第一部分  G1级和G2级胃神经内分泌肿瘤的内镜联合血清学诊断策略及内镜下治疗疗效分析

目的：G1、G2级的胃神经内分泌肿瘤（G-NENs）大多数是体积较小的无功能性肿瘤。单纯胃镜筛查结合组织病理检查的诊断方法往往敏感性、特异性或准确率都不高，并存在较大的主观性。内镜下治疗技术，包括内镜下黏膜切除术（EMR）和内镜下黏膜剥离术（ESD），已成为切除G1、G2级G-NENs的主流手术方式。目前对具体内镜下治疗术式的选择仍存在争议。因此，本研究旨在探讨G1、G2级G-NENs的内镜联合血清学诊断策略，评价EMR和ESD的安全性以及近期和远期疗效。

方法：本研究回顾性分析中国医学科学院肿瘤医院2011年1月至2023年10月住院行内镜下治疗的全部连续100例G-NENs患者的临床资料，比较倾向性评分匹配（PSM）前后EMR组与ESD组病灶的临床病理特征及近、远期疗效。

结果：本研究共纳入100例G-NENs患者，中位年龄54岁。29例术前完善了内镜联合血清学检查，其中血浆嗜铬粒蛋白A（CgA）异常升高24例（82.8%）。内镜联合血清学诊断策略对自身免疫性萎缩性胃炎的诊断准确率可达到100.0%（22/22）。本研究共纳入G-NENs病灶235个，ESD组84个，EMR组151个。ESD组病灶中位长径（5.0 mm，范围0.4～15.0 mm）大于EMR组（2.0 mm，范围0.1～15.0 mm；p＜0.001），ESD组病理分级为G2（23.8%，20/84）、浸润深度达黏膜下层（78.6%，66/84）、T分期为T2期（15.5%，13/84）的病变也均多于EMR组[分别为1.3%（2/151）、51.0%（77/151）和0.7%（1/151），均p＜0.001]。经过PSM两组成功匹配了49对病灶。PSM 后，ESD 组和 EMR 组的整块切除率[分别为 100.0%（49/49）和 100.0%（49/49）]、完整切除率[分别为93.9%（46/49）和100.0%（49/49）]和并发症发生率[分别为0（0/49）和4.1%（2/49）]差异均无统计学意义（均p＞0.05）。ESD组和EMR组所有病灶均未发现切除原部位的复发及远处转移。

结论：内镜联合血清学诊断策略可以提高对G1、G2级G-NENs及其背景黏膜的诊断准确率。内镜下切除手术（EMR和ESD）对于G1、G2级G-NENs来说是一种安全、有效的治疗方式。

【关键词】胃肿瘤、胃神经内分泌肿瘤、内镜联合血清学诊断、内镜下黏膜切除术、内镜下黏膜剥离术、疗效

第二部分  直肠神经内分泌肿瘤内镜下非治愈性切除的危险因素分析

目的：内镜技术是治疗直径＜20mm、分化良好（G1，G2）、仅侵犯黏膜层和黏膜下层，且无远处转移的直肠神经内分泌肿瘤（R-NETs）的主要手段。它可以取得与外科手术相当的疗效，具有手术时间和住院时间更短的优势。然而，内镜下手术存在非治愈性切除的情况，这不仅给患者带来经济上的损失，更是对患者生理及心理的又一次沉重打击。因此，本研究对内镜下治疗的R-NETs非治愈性切除的可能危险因素进行了分析，旨在为临床评估和预防提供参考依据，使患者最大程度获益。

方法：回顾性收集2010年8月至2023年6月期间在中国医学科学院肿瘤医院所有行内镜下治疗的R-NETs的患者数据。根据病灶是否达成治愈性切除，将病例分为两组。采用SPSS统计软件分析R-NETs非治愈性切除的可能危险因素。

结果：本研究共纳入535例R-NETs病例，其中男性321例，女性214例，单发病灶500例，多发病灶35例。总共有585个病灶。在病例为多发病例、病灶分级为G2级或病灶直径≥10mm时，内镜下非治愈性切除的风险更高。Logistic多因素回归分析显示，肿瘤分级G2级（OR=9.562，95%CI：3.019-30.290，p＜0.001）和肿瘤直径≥10mm（OR=8.774，95%CI：3.859-19.949，p＜0.001）是非治愈性切除的独立危险因素，二者也是脉管瘤栓（OR=6.471，95%CI：1.549-27.038，p=0.01；OR=6.684，95%CI：2.307-19.368，p＜0.001）和神经侵犯（OR=8.041，95%CI：1.366-47.335，p=0.021；OR=9.903，95%CI：2.461-39.852，p=0.001）的独立危险因素。肿瘤直径≥10mm（OR=7.307，95%CI：2.383-23.384，p=0.001）是垂直切缘阳性的独立危险因素。

