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Background and objective: Lateral pelvic lymph node (LPLN) metastasis is one of the prominent reasons for local recurrence in patients with rectal neuroendocrine tumors (RNETs). The evaluation criteria of lateral lymph node metastasis for patients and the indications and value of lateral pelvic lymph node dissection (LPLD) have been controversial. Total mesorectal excision (TME), a conventional surgical treatment for RNETs, excluding lateral lymph nodes, may be one of the reasons for postoperative local recurrence. This study aimed to analyze the risk factors for LPLN metastasis in patients with RNETs in order to guide surgical methods. Methods: We searched relevant databases (PubMed, Embase, Medline, Cochrane Library, and Web of Science) for articles published between 1 January 2000 and 1 April 2024 to evaluate the risk factors for LPLN metastasis in patients with RNETs in this meta-analysis. Results: A total of seven articles with 433 patients were included in this study. The overall results showed that a WHO grade > G1, tumor invasion of the muscularis propria or deeper, lymphovascular invasion (LVI), mesorectal lymph node metastasis (MLNM), and distant metastasis (M1) were significant risk factors for LPLN metastasis in patients with RNETs (P <0.05). Conclusion: This study identified key risk factors for LPLN metastasis in patients with RNETs, providing guidance for treatment strategies. A comprehensive evaluation of these risk factors and imaging findings is recommended to tailor personalized treatment strategies that optimize survival outcomes and improve quality of life. Systematic review registration: https://www.crd.york.ac.uk/prospero/ , identifier CRD42024581891. [ABSTRACT FROM AUTHOR]

Purpose: Lateral pelvic lymph node (LPLN) metastasis of rectal neuroendocrine tumors (NETs) is rare, with unknown oncological features. We investigated the oncological impact of LPLN metastasis in patients with rectal NETs. Methods: This study included 214 patients with rectal NETs who underwent curative surgery. We evaluated their clinicopathological characteristics and short- and long-term outcomes. Results: LPLN dissection was performed in 15 patients with LPLN swelling ≥ 7 mm (preoperative imaging); 12 patients had LPLN metastases, 6 of whom had LPLN metastases without mesorectal lymph node metastases (skip metastasis). The short-term outcomes were similar between the groups with and without LPLN dissection. The median follow-up period was 59.4 months, and patients with LPLN metastasis showed significantly shorter disease-free and overall survival rates than those without metastasis. Among 199 patients who did not undergo LPLN dissection, only 1 had LPLN recurrence. In a univariate analysis, tumor depth, tumor grade, and LPLN metastasis were associated with the overall survival. In the multivariate analysis, only LPLN metastasis was an independent predictor of the overall survival. Conclusions: LPLN metastasis is a poor prognostic factor for patients with rectal NETs. LPLN enlargement can be considered an indication for dissection, owing to its high rate of metastasis and associated poor prognosis. [ABSTRACT FROM AUTHOR]

Background: Endoscopic submucosal dissection (ESD) is a safe and effective technique for the treatment of gastrointestinal tumors, including rectal neuroendocrine tumors (r-NETs). However, the relative advantages of traction-assisted ESD for the treatment of small rectal lesions are still debated. Aims: We conducted a study to compare the efficacy and safety of rubber band traction-assisted ESD (RBT-ESD) to conventional ESD (C-ESD). Methods: This study retrospectively analyzed consecutive patients with r-NET treated with ESD between October 2021 and October 2023. Our study assessed differences between the groups in the complete resection rate of lesions, muscular layer injury, surgical complications, operation time, resection speed, time to liquid diet, postoperative hospital stay, hospital cost, and recurrence rate. Results: A total of 119 patients with r-NETs participated in this study (RBT-ESD group, n = 27; C-ESD group, n = 92). The operation time in RBT-ESD group was shorter than in C-ESD group, but the difference was not statistically significant (16.0 min [9.0–22.0 min] vs. 18.0 min [13.3–27.0 min], P = 0.056). However, the resection speed was significantly faster in the RBT-ESD group (6.7 vs. 4.1 mm2/min, P = 0.005). Furthermore, the RBT-ESD group showed significantly less muscular layer injury (P = 0.047) and faster diet recovery (P = 0.035). No significant differences were observed in the complete resection rate, surgical complications, postoperative hospital stay, hospital cost, or recurrence rate between the two groups. Conclusion: For r-NETs of < 2 cm in size, the RBT method did not significantly shorten the operation time but resulted in faster resection speed, less muscular layer injury, and earlier postoperative recovery to a liquid diet. [ABSTRACT FROM AUTHOR]

Background and objectiveLateral pelvic lymph node (LPLN) metastasis is one of the prominent reasons for local recurrence in patients with rectal neuroendocrine tumors (RNETs). The evaluation criteria of lateral lymph node metastasis for patients and the indications and value of lateral pelvic lymph node dissection (LPLD) have been controversial. Total mesorectal excision (TME), a conventional surgical treatment for RNETs, excluding lateral lymph nodes, may be one of the reasons for postoperative local recurrence. This study aimed to analyze the risk factors for LPLN metastasis in patients with RNETs in order to guide surgical methods.MethodsWe searched relevant databases (PubMed, Embase, Medline, Cochrane Library, and Web of Science) for articles published between 1 January 2000 and 1 April 2024 to evaluate the risk factors for LPLN metastasis in patients with RNETs in this meta-analysis.ResultsA total of seven articles with 433 patients were included in this study. The overall results showed that a WHO grade > G1, tumor invasion of the muscularis propria or deeper, lymphovascular invasion (LVI), mesorectal lymph node metastasis (MLNM), and distant metastasis (M1) were significant risk factors for LPLN metastasis in patients with RNETs (P

This study was to evaluate and compare the efficacy and safety of endoscopic mucosal resection (EMR), clip-and-snare assisted endoscopic mucosal resection (CS-EMR), and endoscopic submucosal dissection (ESD) for the endoscopic resection of rectal NETs. A retrospective analysis was performed on 47 patients with rectal NETs who underwent endoscopic treatment in The Second Affiliated Hospital of Soochow University. Manifestations of clinic pathological characteristics, complications, procedure time and hospitalization costs were studied. The complete resection rates with CS-EMR and ESD were significantly higher than those with EMR (CS-EMR vs. EMR, p = 0.038; ESD vs. EMR, p = 0.04), but no significant difference was found between the CS-EMR and ESD groups (p = 0.383). The lateral margin was less distant in the CS-EMR group than in the ESD group and there was no difference with regard to vertical margin (lateral margin distance, 1500 ± 3125 vs.3000 ± 3000 μm; vertical margin distance, 400 ± 275 vs.500 ± 500 μm). Compared to ESD, CS-EMR required less operation time (p < 0.01) and money (p < 0.01) and reduced the length of hospital stays (p < 0.01). The CS-EMR technique is more effective and efficient than EMR for small rectal NETs. In addition, CS-EMR reduces procedure time, duration of post-procedure hospitalization and decreases patients' cost compared to ESD while ensuring sufficient vertical margin distances. [ABSTRACT FROM AUTHOR]

IntroductionThe identification of risk factors for regional lymph node (r-LN) metastasis in rectal neuroendocrine tumors (R-NETs) remains challenging. Our objective was to investigate the risk factors associated with patients diagnosed with R-NETs exhibiting r-LN metastasis.MethodsPatient information was obtained from the Surveillance, Epidemiology, and End Results (SEER) database, complemented by data from the West China Hospital (WCH) databases. The construction cohort comprised patients diagnosed with R-NETs from the SEER database, while cases from the WCH database were utilized as the validation cohort. A novel nomogram was developed to predict the probability of r-LN metastasis, employing a logistic regression model.ResultsUnivariate analysis identified four independent risk factors associated with poor r-LN metastasis: age (HR = 1.027, p < 0.05), grade (HR = 0.010, p < 0.05), T stage (HR = 0.010, p < 0.05), and tumor size (HR = 0.005, p < 0.05). These factors were selected as predictors for nomogram construction.DiscussionThe novel nomogram serves as a reliable tool for predicting the risk of r-LN metastasis, providing clinicians with valuable assistance in identifying high-risk patients and tailoring individualized treatments.

