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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.

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.

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.

BACKGROUND & AIMS: Metformin seems to have anticancer effects. However, it is not clear whether use of glycemia and metformin affect outcomes of patients with advanced pancreatic neuroendocrine tumors (pNETs). We investigated the association between glycemia and progression-free survival (PFS) of patients with pNETs treated with everolimus and/or somatostatin analogues, as well as the association between metformin use and PFS time. METHODS: We performed a retrospective analysis of 445 patients with advanced pNET treated at 24 medical centers in Italy from 1999 through 2015. Data on levels of glycemia were collected at time of diagnosis of pNET, before treatment initiation, and during treatment with everolimus (with or without somatostatin analogues), octreotide, or lanreotide. Diabetes was defined as prior or current use of glycemia control medication and/or fasting plasma glucose level ≥ 126 mg/dL, hemoglobin A1c ≥ 6.5% (48 mmol/L), or a random sample of plasma glucose ≥ 200 mg/dL (11.1 mmol/L), with reported classic symptoms of hyperglycemia or hyperglycemic crisis. Patients were assigned to groups based on diagnosis of diabetes before or during antitumor therapy. PFS was compared between patients with vs without diabetes. Among patients with diabetes, the association between metformin use and PFS was assessed. We performed sensitivity and landmark analyses to exclude patients who developed diabetes while receiving cancer treatment and to exclude a potential immortal time bias related to metformin intake. RESULTS: PFS was significantly longer in patients with diabetes (median, 32.0 months) than without diabetes (median, 15.1 months) (hazard ratio for patients with vs without diabetes, 0.63; 95% confidence interval, 0.50-0.80; P = .0002). PFS of patients treated with metformin was significantly longer (median PFS, 44.2 months) than for patients without diabetes (hazard ratio for survival of patients with diabetes receiving metformin vs without diabetes, 0.45; 95% confidence interval, 0.32-0.62; P < .00001) and longer than for patients with diabetes receiving other treatments (median PFS, 20.8 months; hazard ratio, 0.49; 95% confidence interval, 0.34-0.69; P < .0001). In multivariable analysis, adjusted for other factors associated with outcomes, metformin was associated with longer PFS but level of glycemia was not. Metformin was associated with increased PFS of patients receiving somatostatin analogues and in those receiving everolimus, with or without somatostatin analogues. Sensitivity and landmark analyses produced similar results. CONCLUSIONS: In a retrospective study of patients with pNETs, we found a significant association between metformin use and longer PFS.