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.

New insights in diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms

Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)are rare epithelial neoplasms derived from pluripotent endocrine cells along the gastrointestinal tract and pancreas.GEP-NENs are classified into well-differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas.Despite overlapping morphological features,GEP-NENs vary in molecular biology,epigenetic,clinical behavior,treatment response,and prognosis features and remain an unmet clinical challenge.In this review,we introduce recent updates on the histopathologic classification,including the tumor grading and staging system,molecular genetics,and systemic evaluation of the diagnosis and treatment of GEP-NENs at different anatomic sites,together with some insights into the diagnosis of challenging and unusual cases.We also discuss the application of novel therapeutic approaches for GEP-NENs,including peptide receptor radionuclide therapy,targeted therapy,and immunotherapy with immune checkpoint inhibitors.These findings will help improve patient care with precise diagnosis and individualized treatment of patients with GEP-NENs.

Gastroenteropancreatic neuroendocrine neoplasms:A clinical snapshot

Our understanding about the epidemiological aspects,pathogenesis,molecular diagnosis,and targeted therapies of neuroendocrine neoplasms(NENs)have drastically advanced in the past decade.Gastroenteropancreatic(GEP)NENs originate from the enteroendocrine cells of the embryonic gut which share common endocrine and neural differentiation factors.Most NENs are welldifferentiated,and slow growing.Specific neuroendocrine biomarkers that are used in the diagnosis of functional NENs include insulin,glucagon,vasoactive intestinal polypeptide,gastrin,somatostatin,adrenocorticotropin,growth hormone releasing hormone,parathyroid hormone-related peptide,serotonin,histamine,and 5-hydroxy indole acetic acid(5-HIAA).Biomarkers such as pancreatic polypeptide,human chorionic gonadotrophin subunits,neurotensin,ghrelin,and calcitonin are used in the diagnosis of non-functional NENs.5-HIAA levels correlate with tumour burden,prognosis and development of carcinoid heart disease and mesenteric fibrosis,however several diseases,medications and edible products can falsely elevate the 5-HIAA levels.Organ-specific transcription factors are useful in the differential diagnosis of metastasis from an unknown primary of well-differentiated NENs.Emerging novel biomarkers include circulating tumour cells,circulating tumour DNA,circulating micro-RNAs,and neuroendocrine neoplasms test(NETest)(simultaneous measurement of 51 neuroendocrine-specific marker genes in the peripheral blood).NETest has high sensitivity(85%-98%)and specificity(93%-97%)for the detection of gastrointestinal NENs,and is useful for monitoring treatment response,recurrence,and prognosis.In terms of management,surgery,radiofrequency ablation,symptom control with medications,chemotherapy and molecular targeted therapies are all considered as options.Surgery is the mainstay of treatment,but depends on factors including age of the individual,location,stage,grade,functional status,and the heredity of the tumour(sporadic vs inherited).Medical management is helpful to alleviate the symptoms,manage inoperable lesions,suppress postoperative tumour growth,and manage recurrences.Several molecular-targeted therapies are considered second line to somatostatin analogues.This review is a clinical update on the pathophysiological aspects,diagnostic algorithm,and management of GEP NENs.

Current updates and future directions in diagnosis and management of gastroenteropancreatic neuroendocrine neoplasms

Gastroenteropancreatic neuroendocrine neoplasms are a heterogenous group of rare neoplasms that are increasingly being discovered,often incidentally,throughout the gastrointestinal tract with varying degrees of activity and malignant potential.Confusing nomenclature has added to the complexity of managing these lesions.The term carcinoid tumor and embryonic classification have been replaced with gastroenteropancreatic neuroendocrine neoplasm,which includes gastrointestinal neuroendocrine and pancreatic neuroendocrine neoplasms.A comprehensive multidisciplinary approach is important for clinicians to diagnose,stage and manage these lesions.While histological diagnosis is the gold standard,recent advancements in endoscopy,conventional imaging,functional imaging,and serum biomarkers complement histology for tailoring specific treatment options.In light of developing technology,our review sets out to characterize diagnostic and therapeutic advancements for managing gastroenteropancreatic neuroendocrine tumors,including innovations in radiolabeled peptide imaging,circulating biomarkers,and endoscopic treatment approaches adapted to different locations throughout the gastrointestinal system.