Abstract Background Rectal neuroendocrine tumors (RNETs) are often discovered on screening colonoscopy. Indications for staging and definitive resection are inconsistent in current guidelines. We evaluated the role of grade in guiding staging and procedural decision-making. Methods Patients with biopsy confirmed RNETs between 2004 and 2015 were reviewed. Baseline characteristics, staging investigations (biochemical and imaging), and endoscopic/surgical treatment were recorded. Associations between grade, preoperative staging, interventions, and survival were determined using Fisher-Freeman-Halton Exact, log-rank, and Kaplan-Meier analysis. Results Amongst 139 patients with RNETs, 9% were aged ≥ 75 years and 44% female. Tumor grade was: 73% grade 1 (G1), 18%, grade 2 (G2) and 9% grade 3 (G3). Staging investigations were performed in 52% of patients. All serum chromogranin A and 97% of 24-hour urine 5-hydroxyindoleacetic acid tests were normal. The large majority of staging computed tomography (CT) scans were negative (76%) with subgroup analysis showing no G1 patients with CT identified distant disease compared with 38% of G2 and 50% of G3 patients (p

Conventional endoscopic mucosal resection (cEMR), EMR with a transparent cap, EMR using a ligation device (EMR-L), EMR after circumferential precutting (EMR-P), and endoscopic submucosal dissection (ESD) have been used for resecting rectal neuroendocrine tumors (r-NETs). However, there is no consensus regarding which is the best treatment. This study aimed to compare the outcomes of the aforementioned 5 techniques for resecting r-NETs by network meta-analysis. Electronic databases (PubMed, Cochrane Library, Embase, Ovid Medline, and Web of Science) were systematically searched to include relevant studies published from inception to September 1, 2023. The en bloc resection rate, histologic complete resection rate, positive lateral margin rate, positive vertical margin rate, adverse events rate, and procedure time were compared. A total of 27 studies with a total of 2112 r-NETs were included, and the mean diameter of tumors was 6.24 mm. Pairwise meta-analysis showed that EMR-L and ESD had higher en bloc resection and histologic complete resection rates and lower positive vertical margin rate than those of cEMR in resecting r-NETs. Compared with ESD, EMR-L and EMR-P achieved similar resection rates and significantly shortened the procedure time without increasing adverse events. The network meta-analysis evaluated the surface under the cumulative ranking curves and revealed that EMR-L was the best modality for treating r-NETs considering the comprehensive results of the en bloc resection rate, histologic complete resection rate, positive lateral margin rate, positive vertical margin rate, adverse events rate, and procedure time. EMR-L should be recommended as the first-line endoscopic treatment for small r-NETs. [ABSTRACT FROM AUTHOR]

INTRODUCTION: When initial resection of rectal neuroendocrine tumors (r-NETs) is not R0, persistence of local residue could lead to disease recurrence. This study aimed to evaluate the interest of systematic resection of non-R0 r-NET scars. METHODS: Retrospective analysis of all the consecutive endoscopic revisions and resections of the scar after non-R0 resections of r-NETs. RESULTS: A total of 100 patients were included. Salvage endoscopic procedure using endoscopic submucosal dissection or endoscopic full-thickness resection showed an R0 rate of near 100%. Residual r-NET was found in 43% of cases. DISCUSSION: In case of non-R0 resected r-NET, systematic scar resection by endoscopic full-thickness resection or endoscopic submucosal dissection seems necessary. [ABSTRACT FROM AUTHOR]

Simple Summary: Prior data showed an increasing incidence of rectal neuroendocrine tumors (RNET) in the US. There are limited comprehensive recent data on RNET incidence and time-trends among demographic-specific populations. The aim of this study was to evaluate recent age-specific RNET incidence rates and time-trends in demographic- and tumor-specific populations, using the United States Cancer Statistics (USCS) data covering ~98% of the US population between 2001 and 2020. Our nationwide analysis including 59,846 patients diagnosed with RNET shows a significantly increasing incidence of RNET in younger adults. An age-specific comparative analysis showed a significantly greater increase in younger adults compared to older adults. A sex-specific analysis showed that the increase was mostly driven by younger women and by tumors diagnosed at an early stage. The age-specific difference in RNET incidence was noted in various races. A sensitivity analysis of microscopically confirmed RNET cases showed similar results to the overall analysis. Our study provides comprehensive epidemiological data aiming to guide further investigations on this emerging topic. Prior non-comparative data showed increasing incidence of rectal neuroendocrine tumors (RNET) in the US. We aimed to evaluate age-specific RNET incidence rates and time-trends in demographic- and tumor-specific populations. The RNET age-adjusted incidence rates were calculated from the United States Cancer Statistics (USCS) database between 2001 and 2020. The population was stratified by age into older ( ≥ 55 years) and younger adults (<55 years), as well as by sex and race. The tumors were categorized by their stage at diagnosis into early and late. The annual percentage change (APC) and average APC (AAPC) were estimated using joinpoint regression and Monte Carlo permutation analysis. Pairwise comparison assessed for parallelism and coincidence. There were 59,846 patients diagnosed with RNET between 2001 and 2020 (50.3% women). Overall, the RNET incidence rates during this period were increasing in younger but not older adults (AAPC = 3.12 vs. −1.10; AAPC difference = 4.22, p < 0.001), with non-identical non-parallel data (p-values < 0.001). While similar results were seen in men, a greater age-specific difference was noted in women (AAPC = 3.31 vs. −1.10; AAPC difference = 4.41, p = 0.003). The difference between younger and older adults was seen in non-Hispanic White (AAPC-difference = 4.89; p < 0.001) and non-Hispanic Black (AAPC-difference = 3.33; p = 0.03) patients, and, in most years, among Hispanic and Non-Hispanic Asian/Pacific Islander patients, and it was mostly driven by early-stage tumors (AAPC-difference = 3.93; p < 0.001). The nationwide data show a significantly increasing RNET incidence in younger adults, most notably in younger women and in early-stage tumors, seen in various races. Future studies should evaluate RNET risk factors and outcomes in demographic-specific populations. [ABSTRACT FROM AUTHOR]

The genetic characteristics of rectal neuroendocrine tumors (R-NETs) were poorly understood. Depicting the genetic characteristics may provide a biological basis for prognosis prediction and novel treatment development. Tissues of 18 R-NET patients were analyzed using whole-exome sequencing. The median tumor mutation burden (TMB) and microsatellite instability (MSI) were 1.15 Muts/MB (range, 0.03-23.28) and 0.36 (range, 0.00-10.97), respectively. Genes involved in P53 signaling, PI3K-AKT signaling, DNA damage repair, WNT signaling, etc. were frequently altered. Higher TMB (P = 0.078), higher CNV (P = 0.110), somatic mutation of CCDC168 (P = 0.049), HMCN1 (P = 0.040), MYO10 (P = 0.007), and amplification of ZC3H13 (P < 0.001) were associated with shorter OS. Potentially targetable gene alterations (PTGAs) were seen in 72% of the patients. FGFR1 amplification (22%) was the most common PTGA followed by BARD1 and BRCA2 mutation (each 17%). As for gene variations associated with th e efficacy of immune checkpoint blockade (ICB), FAT1 alteration (39%) and PTEN depletion (28%) were commonly observed. In conclusion, frequently altered oncogenic pathways might contribute to the development and progression of R-NETs. Gene alterations significantly associated with prognosis might be potential novel targets. Targeted therapy might be a promising strategy as targetable alterations were prevalent in R-NETs. FAT1 alteration and PTEN depletion might be the main genetic alterations influencing the response to ICB besides overall low TMB and MSI in R-NETs. [ABSTRACT FROM AUTHOR]

