Background: 206) is a fully human monoclonal antibody binding to cytotoxic T-lymphocyteassociated antigen 4 (CTLA4) on T cells that stimulates the immune system by blocking the CTLA4-negative regulatory signal. Combination with standard chemotherapy may strengthen antitumor therapy. This is a phase Ib, multisite, openlabel, nonrandomized dose escalation trial evaluating the safety, tolerability, and maximum tolerated dose (MTD) of tremelimumab combined with gemcitabine in patients with metastatic pancreatic cancer.Patients and methods: Gemcitabine (1000 mg/m 2 on days 1, 8, and 15 of each 28-day cycles) was administrated with escalating doses of i.v. tremelimumab (6, 10, or 15 mg/kg) on day 1 of each 84-day cycle for a maximum of 4 cycles. The first 18 patients had an initial 4-week gemcitabine-only lead-in period. Dose-limiting toxicities (DLTs) related to tremelimumab were evaluated during the first 6 weeks after the first dose of tremelimumab. No DLTs related to tremelimumab were observed at any dose, even when the maximum dose established for tremelimumab (15 mg/kg) was used. Most frequent grade 3/4 toxicities were asthenia (11.8%) and nausea (8.8%). Only one patient had a serious drug-related event (diarrhea with dehydration). The median overall survival was 7.4 months (95% confidence interval 5.8-9.4 months). At the end of treatment, two patients achieved partial response. Both patients received tremelimumab 15-mg/kg group (n = 2/19, 10.5%).
Conclusion:Tremelimumab plus gemcitabine demonstrated a safety and tolerability profile, warranting further study in patients with metastatic pancreatic cancer.ClinicalTrials.gov ID: NCT00556023.
Bariatric patients are difficult to assess clinically for signs of postoperative complication. Diagnostic laparoscopy (DL) is used to investigate patients suspicious for complications such as anastomotic leak (AL) and intra-abdominal hemorrhage (IH). Most bariatric surgeons use DL in the presence of sustained tachycardia; however, the rate of this procedure and its clinical value have not been sufficiently investigated.A retrospective review of patients undergoing bariatric surgery from January 2010 to December 2011 was performed. Data from 4 collaborative bariatric centres of excellence were included in this analysis. From among all elective bariatric procedures, cases that required early reoperation were selected for further evaluation.A total of 1001 elective bariatric procedures were identified. Of these, 952 (95%) were primary bariatric procedures, including 866 (91%) Roux-en-Y gastric bypasses and 86 (9%) sleeve gastrectomies. The remaining 48 cases represented revisional proced ures. Of these, 11 patients (1.1%) returned to the operating room within 72 hours for DL: 64% were primary cases (n = 7) and 36% revisional cases (n = 4). Intraoperative findings included AL (45%, n = 5), IH (27%, n = 3), no pathology identified (18%, n = 2) and small bowel obstruction (9%, n = 1). Of the 9 patients with complications, all were tachycardic (heart rate > 100 beats/min), and 4 of the 5 patients with AL were febrile (t > 37.5). There were no reported adverse events directly related to the use of DL.Diagnostic laparoscopy is a useful and safe option for both the diagnosis and treatment of suspected complications after bariatric surgery. The majority of patients returning to operating room had significant findings, and all were treated laparoscopically. Persistent postoperative tachycardia or fever were highly predictive of positive findings during DL. An emphasis on early decisionmaking and expeditious return to the operating room for laparoscopy should be the standard for bariatric patients on clinical suspicion of a postoperative complication.
4Changes of active and total ghrelin, GLP-1 and PYY following restrictive bariatric surgery and their impact on satiety: comparison of sleeve gastrectomy and adjustable gastric banding. A
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