结论：综上所述，肿瘤分级（G2）和肿瘤直径（≥10mm）是内镜下治疗R-NETs非治愈性切除的独立危险因素。

【关键词】结直肠肿瘤、直肠神经内分泌肿瘤、非治愈性切除、风险因素

第三部分  内镜下治疗十二指肠非壶腹部神经内分泌肿瘤的有效性及安全性分析

目的：十二指肠非壶腹部神经内分泌肿瘤（NAD-NETs）是一类罕见疾病。近年来，NAD-NETs的发病率呈上升趋势。对于直径≤10 mm、局限于黏膜层及黏膜下层且无淋巴结或远处转移的NAD-NETs，推荐行内镜下切除（ER）。主要包括EMR和ESD。然而，ER治疗NAD-NETs的有效性、安全性及预后仍不清楚。

方法：回顾性收集2011年11月至2021年4月期间在中国医学科学院肿瘤医院所有接受ER治疗的NAD-NETs患者的病例资料。统计分析整块切除率、完整切除率、病理完整切除率、并发症发生率及预后等临床结果。

结果：本研究共纳入12例NAD-NETs病例。2例行EMR治疗，10例行ESD治疗。EMR组2例均完成整块切除（100%），1例（50%）实现完整切除，1例（50%）实现病理完整切除，而ESD组这三项数据分别为90%（9/10）、80%（8/10）和80%（8/10）。ESD组有1例（10%）发生术中穿孔，两组均未出现延迟性穿孔、术中出血或迟发性出血。在中位随访时间65个月的随访期间内，所有患者均未发现病变残留、复发或远处转移。

结论：对于直径≤10 mm、局限于黏膜层及黏膜下层且无淋巴结或远处转移的NAD-NETs，ER（EMR和ESD）是一种安全、有效、可行的治疗方式。

【关键词】十二指肠肿瘤、十二指肠非壶腹部神经内分泌肿瘤、内镜下黏膜切除术、内镜下黏膜剥离术、疗效

Part 1  Endoscopic combined serological diagnostic strategies and endoscopic treatment efficacy analysis for G1 and G2 stage gastric neuroendocrine neoplasms

Background Most gastric neuroendocrine neoplasms (G-NENs) in stages G1 and G2 are typically small, non-functional tumors. Current diagnostic methods that involve a combination of simple gastroscopy screening and histopathological examination often exhibit low sensitivity, specificity, and accuracy, while also being highly subjective. Endoscopic treatment techniques, such as EMR and ESD, have emerged as the primary surgical approaches for resecting G1 and G2 stage G-NENs. However, the selection of specific endoscopic treatment methods remains a topic of debate. This study aims to investigate an endoscopic combined serological diagnosis strategy for G1 and G2 stage G-NENs, as well as assess the safety, short-term, and long-term efficacy of EMR and ESD.

Methods This study retrospectively analyzed the clinical data of 100 consecutive patients with G-NENs who underwent endoscopic treatment at the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2011 to October 2023. The study compared the EMR group before and after propensity score matching (PSM) with clinicopathological characteristics, as well as the short-term and long-term efficacy of lesions in the ESD group.

Results A total of 100 patients with G-NENs were included in this study, with a median age of 54 years. Prior to surgery, 29 cases underwent endoscopic combined serological examination, revealing that 24 cases (82.8%) had abnormally elevated plasma chromogranin A (CgA). The diagnostic accuracy of the endoscopic combined with serological diagnosis strategy for autoimmune atrophic gastritis was 100.0% (22/22). This study included a total of 235 G-NENs lesions, with 84 in the ESD group and 151 in the EMR group. Lesions in the ESD group had a median diameter of 5.0 mm (range 0.4-15.0 mm), which was larger than that in the EMR group (2.0 mm, range 0.1-15.0 mm; P0.05). No recurrence or distant metastasis at the original site of resection was observed in any lesions from the ESD or EMR group.

Conclusions The diagnostic accuracy of G1 and G2 stage G-NENs and their background mucosa can be improved by combining endoscopy with serology. Endoscopic resection surgeries (EMR and ESD) have been shown to be safe and effective treatments for G1 and G2 stage G-NENs.

