Search

Few studies have been published on the long-term outcomes of patients with gastric neuroendocrine tumors (gNETs). We analyzed their management over a two-decade period, focusing on endoscopic and clinical outcomes. Clinical, laboratory, endoscopic, surgical, and histopathological data from Types 1 and 3 gNETs histologically diagnosed between March 2000 and December 2021 at the European Institute of Oncology (IEO, Milan) were retrospectively collected. Sixty-nine patients were included (60 Type 1, 9 Type 3): 53 (77%) were treated endoscopically, 6 (9%) surgically, and 10 (14%) did not receive any treatment. Overall, 293 lesions were removed endoscopically: 74% by forceps, 20% by endoscopic mucosal resection (EMR), and 5% by endoscopic submucosal dissection (ESD). No differences were observed between EMR and ESD in terms of complete resection rate (p value = .50) and complications rate (p value = .084). The median follow-up period was 5.8 years (range: 0.3-20.5), during which no gNET-related deaths were observed. Metachronous gNETs developed in 60% of patients with Type 1 gNET. Six patients with lymph node metastases (LNM) were younger (p value = .006) and had larger lesions (p value <.001) than patients without LNM. Most Type 1 gNETs were successfully excised using forceps, with EMR and ESD being equally effective. The presence of incomplete resection was not associated with a worse prognosis, which remains excellent in this highly recurrent disease. Younger age and a size ≥10 mm were associated with an increased risk of LNM. CLINICAL TRIAL REGISTRATION: Project code UID 2854.

This study tested the hypothesis that bowel preparation with mannitol should not affect the colonic concentration of H2 and CH4. Therefore, the SATISFACTION study, an international, multicenter, randomized, parallel-group phase II–III study investigated this issue. The phase II dose-finding part of the study evaluated H2, CH4, and O2 concentrations in 179 patients randomized to treatment with 50 g, 100 g, or 150 g mannitol. Phase III of the study compared the presence of intestinal gases in 680 patients randomized (1:1) to receive mannitol 100 g in single dose or a standard split-dose 2 L polyethylene glycol (PEG)-Asc preparation (2 L PEG-Asc). Phase II results showed that mannitol did not influence the concentration of intestinal gases. During phase III, no patient in either group had H2 or CH4 concentrations above the critical thresholds. In patients with H2 and/or CH4 levels above detectable concentrations, the mean values were below the risk thresholds by at least one order of magnitude. The results also highlighted the effectiveness of standard washing and insufflation maneuvers in removing residual intestinal gases. In conclusion, bowel cleansing with mannitol was safe as the concentrations of H2 and CH4 were the same as those found in patients prepared with 2 L PEG-Asc. In both groups, the concentrations of gases were influenced more by the degree of cleansing achieved and the insufflation and washing maneuvers performed than by the preparation used for bowel cleansing. The trial protocol was registered with ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT04759885) and with EudraCT (eudract_number: 2019-002856-18).

This study aimed to define the pharmacokinetics (PKs) of oral mannitol used as an osmotic laxative for bowel preparation for colonoscopy. The PKs of oral mannitol was evaluated in a substudy as part of a phase II dose-finding, international, multicenter, randomized, parallel-group, endoscopist-blinded study. Patients were randomly assigned to take 50, 100, or 150 g mannitol. Venous blood samples were drawn at baseline (T0), 1 h (T1), 2 h (T2), 4 h (T4), and 8 h (T8) after completion of mannitol self-administration. The mean mannitol plasma concentrations (mg/ml) were dose-dependent with a consistent difference among doses. The mean maximum concentration (Cmax) ± SD was 0.63 ± 0.15, 1.02 ± 0.28, and 1.36 ± 0.39 mg/ml, in the three dosage groups, respectively. The mean area under the curve from zero to infinity (AUC0−∞) was 2.667 ± 0.668, 4.992 ± 1.706, and 7.403 ± 3.472 mg/ml*h in the 50, 100, and 150 g mannitol dose groups, respectively. Bioavailability was similar in the three dose groups and was just over 20% (0.243 ± 0.073, 0.209 ± 0.081, and 0.228 ± 0.093 in the 50, 100, and 150 g mannitol dose groups, respectively). The present study showed that the bioavailability of oral mannitol is just over 20% and is similar for the three tested doses (50, 100, and 150 g). The linear increase in Cmax, AUC0−t8, and AUC0−∞ must be considered when choosing the oral mannitol dose for bowel preparation to avoid its systemic osmotic effects.

Background: Successful bowel preparation (BP) for colonoscopy depends on the instructions, diet, the laxative product, and patient adherence, which all affect colonoscopy quality. Nevertheless, there are no laxatives which combine effectiveness, safety, easy self-administration, good patient acceptance, and low cost. However, mannitol, a sugar alcohol, could be an attractive candidate for use in clinical practice if it is shown to demonstrate adequate efficacy and safety. Aims: The present phase II dose-finding study compared three doses of mannitol (50, 100, and 150 g) to identify the best dose to be used in a subsequent phase III study. Methods: The Boston Bowel Preparation Scale, caecal intubation rate, adherence, acceptability, and safety profile, including measurement of potentially dangerous colonic gas concentrations (CH4, H2, O2), were considered in all patients. A weighted algorithm was used to identify the best mannitol dose for use in the subsequent study. Results: The per-protocol population included 60 patients in the 50 g group, 54 in the 100 g group, and 49 in the 150 g group. The 100 g dose was the best as it afforded optimal colon cleansing efficacy (94.4% of patients had adequate BP), adherence, acceptability, and safety, including negligible gas concentrations. Conclusions: The present study demonstrated that the colon cleansing efficacy and safety of mannitol were dose dependent. Conversely, gas concentrations were not dose dependent and negligible in all patients. Combined evaluation of efficacy, tolerability, and safety, using a weighted algorithm, determined that mannitol 100 g was the best dose for the phase III study.