Simple Summary: Rectal neuroendocrine neoplasms are increasing in incidence due in part to increased use of colonoscopy for colon cancer screening. These lesions can be difficult to characterise by endoscopists and, therefore, may be removed using an inappropriate endoscopic technique. Rectal neuroendocrine tumours should be fully staged prior to resection and this will help determine the best endoscopic approach for removal. Post resection, some of these tumours require ongoing surveillance. This article provides a detailed review of current evidence available to optimise assessment and removal of these lesions and approaches to surveillance for patients with rectal neuroendocrine tumours. Rectal neuroendocrine neoplasms are increasing in incidence, in part due to increased endoscopic procedures being performed for bowel cancer screening. Whilst most of these lesions are low-grade well-differentiated neuroendocrine tumours, they can have a varied clinical behaviour. Frequently, these lesions are incorrectly characterised at endoscopy and, therefore, incompletely excised using standard polypectomy techniques. Furthermore, some cases are not fully staged prior to or post resection. In this article we discuss the endoscopic and surgical options available to improve the likelihood of achieving an R0 resection and the staging procedures that should be used in these NETs. We also review factors that may suggest a higher risk of nodal involvement or recurrence. This information may help determine whether endoscopic or surgical resection techniques should be considered. In cases of R1 resection we discuss the management options available and the long-term surveillance options and when these should be offered to patients. [ABSTRACT FROM AUTHOR]

Rectal neuroendocrine tumors (rNETs) are potentially malignant lesions. In our study, we aimed to retrospectively check whether the rectal neuroendocrine tumors were found in colonoscopy examinations carried out as a part of Polish colonoscopy screening program (PCSP). We retrospectively analyzed the colonoscopy and histopathological database of examinations conducted as a part of PCSP in our institution in the years 2005–2021. We also checked the method by which the tumor was removed, its characteristics based on photo documentations and followed up the patients. The 10568 colonoscopy examinations were performed in PCSP in the years 2005–2021. Seven patients with a mean age of 53 with rNETs (1 in every 1510 colonoscopy) were detected. The polyp mean size was 5 mm. All the lesions were well differentiated tumors. First half of the colonoscopy examinations was performed in the years 2005–2012 and in that time three rNETs were detected, four rNETs were detected in the years 2012–2021. Even despite their typical appearance the neuroendocrine origin was not suspected in majority of cases and all tumors, except one, were removed with improper method. One of the patients underwent transanal endoscopic microsurgery of the scar. All patients are disease free in median follow-up of 108 months. Rectal NETs are detected in the screening colonoscopy program. In majority of cases, they are not suspected by endoscopists on colonoscopy, but diagnosed after removal in histopathological examinations. There is a need of education of endoscopists in recognition and methods of treatment of rNETs. [ABSTRACT FROM AUTHOR]

Introduction: The incidence of rectal neuroendocrine tumors (r-NETs) is increasing, and most small r-NETs can be treated endoscopically. The optimal endoscopic approach is still debatable. Conventional endoscopic mucosal resection (EMR) leads to frequent incomplete resection. Endoscopic submucosal dissection (ESD) allows higher complete resection rates but is also associated with higher complication rates. According to some studies, cap-assisted EMR (EMR-C) is an effective and safe alternative for endoscopic resection of r-NETs. Aims: This study aimed to evaluate the efficacy and safety of EMR-C for r-NETs ≤10 mm without muscularis propria invasion or lymphovascular infiltration. Methods: Single-center prospective study including consecutive patients with r-NETs ≤10 mm without muscularis propria invasion or lymphovascular invasion confirmed by endoscopic ultrasound (EUS), submitted to EMR-C between January 2017 and September 2021. Demographic, endoscopic, histopathologic, and follow-up data were retrieved from medical records. Results: A total of 13 patients (male: 54%; n = 7) with a median age of 64 (interquartile range: 54–76) years were included. Most lesions were located at the lower rectum (69.2%, n = 9), and median lesion size was 6 (interquartile range: 4.5–7.5) mm. On EUS evaluation, 69.2% (n = 9) of tumors were limited to muscularis mucosa. EUS accuracy for the depth of invasion was 84.6%. We found a strong correlation between size measurements by histology and EUS (r = 0.83, p < 0.01). Overall, 15.4% (n = 2) were recurrent r-NETs and had been pretreated by conventional EMR. Resection was histologically complete in 92% (n = 12) of cases. Histologic analysis revealed grade 1 tumor in 76.9% (n = 10) of cases. Ki-67 index was inferior to 3% in 84.6% (n = 11) of cases. The median procedure time was 5 (interquartile range: 4–8) min. Only 1 case of intraprocedural bleeding was reported and was successfully controlled endoscopically. Follow-up was available in 92% (n = 12) of cases with a median follow-up of 6 (interquartile range: 12–24) months with no evidence of residual or recurrent lesion on endoscopic or EUS evaluation. Conclusion:EMR-C is fast, safe, and effective for resection of small r-NETs without high-risk features. EUS accurately assesses risk factors. Prospective comparative trials are needed to define the best endoscopic approach.

Abstract Objectives Endoscopic submucosal resection with band ligation (ESMR‐L) and endoscopic submucosal dissection (ESD) are both standard endoscopic resection methods for rectal neuroendocrine tumors (NETs)

Background The histologically complete resection (CR) rate of small rectal neuroendocrine tumors (RNETs) is unsatisfactory at the first endoscopy. Risk factors and clinical outcomes associated with incomplete resection (IR) have not been explicitly elucidated. This study aims to explore the relevant factors of IR. Methods This retrospective study reviewed patients with small RNETs (≤10 mm) in eight centers from January 2013 to December 2021. Clinicopathological characteristics and clinical outcomes were compared between the CR and IR groups, and the polypectomy and advanced treatment groups. Results Of the 326 patients included, 83 (25.5%) were diagnosed with IR. Polypectomy (odds ratio [OR]   =   16.86), a central depression (OR = 7.50), and treatment in the early period (OR = 2.60) were closely associated with IR. Further analysis revealed that an atypical hyperemic appearance (OR = 7.49) and treatment in the early period (OR = 2.54) were significantly associated with the inappropriate use of polypectomy (both P  <   0.05). In addition, a total of 265 (81.3%) were followed up with a median follow-up period of 30.9 months. No death, metastasis, or recurrence was found during the follow-up period. Conclusions Polypectomy, a central depression, and treatment in the early period were risk factors for IR. Further, an atypical hyperemic appearance and treatment in the early period were significant predisposing factors for inappropriate choice of polypectomy. For histologically incompletely resected small RNETs, follow-up may be a safe and feasible alternative to rigorous salvage therapy. [ABSTRACT FROM AUTHOR]

Background: The diagnosis and surgical strategy of lateral lymph node metastases of rectal neuroendocrine tumors are still controversial. At present, the major diagnostic means rely on imaging examinations, but will be affected by the size of lymph nodes leading to false negativity. We provide a new technique to determine lateral lymph node metastases during surgery. Clinical case: A 68-year-old man developed abdominal pain, bloating and fever for a month. Colonoscopy revealed the mass is 2.4 cm x 2.0 cm in size, with a wide stratum, poor mobility, and a rough but intact surface mucosa. Therefore, rectal neuroendocrine tumors (R-NET) were diagnosed. Multiple imaging methods, such as CT, octreotide imaging and endoscopic ultrasonography, have not found lateral lymph node metastases from rectal neuroendocrine tumors. But indocyanine green (ICG)-enhanced near-infrared fluorescence-guided imaging during surgery found left lateral lymph nodes metastases, which was proved by postoperative pathological examination. Conclusions: We believe that applying ICG-enhanced near-infrared fluorescence-guided imaging in laparoscope can improve the detection of positive LLNs in those R-NET patients who did not reveal LNM on imaging examinations. [ABSTRACT FROM AUTHOR]