Keywords Gastric tumors; gastric neuroendocrine neoplasms; endoscopy combined with serological diagnosis; EMR; ESD; efficacy

Part 2  Analysis of risk factors for non-curative endoscopic resection of rectal neuroendocrine tumors

Background Endoscopic technology is the primary approach for managing rectal neuroendocrine tumors (R-NETs) with a diameter of <20 mm, well-differentiated (G1, G2), limited to the mucosa and submucosa, and without distant metastasis. It can yield outcomes comparable to surgery, with the added benefits of shorter operation times and hospital stays. However, endoscopic procedures may result in non-curative resections, leading to financial losses and impacting patients both physically and psychologically. This study examines potential risk factors for non-curative resections of R-NETs treated with endoscopy, aiming to offer insights for clinical evaluation and prevention to enhance patient outcomes.

Methods The data of patients with R-NETs who underwent endoscopic treatment at the Cancer Hospital of the Chinese Academy of Medical Sciences from August 2010 to June 2023 were retrospectively collected. The cases were categorized into two groups based on whether the lesions were successfully resected. SPSS statistical software was utilized to analyze potential risk factors associated with non-curative resection of R-NETs.

Results A total of 535 cases of R-NETs were analyzed in this study, comprising 321 males and 214 females. Among these cases, 500 had single lesions while 35 had multiple lesions, resulting in a total of 585 lesions. Cases with multiple lesions graded as G2 or with a lesion diameter ≥10mm had a higher risk of endoscopic non-curative resection. Logistic multifactor regression analysis revealed that tumor grade G2 (OR=9.562, 95%CI: 3.019-30.290, p<0.001) and tumor diameter ≥10mm (OR=8.774, 95%CI: 3.859-19.949, p<0.001) were independent risk factors for non-curative resection. Additionally, vascular tumor thrombus (OR=6.471, 95%CI: 1.549-27.038, p=0.01; OR=6.684, 95%CI: 2.307-19.368, p<0.001) and nerve invasion (OR=8.041, 95%CI: 1.366-47.335, p=0.021; OR=9.903, 95%CI: 2.461-39.852, p=0.001) were also identified as independent risk factors. Furthermore, tumor diameter ≥10mm (OR=7.307, 95%CI: 2.383-23.384, p=0.001) was found to be an independent risk factor for positive vertical resection margins.

Conclusions In summary, tumor grade (G2) and tumor diameter (≥10 mm) are independent risk factors for non-curative resection of R-NETs under endoscopic treatment.

Keywords Colorectal tumors; rectal neuroendocrine tumors; non-curative resection; risk factors

Part 3  Treatment outcomes of endoscopic resection for nonampullary duodenal neuroendocrine tumors

Background The incidence rate of duodenal neuroendocrine tumors has been increasing in recent years. Endoscopic resection (EMR, ESD) is recommended for nonampullary duodenal neuroendocrine tumors (NAD-NETs) ≤10 mm in diameter that are confined to the submucosal layer and without lymph node or distant metastasis. However, the efficacy and safety of and indications for EMR/ESD remain unclear.

Methods Between November 2011 and April 2021, 12 NAD-NETs in 12 patients who underwent either EMR or ESD were analyzed retrospectively. The rates of en bloc resection, complete resection, pathologic complete resection, margin involvement, lymphovascular invasion, perineural invasion, complications and prognosis were determined during follow-up (median observation period 53.0 months).

Results EMR was performed for two tumors, and ESD was performed for 10 tumors. En bloc resection was performed for both tumors (100%) in the EMR group, and complete resection was achieved in one case (50%). Pathological complete resection was achieved in one case (50%), while in the ESD group, these three rates were 90% (9/10), 80% (8/10), and 80% (8/10), respectively. Intraoperative perforation occurred in one patient (10%) during ESD treatment, with no intraoperative or delayed bleeding in either group. Recurrence and distant metastasis were not observed during the mean follow-up period of 53.0 months (range 18–131 months).

Conclusions For nonampullary duodenal neuroendocrine tumors that measure ≤10 mm in size, are confined to the submucosal layer and have neither suspicious lymph nodes nor distant metastasis, ER (EMR and ESD) may be a safe, effective, and feasible endoscopic technique for removing them.

Keywords Duodenal tumors; nonampullary duodenal neuroendocrine tumors; EMR; ESD; efficacy