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Purpose: Gastrinoma with Zollinger–Ellison syndrome (ZES) may occur sporadically (Sp) or as part of the inherited syndrome of multiple endocrine neoplasia 1 (MEN-1). Data comparing Sp and MEN-1/ZES are scanty. We aimed to identify and compare their clinical features. Methods: Consecutive patients with ZES were evaluated between 1992 and 2020 among a monocentric Italian patient cohort. Results: Of 76 MEN-1 patients, 41 had gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN), 18 of whom had ZES; of 320 Sp-GEP-NEN, 19 had Sp-ZES. MEN-1/ZES patients were younger (p = 0.035) and the primary MEN-1/ZES gastrinoma was smaller than Sp-ZES (p = 0.030). Liver metastases occurred in both groups, but only Sp-ZES developed extrahepatic metastases. 13 Sp-ZES and 8 MEN-1/ZES underwent surgery. 8 Sp-ZES and 7 MEN-1/ZES received somatostatin analogs (SSAs). Median overall survival (OS) was higher in MEN-1/ZES than in Sp-ZES (310 vs 168 months, p = 0.034). At univariate-logistic regression, age at diagnosis (p = 0.01, OR = 1.1), G3 grading (p = 0.003, OR = 21.3), Sp-ZES (p = 0.02, OR = 0.3) and presence of extrahepatic metastases (p = 0.001, OR = 7.2) showed a significant association with OS. At multivariate-COX-analysis, none of the variables resulted significantly related to OS. At univariate-logistic regression, age (p = 0.04, OR = 1.0), size (p = 0.039, OR = 1.0), G3 grade (p = 0.008, OR = 14.6) and extrahepatic metastases (p = 0.005, OR = 4.6) were independently associated with progression-free survival (PFS). In multivariate-COX-analysis, only extrahepatic metastases (p = 0.05, OR = 3.4) showed a significant association with PFS. Among SSAs-treated patients, MEN-1/ZES showed better PFS (p = 0.0227). After surgery, the median PFS was 126 and 96 months in MEN-1 and Sp, respectively. Conclusion: MEN-1/ZES patients generally show better OS and PFS than Sp-ZES as well as better SSAs response.

Rectal neuroendocrine neoplasms (r-NENs) are considered among the most frequent digestive NENs, together with small bowel NENs. Their incidence has increased over the past few years, and this is probably due to the widespread use of endoscopic screening for colorectal cancer and the advanced endoscopic procedures available nowadays. According to the current European Neuroendocrine Tumor Society (ENETS) guidelines, well-differentiated r-NENs smaller than 10 mm should be endoscopically removed in view of their low risk of local and distant invasion. R-NENs larger than 20 mm are candidates for surgical resection because of their high risk of distant spreading and the involvement of the muscularis propria. There is an area of uncertainty regarding tumors between 10 and 20 mm, in which the metastatic risk is intermediate and the endoscopic treatment can be challenging. Once removed, the indications for surveillance are scarce and poorly codified by international guidelines, therefore in this paper, a possible algorithm is proposed.

Purpose: Zollinger Ellison syndrome (ZES) is a rare syndrome caused by gastrin hypersecretion from a gastrinoma. Gastrinoma treatment has two goals: the control of acid hypersecretion and the control of tumor growth. While therapy for the syndrome is univocally based on proton pump inhibitors, the one for disease control is still debated. We here aimed at evaluating the role of somatostatin analogs (SSAs) in the control of tumor progression in a series of ZES patients. Methods: A retrospective analysis of a prospectively collected database of ZES patients, followed and managed from 1990 to 2019, was performed. The patients’ clinical, pathological, treatment, and follow-up data were analyzed. Data regarding SSAs therapy start, dosage, duration, and side effects were collected. Results: 33 patients with ZES were diagnosed. Fourteen patients (42%) had a grade 1 (G1) neuroendocrine neoplasm (NEN), five had G2 (15%), none had G3. Fifteen patients (45%) had metastatic disease. Overall, 12 (36%) underwent SSAs therapy. The median treatment duration was 36 months. Eight patients (67%) had a sustained response to SSAs, four (33%) showed an early progression, with a significant difference in terms of PFS between the patients with early and late progression (84 vs 2 months, p = 0.004). No differences in terms of OS and PFS were observed between the treated and non-treated patients, despite the proportion of metastatic patients was greater in the SSAs-treated group (75% vs 29% in the non-treated group, p = 0.01). Conclusion: Present data support the use of SSAs in ZES, considering that gastrinoma is mainly a well-differentiated low-grade tumor (G1 or G2), with a high expression of somatostatin receptors.

