(1-2 cm)of lesions had infiltrated more than 2000μm beneath the muscularis mucosae.CONCLUSION EFTR has shown superior performance in the resection of small R-NENs compared with that of ESD.展开更多
BACKGROUND Gallbladder neuroendocrine carcinoma(NEC)represents a subtype of gallbladder malignancies characterized by a low incidence,aggressive nature,and poor prognosis.Despite its clinical severity,the genetic alte...BACKGROUND Gallbladder neuroendocrine carcinoma(NEC)represents a subtype of gallbladder malignancies characterized by a low incidence,aggressive nature,and poor prognosis.Despite its clinical severity,the genetic alterations,mechanisms,and signaling pathways underlying gallbladder NEC remain unclear.CASE SUMMARY This case study presents a rare instance of primary gallbladder NEC in a 73-year-old female patient,who underwent a radical cholecystectomy with hepatic hilar lymphadenectomy and resection of liver segments IV-B and V.Targeted gene sequencing and bioinformatics analysis tools,including STRING,GeneMANIA,Metascape,TRRUST,Sangerbox,cBioPortal and GSCA,were used to analyze the biological functions and features of mutated genes in gallbladder NEC.Twelve mutations(APC,ARID2,IFNA6,KEAP1,RB1,SMAD4,TP53,BTK,GATA1,GNAS,and PRDM3)were identified,and the tumor mutation burden was determined to be 9.52 muts/Mb via targeted gene sequencing.A protein-protein interaction network showed significant interactions among the twelve mutated genes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were used to assess mutation functions and pathways.The results revealed 40 tumor-related pathways.A key regulatory factor for gallbladder NEC-related genes was identified,and its biological functions and features were compared with those of gallbladder carcinoma.CONCLUSION Gallbladder NEC requires standardized treatment.Comparisons with other gallbladder carcinomas revealed clinical phenotypes,molecular alterations,functional characteristics,and enriched pathways.展开更多
Compared with colorectal adenocarcinoma,neuroendocrine neoplasms(NENs),which affect the colon and rectum,are uncommon tumor conditions that have received relatively limited attention in basic research.Furthermore,the ...Compared with colorectal adenocarcinoma,neuroendocrine neoplasms(NENs),which affect the colon and rectum,are uncommon tumor conditions that have received relatively limited attention in basic research.Furthermore,the scarcity of these NENs has hindered extensive clinical investigations,thereby leading to a dearth of robust evidence for guiding clinical practice and impeding the establishment of standardized approaches for diagnosis and treatment.However,with the increasing awareness of population screening,as well as the increasing popularity of colonoscopy screening programs,the incidence of colorectal NENs has gradually increased.Moreover,some high-grade NENs are highly malignant and invasive,thereby leading to poor treatment outcomes and prognoses.These challenges have elicited increased attention from clinical physicians,thus prompting researchers to explore relevant studies using limited specimens and clinical data.This scenario has resulted in preliminary findings that provide evidence for addressing diagnostic and therapeutic challenges associated with NENs of the colon and rectum.In this article,we review recent literature reports and summarize the advances regarding the diagnosis and treatment of colorectal NENs.展开更多
Neuroendocrine tumors are a rare cancer,with those arising in gastric tissue even less commonly.With increasing recognition through endoscopy,these tumors are diagnosed in more patients each year.As a rare and growing...Neuroendocrine tumors are a rare cancer,with those arising in gastric tissue even less commonly.With increasing recognition through endoscopy,these tumors are diagnosed in more patients each year.As a rare and growing entity,our understanding of these tumors,the way we characterize them,and treatment are changing rapidly.Thus,we sought to provide an updated review of pathology and management,highlighting the latest guidelines and evidence for surgical treatment.Much of the general treatment paradigm is from consensus guidelines put forth by the European Neuroendocrine Tumor Society and the North American Neuroendocrine Tumor Society;however,future research is needed to help guide further surgical decision-making around intermediate grade and intermediate size type Ⅲ tumors,as well as systemic therapies in the perioperative and nonoperative settings for high-grade tumors.展开更多
BACKGROUND Early esophageal neuroendocrine carcinoma(E-NEC)is a rare but aggressive malignancy with poorly understood endoscopic features.Despite advancements in multi-model endoscopy,including white light endoscopy,m...BACKGROUND Early esophageal neuroendocrine carcinoma(E-NEC)is a rare but aggressive malignancy with poorly understood endoscopic features.Despite advancements in multi-model endoscopy,including white light endoscopy,magnifying end-oscopy narrow-band imaging(NBI),and endoscopic ultrasonography(EUS),the diagnostic characteristics of early E-NEC remain unclear.Comprehensive evalu-ation using these techniques can improve early detection and guide clinical management.This study aimed to investigate the endoscopic features of early E-NEC using multiple imaging modalities.We hypothesized that specific endos-copic patterns,such as irregular microvascular morphology or signs of submu-cosal invasion,could reliably distinguish early E-NEC from other esophageal lesions.AIM To characterize early E-NEC using multi-model endoscopy and identify diag-nostic endoscopic features.METHODS Clinical data of four patients with esophageal submucosal lesions identified by gastroscopy and pathologically diagnosed as E-NEC in the Department of Gastroenterology,The First Affiliated Hospital of Zhejiang University School of Medicine between January 2020 and August 2024 were retrospectively analyzed,and their manifestations under multi-model endoscopy were observed.Grayscale values of ultrasound images in three patients with E-NEC and eight with esophageal leiomyoma were calculated using Image J software and compared using the Mann-Whitney U test.Neuroendocrine neoplasms(NENs)are a rare heterogeneous group of epithelial tumors that originate from peptidergic neurons and neuroendocrine cells,and are characterized by neuroendocrine differentiation.NENs include well-differen-tiated neuroendocrine tumors(NETs),poorly differentiated neuroendocrine carcinomas(NECs),and mixed neuroen-docrine-non-NENs[1],which exhibit a wide range of biological behaviors,from indolent,slow-growing lesions to highly aggressive and metastatic malignancies[2].NENs have the