Therapeutic strategies for gastroenteropancreatic neuroendocrine neoplasms: State-of-the-art and future perspectives

Although gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)have always been considered rare tumors,their incidence has risen over the past few decades.They represent a highly heterogeneous group of neoplasms with several prognostic factors,including disease stage,proliferative index(Ki67),and tumor differentiation.Most of these neoplasms express somatostatin receptors on the cell surface,a feature that has important implications in terms of prognosis,diagnosis,and therapy.Although International Guidelines propose algorithms aimed at guiding therapeutic strategies,GEP-NEN patients are still very different from one another,and the need for personalized treatment continues to increase.Radical surgery is always the best option when feasible;however,up to 80%of cases are metastatic upon diagnosis.Regarding medical treatments,as GEP-NENs are characterized by relatively long overall survival,multiple therapy lines are adopted during the lifetime of these patients,but the optimum sequence to be followed has never been clearly defined.Furthermore,although new molecular markers aimed at predicting the response to therapy,as well as prognostic scores,are currently being studied,their application is still far from being part of daily clinical practice.As they represent a complex disease,with therapeutic protocols that are not completely standardized,GEP-NENs require a multidisciplinary approach.This review will provide an overview of the available therapeutic options for GEP-NENs and attempts to clarify the possible approaches for the management of these patients and to discuss future perspectives in this field.

Role of surgical treatments in high-grade or advanced gastroenteropancreatic neuroendocrine neoplasms

Over the last 40 years,the incidence and prevalence of gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)have continued to increase.Compared to other epithelial neoplasms in the same organ,GEP-NENs exhibit indolent biological behavior,resulting in more chances to undergo surgery.However,the role of surgery in high-grade or advanced GEP-NENs is still controversial.Surgery is associated with survival improvement of well-differentiated highgrade GEP-NENs,whereas poorly differentiated GEP-NENs that may benefit from resection require careful selection based on Ki67 and other tissue biomarkers.Additionally,surgery also plays an important role in locally advanced and metastatic disease.For locally advanced GEP-NENs,isolated major vascular involvement is no longer an absolute contraindication.In the setting of metastatic GEP-NENs,radical intended surgery is recommended for patients with low-grade and resectable metastases.For unresectable metastatic disease,a variety of surgical approaches,including cytoreduction of liver metastasis,liver transplantation,and surgery after neoadjuvant treatment,show survival benefits.Primary tumor resection in GEP-NENs with unresectable metastatic disease is associated with symptom control,prolonged survival,and improved sensitivity toward systemic therapies.Although there is no established neoadjuvant or adjuvant strategy,increasing attention has been given to this emerging research area.Some studies have reported that neoadjuvant therapy effectively reduces tumor burden,improves the effectiveness of subsequent surgery,and decreases surgical complications.

Current status of surgical management of patients with gastroenteropancreatic neuroendocrine neoplasms

Neuroendocrine neoplasms(NENs)of the gastroenteropancreatic system are rare and heterogeneous tumours,yet with increasing prevalence.The most frequent primary sites are the small intestine,rectum,pancreas,and stomach.For a localized disease,surgical resection with local lymph nodes is usually curative with good overall and disease free survival.More complex situation is the treatment of locally advanced lesions,liver metastases,and,surprisingly,small asymptomatic tumours of the rectum and pancreas.In this review,we focus on the current role of surgical management of gastroenteropancreatic NENs.We present surgical approach for the most frequent primary sites.We highlight the role of endoscopic surgery and the watch-and-wait strategy for selected cases.As liver metastases pose an important clinical challenge,we present current indications and contraindications for liver resection and a role of liver transplantation for metastatic NENs.

