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Pancreatic surgery is complicated by untreated fluid leakage, but no tenable techniques exist to detect and close leakage sites during surgery. A novel hydrogel called SmartPAN has been developed to meet this need and is here assessed for safety before trials on human patients. First, resazurin assays were used to test the cytotoxic effects of SmartPAN's active bromothymol blue (BTB) indicator and its solution of phosphate-buffered saline (PBS) on normal (HPDE: human pancreatic duct epithelial) or carcinomic (FAMPAC) human pancreatic cells. Cells incubated with BTB showed no significant reduction in cell viability below threshold safety levels. However, PBS had a mild cytotoxic effect on FAMPAC cells. Second, SmartPAN's pathological effects were evaluated in vivo by applying 4-ml SmartPAN to a porcine (Sus scrofa domesticus) model of pancreatic resection. There were no significant differences in macroscopic and microscopic pathologies between pigs treated with SmartPAN or saline. Third, measurements using HPLC-MS/MS demonstrate that BTB does not cross into the bloodstream and was eliminated from the body within 2 days of surgery. Overall, SmartPAN appears safe in the short term and ready for first-in-human trials because its components are either biocompatible or quickly neutralized by dilution and drainage., (© 2022 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Postoperative pancreatic fistula is a major surgical complication that can follow pancreatic resection. Postoperative pancreatic fistula can develop as a consequence of leaking pancreatic fluid, which calls for an intraoperative indicator of leakage. But suitable indicators of pancreatic leakage have yet to be found. This study details the evidence-based development and early efficacy assessments of a novel pancreatic leakage indicator (SmartPAN), following the IDEAL framework of product development. We developed 41 SmartPAN prototypes by combining indicators of pancreatic fluid with a polysaccharide-microsphere matrix. The prototypes were assessed in vitro using porcine ( Sus scrofa domesticus ) pancreatic tissue and ex vivo with human pancreatic fluid. From these initial tests, we chose a hydrogel-based compound that uses the pH indicator bromothymol blue to detect alkali pancreatic fluid. This prototype was then assessed in vivo for usability, effectiveness and reliability using a porcine model. Treatment groups were defined by SmartPAN-reaction at initial pancreatic resection: indicator-positive or negative. Indicator-positive individuals randomly received either targeted closure of leakage sites or no further closure. We assessed SmartPAN's reliability and effectiveness by monitoring abdominal drainage for amylase and with relaparotomy after 48 h. SmartPAN responses were consistent between both surgical procedures and conformed to amylase measurements. In conclusion, we have developed the first surgery-ready indicator for predicting the occurrence of pancreatic leakage during pancreatic resection. SmartPAN can enable targeted prophylactic closure in a simple and reliable way, and thus may reduce the impact of postoperative pancreatic fistula by guiding peri- and post-operative management.

Background: Pasireotide was recently suggested for the prevention of postoperative pancreatic fistula (POPF) after pancreatic surgery. However, its efficacy remains to be controversially dicussed. Therefore, we conducted a systematic review and meta-analysis to assess the efficacy of pasireotide for preventing POPF after pancreatic surgery., Method: A systematic literature search was conducted in PubMed, Web of Science, and The Cochrane Library to identify clinical studies investigating the efficacy of pasireotide after pancreatic surgery. The identified studies were critically appraised, and meta-analyses were then performed. The study was performed in accordance with PRISMA guidelines and was registered at the PROSPERO study database (CRD42018112334)., Results: Four studies with a total of 919 patients were included: 418 with pasireotide treatment and 501 controls. Meta-analysis showed that pasireotide could reduce neither clinically relevant POPF rate (OR = 0.78; 95% CI, 0.49-1.24; P = 0.29) nor overall POPF rate (OR = 0.94; 95% CI, 0.60-1.48; P = 0.80) after pancreatic resections. There were no significant differences in delayed gastric emptying, mortality, and postoperative hospital stay after pancreatic surgery. However, pasireotide reduces readmission after pancreatic surgery (OR = 0.61; 95% CI, 0.44-0.85; P = 0.004). Subgroup analyses revealed that prophylactic use of pasireotide did not reduce the incidence of clinically relevant POPF after pancreaticoduodenectomy or distal pancreatectomy compared with the control., Conclusion: Based on the available evidence, use of pasireotide may not reduce clinically relevant POPF as well as it may not improve postoperative course substantially after pancreatic surgery. Further investigator-initiated high-quality trials are needed.

Purpose: The purpose of this study was to evaluate the diagnosis and surgical management of insulinomas in a single-center setting. Methods: Demographic details, clinical presentation, preoperative diagnosis, surgical strategy, and outcomes of 33 consecutive patients who underwent surgery for insulinoma were analyzed retrospectively. Results: The median time from the first onset of symptoms to diagnosis was 24 months (range 3 days to 50 years). All cases presented with Whipple's triad and had a fasting insulin to glucose ratio higher than 0.33. The preoperative detection rates of transabdominal ultrasonography, CT, MRI, and EUS were 22 % (2/9), 72 % (23/32), 75 % (9/12), and 80 % (4/5), respectively. Intraoperative manual palpation localized all cases. Enucleation was performed in 58 % of cases (19/33), partial pancreatic resection in 39 % (13/33), and enucleation plus partial resection in 3 % (1/33). Pancreatic fistula was the most common complication and occurred in 15 patients (45 %), including seven grade A, five grade B, and three grade C fistulas. There was no mortality. When compared with partial pancreatectomy, enucleation held a significant advantage in operative time and operative bleeding, with no significant differences in demographic data and postoperative complications. During a median follow-up period of 32 months, two patients were lost to follow-up and the remaining 31 patients were without evidence of recurrence. Conclusions: A fasting insulin release index larger than 0.3 is a reliable indicator for the diagnosis of insulinoma. Intraoperative palpation by an experienced surgeon can effectively complement an uncertain preoperative localization. Compared with partial pancreatic resection, enucleation showed significant benefit in terms of intraoperative blood loss and operation time. [ABSTRACT FROM AUTHOR]