capacity for whole-body distribution,with gastroenteropan-creatic NENs comprising approximately 60%-75%of cases,followed by those in the lungs and mediastinum[3].Eso-phageal NENs(E-NENs)are extremely rare,accounting for only approximately 1.6%of all NENs and occurring far less frequently than other gastrointestinal NENs[4].However,with advancements in early cancer screening and diagnostic techniques,the incidence of E-NENs has gradually increased in recent decades[5].Among E-NENs,<1%are well-differ-entiated NETs,with the vast majority being poorly differentiated small cell NECs[6,7].Nevertheless,esophageal NEC(E-NEC)accounts for only 0.05%-7.6%of all esophageal malignant tumors[8,9],and is characterized by aggressive behavior,rapid progression,and early metastasis.E-NEC primarily affects middle-aged and older individuals,with a higher prevalence in males[10].The tumor-node-metastasis staging system of E-NEC mirrors that of esophageal squamous cell carcinoma(ESCC)[11,12].Early E-NEC is defined as lesions limited to the mucosal or submucosal layer(stages T1a and T1b),with or without nodal metastasis.Clinically,we found that early E-NEC often presents with absent or non-specific symptoms,such as mild dysphagia or retrosternal discomfort,which are easily overlooked or mistaken for benign esophageal conditions such as leiomyoma.Conventional imaging and tumor markers frequently fail to detect early lesions,and endoscopic biopsy results may be inconclusive due to submucosal tumor growth and the overlying normal epithelium[13].As a result,E-NEC is frequently diagnosed at an advanced stage(31%-90%of cases)when regional lymph node or distant metastases have already occurred,contributing to its poor prognosis[2,13,14].Studies have reported a median survival of approximately 11 months and 5-year survival rate of<10%[14].Given these challenges,early detection using endoscopy is essential for improving patient outcomes.展开更多
This study highlights the significance of considering pituitary neuroendocrine tumor volume when determining the appropriate line of therapy for patients with acromegaly.The findings suggest that,although tumor volume...This study highlights the significance of considering pituitary neuroendocrine tumor volume when determining the appropriate line of therapy for patients with acromegaly.The findings suggest that,although tumor volume may assist in predicting the need for more aggressive treatment strategies,it is not a reliable indicator of disease persistence following surgical intervention.Further research is warranted to investigate additional factors influencing acromegaly treatment outcomes to enhance patient care.展开更多
BACKGROUND Gastric neuroendocrine carcinomas(NECs)exhibit aggressive features,such as rapid growth,higher rate of metastasis,and a generally unfavorable prognosis compared to gastric adenocarcinoma.As a result,therape...BACKGROUND Gastric neuroendocrine carcinomas(NECs)exhibit aggressive features,such as rapid growth,higher rate of metastasis,and a generally unfavorable prognosis compared to gastric adenocarcinoma.As a result,therapeutic options for NECs remain limited,contributing to the poor prognosis of patients.Immunotherapy has emerged as a promising treatment strategy and demonstrated the potential to partially improve the survival and prognosis of patients with NECs.Nevertheless,the unique clinical response termed pseudoprogression(PsP)has garnered considerable attention in the context of immunotherapy.CASE SUMMARY Presented here is a case of NEC recurrence five and a half months after radical gastric surgery.The 45-year-old male patient underwent combination treatment involving a PD-1 blocker and tyrosine kinase inhibitors and encountered two instances of PsP during treatment.The patient ultimately achieved a durable treatment response without altering his treatment regimens,resulting in a substantial therapeutic benefit.CONCLUSION This case report aimed to provide the authors’experience with the diagnosis of PsP and treatment strategies for PsP in ongoing immunotherapy.展开更多
BACKGROUND Colonic neuroendocrine carcinomas(NECs)are highly malignant and invasive with poor prognosis.Long noncoding RNAs(LncRNAs)participate in the tumorigenesis and metastasis of multiple cancers AIM To detect the...BACKGROUND Colonic neuroendocrine carcinomas(NECs)are highly malignant and invasive with poor prognosis.Long noncoding RNAs(LncRNAs)participate in the tumorigenesis and metastasis of multiple cancers AIM To detect the roles and mechanisms of lncRNA prostate cancer associated transcript 6(PCAT6)in the progression of colonic NEC.METHODS Human NEC and adjacent normal samples were collected for immunohistochemistry staining of CgA and real-time quantitative polymerase chain reaction(RT-qPCR)of PCAT6 mRNA level.Subcutaneous xenograft tumor model and lung metastasis model were established in nude mice.The lung tissues were stained by hematoxylin and eosin to assess pulmonary metastasis.The expression of epithelial-mesenchymal transition(EMT)-related markers and pathway-related genes was measured by RT-qPCR and western blotting.CD56 expression was assessed by immunofluorescence staining.The biological functions of PCAT6 were examined by cell counting kit-8,colony formation assays,Transwell assays and wound healing assays.The interaction between PCAT6 and its potential downstream target was verified by luciferase reporter assays.RESULTS LncRNA PCAT6 was upregulated in human NEC samples and LCC-18 cells,and its high expression was positively correlated with poor prognosis in patients with colonic NEC.Additionally,the expression of PCAT6 was positively associated with the proliferation,migration,invasion,and EMT of LCC-18 cells.Moreover,PCAT6 facilitated tumor growth,lung metastasis and EMT in xenografts.Mechanistically,PCAT6 promoted the activation of MAPK to enhance the EMT in colonic NEC by targeting miR-326.CONCLUSION In conclusion,lncRNA PCAT6 accelerates the process of colonic NEC by activating ERK/p38 MAPK signaling through targeting miR-326.These results might provide useful information for exploring the potential therapeutic targets in colonic NEC.展开更多