Background: Stage 1 rectal neuroendocrine tumors (NETs) are best treated with endoscopic submucosal dissection (ESD) or transanal endoscopic microsurgery (TEM) for local resection., Aim: To investigate the safety and efficacy of ESD and TEM for local resection of stage 1 rectal NETs., Methods: This retrospective observational analysis included patients with clinical stage 1 rectal NETs (cT1N0M0, less than 20 mm) who underwent ESD or TEM. The ESD and TEM groups were matched to ensure that they had comparable lesion sizes, lesion locations, and pathological grades. We assessed the differences between groups in terms of en bloc resection rate, R0 resection rate, adverse event rate, recurrence rate, and hospital stay and cost., Results: Totally, 128 Lesions (ESD = 84; TEM = 44) were included, with 58 Lesions within the matched groups (ESD = 29; TEM = 29). Both the ESD and TEM groups had identical en bloc resection (100.0% vs 100.0%, P = 1.000), R0 resection (82.8% vs 96.6%, P = 0.194), adverse event (0.0% vs 6.9%, P = 0.491), and recurrence (0.0% vs 3.4%, P = 1.000) rates. Nevertheless, the median hospital stay [ESD: 5.5 (4.5-6.0) vs TEM: 10.0 (7.0-12.0) days; P < 0.001], and cost [ESD: 11.6 (9.8-12.6) vs TEM: 20.9 (17.0-25.1) kilo-China Yuan, P < 0.001] were remarkably shorter and less for ESD., Conclusion: Both ESD and TEM were well-tolerated and yielded favorable outcomes for the local removal of clinical stage 1 rectal NETs. ESD exhibits shorter hospital stay and fewer costs than TEM., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.)

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 development. 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., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article. Talal AH reports grant and research support from Gilead, Abbott Laboratories, Novo Nordisk, AstraZeneca, and Salix. Additionally, Talal AH serves on committees or as an advisor for Gilead, AbbVie, and Novo Nordisk., (©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.)

The gut microbiota plays a significant role in the initiation and progression of tumors, but its role in rectal neuroendocrine tumors (rNETs) remains unclear. Fecal samples were collected from 19 healthy individuals and 21 rNET patients,with the rNET cohort further divided into metastatic (rNETs-M) and non-metastatic (rNETs-nM) groups. Using metagenomic high-throughput sequencing, we analyzed the diversity, species composition, and functional characteristics of the gut microbiota. We applied a random forest model to identify potential microbial biomarkers for predicting rNET and specifically distinguishing rNETs-M cases. Alpha diversity analysis revealed that species diversity was lower in the rNETs group than in the control group. In contrast, the rNETs-M group exhibited higher species diversity than the rNETs-nM group. Beta diversity analysis demonstrated significant differences in community structure between the rNETs and control groups between the rNET-M and rNETs-nM groups. Notably, in the rNETs group, the abundance of potential pathogens such as Escherichia coli and Shigella was elevated.Furthermore, the rNETs-M group exhibited an increased abundance of potential pathogens such as Alistipes. KEGG enrichment analysis indicated that these distinct microbiota play a significant role in environmental information processing, genetic information processing, and metabolic pathways. Random forest analysis and ROC curve results identified Lachnospira pectinoschiza (AUC=0.885), Parasutterella muris (AUC=0.862), Sodaliphilus pleomorphus(AUC=0.956), Methylobacterium iners (AUC=0.971) as biomarkers with significant discriminatory value., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Abstract Background Transanal endoscopic microsurgery (TEM) has been accepted worldwide for the treatment of local rectal lesions. We aimed to assess the efficacy and safety of TEM in the treatment of rectal neuroendocrine tumors (RNET). Methods A retrospective study of patients who had undergone TEM for RNET at our institution between December 2006 and June 2019 was performed. Demographic and tumor characteristics, operative and pathological details, complications, anal function questionnaires, and follow-up data were included. Results A total of 144 patients was included. TEM was performed as primary excision in 54 patients, after endoscopic forceps biopsy in 57 patients, and after incomplete resection by endoscopic excision in 33 patients. The median size of all primary tumors was 0.6 cm (range, 0.3–2.0 cm), and the negative resection margin was achieved in 142 (98.6%) patients. Postoperative complications (referring to only bleeding) occurred in 3 (2.1%) patients and was successfully managed with conservative method. After a median follow-up of 75.5 months after surgery, 3 patients died of other causes, and 2 patients suffered metastasis. An anal function questionnaire was posted 24 months after TEM. Among the results, 3 (2.1%) patients complained of major low anterior resection syndrome (LARS), including 1 (0.7%) who suffered from complete incontinence, while 6 (4.2%) patients had minor LARS. Conclusions TEM has satisfying long-term outcomes and relatively low anal function disturbance as for the treatment of small RNET. TEM also acts as a preferred salvage treatment for incomplete endoscopic excision.

ABSTRACT BACKGROUND: A common site of neuroendocrine tumors (NETs) is the rectum. The technique most often used is endoscopic mucosal resection with saline injection. However, deep margins are often difficult to obtain because submucosal invasion is common. Underwater endoscopic mucosal resection (UEMR) is a technique in which the bowel lumen is filled with water rather than air, precluding the need for submucosal lifting. OBJECTIVE: This study aimed to evaluate the efficacy and safety of UEMR for removing small rectal neuroendocrine tumors (rNETs). METHODS: Retrospective study with patients who underwent UEMR in two centers. UEMR was performed using a standard colonoscope. No submucosal injection was performed. Board-certified pathologists conducted histopathologic assessment. RESULTS: UEMR for small rNET was performed on 11 patients (nine female) with a mean age of 55.8 years and 11 lesions (mean size 7 mm, range 3-12 mm). There were 9 (81%) patients with G1 rNET and two patients with G2, and all tumors invaded the submucosa with only one restricted to the mucosa. None case showed vascular or perineural invasion. All lesions were removed en bloc. Nine (81%) resections had free margins. Two patients had deep margin involvement; one had negative biopsies via endoscopic surveillance, and the other was lost to follow-up. No perforations or delayed bleeding occurred. CONCLUSION: UEMR appeared to be an effective and safe alternative for treatment of small rNETs without adverse events and with high en bloc and R0 resection rates. Further prospective studies are needed to compare available endoscopic interventions and to elucidate the most appropriate endoscopic technique for resection of rNETs.

Rectal neuroendocrine tumors (R-NETs) usually invade the submucosa, and so complete resection is difficult. The treatment of choice for R-NETs ≤10 mm in size is endoscopic resection, but there is still controversy concerning the best endoscopic method. This study evaluated the efficacy and safety of ligation-assisted endoscopic submucosal resection combined with endoscopic ultrasonography (ESMR-LUS) for treatment of R-NETs. We retrospectively analyzed the data of 101 patients with R-NETs ≤10 mm in size who underwent ESMR-LUS (n = 48) or conventional ligation-assisted endoscopic submucosal resection (ESMR-L; n = 53) between May 2019 and September 2021 at the 900th Hospital of Joint Logistics Support Force. Complete resection rate, pathological complete resection rate, procedure time, and adverse events were compared between the two groups of patients. The endoscopic complete resection rate was slightly higher in the ESMR-LUS group than in the ESMR-L group (100 vs. 96.2%, p =.496). The pathological complete resection rate was also slightly higher in the ESMR-LUS group (97.9 vs. 88.7%, p =.152), these findings, though statistically non-significant, have practical clinical significance. Margin involvement was less common in ESMR-LUS patients than in ESMR-L patients (1 vs. 6). Involvement of the lateral resection margin was found one patient in the ESMR-LUS group versus two patients in the ESMR-L group, and deep resection margin involvement in no patient in the ESMR-LUS group versus four patients in the ESMR-L group. Mean procedure time was longer in the ESMR-LUS group than in the ESMR-L group (11.08 ± 1.89 min vs. 9.38 ± 2.09 min, p =.061). Immediate bleeding occurred in two patients in the ESMR-LUS group vs. seven patients in the ESMR-L group. Two patients in the ESMR-L group also suffered perforation; both patients were successfully treated by endoscopy. ESMR-LUS appears to be a safe and effective technique for removal of small rectal NETs confined to the submucosal layer without metastasis. Further studies are warranted to compare the efficacy and safety of different methods. [ABSTRACT FROM AUTHOR]