Clinicopathologic characteristics and prognosis of gastroenteropancreatic neuroendocrine neoplasms: a multicenter study in South China

Background: Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs) are a heterogeneous group of rare tumors. Many issues in terms of epidemiologic features, pathogenesis, and treatment of GEP-NENs are still under discussion. Our study aimed to analyze the clinicopathologic characteristics and prognosis of Chinese patients with GEP-NENs.Methods: Complete clinicopathologic data and survival information of 1183 patients with GEP-NENs treated between 2005 and 2015 were collected from five medical centers in Guangdong Province, China. Patient survival was estimated using the Kaplan–Meier method and analyzed using the log-rank test; prognostic factors were analyzed using the Cox proportional hazards model.Results: The most common tumor location was the rectum(37.4%), followed by the pancreas(28.1%), stomach(20.7%), small intestine(7.2%), appendix(3.4%), and colon(3.3%). After initial definitive diagnosis, 1016(85.9%) patients underwent surgery. The 1-, 3-, and 5-year overall survival(OS) rates for the entire cohort were 87.9%, 78.5%, and 72.8%, respectively. The 3-year OS rates of patients with G1, G2, and G3 tumors were 93.1%, 82.7%, and 43.1%, respectively(P < 0.001). The 3-year OS rates of patients with stage I, II, III, and IV tumors were 96.0%, 87.3%, 64.0%, and 46.8%, respectively(P < 0.001). Patients with distant metastasis who underwent palliative surgery had a longer survival than those who did not(P = 0.003). Similar survival benefits of palliative surgery were observed in patients with neuroendocrine tumor(P y, M category, and sur= 0.031) or neuroendocrine carcinoma(P gery were found to be independent prog= 0.046). In multivariate analysis, age, grade, N categornostic factors.Conclusions: Patients with GEP-NENs who are women, younger than 50 years old, have smaller tumor size, have lower tumor grade, have lower T/N/M category, and who undergo surgery can have potentially longer survival time. Our data showed that surgery can improve the prognosis of GEP-NEN patients with distant metastasis. However, randomized controlled trials need to be conducted to establish the optimal criteria for selecting patients to undergo surgery.

Clinicopathological features and survival analysis of gastroenteropancreatic neuroendocrine neoplasms: a retrospective study in a single center of China

Objective： To investigate the clinicopathological features, survival and prognostic factors for gastroenteropancreatic neuroendocrine neoplasms（GEP-NENs） in a Chinese population.Methods： We investigated 154 consecutive patients（88 males, 66 females; median age 56 years, age range 9-86 years） diagnosed with GEP-NENs between 2001 and 2013 at The Affiliated Hospital of Qingdao University. Demographic, clinical and pathological variables and survival data were retrieved.Results： The pancreas was the most common site of involvement（63/154, 40.9%）. Tumor size varied from 0.3 to 16.0 cm（median, 1.2 cm）. The patients were followed up for a median period of 22 months（range, 1-157 months）. The estimated 3- and 5-year overall survival（OS） rates for all patients were 84.0% and 81.9%, respectively. Multivariate analysis showed that larger tumor size, lymphatic metastases and distant metastases were significant predictors for poor survival outcome.Conclusions： Our data provide further information on the clinicopathological features of GEP-NENs in China. Additionally, we identified tumor size, lymphatic metastases and distant metastases as independent prognostic factors for long-term survival.

Utility of CT in differentiating liver metastases of well-differentiated gastroenteropancreatic neuroendocrine neoplasms from poorly-differentiated neuroendocrine neoplasms