In this article,we discussed the article by Zeng et al,published in a recent issue of the World Journal of Gastroenterology.The publication represents a significant advancement in the prognostic evaluation of rectal n...In this article,we discussed the article by Zeng et al,published in a recent issue of the World Journal of Gastroenterology.The publication represents a significant advancement in the prognostic evaluation of rectal neuroendocrine neoplasms.The GATIS score is a single nomogram model that incorporates five key progno-stic factors:Tumor grade;T stage;tumor size;age;and the prognostic nutritional index.This innovation optimizes the prognostic process,delivering more accurate predictions of overall survival and progression-free survival compared to tradi-tional TNM staging and World Health Organization classification systems.The findings of the study were based on a retrospective analysis spanning 12 years and involving 1408 patients from 17 reference centers in China.In this editorial,we specifically examined the strengths and limitations of the study,the clinical implications of the GATIS score,and the questions arising from its conclusions.展开更多
BACKGROUND Neuroendocrine tumors(NETs)are an important type of neoplastic disease of the digestive tract.There is little data on NETs originating from the pancreato-hepato-biliary region of the digestive tract in Paki...BACKGROUND Neuroendocrine tumors(NETs)are an important type of neoplastic disease of the digestive tract.There is little data on NETs originating from the pancreato-hepato-biliary region of the digestive tract in Pakistan.AIM To evaluate different types of pancreato-hepatobiliary NETs(PHB-NET)diagnosed with endoscopic ultrasound(EUS)and to identify factors associated with high-grade NETs.METHODS All patients diagnosed with PHB-NET through EUS-guided biopsy were included in the study.The site of origin,histology,and grade of PHB-NETs were noted and factors associated with high-grade lesions were analyzed.SPSS,version 20.0 was used for statistical analysis.RESULTS A total of 36 patients with PHB-NET were included.Males and females were equal in numbers,i.e.,18(50%)each.The mean age was 48±15.7 years with an age range of 17-70 years.The most common sites of origin of PHB-NET were:Pancreas 20(55.6%),porta hepatis mass 8(22.2%),perigastric mass 3(8.3%)and others 5(13.9%).The mean size of the PHB-NETs was 34.7±22.5 mm.Among pancreatic NETs,the most commonly affected areas were body 9,tail 5,and head 5.Only 4(11.1%)PHB-NETs were functioning,all of which were insulinomas originating from the body or tail of the pancreas.Two-thirds of PHB-NETs,24(66.6%),were benign(WHO grade I:19;grade 2:5)while one-third 12(33.3%)were neuroendocrine cancers(NEC)(WHO grade III).Histological types were large cell 17(47.2%),small cell 8(22.2%),mixed 1(2.8%),and undetermined 10(27.8%).Factors associated with NECs were age>40 years(P=0.016),extra-pancreatic origin of the lesion(P=0.014),and small cell histologic type(P<0.001).CONCLUSION The most common site of PHB-NET detected through EUS was the pancreas.Although most were benign,about one-third were high-grade cancers.Insulinoma was the most common functioning tumor.NECs were associated with advanced age,extra-pancreatic origin,and small-cell histology.展开更多
BACKGROUND Liver metastases are very common in pancreatic neuroendocrine tumors(pNETs).When surgical resection is possible,it is typically associated with survival benefits in patients with pNET and liver metastases.P...BACKGROUND Liver metastases are very common in pancreatic neuroendocrine tumors(pNETs).When surgical resection is possible,it is typically associated with survival benefits in patients with pNET and liver metastases.Patient-derived organoids are a powerful preclinical platform that show great potential for predicting treatment response,and they have been increasingly applied in precision medicine and cancer research.CASE SUMMARY A 51-year-old man was admitted to the hospital with the chief complaint of in-termittent dull pain in the upper abdomen for over 3 years.Computerized to-mography showed multiple space-occupying lesions in the liver and a neoplasm in the pancreatic body.Pathological results suggested a grade 3 pancreas-derived hepatic neuroendocrine tumor.In combination with relevant examinations,the patient was diagnosed with pNET with liver metastases(grade 3).Transarterial chemoembolization was initially performed with oxaliplatin and 5-fluorouracil,after which the chemotherapy regimen was switched to liposomal irinotecan and cisplatin for a subsequent perfusion,guided by organoid-based drug sensitivity testing.Following interventional treatment,the tumor had decreased in size.However,due to poor treatment compliance and the patient’s preference for sur-INTRODUCTION Pancreatic neuroendocrine tumors(pNETs)are a rare and heterogeneous group of neoplasms arising from pancreatic islet cells,with variations in histology,clinical characteristics,and prognosis[1].They may present as non-infiltrative,slow-growing tumors,locally invasive tumors,or even rapidly metastasizing tumors[2].Most metastases localize to the liver,and approximately 28%-77%of patients with pNETs will experience liver metastases in their lifetime[3].Patients with liver metastases may be subjected to local complications such as biliary obstruction,liver insufficiency,and carcinoid syndrome.Additionally,liver metastases are a major risk factor for the prognosis of patients with pNETs[4].When feasible,surgical resection is significantly associated with the best long-term survival outcomes[5].Therefore,for patients with pNET liver metastases,comprehensive assessment and multidisciplinary approaches are required to determine the feasibility of surgical resection and the optimal treatment to improve the prognosis.Over the past decade,the advent of in vitro three-dimensional technologies including organoids has revolutionized the development of human cancer models.Patient-derived organoids(PDOs),an in vitro three-dimensional microstructure,can faithfully recapitulate the intricate spatial architecture and cell heterogeneity of the tissue,and simulate the biological behaviors and functions of parental tumors while preserving biological,genetic and molecular features[6,7].As a po-werful preclinical platform,PDOs have been increasingly applied in precision medicine and cancer research.Importantly,there is a significant association between the use of PDO-based drug sensitivity testing and clinical responses to chemotherapy,radiotherapy and targeted therapy in multiple cancer types[8-10].Although gastroenteropancreatic neuroendocrine neoplasm organoids have been confirmed to retain the pathohistological and functional phenotypes of parental tumors[7],their roles in the prediction of clinical outcomes have not been presented.Here,we report a case of pNET with liver metastases who successfully received surgical resection after personalized treatment guided by PDO-based drug sensitivity testing,resulting in a favorable prognosis.展开更多