The optimal surgical management for 10- to 20-mm rectal neuroendocrine tumors (RNET) is still a matter of debate. This study aimed to explore the optimal surgical approach for 10- to 20-mm RNET by comparing the outcomes between local excision and radical resection. We extracted clinicopathological information of 10- to 20-mm RNET from the Surveillance, Epidemiology, and End Results (SEER) database. The 1:2 propensity score matching (PSM) method was used to balance the imbalanced baseline covariates (P < 0.05) between the local excision group and radical resection group. A Cox proportional hazards model was used to identify the risk factors associated with cancer-specific survival (CSS) and overall survival (OS). A total of 531 RNET patients 10–20 mm in size were included. Patients receiving radical resection had larger tumor sizes (P < 0.001), higher T stages (P < 0.001), higher N stages (P < 0.001), higher M stages (P = 0.002) and higher grades (P = 0.041). For 10–20 mm RNET patients, radical resection had no survival benefit compared with local excision (CSS: HR = 2.048, 95% CI 0.553–7.576, P = 0.283; OS: HR = 1.090, 95% CI 0.535–2.219, P = 0.813). After 1:2 PSM, there was no significant difference between local excision and radical resection. Radical resection still had no survival benefit over local excision (CSS: HR = 0.449, 95% CI 0.050–4.022, P = 0.474; OS: HR = 1.408, 95% CI 0.488–4.061, P = 0.527). In a multivariate analysis of CSS, age > 60 years old (P = 0.005), tumour size 14–20 mm (P = 0.011) and M1 stage (P < 0.001) were identified as independent prognostic factors for worse CSS. In multivariate analysis of OS, age>60 years (P ＜0.001), male sex (P = 0.007), black race (P = 0.016), and T2/T3/T4 stage (P = 0.007) were significantly associated with worse OS. N stage was not an independent predictive factor for CSS and OS. This study revealed that for 10- to 20-mm RNET patients, there was no survival benefit for radical resection compared with local excision, which suggested that local excision may be an adequate treatment for these patients. [ABSTRACT FROM AUTHOR]

Abstract Background To compare the outcomes of modified endoscopic mucosal resection (m-EMR) and endoscopic submucosal dissection (ESD) for rectal neuroendocrine tumors (NETs) and evaluate the value of endoscopic morphology classification in endoscopic resection (ER). Methods Patients with rectal NET diameters less than 2 cm who were treated between April 2007 and January 2019 were enrolled. The endoscopic morphology of rectal NETs was classified based on the endoscopic views. Patients who underwent ESD and m-EMR were compared. Baseline characteristics as well as en bloc resection, complete resection, the procedure time, adverse events and the risk factors associated with incomplete resection were analyzed. Results A total of 429 patients with 449 rectal NETs were enrolled for the classification of endoscopic morphology and were classified into four types (Ia, IIb, II, and III). There were 79 patients in the m-EMR group and 259 patients in the ESD group before matching. Propensity score matching created 77 pairs between the two groups that were well balanced. The mean procedure time was significantly shorter for m-EMR than for ESD (9.1 ± 4.4 min vs 16.0 ± 7.9 min, P = 0.000). The rates of en bloc resection (98.7% vs 100%; P = 1.000), complete resection (90.9% vs 93.5%, P = 0.548) and adverse events (2.6% vs 2.6%, P = 1.000) were similar between the two groups. Univariate and multivariate analyses showed that histopathological grade and endoscopic morphology were associated with incomplete resection. Conclusion Both ESD and m-EMR are effective and safe for the treatment of rectal NETs. Endoscopic morphology should be considered along with histopathological grade for ER.

Background: Transanal endoscopic microsurgery (TEM) has been accepted worldwide for the treatment of local rectal lesions. We aimed to assess the efficacy and safety of TEM in the treatment of rectal neuroendocrine tumors (RNET). Methods: A retrospective study of patients who had undergone TEM for RNET at our institution between December 2006 and June 2019 was performed. Demographic and tumor characteristics, operative and pathological details, complications, anal function questionnaires, and follow-up data were included. Results: A total of 144 patients was included. TEM was performed as primary excision in 54 patients, after endoscopic forceps biopsy in 57 patients, and after incomplete resection by endoscopic excision in 33 patients. The median size of all primary tumors was 0.6 cm (range, 0.3–2.0 cm), and the negative resection margin was achieved in 142 (98.6%) patients. Postoperative complications (referring to only bleeding) occurred in 3 (2.1%) patients and was successfully managed with conservative method. After a median follow-up of 75.5 months after surgery, 3 patients died of other causes, and 2 patients suffered metastasis. An anal function questionnaire was posted 24 months after TEM. Among the results, 3 (2.1%) patients complained of major low anterior resection syndrome (LARS), including 1 (0.7%) who suffered from complete incontinence, while 6 (4.2%) patients had minor LARS. Conclusions: TEM has satisfying long-term outcomes and relatively low anal function disturbance as for the treatment of small RNET. TEM also acts as a preferred salvage treatment for incomplete endoscopic excision. [ABSTRACT FROM AUTHOR]

Background: There is no literature that mainly searched for rectal neuroendocrine tumor (rNET) using transanal minimal invasive surgery (TAMIS). We report our clinical experiences of TAMIS for rectal neuroendocrine tumors to evaluate the feasibility and safety. Methods: Between December 2010 and March 2020, the 25 consecutive patients with rectal neoplasma underwent the TAMIS procedure performed by single laparoscopic surgeon at the two hospitals. Of these, ten patients with rectal neuroendocrine tumors were reviewed retrospectively. The full-thickness excision down to the outer fatty tissues was completed using TAMIS technique. Clinicopathological findings, perioperative and postoperative complications were recorded. Results: TAMIS for small rNET was successfully completed in all cases. There were seven cases with a tumor size of less than 10 mm, and three cases with a tumor size between 10 and 15 mm. Six patients underwent the primary tumor excision; the remaining four patients underwent resection for the scar after endoscopic procedure. The median surgical duration was 80.5 (53–124) minutes and the median blood loss was 1 (1–12) ml. All removed tumors in the 6 primary excisions were diagnosed as neuroendocrine tumor G1. The margins of specimens were completely free in all cases. Among the four patients after endoscopic procedure, all had no histological evidence of residual tumor. The median length of hospital stay was 7 days postoperatively. There was no post-operative mortality or severe complication. The median length of observation was 54 months. No recurrence, no local or distant metastasis and no mortality of all patients were observed. Conclusions: TAMIS is safety and feasible procedure for small rNET. Further experience and clinical trials are needed to fully define the advantages, disadvantages, and indications of TAMIS for rNET. [ABSTRACT FROM AUTHOR]

Background: The number of patients diagnosed with rectal neuroendocrine tumors (R-NETs) is increasing year by year. An integrated survival predictive model is required to predict the prognosis of R-NETs. The present study is aimed at exploring epidemiological characteristics of R-NETs based on a retrospective study from the Surveillance, Epidemiology, and End Results (SEER) database and predicting survival of R-NETs with machine learning.Methods: Data of patients with R-NETs were extracted from the SEER database (2000–2017), and data were also retrospectively collected from a single medical center in China. The main outcome measure was the 5-year survival status. Risk factors affecting survival were analyzed by Cox regression analysis, and six common machine learning algorithms were chosen to build the predictive models. Data from the SEER database were divided into a training set and an internal validation set according to the year 2010 as a time point. Data from China were chosen as an external validation set. The best machine learning predictive model was compared with the American Joint Committee on Cancer (AJCC) seventh staging system to evaluate its predictive performance in the internal validation dataset and external validation dataset.Results: A total of 10,580 patients from the SEER database and 68 patients from a single medical center were included in the analysis. Age, gender, race, histologic type, tumor size, tumor number, summary stage, and surgical treatment were risk factors affecting survival status. After the adjustment of parameters and algorithms comparison, the predictive model using the eXtreme Gradient Boosting (XGBoost) algorithm had the best predictive performance in the training set [area under the curve (AUC) = 0.87, 95%CI: 0.86–0.88]. In the internal validation, the predictive ability of XGBoost was better than that of the AJCC seventh staging system (AUC: 0.90 vs. 0.78). In the external validation, the XGBoost predictive model (AUC = 0.89) performed better than the AJCC seventh staging system (AUC = 0.83).Conclusions: The XGBoost algorithm had better predictive power than the AJCC seventh staging system, which had a potential value of the clinical application.

