Objectives: Our aim was to investigate the clinical outcome of patients with well-differentiated gastric, duodenal, and rectal neuroendocrine tumors after treatment with incomplete endoscopic resection due to the finding of microscopic positive resection margins (R1). Methods: This is a retrospective analysis of consecutive patients with type 1 gastric, non-ampullary non-functioning duodenal, or rectal neuroendocrine neoplasms with positive R1 margins after endoscopic resection. The rate of tumor recurrence and progression-free survival were considered to be the study’s main endpoints. Statistical analysis was performed using MedCalc^® v.17 software and a p-value of <0.05 was considered significant. A Cox proportional-hazard regression was performed to identify risk factors for disease recurrence/progression. Results: After evaluating 110 patients, a total of 58 patients were included in the final analysis (15 gastric NENs, 12 duodenal NENs, and 31 rectal NENs). After evidence of endoscopic R1 resection had been gathered, 26 patients (44.8%) underwent an endoscopic/surgical extension of the previous resection. Tumor progression (all local recurrences) occurred in five out of fifty-eight patients (8.6%) with a median PFS of 36 months. There were no tumor-related deaths. G2 grading and the gastric primary tumor site were the only features significantly associated with the risk of recurrence of the disease (HR: 11.97 [95% CI: 1.22–116.99], HR: 12.54 [95% CI: 1.28–122.24], respectively). Conclusions: Tumor progression rarely occurs in patients with microscopic positive margin excision (R1) after endoscopic resection and does not seem to affect patients’ clinical outcomes.

Background: Neuroendocrine neoplasms (NENs) are slow-growing tumors. Sarcopenia is defined as the loss of muscle mass, strength, and physical performance. First-line NEN therapy is somatostatin analogs, which could be responsible for malabsorption conditions, such as pancreatic exocrine insufficiency (EPI) with underlying sarcopenia. Aim: Evaluate the prevalence of sarcopenia in patients with NENs at diagnosis and during follow-up. Methods: A retrospective single-center study was conducted, including patients with advanced intestinal NENs G1/G2 (excluded pancreatic NENs). CT scans were analyzed at diagnosis and after 6 months of therapy, and the skeletal muscle index was assessed. Results: A total of 30 patients (F:M = 6:24) were enrolled, with the following primary tumor sites: 25 in the ileum, 1 stomach, 2 jejunum, and 2 duodenum. At diagnosis, 20 patients (66.6%) showed sarcopenic SMI values, and 10 patients (33.3%) showed non-sarcopenic SMI values. At follow-up, three more patients developed sarcopenic SMI values. Statistical significance in relation to the presence of sarcopenia was found in the group of patients with carcinoid syndrome (p = 0.0178), EPI (p = 0.0018), and weight loss (p = 0.0001). Conclusion: Sarcopenia was present in 2/3 of the patients with advanced intestinal NENs at the diagnosis and during the follow-up. It is reasonable to consider this condition to improve clinical outcomes.

Type 1 gastric neuroendocrine tumors (T1-gNETs) are typically indolent. Current guidelines suggest endoscopic surveillance for lesions ≤10 mm, mainly based on expert consensus. To evaluate outcomes in patients with T1-gNETs ≤10 mm managed by endoscopic surveillance. This dual-center retrospective study (2000-2023) included patients from two Western ENETS Centers of Excellence with T1-gNETs ≤10 mm under surveillance. Primary endpoints were disease progression rate and progression-free survival (PFS); p < 0.05 was considered significant. A total of 125 patients (66.4 % female; median age 59.5 years) with a median tumor size of 3 mm were analyzed. Most tumors were G1 (92.8 %), and 75.2 % had ≤5 lesions. Over a median follow-up of 72 months, progression occurred in 5 patients (4 %), with no metastases. Low-grade dysplasia was found in 2.4 % and early gastric cancer in 1.6 %. Eleven patients (8.8 %) died, none from tumor-related causes. Restricted mean survival time was 266.5 months. The 5-year PFS rate was 97.8 %. Having ≤5 lesions was significantly associated with lower progression risk (HR = 0.14, 95 % CI: 0.014-0.76, p = 0.022). T1-gNETs ≤10 mm show low progression risk and can be safely managed with lifelong surveillance. In patients with solitary or few lesions, extended intervals may be appropriate.

INTRODUCTION: Type 1 gastric neuroendocrine tumors (T1g-NETs) are well-differentiated lesions with excellent survival but frequent recurrence. Tumor size is the main prognostic factor, yet optimal management for tumors >1 cm remains uncertain. This study aimed to evaluate treatment strategies and outcomes in patients with T1g-NETs>1 cm. METHODS: We conducted a retrospective multicenter study including 106 adults with T1g-NETs >1 cm. Clinicopathologic and management data were collected. The primary outcome event was a composite unfavorable outcome, defined as recurrence or progression, used to analyze progression-free survival (PFS) as the main time-to-event outcome. Analyses included multinomial logistic regression, Cox models, and Kaplan–Meier curves ( P < 0.05). RESULTS: Among 106 patients (58.5% female; median age 59), median tumor size was 15 mm. Most tumors were Grade 1 (61.4%) or Grade 2 (37.7%), with median Ki-67 of 2%. Endoscopic resection was performed in 76 patients (71.7%), surgery in 33 (31.1%, including 13 initially treated endoscopically), and 10 (9.4%) were surveilled. Over a median 61-month follow-up, 24 patients (22.6%) recurred, 8 (7.5%) progressed; only 2 deaths (1.9%) were tumor-related. Larger tumors were associated with unfavorable outcome ( P = 0.005), with lesions ≥24 mm predicting shorter PFS (hazard ratio 3.93; P < 0.001). Endoscopic submucosal dissection and modified-endoscopic mucosal resection were associated with a significantly longer PFS ( P = 0.004). R0 resection showed a borderline protective effect. Five-year overall survival approached 95%. DISCUSSION: T1g-NETs > 1 cm frequently recur and may exhibit aggressive potential, particularly when lesions are larger. When endoscopic resection is feasible, endoscopic submucosal dissection or modified-endoscopic mucosal resection should be preferred to optimize outcomes.

Gastric neuroendocrine tumors (NETs) are increasingly diagnosed as incidental findings during upper gastrointestinal endoscopy. For the gastroenterologist, the crucial challenge is not only at the time of endoscopic recognition but also when the pathology report states “well-differentiated gastric NET”. At that moment, the key clinical question is how to manage it correctly. Gastric NETs are biologically heterogeneous, and their management depends primarily on the pathophysiological setting in which they arise. Type 1 tumors develop in chronic atrophic gastritis and are usually indolent; type 2 tumors arise in the context of gastrinoma and MEN1; type 3 tumors are sporadic and carry a substantially higher metastatic risk. Consequently, the same histological label may correspond to profoundly different clinical scenarios. This review addresses what the gastroenterologist should do after receiving an incidental histological diagnosis of gastric NET, how to reconstruct the gastric background, when to suspect a sporadic type 3 lesion, how to select patients for endoscopic treatment versus staging or surgery, and how to interpret incomplete endoscopic resection. Particular attention is devoted to the emerging concept of proton pump inhibitor-associated gastric NETs, which may represent a distinct gastrin-driven subgroup with lower malignant potential than truly sporadic type 3 tumors. A practical algorithm and a clinicopathological comparison of the classic three gastric NET types are provided to support decision-making in daily practice.