As a practicing anatomic pathologist specialized in urologic pathology,a vast difference may be observed between what pathologists designate as neuroendocrine(or small cell)carcinoma of the prostate,and what clinician...As a practicing anatomic pathologist specialized in urologic pathology,a vast difference may be observed between what pathologists designate as neuroendocrine(or small cell)carcinoma of the prostate,and what clinicians or basic scientists define as such.展开更多
BACKGROUND Rectal neuroendocrine tumors(NETs)smaller than 10 mm and well-differentiated tumors are generally considered to have a low risk of lymph node and distant metastasis,making them suitable for endoscopic resec...BACKGROUND Rectal neuroendocrine tumors(NETs)smaller than 10 mm and well-differentiated tumors are generally considered to have a low risk of lymph node and distant metastasis,making them suitable for endoscopic resection.In contrast,tumors≥20 mm in size typically require surgical resection.However,the optimal management of intermediate-sized(10-15 mm)rectal NETs remains controversial.AIM To compare the clinical outcomes of endoscopic resection of rectal NETs<1 cm and those 1-1.5 cm in size.METHODS A retrospective study was conducted on 1056 patients with rectal NETs treated at the Samsung Medical Center between January 2005 and June 2021.After propensity score matching(1:10)for age,sex,and type of endoscopic resection,225 patients with tumors<1 cm in size and 27 patients with tumors 1-1.5 cm in size were analyzed.RESULTS Surgical resection was more frequent in the 1-1.5 cm group(37.2%)than in the<1 cm group(10.7%)(P<0.01).Endoscopic submucosal dissection was also more commonly performed in the 1-1.5 cm group(48.1%vs 18.5%,P<0.01).Negative resection margins were achieved in 97.2%of the patients,with no significant difference between the groups(P=0.22).No lymphovascular invasion was observed.During a median follow-up of 54 months,no recurrence occurred in the 1-1.5 cm group,while one case of metachronous recurrence was noted in the<1 cm group(P=1.00).There was no significant difference in recurrence-free survival(P=0.48).CONCLUSION Endoscopic resection of 1-1.5 cm grade 1 rectal NETs yielded comparable outcomes to those<1 cm in size,suggesting its feasibility as a treatment.展开更多
文摘Rectal neuroendocrine neoplasms pose significant challenges due to their varied presentations and prognoses.Traditional prognostic models,while useful,often fall short of accurately predicting clinical outcomes for these patients.This article discusses the development and implications of a novel prognostic tool,the GATIS score,which aims to enhance predictive accuracy and guide treatment strategies more effectively than current methods.Utilizing data from a large cohort and employing sophisticated statistical models,the GATIS score integrates clinical and pathological markers to provide a nuanced assessment of prognosis.We evaluate the potential of this score to transform clinical decision-making processes,its integration into current medical practices,and future directions for its develo-pment.The integration of genetic markers and other biomarkers could further refine its predictive power,highlighting the ongoing need for innovation in the management of rectal neuroendocrine neoplasms.
文摘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.
文摘BACKGROUND Gastric neuroendocrine tumors(G-NETs)are rare tumors originating from enterochromaffin-like cells,with an incidence of 0.4 per 100000 annually.There are three main types:(1)Type I,linked to chronic atrophic gastritis and hypergastrinemia,makes up 75%–80%of G-NETs;(2)Type II,associated with Zollinger-Ellison syndrome(ZES)and multiple endocrine neoplasia,comprises 5%;and(3)Type III,sporadic tumors with a higher metastatic potential,accounting for 15%–25%.Diagnosis involves endoscopy,biopsy,and histological examination.Additional methods include serum gastrin testing,immunohistochemistry,and imaging techniques such as computer tomography or magnetic resonance imaging for detecting metastasis.Type I treatment usually involves endoscopic resection(ER),with surgical resection for recurrence.Somatostatin analogs(SSAs)can reduce tumor size,and the prognosis is generally excellent.Type II treatment centers on surgical removal of the gastrinoma,with ER for smaller lesions and SSAs for symptom management.Type III requires surgical resection(partial or total gastrectomy)with lymph node dissection,and possibly chemotherapy.This type has a worse prognosis due to its aggressive nature.Emerging treatments like Peptide Receptor Radionuclide Therapy are promising for advanced cases,and ongoing research into immunotherapies is expanding future treatment options.Regular endoscopic follow-up is crucial to monitor for recurrence or metastasis across all types.Our literature review explores the current perspectives on G-NETs and highlights the importance of further research to improve diagnostic precision and treatment,particularly for those associated with less favorable cases.AIM To improve diagnostic precision and treatment,particularly for those associated with less favorable cases.METHODS A systematic search was conducted in PubMed,Scopus,and Web of Science until September 2024.Two independent reviewers screened titles,abstracts,and full texts for eligibility based on G-NET treatment in adults.Eligible studies included cohort studies,clinical trials,case series,and case reports,while in vitro,pediatric,and non-English studies were excluded.Relevant data were extracted independently,and disagreements were resolved through discussion.Study quality was assessed using appropriate tools.RESULTS G-NETs are rare,classified into three types:(1)Type I;(2)Type II;and(3)Type III.Type I G-NETs,often associated with chronic atrophic gastritis,are typically slow-growing and low-grade,with favorable outcomes following surgical resection.Type II G-NETs arise in hypergastrinemia conditions like multiple endocrine neoplasia and ZES,showing moderate malignancy risk.Type III G-NETs,the most aggressive and least common,present with distant metastases and poor prognosis.Diagnosis relies on endoscopy,imaging,and biomarkers like chromogranin A.Treatment varies by type,ranging from ER to aggressive surgery and chemotherapy for advanced cases.Regular follow-up is essential to monitor recurrence,particularly for type III G-NETs.CONCLUSION G-NETs require tailored diagnosis and treatment based on type and stage.Types I and II generally have better prognosis,while types III and IV are linked to poorer outcomes due to invasion and metastasis.Treatment strategies vary from ER for type I to extensive surgery for type III.Emerging therapies,like somatostatin analogs and peptide-receptor radionuclide therapies,show promise in advanced cases.Further research is essential to improve early diagnosis and treatment,particularly for high-risk lesions.