BackgroundLymph node metastasis of rectal neuroendocrine tumors (RNETs) predicts poor prognosis. However, the assessment of lymph node metastasis remains a challenge. It has been reported that 68Ga-DOTANOC and 18F-FDG PET-CT scans could be employed in the work-up of rectal neuroendocrine tumors (RNETs). This study aimed to assess both tracers’ ability to identify primary tumors and lymph node (LN) metastasis in RNETs.MethodsA total of 537 patients with RNETs were enrolled from January 2014 to January 2021. Both 68Ga-DOTANOC and 18F-FDG PET-CT scans were used to evaluate primary tumors and LN group metastasis. PET images were evaluated through visual and semiquantitative assessment. Receiver Operating Characteristics (ROC) curve analysis was used to investigate the performance of SUVmax of 68Ga-DOTANOC and 18F-FDG PET in predicting LN group metastasis.ResultsFifty-two patients with preoperative 68Ga-DOTANOC with 18F-FDG PET-CT scans underwent endoscopic biopsy or dissection of the primary tumor, while 11 patients underwent rectal surgery together with regional LN dissection. For primary tumors, 68Ga-DOTANOC had a sensitivity of 89.58% and a positive predictive value (PPV) of 95.56% through visual assessment, while 18F-FDG PET-CT showed 77.08% sensitivity and 97.37% PPV. For the prediction of LN group metastasis, 68Ga-DOTANOC PET-CT had 77.78% sensitivity and 91.67% specificity, while 18F-FDG PET-CT had 38.89% sensitivity and 100% specificity according to visual assessment. The area under the ROC curves (AUC) for 68Ga-DOTANOC PET/CT was 0.852 (95%CI:0.723-0.981) with an optimal SUVmax cut-off value of 2.25, while the AUC for 18F-FDG PET were 0.664 (95%CI:0.415-0.799) with an optimal SUVmax cut-off value of 1.05.ConclusionsThis study showed that 68Ga-DOTANOC PET-CT was a promising tool for detecting LN metastasis in RNETs with high sensitivity and specificity in visual assessment and semiquantitative assessment, which was better than 18F-FDG PET-CT.

Background: Lymph node metastasis of rectal neuroendocrine tumors (RNETs) predicts poor prognosis. However, the assessment of lymph node metastasis remains a challenge. It has been reported that 68Ga-DOTANOC and 18F-FDG PET-CT scans could be employed in the work-up of rectal neuroendocrine tumors (RNETs). This study aimed to assess both tracers' ability to identify primary tumors and lymph node (LN) metastasis in RNETs. Methods: A total of 537 patients with RNETs were enrolled from January 2014 to January 2021. Both 68Ga-DOTANOC and 18F-FDG PET-CT scans were used to evaluate primary tumors and LN group metastasis. PET images were evaluated through visual and semiquantitative assessment. Receiver Operating Characteristics (ROC) curve analysis was used to investigate the performance of SUVmax of 68Ga-DOTANOC and 18F-FDG PET in predicting LN group metastasis. Results: Fifty-two patients with preoperative 68Ga-DOTANOC with 18F-FDG PET-CT scans underwent endoscopic biopsy or dissection of the primary tumor, while 11 patients underwent rectal surgery together with regional LN dissection. For primary tumors, 68Ga-DOTANOC had a sensitivity of 89.58% and a positive predictive value (PPV) of 95.56% through visual assessment, while 18F-FDG PET-CT showed 77.08% sensitivity and 97.37% PPV. For the prediction of LN group metastasis, 68Ga-DOTANOC PET-CT had 77.78% sensitivity and 91.67% specificity, while 18F-FDG PET-CT had 38.89% sensitivity and 100% specificity according to visual assessment. The area under the ROC curves (AUC) for 68Ga-DOTANOC PET/CT was 0.852 (95%CI:0.723-0.981) with an optimal SUVmax cut-off value of 2.25, while the AUC for 18F-FDG PET were 0.664 (95%CI:0.415-0.799) with an optimal SUVmax cut-off value of 1.05. Conclusions: This study showed that 68Ga-DOTANOC PET-CT was a promising tool for detecting LN metastasis in RNETs with high sensitivity and specificity in visual assessment and semiquantitative assessment, which was better than 18F-FDG PET-CT. [ABSTRACT FROM AUTHOR]

Background: This retrospective study aimed to identify key factors affecting the rate of complete resection for non-metastatic rectal neuroendocrine tumors (NETs) using both transanal local excision (TLE) and endoscopic submucosal dissection (ESD). Methods: Records in the past 10 years were retrieved, for a total of 95 patients diagnosed with non-metastatic rectal NETs sized between 10-20 mm. Treatment outcomes were first compared between TLE and ESD to identify significantly associated factors. Monofactor analysis was then performed between complete and local resections to identify risk factors, which were then subjected to a multivariable analysis to identify independent risk factors. Results: Treatment outcomes between TLE and ESD were significantly associated with depth of invasion (P=0.039) and complete/local resection (P=0.048). By monofactor analysis between complete and local resections, depth of invasion, tumor size, tumor stage and endoscopic manifestation were identified to be risk factors (P=0.014, 0.003, 0.002 and 0.028, respectively). In subsequent multivariable analysis, depth of invasion and tumor size were independent risk factors, with odds ratio of 18.838 and 37.223, and 95% confidence interval of 1.242-285.800 and 2.839-488.078, respectively. Conclusion: Depth of invasion and tumor size were independent risk factors that significantly affect the complete resection rate of 10-20 mm non-metastatic rectal NETs.

Background and Aim: Endoscopic resection is highly effective treatment option for rectal neuroendocrine tumors (NETs) as they usually present as small localized tumors. However, there are no well‐established surveillance strategies following endoscopic resection. We established our own protocol for the surveillance of rectal NETs after endoscopic resection since 2013. This study aimed to assess the outcome and to optimize the surveillance strategies after endoscopic resection. Methods: We retrospectively analyzed the data of patients with endoscopically treated rectal NETs between January 2013 and April 2018 at Samsung Medical Center. We analyzed 337 patients with a median follow‐up duration of 35.0 months (min–max: 12.0–88.3). Results: A total of 329 (97.6%) patients had tumors ≤ 1 cm in size, and eight (2.4%) patients had tumors > 1 cm in diameter. Synchronous rectal NETs were diagnosed in nine (2.7%) patients. Thirteen (3.9%) patients were identified as having positive resection margins. Regardless of the salvage treatment, none of these patients developed recurrence. Metachronous rectal NETs were diagnosed in nine (2.7%) patients. Metachronous lesions were associated with the number of synchronous lesions at initial diagnosis (P < 0.001, hazard ratio = 1.75, 95% confidence interval = 1.38–2.23). Extracolonic metastasis was not detected in this study. Conclusion: Although initial screening for detecting metastatic lesions using computed tomography is recommended, repeated imaging for detecting extracolonic recurrence was not necessary for small non‐metastatic rectal NETs. However, regular endoscopic follow‐up seems reasonable, especially in case of synchronous rectal NETs, for detecting metachronous rectal NETs. [ABSTRACT FROM AUTHOR]