Objective： To determine the capability of dynamic enhanced computed tomography（CT） to differentiate liver metastases（LMs） of well-differentiated from poorly-differentiated gastroenteropancreatic neuroendocrine neoplasms（GEP-NENs）.Methods： Patients with LMs of GEP-NENs who underwent dynamic enhanced CT examination in Peking University Cancer Hospital from January 2009 to October 2015 were included and data were retrospectively analyzed. We assessed the qualitative and quantitative CT features to identify the significant differentiating CT features of LMs of poorly-differentiated GEP-NENs from those of well-differentiated GEP-NENs using univariate analysis and a multivariate logistic regression model.Results： The study included 22 patients with LMs of well-differentiated GEP-NENs and 32 patients with LMs of poorly-differentiated GEP-NENs. Univariate analysis revealed statistically significant differences between the LMs of well-and poorly-differentiated GEP-NENs in terms of feeding arteries（36.4% vs. 75.0%, χ2=8.061,P=0.005）, intratumoral neovascularity（18.2% vs. 59.4%, χ2=9.047, P=0.003）, lymphadenopathy（27.3% vs. 81.2%,χ2=15.733, P〈0.001）, tumor-to-aortic ratio in the hepatic arterial and portal venous phase（T-A/AP： 0.297±0.080 vs.0.251±0.059, t=2.437, P=0.018; T-A/PVP： 0.639±0.138 vs. 0.529±0.117, t=3.163, P=0.003） and tumor-to-liver ratio in the hepatic arterial phase（T-L/AP： 1.108±0.267 vs. 0.907±0.240, t=2.882, P=0.006）. The LMs of poorlydifferentiated GEP-NENs showed more feeding arteries, more intratumoral neovascularity, more lymphadenopathy and a lower tumor-to-aortic ratio. Multivariate analysis suggested that intratumoral neovascularity [P=0.015, OR=0.108, 95% confidence interval（95% CI）, 0.018–0.646], lymphadenopathy（P=0.001,OR=0.055, 95% CI, 0.009–0.323） and T-A/PVP（P=0.004, OR=5.3 E–5, 95% CI, 0.000–0.044） were independent factors for differentiating LMs of poorly-differentiated from well-differentiated GEP-NENs.Conclusions： Dynamic enhanced CT features（intratumoral neovascularity, lymphadenopathy and T-A/PVP）are useful in the pathological classification of LMs of GEP-NENs.

Advances in the imaging of gastroenteropancreatic neuroendocrine neoplasms

Gastroenteropancreatic neuroendocrine neoplasms comprise a heterogeneous group of tumors that differ in their pathogenesis,hormonal syndromes produced,biological behavior and consequently,in their requirement for and/or response to specific chemotherapeutic agents and molecular targeted therapies.Various imaging techniques are available for functional and morphological evaluation of these neoplasms and the selection of investigations performed in each patient should be customized to the clinical question.Also,with the increased availability of cross sectional imaging,these neoplasms are increasingly being detected incidentally in routine radiology practice.This article is a review of the various imaging modalities currently used in the evaluation of neuroendocrine neoplasms,along with a discussion of the role of advanced imaging techniques and a glimpse into the newer imaging horizons,mostly in the research stage.

Diagnosis, treatment, and current concepts in the endoscopic management of gastroenteropancreatic neuroendocrine neoplasms

Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)are rare tumors derived from the neuroendocrine cell system,which that have increased in incidence and prevalence in recent years.Despite improvements in radiological and metabolic imaging,endoscopy still plays a pivotal role in the number of GEPNENs.Tumor detection,characterization,and staging are essential in management and treatment planning.Upper and lower gastrointestinal(GI)endoscopy is essential for correct localization of the primary tumor site of GI NENs.Endoscopic ultrasonography(EUS)has an important role in the imaging and tissue acquisition of pancreatic NENs and locoregional staging of GI neuroendocrine tumors.Correct staging and histological diagnosis have important prognostic implications.Endoscopic operating techniques allow the removal of small GI NENs in the early stage of mucosal or submucosal invasion of the intestinal wall.Preoperative EUS-guided techniques may help the surgeon locate small and deep tumors,thus avoiding formal pancreatic resections in favor of parenchymal-sparing surgery.Finally,locoregional ablative treatments have been proposed in recent studies with promising results in selected patients.

Clinicopathological features and prognostic factors associated with gastroenteropancreatic mixed neuroendocrine non-neuroendocrine neoplasms in Chinese patients