文摘BACKGROUND Neuroendocrine tumors(NETs)are rare malignancies arising from the diffuse neuroendocrine system,often in the gastroenteropancreatic(GEP)tract.GEP-NETs,primarily involving the intestines(50%)and pancreas(30%),may occa-sionally secrete hormones,causing syndromes.Diagnosis relies on markers like chromogranin A,synaptophysin,and Ki-67,along with imaging modalities.Ri-sing NETs incidence is attributed to advancements in diagnostic modalities,parti-cularly endoscopic ultrasonography(EUS).EUS demonstrates high accuracy in detecting small lesions,assessing tumor depth,and identifying locoregional lymph nodes.Despite its proven diagnostic utility,there is limited data on EUS's role in evaluating GEP-NETs in resource-constrained settings like Pakistan.AIM To evaluate the diagnostic role of EUS in characterizing GEP-NETs based on clinical,histopathological,tumor grading,and site-specific differences.METHODS This single-center retrospective descriptive study was conducted at Aga Khan University Hospital,Karachi,a tertiary care hospital,from January 2021 to December 2023.Fourteen adult patients(≥18 years)with suspected NETs who underwent EUS and were diagnosed via histopathology were included.Data on demographics,clinical features,radiological findings,and histopathological characteristics were collected.Descriptive analysis was performed using SPSS version 23,with descriptive statistics expressed as means±SD for continuous variables and frequencies/percentages for categorical data.RESULTS A total of 14 adult GEP-NETs patients who underwent EUS were included,with a mean age of 52±14 years and the majority being male(71.4%).Common clinical presentations included weight loss(85.7%)and abdominal pain(78.6%).Computed tomography scans were performed in 92.9%of cases,with pancreatic masses detected in 42.9%of patients.EUS-guided fine needle biopsy(FNB)had a 100%diagnostic yield.The pancreas was the most common tumor site(57.1%).Histopathology revealed 78.6%of cases as well-differentiated NETs with 42.9%being grade II.Metastases were seen in 57.1%of patients,with the liver being the most common site.Surgical interventions were performed in 28.6%of patients,and all patients were alive at the time of study analysis.CONCLUSION EUS,with accurate imaging and effective EUS-FNB,is the gold standard for GEP-NET diagnosis,aiding tumor assessment and prognosis.Larger studies are needed to validate its impact on management outcomes.
文摘BACKGROUND Primary hepatic neuroendocrine tumors(PHNETs)are extremely rare tumors originating from neuroendocrine cells.Due to lack of neuroendocrine symptoms and specific radiographic characteristics,PHNETs are challenging to differentiate from other liver tumors.CASE SUMMARY This case involved a 67-year-old male who was admitted with a discovered hepatic mass and a suspicious lung lesion.Primary hepatic carcinoma was initially speculated based on the characteristic magnetic resonance imaging findings.The patient underwent a laparoscopic right partial hepatectomy,and subsequent immunohistochemical examination revealed a HNET.To exclude other potential origins,a positron emission tomography-computed tomography scan and gastrointestinal endoscopy were performed,leading to a final diagnosis of PHNETs.Then we conducted a literature review using the PubMed database,identifying 99 articles and 317 cases related to PHNETs.The characteristics,diagnostic methods,and treatment of PHNETs have been described.Finally,we elaborate on the presumed origins,pathological grades,clinical features,diagnosed methods,and treatments associated with PHNETs.CONCLUSION The diagnosis of PHNETs was primarily an exclusionary process.A definitive diagnosis of PHNETs relied mainly on immunohistochemical markers(chromogranin A,synaptophysin,and cluster of differentiation 56)and exclusion of primary foci in other organs.Radical surgery was the preferred treatment for early-stage tumors.
文摘Neuroendocrine neoplasms are a group of tumors with heterogenous malignancy that evolve from neuroendocrine cells,most frequently in the gastrointestinal tract and in the lung.The latest 2021 World Health Organization(WHO)classification of lung tumors defines neuroendocrine neoplasms of the lung as an independent group of tumors,including typical and atypical neuroendocrine tumors and small cell and large cell neuroendocrine carcinomas.Although the overall nomenclature is essentially unchanged from the fourth WHO classification,there are several clinically relevant updates.In this review article,we discuss the epidemiological,clinical,diagnostic,therapeutic and prognostic features of these fascinating neoplasms,including the latest insights,current challenges and future perspectives.
基金supported by the National Natural Science Foundation of China(82104596)the Shenzhen Key Medical Discipline Construction Fund&Sanming Project of Medicine in Shenzhen(SZSM202111002)+1 种基金the Medicine-Engineering Interdisciplinary Research Foundation of Shenzhen University(2023YG019)the Shenzhen Science and Technology Program(GJHZ20220913143005010)。
文摘Neuroendocrine neoplasms(NENs)are highly heterogeneous and potentially malignant tumors arising from secretory cells of the neuroendocrine system.Gastroenteropancreatic NENs(GEP-NENs)are the most common subtype of NENs.Historically,GEP-NENs have been regarded as infrequent and slow-growing malignancies;however,recent data have demonstrated that the worldwide prevalence and incidence of GEP-NENs have increased exponentially over the last three decades.In addition,an increasing number of studies have proven that GEP-NENs result in a limited life expectancy.These findings suggested that the natural biology of GEP-NENs is more aggressive than commonly assumed.Therefore,there is an urgent need for advanced researches focusing on the diagnosis and management of patients with GEP-NENs.In this review,we have summarized the limitations and recent advancements in our comprehension of the epidemiology,clinical presentations,pathology,molecular biology,diagnosis,and treatment of GEP-NETs to identify factors contributing to delays in diagnosis and timely treatment of these patients.
基金Supported by National Natural Science Foundation of China,No.82004298Jiangsu Graduate Research and Practice Innovation Program,China,No.KYCX23_2090.
文摘BACKGROUND Recently,several endoscopic techniques have been used to improve the R0 resection rate of rectal neuroendocrine neoplasms(R-NENs).However,none of these methods can achieve 100%complete resection(CR),particularly in the vertical direction.Endoscopic full-thickness resection(EFTR)has proven to be an effective method for the treatment of submucosal tumors but is seldom utilized in the eradication of R-NENs.AIM To review cases of R-NENs removed using EFTR and to evaluate the safety and efficacy of this technique.METHODS This retrospective cohort study enrolled 160 patients with pathologically confirmed R-NENs,including 132 who underwent endoscopic submucosal dissection(ESD)and 28 who underwent EFTR.Lesions were categorized as<1 cm,1-2 cm,and>2 cm in size.CR rate,en bloc resection rate,operation time,and complications were evaluated.Subgroup analyses and follow-up were also performed.RESULTS EFTR achieved 100%CR rates for lesions<1 cm and 1-2 cm,compared with 67.0%and 50.0%,respectively,in the ESD group.En bloc resection and successful removal of the R-NENs were achieved in all patients.Meanwhile,EFTR showed performance comparable to ESD in terms of operation time,hospitalization cost,and postoperative adverse events,except for a one-day longer hospital stay.We also analyzed the invasion depth of R-NENs based on full-thickness specimens.The data showed that 80%of lesions(<1 cm)and 85.7%of lesions(1-2 cm)had invaded the SM3 level or deeper at the time of resection.For ESD specimens,46.6%(<1 cm)and 89.3%(1-2 cm)of lesions had infiltrated more than 2000μm beneath the muscularis mucosae.CONCLUSION EFTR has shown superior performance in the resection of small R-NENs compared with that of ESD.