Short bowel syndrome (SBS) is a rare malabsorptive disorder as a result of the loss of bowel mass mostly secondary to surgical resection of the small intestine. Other causes are vascular diseases, neoplasms or inflammatory bowel disease. The spectrum of the disease is widely variable from single micronutrient malabsorption to complete intestinal failure, depending on the remaining length of the small intestine, the anatomical portion of intestine and the function of the remnant bowel. Over the last years, the management of affected patients has remarkably improved with the increase in patients’ quality of life and survival, mainly thanks to advances in home-based parenteral nutrition (PN). In the last ten years new treatment strategies have become available together with increasing experience and the encouraging results with new drugs, such as teduglutide, have added a new dimension to the management of SBS. This review aims to summarize the knowledge available in the current literature on SBS epidemiology, pathophysiology, and its surgical (including intestinal lengthening procedures and intestinal transplantation) and medical management with emphasis on the recent advances. Moreover, this review attempts to provide the new understanding and recent approaches to SBS complications such as sepsis, catheter thrombosis, and intestinal failure-associated liver disease.

Neuroendocrine neoplasms (NENs) are rare neoplasms with heterogeneous clinical behavior. Alteration in human microbiota was reported in association with carcinogenesis in different solid tumors. However, few studies addressed the role of microbiota in NEN. We here aimed at evaluating the presence of bacterial infiltration in neuroendocrine tumoral tissue. To assess the presence of bacteria, 20 specimens from pancreatic NEN (pan-NEN) and 20 from intestinal NEN (I-NEN) were evaluated through Fluorescent In situ Hybridization and confocal microscopy. Demographic data, pre-operative investigations, operative findings, pathological diagnosis, follow-up, and survival data were evaluated. Among I-NEN, bacteria were detected in 15/20 (75%) specimens, with high variability in microbial distribution. In eight patients, a high infiltration of microorganisms was observed. Among pan-NEN, 18/20 (90%) showed microorganisms’ infiltration, with a homogeneous microbial distribution. Bacterial localization in pan-NEN was observed in the proximity of blood vessels. A higher bacterial infiltration in the tumoral specimen as compared with non-tumoral tissue was reported in 10/20 pan-NEN (50%). No significant differences were observed in mean bacterial count according to age, sex, ki67%, site, tumor stage. Mean bacterial count did not result to be a predictor of disease-specific survival. This preliminary study demonstrates the presence of a significant microbiota in the NEN microenvironment. Further research is needed to investigate the potential etiological or clinical role of microbiota in NEN.

Inflammation and immunity are linked to intestinal adenoma (IA) and colorectal cancer (CRC) development. The gut microbiota is associated with CRC risk. Epithelial barrier dysfunction can occur, possibly leading to increased intestinal permeability in CRC patients. We conducted a case-control study including 100 incident histologically confirmed CRC cases, and 100 IA and 100 healthy subjects, matched to cases by center, sex and age. We performed 16S rRNA gene analysis of blood and applied conditional logistic regression. Further analyses were based on negative binomial distribution normalization and Random Forest algorithm. We found an overrepresentation of blood 16S rRNA gene copies in colon cancer as compared to tumor-free controls. For high levels of gene copies, community diversity was higher in colon cancer cases than controls. Bacterial taxa and operational taxonomic unit abundances were different between groups and were able to predict CRC with an accuracy of 0.70. Our data support the hypothesis of a higher passage of bacteria from gastrointestinal tract to bloodstream in colon cancer. This result can be applied on non-invasive diagnostic tests for colon cancer control.