Purpose: For rectal neuroendocrine tumors (NETs) ≤ 10 mm, endoscopic resection is a standard treatment. However, there is no consensus whether additional surgery should be performed for patients at risk of lymph node metastasis (LNM) after endoscopic resection. The purpose of this study was to analyze the results of endoscopic resection and additional surgery of rectal NETs, thereby clarify the characteristics of cases with LNM. Methods: This study was a multicenter retrospective cohort study conducted at 12 Japanese institutions. A total of 132 NETs ≤ 10 mm were analyzed regarding various therapeutic results. A comparative analysis was performed by dividing the cases into two groups that underwent additional surgery or not. Furthermore, the relationship between tumor size and LNM was examined. Results: The endoscopic treatments were 12 endoscopic mucosal resections (EMR), 58 endoscopic submucosal resections with ligation (ESMR-L), 29 precutting EMRs, and 33 endoscopic submucosal dissections (ESD). The R0 resection rates of EMR were 41.7%, and compared to this rate, other three treatments were 86.2% (p < 0.001), 86.2% (p = 0.005), and 97.0% (p < 0.001), respectively. There were 41 non-curative cases (31.1%), and 13 had undergone additional surgery. Then, LNM was observed in 4 of the 13 patients, with an overall rate of LNM of 3.0% (4/132). The rate of positive lymphatic invasion and the rate of LNM by tumor size ≤ 6 mm and 7–10 mm were 9.7 vs. 15.4% (p = 0.375) and 0 vs. 10.3% (p = 0.007). Conclusions: A multicenter study revealed the priority of each endoscopic resection and the low rate of LNM for rectal NETs ≤ 6 mm. [ABSTRACT FROM AUTHOR]

Background: To compare the outcomes of modified endoscopic mucosal resection (m-EMR) and endoscopic submucosal dissection (ESD) for rectal neuroendocrine tumors (NETs) and evaluate the value of endoscopic morphology classification in endoscopic resection (ER).Methods: Patients with rectal NET diameters less than 2 cm who were treated between April 2007 and January 2019 were enrolled. The endoscopic morphology of rectal NETs was classified based on the endoscopic views. Patients who underwent ESD and m-EMR were compared. Baseline characteristics as well as en bloc resection, complete resection, the procedure time, adverse events and the risk factors associated with incomplete resection were analyzed.Results: A total of 429 patients with 449 rectal NETs were enrolled for the classification of endoscopic morphology and were classified into four types (Ia, IIb, II, and III). There were 79 patients in the m-EMR group and 259 patients in the ESD group before matching. Propensity score matching created 77 pairs between the two groups that were well balanced. The mean procedure time was significantly shorter for m-EMR than for ESD (9.1 ± 4.4 min vs 16.0 ± 7.9 min, P = 0.000). The rates of en bloc resection (98.7% vs 100%; P = 1.000), complete resection (90.9% vs 93.5%, P = 0.548) and adverse events (2.6% vs 2.6%, P = 1.000) were similar between the two groups. Univariate and multivariate analyses showed that histopathological grade and endoscopic morphology were associated with incomplete resection.Conclusion: Both ESD and m-EMR are effective and safe for the treatment of rectal NETs. Endoscopic morphology should be considered along with histopathological grade for ER. [ABSTRACT FROM AUTHOR]

Abstract Rectal neuroendocrine tumor (RNET) lymphovascular invasion (LVI) is regarded as an important predictor of nodal metastasis after endoscopic resection (ER). However, little is known about the frequency of immunohistochemical detection of LVI in RNETs. This study was performed to establish the actual detection of LVI rate in RNETs ≤10 mm and to evaluate associated clinical outcomes. We retrospectively reviewed the records for 98 consecutive patients treated by ER with a total of 102 RNETs ≤10 mm. Tissue sections were labeled with hematoxylin–eosin (HE) stain, the D2‐40 monoclonal antibody to evaluate lymphatic invasion, and Elastica van Gieson (EVG) stain to detect venous invasion. LVI detection rate by HE versus immunohistochemical analysis was compared. Follow‐up findings and clinical outcomes were also evaluated for 91 patients who were followed for ≥12 months. Lymphatic and venous invasion were detected using HE staining alone in 6.9% and 3.9% of patients, respectively, whereas they were detected using D2‐40 and EVG staining in 20.6% and 47.1% of the patients, respectively. Thus, the LVI detection frequency using D2‐40 and EVG staining (56.9%) was significantly higher than with HE (8.8%). Two out of seven patients who required additional surgery had regional lymph node metastases. However, among the 84 patients who were followed up without surgery, no distant metastases or recurrences were detected. Compared with HE staining, immunohistochemical analysis significantly increased the frequency of LVI detection in RNETs ≤10 mm. However, the clinical impact of LVIs detected using immunohistochemical analysis remains unclear. Clarification of the actual role of LVI using immunohistochemical analysis requires a patient long‐term follow‐up and outcomes.

Introduction: The aim of the study was to analyze the clinicopathologic characteristics and prognostic factors of hindgut-rectal neuroendocrine neoplasms.Material and methods: The study included 38 patients with rectal neuroendocrine tumors who were treated at the Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland from February 2010 to December 2015. The clinicopathological data were retrospectively reviewed, extracted, analyzed, and patients were followed up to determine their survival status. Follow-up data were available for all 38 patients. Uni- and multivariate Cox regression analyses were performed to determine the prognostic factors significantly associated with overall survival.Results: The tumors occurred mostly in the middle and lower rectum, and the most typical symptoms experienced by patients were hematochezia and diarrhea. The median distance between the tumors and the anal edges was 4.7 ±1.3 cm, and the median diameter of the tumors was 0.9 ±1.2 cm. The major pathological types were neuroendocrine neoplasm G1 in 31 patients, and neuroendocrine neoplasm G2 in 7 patients. Tumor-node-metastasis (TNM) stages I, II, III and IV tumors accounted for 76.3% (29/38), 5.3% (2/38), 7.9% (3/38) and 10.5% (4/38) of patients, respectively. The main treatment method was transanal extended excision or endoscopic resection. The 1-, 3- and 5-year survival rates of the whole group of patients were 100%, 83.7%, and 75.3%, respectively.Conclusions: Univariate analysis showed that age (p = 0.022), tumor diameter (p < 0.001), histological type (p < 0.001), and TNM stage (p < 0.001) were all prognostic factors. [ABSTRACT FROM AUTHOR]