基金Supported by School-Level Key Projects at Bengbu Medical College,No.2021byzd109.
文摘BACKGROUND Gallbladder neuroendocrine carcinoma(NEC)represents a subtype of gallbladder malignancies characterized by a low incidence,aggressive nature,and poor prognosis.Despite its clinical severity,the genetic alterations,mechanisms,and signaling pathways underlying gallbladder NEC remain unclear.CASE SUMMARY This case study presents a rare instance of primary gallbladder NEC in a 73-year-old female patient,who underwent a radical cholecystectomy with hepatic hilar lymphadenectomy and resection of liver segments IV-B and V.Targeted gene sequencing and bioinformatics analysis tools,including STRING,GeneMANIA,Metascape,TRRUST,Sangerbox,cBioPortal and GSCA,were used to analyze the biological functions and features of mutated genes in gallbladder NEC.Twelve mutations(APC,ARID2,IFNA6,KEAP1,RB1,SMAD4,TP53,BTK,GATA1,GNAS,and PRDM3)were identified,and the tumor mutation burden was determined to be 9.52 muts/Mb via targeted gene sequencing.A protein-protein interaction network showed significant interactions among the twelve mutated genes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were used to assess mutation functions and pathways.The results revealed 40 tumor-related pathways.A key regulatory factor for gallbladder NEC-related genes was identified,and its biological functions and features were compared with those of gallbladder carcinoma.CONCLUSION Gallbladder NEC requires standardized treatment.Comparisons with other gallbladder carcinomas revealed clinical phenotypes,molecular alterations,functional characteristics,and enriched pathways.
文摘Compared with colorectal adenocarcinoma,neuroendocrine neoplasms(NENs),which affect the colon and rectum,are uncommon tumor conditions that have received relatively limited attention in basic research.Furthermore,the scarcity of these NENs has hindered extensive clinical investigations,thereby leading to a dearth of robust evidence for guiding clinical practice and impeding the establishment of standardized approaches for diagnosis and treatment.However,with the increasing awareness of population screening,as well as the increasing popularity of colonoscopy screening programs,the incidence of colorectal NENs has gradually increased.Moreover,some high-grade NENs are highly malignant and invasive,thereby leading to poor treatment outcomes and prognoses.These challenges have elicited increased attention from clinical physicians,thus prompting researchers to explore relevant studies using limited specimens and clinical data.This scenario has resulted in preliminary findings that provide evidence for addressing diagnostic and therapeutic challenges associated with NENs of the colon and rectum.In this article,we review recent literature reports and summarize the advances regarding the diagnosis and treatment of colorectal NENs.
文摘Neuroendocrine tumors are a rare cancer,with those arising in gastric tissue even less commonly.With increasing recognition through endoscopy,these tumors are diagnosed in more patients each year.As a rare and growing entity,our understanding of these tumors,the way we characterize them,and treatment are changing rapidly.Thus,we sought to provide an updated review of pathology and management,highlighting the latest guidelines and evidence for surgical treatment.Much of the general treatment paradigm is from consensus guidelines put forth by the European Neuroendocrine Tumor Society and the North American Neuroendocrine Tumor Society;however,future research is needed to help guide further surgical decision-making around intermediate grade and intermediate size type Ⅲ tumors,as well as systemic therapies in the perioperative and nonoperative settings for high-grade tumors.
基金Supported by National Natural Science Foundation of China,No.82370570.
文摘BACKGROUND Early esophageal neuroendocrine carcinoma(E-NEC)is a rare but aggressive malignancy with poorly understood endoscopic features.Despite advancements in multi-model endoscopy,including white light endoscopy,magnifying end-oscopy narrow-band imaging(NBI),and endoscopic ultrasonography(EUS),the diagnostic characteristics of early E-NEC remain unclear.Comprehensive evalu-ation using these techniques can improve early detection and guide clinical management.This study aimed to investigate the endoscopic features of early E-NEC using multiple imaging modalities.We hypothesized that specific endos-copic patterns,such as irregular microvascular morphology or signs of submu-cosal invasion,could reliably distinguish early E-NEC from other esophageal lesions.AIM To characterize early E-NEC using multi-model endoscopy and identify diag-nostic endoscopic features.METHODS Clinical data of four patients with esophageal submucosal lesions identified by gastroscopy and pathologically diagnosed as E-NEC in the Department of Gastroenterology,The First Affiliated Hospital of Zhejiang University School of Medicine between January 2020 and August 2024 were retrospectively analyzed,and their manifestations under multi-model endoscopy were observed.Grayscale values of ultrasound images in three patients with E-NEC and eight with esophageal leiomyoma were calculated using Image J software and compared using the Mann-Whitney U test.Neuroendocrine neoplasms(NENs)are a rare heterogeneous group of epithelial tumors that originate from peptidergic neurons and neuroendocrine cells,and are characterized by neuroendocrine differentiation.NENs include well-differen-tiated neuroendocrine tumors(NETs),poorly differentiated neuroendocrine carcinomas(NECs),and mixed neuroen-docrine-non-NENs[1],which exhibit a wide range of biological behaviors,from indolent,slow-growing lesions to highly aggressive and metastatic malignancies[2].NENs have the capacity for whole-body distribution,with gastroenteropan-creatic NENs comprising approximately 60%-75%of cases,followed by those in the lungs and mediastinum[3].Eso-phageal NENs(E-NENs)are extremely rare,accounting for only approximately 1.6%of all NENs and occurring far less frequently than other gastrointestinal NENs[4].However,with advancements in early cancer screening and diagnostic techniques,the incidence of E-NENs has gradually increased in recent decades[5].Among E-NENs,<1%are well-differ-entiated NETs,with the vast majority being poorly differentiated small cell NECs[6,7].Nevertheless,esophageal NEC(E-NEC)accounts for only 0.05%-7.6%of all esophageal malignant tumors[8,9],and is characterized by aggressive behavior,rapid progression,and early metastasis.E-NEC primarily affects middle-aged and older individuals,with a higher prevalence in males[10].The tumor-node-metastasis staging system of E-NEC mirrors that of esophageal squamous cell carcinoma(ESCC)[11,12].Early E-NEC is defined as lesions limited to the mucosal or submucosal layer(stages T1a and T1b),with or without nodal metastasis.Clinically,we found that early E-NEC often presents with absent or non-specific symptoms,such as mild dysphagia or retrosternal discomfort,which are easily overlooked or mistaken for benign esophageal conditions such as leiomyoma.Conventional imaging and tumor markers frequently fail to detect early lesions,and endoscopic biopsy results may be inconclusive due to submucosal tumor growth and the overlying normal epithelium[13].As a result,E-NEC is frequently diagnosed at an advanced stage(31%-90%of cases)when regional lymph node or distant metastases have already occurred,contributing to its poor prognosis[2,13,14].Studies have reported a median survival of approximately 11 months and 5-year survival rate of<10%[14].Given these challenges,early detection using endoscopy is essential for improving patient outcomes.