BACKGROUND The incidence of mixed neuroendocrine-non-neuroendocrine neoplasms(MiNEN)is low.To improve our understanding of this rare tumor type and optimally guide clinical treatment,associated risk factors,clinical manifestations,and prognosis must be explored.AIM To identify risk factors that influence the prognosis of patients with gastroenteropancreatic MiNEN(GEP-MiNEN).METHODS We retrospectively analyzed the clinical data of 46 patients who were diagnosed with GEP-MiNEN at the First Affiliated Hospital of Bengbu Medical College(Anhui,China)between January 2013 and December 2017.Risk factors influencing the prognosis of the patients were assessed using Kaplan-Meier curves and cox regression models.We compared the results with 55 randomly selected patients with gastroenteropancreatic GEP neuroendocrine tumors,47 with neuroendocrine carcinomas(NEC),and 58 with poorly differentiated adenocarcinoma.RESULTS Among the 46 patients with GEP-MiNEN,thirty-five had gastric tumors,nine had intestinal tumors(four in the small intestine and five in the colon and rectum),and two had pancreatic tumors.The median age of the patients was 66(41-84)years,and the male-to-female ratio was 2.83.Thirty-three(71.7%)patients had clinical stage III and IV cancers.Distant metastasis occurred in 14 patients,of which 13 had metastasis to the liver.The follow-up period was 11-72 mo,and the median overall survival was 30 mo.Ki-67 index≥50%,high proportion of NEC,lymph node involvement,distant metastasis,and higher clinical stage were independent risk factors affecting the prognosis of patients with GEP-MiNEN.The median overall survival was shorter for patients with NEC than for those with MiNEN(14 mo vs 30 mo,P=0.001),but did not significantly differ from those with poorly differentiated adenocarcinoma and MiNEN(30 mo vs 18 mo,P=0.453).CONCLUSION A poor prognosis is associated with rare,aggressive GEP-MiNEN.Ki-67 index,tumor composition,lymph node involvement,distant metastasis,and clinical stage are important factors for patient prognosis.

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.

GATIS score:An innovative prognostic score for rectal neuroendocrine neoplasms

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.

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.

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.

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

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

Evaluation of the GATIS score for predicting prognosis in rectal neuroendocrine neoplasms

The GATIS score,developed by Zeng et al,represents a significant advancement in predicting the prognosis of patients with rectal neuroendocrine neoplasms(RNENs).This study,which included 1408 patients from 17 major medical centres in China over 12 years,introduces a novel prognostic model based on the tumour grade,T stage,tumour size,age,and the prognostic nutritional index.Compared with traditional methods such as the World Health Organization classification and TNM staging systems,the GATIS score has superior predictive power for overall survival and progression-free survival.With a C-index of 0.915 in the training set and 0.812 in the external validation set,the GATIS score’s robustness and reliability are evident.The study’s use of a large,multi-centre cohort and rigorous validation processes underscore its significance.The GATIS score offers clinicians a powerful tool to accurately predict patient outcomes,guide treatment decisions,and improve follow-up strategies.This development represents a crucial step forwards in the management of R-NENs,addressing the complexity and variability of these tumours and setting a new benchmark for future research and clinical practice.

Different lymph node staging systems for predicting the prognosis of colorectal neuroendocrine neoplasms

BACKGROUND Colorectal neuroendocrine neoplasms(NENs)are a rare malignancy that primarily arises from the diffuse distribution of neuroendocrine cells in the colon and rectum.Previous studies have pointed out that the status of lymph node may be used to predict the prognosis.AIM To investigate the predictive values of lymph node ratio(LNR),positive lymph node(PLN),and log odds of PLNs(LODDS)staging systems on the prognosis of colorectal NENs treated surgically,and compare their predictive values.METHODS This cohort study included 895 patients with colorectal NENs treated surgically from the Surveillance,Epidemiology,and End Results database.The endpoint was mortality of patients with colorectal NENs treated surgically.X-tile software was utilized to identify most suitable thresholds for categorizing the LNR,PLN,and LODDS.Participants were selected in a random manner to form training and testing sets.The prognosis of surgically treating colorectal NENs was examined using multivariate cox analysis to assess the associations of LNR,PLN,and LODDS with the prognosis of colorectal NENs.C-index was used for assessing the predictive effectiveness.We conducted a subgroup analysis to explore the different lymph node staging systems’predictive values.RESULTS After adjusting all confounding factors,PLN,LNR and LODDS staging systems were linked with mortality in patients with colorectal NENs treated surgically(P<0.05).We found that LODDS staging had a higher prognostic value for patients with colorectal NENs treated surgically than PLN and LNR staging systems.Similar results were obtained in the different G staging subgroup analyses.Furthermore,the area under the receiver operating characteristic curve values for LODDS staging system remained consistently higher than those of PLN or LNR,even at the 1-,2-,3-,4-,5-and 6-year follow-up periods.CONCLUSION LNR,PLN,and LODDS were found to significantly predict the prognosis of patients with colorectal NENs treated surgically.