SmartPAN: In vitro and in vivo proof‐of‐safety assessments for an intra‐operative predictive indicator of postoperative pancreatic fistula

Abstract

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.

Intraoperative visualisation of pancreatic leakage (ViP): study protocol for an IDEAL Stage I Post Market Clinical Study

“…Degradable starch microspheres are routinely used as haemostatic (Arista by BD, NJ, USA) and embolic agents (EmboCept S by PharmaCept, Berlin, Germany or EmboLog S by Serumwerk Bernburg, Germany). Pharmacokinetic measurements demonstrated that BTB was not detectable in abdominal drainage 2 days after surgery and it could not be detected in the bloodstream 27. Overall, the components of SmartPAN are either biocompatible or quickly neutralised by dilution and drainage.…”

“…Pharmacokinetic measurements demonstrated that BTB was not detectable in abdominal drainage 2 days after surgery and it could not be detected in the bloodstream. 27 Overall, the components of SmartPAN are either biocompatible or quickly neutralised by dilution and drainage. Usage of SmartPAN in this study is fully aligned to its field of application according to CE-approved market-registration.…”

“… 26 Preclinical safety assessments did not show cytotoxicity at concentrations used in practise. 27 It was shown that SmartPAN consists of components that are either biocompatible or quickly neutralised by dilution and drainage. Therefore, the preclinical IDEAL stage 0 has been completed 28 with proof of efficacy and safety providing a derisked translation to first-in-human studies.…”

“…In a consecutive preclinical randomised efficacy trial, SmartPAN was capable of precisely detecting sites associated with biochemical leak and subsequent clinical POPF-symptoms with high sensitivity and specificity, thereby guiding effective closure 26. Preclinical safety assessments did not show cytotoxicity at concentrations used in practise 27. It was shown that SmartPAN consists of components that are either biocompatible or quickly neutralised by dilution and drainage.…”

Cavitron ultrasonic surgical aspirator (CUSA) compared with conventional pancreatic transection in distal pancreatectomy: study protocol for the randomised controlled CUSA-1 pilot trial

“…The application of somatostatin analogues also failed to significantly reduce the rate of POPF development 18 19. The recently developed intraoperative pancreatic leakage indicator ‘SmartPAN’, a device for the immediate detection of pancreatic leakages, is currently being investigated 20…”