文摘This study highlights the significance of considering pituitary neuroendocrine tumor volume when determining the appropriate line of therapy for patients with acromegaly.The findings suggest that,although tumor volume may assist in predicting the need for more aggressive treatment strategies,it is not a reliable indicator of disease persistence following surgical intervention.Further research is warranted to investigate additional factors influencing acromegaly treatment outcomes to enhance patient care.
基金Wu Jieping Medical Foundation,No.320.6750.2021-02-113.
文摘BACKGROUND Gastric neuroendocrine carcinomas(NECs)exhibit aggressive features,such as rapid growth,higher rate of metastasis,and a generally unfavorable prognosis compared to gastric adenocarcinoma.As a result,therapeutic options for NECs remain limited,contributing to the poor prognosis of patients.Immunotherapy has emerged as a promising treatment strategy and demonstrated the potential to partially improve the survival and prognosis of patients with NECs.Nevertheless,the unique clinical response termed pseudoprogression(PsP)has garnered considerable attention in the context of immunotherapy.CASE SUMMARY Presented here is a case of NEC recurrence five and a half months after radical gastric surgery.The 45-year-old male patient underwent combination treatment involving a PD-1 blocker and tyrosine kinase inhibitors and encountered two instances of PsP during treatment.The patient ultimately achieved a durable treatment response without altering his treatment regimens,resulting in a substantial therapeutic benefit.CONCLUSION This case report aimed to provide the authors’experience with the diagnosis of PsP and treatment strategies for PsP in ongoing immunotherapy.
文摘BACKGROUND Colonic neuroendocrine carcinomas(NECs)are highly malignant and invasive with poor prognosis.Long noncoding RNAs(LncRNAs)participate in the tumorigenesis and metastasis of multiple cancers AIM To detect the roles and mechanisms of lncRNA prostate cancer associated transcript 6(PCAT6)in the progression of colonic NEC.METHODS Human NEC and adjacent normal samples were collected for immunohistochemistry staining of CgA and real-time quantitative polymerase chain reaction(RT-qPCR)of PCAT6 mRNA level.Subcutaneous xenograft tumor model and lung metastasis model were established in nude mice.The lung tissues were stained by hematoxylin and eosin to assess pulmonary metastasis.The expression of epithelial-mesenchymal transition(EMT)-related markers and pathway-related genes was measured by RT-qPCR and western blotting.CD56 expression was assessed by immunofluorescence staining.The biological functions of PCAT6 were examined by cell counting kit-8,colony formation assays,Transwell assays and wound healing assays.The interaction between PCAT6 and its potential downstream target was verified by luciferase reporter assays.RESULTS LncRNA PCAT6 was upregulated in human NEC samples and LCC-18 cells,and its high expression was positively correlated with poor prognosis in patients with colonic NEC.Additionally,the expression of PCAT6 was positively associated with the proliferation,migration,invasion,and EMT of LCC-18 cells.Moreover,PCAT6 facilitated tumor growth,lung metastasis and EMT in xenografts.Mechanistically,PCAT6 promoted the activation of MAPK to enhance the EMT in colonic NEC by targeting miR-326.CONCLUSION In conclusion,lncRNA PCAT6 accelerates the process of colonic NEC by activating ERK/p38 MAPK signaling through targeting miR-326.These results might provide useful information for exploring the potential therapeutic targets in colonic NEC.
文摘In this article,we discussed the article by Zeng et al,published in a recent issue of the World Journal of Gastroenterology.The publication represents a significant advancement in the prognostic evaluation of rectal neuroendocrine neoplasms.The GATIS score is a single nomogram model that incorporates five key progno-stic factors:Tumor grade;T stage;tumor size;age;and the prognostic nutritional index.This innovation optimizes the prognostic process,delivering more accurate predictions of overall survival and progression-free survival compared to tradi-tional TNM staging and World Health Organization classification systems.The findings of the study were based on a retrospective analysis spanning 12 years and involving 1408 patients from 17 reference centers in China.In this editorial,we specifically examined the strengths and limitations of the study,the clinical implications of the GATIS score,and the questions arising from its conclusions.