Introduction: The aim of the study was to introduce a new endoscopic technology, clip-and-snare assisted endoscopic submucosal resection (CS-ESMR), for treatment of rectal neuroendocrine tumors (NETs) and then to investigate the therapeutic value of CS-ESMR., Methods: In this retrospective study, 67 patients who underwent endoscopic treatment of rectal NETs from March 2017 to December 2021 were analyzed. According to the endoscopic resection methods (endoscopic mucosal resection [EMR], CS-ESMR, and endoscopic submucosal dissection [ESD]), the cases were divided into CS-ESMR group (27 cases), ESD group (31 cases), and EMR group (9 cases). The pathological R0 resection rate and the incidence of adverse events (bleeding and perforation) were compared among the three groups., Results: There was a significant difference about the pathological R0 resection between the CS-ESMR group and the EMR group and between the CS-ESMR group and the ESD group (both p < 0.05). Compared with ESD group, the procedure time, intraoperative bleeding, and the cost of CS-ESMR group are significantly decreased ( p < 0.001, p < 0.05, p < 0.001, respectively)., Conclusion: CS-ESMR may be a safe and effective treatment for rectal NETs with a diameter of less than 10 mm, without muscularis propria invasion and metastasis., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Rectal neuroendocrine tumors (RNETs) have become common in recent years and are good candidates for endoscopic resection (ER). To achieve clear resection margins, more advanced techniques such as endoscopic submucosal dissection, endoscopic submucosal resection with a ligation device, and cap-assisted endoscopic mucosal resection are available for ER. After ER, lymphovascular invasion (LVI) is regarded as an important predictor of nodal metastasis. Previous studies have shown that small RNETs with LVI were uncommon (0-8.3%). However, using immunohistochemical analysis, a recent study revealed the frequent occurrence of LVI in small RNETs in a systematic manner (46.7%). There is a possibility that the actual detection rate of LVI in small RNETs is not always evaluated accurately because of the limited detection sensitivity of conventional hematoxylin-eosin staining. In addition, the correlation between LVI detected using immunohistochemical analysis and the development of metastasis remains unclear. Further prospective studies are required to clarify the role of LVI detected using immunohistochemical analysis. [ABSTRACT FROM AUTHOR]

Objective:Endoscopic mucosal resection (EMR), including conventional EMR (c-EMR) and modified EMR (m-EMR), was applied to remove small rectal neuroendocrine tumors (NETs). We aim to evaluate treatment outcomes of endoscopic submucosal dissection (ESD), m-EMR and c-EMR for rectal NETs <16 mm. Methods:The PubMed, Cochrane Library and Elsevier Science Direct were searched to identify eligible articles. After quality assessment and data extraction, meta-analysis was performed. The main outcomes were complete resection rate, overall complication rate, procedure time and local recurrence rate. Results:Compared with c-EMR, ESD could achieve higher complete resection rate (OR = 4.38, 95%CI: 2.43–7.91,p < 0.00001) without increasing overall complication rates (OR = 2.21, 95%CI: 0.56–8.70,p = 0.25). However, ESD was more time-consuming than c-EMR (MD = 6.72, 95%CI: 5.84–7.60,p < 0.00001). Compared with m-EMR, ESD did not differ from m-EMR in complete resection and overall complication rates (OR = 0.80, 95%CI: 0.51–1.27,p = 0.34; OR = 1.91, 95%CI: 0.75–4.86,p = 0.18, respectively). However, ESD was more time-consuming than m-EMR (MD = 12.21, 95%CI: 7.78–16.64,p < 0.00001). Compared with c-EMR, m-EMR could achieve higher complete resection rate (OR = 4.23, 95%CI: 2.39–7.50,p < 0.00001) without increasing overall complication rate (OR = 1.07, 95%CI: 0.35–3.32,p = 0.90). Moreover, m-EMR was not time-consuming than c-EMR (MD = 2.01, 95%CI: −0.37–4.40,p= 0.10). The local recurrence rate was 0.84% (9/1067) during follow-up. Conclusions:Both ESD and m-EMR have great advantages over c-EMR in complete resection rate without increasing safety concern while m-EMR shares similar outcomes with ESD for rectal NETs <16 mm. The results should be confirmed by well-designed, multicenter, randomized controlled trials with large samples and long-term follow-ups from more countries. [ABSTRACT FROM PUBLISHER]

Rectal neuroendocrine tumor (RNET) lymphovascular invasion (LVI) is regarded as an important predictor of nodal metastasis after endoscopic resection (ER). However, little is known about the frequency of immunohistochemical detection of LVI in RNETs. This study was performed to establish the actual detection of LVI rate in RNETs ≤10 mm and to evaluate associated clinical outcomes. We retrospectively reviewed the records for 98 consecutive patients treated by ER with a total of 102 RNETs ≤10 mm. Tissue sections were labeled with hematoxylin-eosin (HE) stain, the D2-40 monoclonal antibody to evaluate lymphatic invasion, and Elastica van Gieson (EVG) stain to detect venous invasion. LVI detection rate by HE versus immunohistochemical analysis was compared. Follow-up findings and clinical outcomes were also evaluated for 91 patients who were followed for ≥12 months. Lymphatic and venous invasion were detected using HE staining alone in 6.9% and 3.9% of patients, respectively, whereas they were detected using D2-40 and EVG staining in 20.6% and 47.1% of the patients, respectively. Thus, the LVI detection frequency using D2-40 and EVG staining (56.9%) was significantly higher than with HE (8.8%). Two out of seven patients who required additional surgery had regional lymph node metastases. However, among the 84 patients who were followed up without surgery, no distant metastases or recurrences were detected. Compared with HE staining, immunohistochemical analysis significantly increased the frequency of LVI detection in RNETs ≤10 mm. However, the clinical impact of LVIs detected using immunohistochemical analysis remains unclear. Clarification of the actual role of LVI using immunohistochemical analysis requires a patient long-term follow-up and outcomes. [ABSTRACT FROM AUTHOR]

Clinically detected neuroendocrine neoplasms of the rectum have increased 10- to 30-fold in frequency over the past 45 years in Germany. Endoscopic ultrasonography is the method of choice for exact determination of the size of the tumor, depth of infiltration and detection of local lymph node metastases. Well-differentiated neuroendocrine tumors ≤ 10.0 mm in size that do not infiltrate the muscularis propria can be endoscopically resected. In the case of lymphatic or blood vessel invasion or spread to lymph nodes, surgical lymph node dissection is indicated. The management of well-differentiated, neuroendocrine rectal tumors 10.1-20 mm in size is still a matter of debate. Old age and multimorbidity favor a conservative endoscopic approach; however, in the case of fit young patients, surgical management has to be considered. For neuroendocrine rectal neoplasms ≥ 20 mm in size, the risk of metastatic spread increases to 60-80 % indicating that an endoscopic resection is not adequate. Due to the introduction of screening colonoscopy, neuroendocrine rectal tumors are nowadays diagnosed mostly at a prognostically favorable early stage. [ABSTRACT FROM AUTHOR]

Rectal neuroendocrine tumors (rNETs) measuring less than 10 mm in diameter are defined as small rNETs. Due to the low risk of distant invasion and metastasis, endoscopic treatments, including modified endoscopic mucosal resection, endoscopic submucosal dissection, and other transanal surgical procedures, are effective. This review article proposes a follow-up plan according to the size and histopathology of the tumor after operation., Competing Interests: Conflict-of-interest statement: There is no conflict of interest in this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The histologically complete resection (CR) rate of small rectal neuroendocrine tumors (RNETs) is unsatisfactory at the first endoscopy. Risk factors and clinical outcomes associated with incomplete resection (IR) have not been explicitly elucidated. This study aims to explore the relevant factors of IR., Methods: This retrospective study reviewed patients with small RNETs (≤10 mm) in eight centers from January 2013 to December 2021. Clinicopathological characteristics and clinical outcomes were compared between the CR and IR groups, and the polypectomy and advanced treatment groups., Results: Of the 326 patients included, 83 (25.5%) were diagnosed with IR. Polypectomy (odds ratio [OR]   =   16.86), a central depression (OR = 7.50), and treatment in the early period (OR = 2.60) were closely associated with IR. Further analysis revealed that an atypical hyperemic appearance (OR = 7.49) and treatment in the early period (OR = 2.54) were significantly associated with the inappropriate use of polypectomy (both P  <   0.05). In addition, a total of 265 (81.3%) were followed up with a median follow-up period of 30.9 months. No death, metastasis, or recurrence was found during the follow-up period., Conclusions: Polypectomy, a central depression, and treatment in the early period were risk factors for IR. Further, an atypical hyperemic appearance and treatment in the early period were significant predisposing factors for inappropriate choice of polypectomy. For histologically incompletely resected small RNETs, follow-up may be a safe and feasible alternative to rigorous salvage therapy., (© The Author(s) 2022. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University.)