文摘BACKGROUND Neuroendocrine tumors(NETs)are an important type of neoplastic disease of the digestive tract.There is little data on NETs originating from the pancreato-hepato-biliary region of the digestive tract in Pakistan.AIM To evaluate different types of pancreato-hepatobiliary NETs(PHB-NET)diagnosed with endoscopic ultrasound(EUS)and to identify factors associated with high-grade NETs.METHODS All patients diagnosed with PHB-NET through EUS-guided biopsy were included in the study.The site of origin,histology,and grade of PHB-NETs were noted and factors associated with high-grade lesions were analyzed.SPSS,version 20.0 was used for statistical analysis.RESULTS A total of 36 patients with PHB-NET were included.Males and females were equal in numbers,i.e.,18(50%)each.The mean age was 48±15.7 years with an age range of 17-70 years.The most common sites of origin of PHB-NET were:Pancreas 20(55.6%),porta hepatis mass 8(22.2%),perigastric mass 3(8.3%)and others 5(13.9%).The mean size of the PHB-NETs was 34.7±22.5 mm.Among pancreatic NETs,the most commonly affected areas were body 9,tail 5,and head 5.Only 4(11.1%)PHB-NETs were functioning,all of which were insulinomas originating from the body or tail of the pancreas.Two-thirds of PHB-NETs,24(66.6%),were benign(WHO grade I:19;grade 2:5)while one-third 12(33.3%)were neuroendocrine cancers(NEC)(WHO grade III).Histological types were large cell 17(47.2%),small cell 8(22.2%),mixed 1(2.8%),and undetermined 10(27.8%).Factors associated with NECs were age>40 years(P=0.016),extra-pancreatic origin of the lesion(P=0.014),and small cell histologic type(P<0.001).CONCLUSION The most common site of PHB-NET detected through EUS was the pancreas.Although most were benign,about one-third were high-grade cancers.Insulinoma was the most common functioning tumor.NECs were associated with advanced age,extra-pancreatic origin,and small-cell histology.
基金Supported by Chongqing Natural Science Foundation General Project,No.CSTB2023NSCQ-MSX0182 and No.CSTB2023NSCQMSX0252Clinical Research Special Project of The Second Affiliated Hospital of Army Medical University,No.2024 F022.
文摘BACKGROUND Liver metastases are very common in pancreatic neuroendocrine tumors(pNETs).When surgical resection is possible,it is typically associated with survival benefits in patients with pNET and liver metastases.Patient-derived organoids are a powerful preclinical platform that show great potential for predicting treatment response,and they have been increasingly applied in precision medicine and cancer research.CASE SUMMARY A 51-year-old man was admitted to the hospital with the chief complaint of in-termittent dull pain in the upper abdomen for over 3 years.Computerized to-mography showed multiple space-occupying lesions in the liver and a neoplasm in the pancreatic body.Pathological results suggested a grade 3 pancreas-derived hepatic neuroendocrine tumor.In combination with relevant examinations,the patient was diagnosed with pNET with liver metastases(grade 3).Transarterial chemoembolization was initially performed with oxaliplatin and 5-fluorouracil,after which the chemotherapy regimen was switched to liposomal irinotecan and cisplatin for a subsequent perfusion,guided by organoid-based drug sensitivity testing.Following interventional treatment,the tumor had decreased in size.However,due to poor treatment compliance and the patient’s preference for sur-INTRODUCTION Pancreatic neuroendocrine tumors(pNETs)are a rare and heterogeneous group of neoplasms arising from pancreatic islet cells,with variations in histology,clinical characteristics,and prognosis[1].They may present as non-infiltrative,slow-growing tumors,locally invasive tumors,or even rapidly metastasizing tumors[2].Most metastases localize to the liver,and approximately 28%-77%of patients with pNETs will experience liver metastases in their lifetime[3].Patients with liver metastases may be subjected to local complications such as biliary obstruction,liver insufficiency,and carcinoid syndrome.Additionally,liver metastases are a major risk factor for the prognosis of patients with pNETs[4].When feasible,surgical resection is significantly associated with the best long-term survival outcomes[5].Therefore,for patients with pNET liver metastases,comprehensive assessment and multidisciplinary approaches are required to determine the feasibility of surgical resection and the optimal treatment to improve the prognosis.Over the past decade,the advent of in vitro three-dimensional technologies including organoids has revolutionized the development of human cancer models.Patient-derived organoids(PDOs),an in vitro three-dimensional microstructure,can faithfully recapitulate the intricate spatial architecture and cell heterogeneity of the tissue,and simulate the biological behaviors and functions of parental tumors while preserving biological,genetic and molecular features[6,7].As a po-werful preclinical platform,PDOs have been increasingly applied in precision medicine and cancer research.Importantly,there is a significant association between the use of PDO-based drug sensitivity testing and clinical responses to chemotherapy,radiotherapy and targeted therapy in multiple cancer types[8-10].Although gastroenteropancreatic neuroendocrine neoplasm organoids have been confirmed to retain the pathohistological and functional phenotypes of parental tumors[7],their roles in the prediction of clinical outcomes have not been presented.Here,we report a case of pNET with liver metastases who successfully received surgical resection after personalized treatment guided by PDO-based drug sensitivity testing,resulting in a favorable prognosis.
文摘As a practicing anatomic pathologist specialized in urologic pathology,a vast difference may be observed between what pathologists designate as neuroendocrine(or small cell)carcinoma of the prostate,and what clinicians or basic scientists define as such.
文摘BACKGROUND Rectal neuroendocrine tumors(NETs)smaller than 10 mm and well-differentiated tumors are generally considered to have a low risk of lymph node and distant metastasis,making them suitable for endoscopic resection.In contrast,tumors≥20 mm in size typically require surgical resection.However,the optimal management of intermediate-sized(10-15 mm)rectal NETs remains controversial.AIM To compare the clinical outcomes of endoscopic resection of rectal NETs<1 cm and those 1-1.5 cm in size.METHODS A retrospective study was conducted on 1056 patients with rectal NETs treated at the Samsung Medical Center between January 2005 and June 2021.After propensity score matching(1:10)for age,sex,and type of endoscopic resection,225 patients with tumors<1 cm in size and 27 patients with tumors 1-1.5 cm in size were analyzed.RESULTS Surgical resection was more frequent in the 1-1.5 cm group(37.2%)than in the<1 cm group(10.7%)(P<0.01).Endoscopic submucosal dissection was also more commonly performed in the 1-1.5 cm group(48.1%vs 18.5%,P<0.01).Negative resection margins were achieved in 97.2%of the patients,with no significant difference between the groups(P=0.22).No lymphovascular invasion was observed.During a median follow-up of 54 months,no recurrence occurred in the 1-1.5 cm group,while one case of metachronous recurrence was noted in the<1 cm group(P=1.00).There was no significant difference in recurrence-free survival(P=0.48).CONCLUSION Endoscopic resection of 1-1.5 cm grade 1 rectal NETs yielded comparable outcomes to those<1 cm in size,suggesting its feasibility as a treatment.
