Impact of Hypothermic Preservation on Tissue Yield and Viability in Pig Pancreata

Introduction

Chronic shortage of quality human cadaveric pancreata limits islet transplantation. Porcine islet xenotransplantation is being explored to increase the donor pool. For clinical-ready islets, centralized animal husbandry, Current Good Manufacturing Practice–regulated processing facilities, and organ transportation support are required. Amount of cold ischemia time (CIT) before isolation significantly affects transplantation. The goal of this study was to determine the maximum safe CIT of whole pancreata before islet isolation.

Materials and Methods

Pancreata were rapidly removed from Yorkshire pigs (age, 14–22 days) and stored in modified University of Wisconsin solution or in EuroCollins solution at 4^°C. Pancreata were processed with <1 hour CIT (control) or stored for 4 or 12 hours before isolation. Islet yield and percent purity and viability were determined after 7 days of in vitro tissue culture and maturation. Samples from nonprocessed pancreata were collected and snap-frozen in liquid nitrogen at 0, 3, 6, 9, 12, 15, and 24 hours of preservation, then analyzed for adenosine diphosphate/adenosine triphosphate ratio as a measure of tissue energetics.

Results

Up to 12 hours in cold storage had no significant impact on overall islet yield after 7 days of in vitro culture compared with controls; islet yield at the end of the maturation process was 28,700 ± 500 islet equivalents per pancreas (mean ± SEM control yield, 30,300 ± 900 islet equivalents per pancreas); islet purity was 75 ± 5% compared with 74 ± 5% in controls. Islet viability was significantly reduced at 12 hours compared with controls (80 ± 6% vs 96 ± 5%; P < .05). The tissue adenosine diphosphate/adenosine triphosphate ratio was maintained within the first 6 hours (1.6 ± 0.1 to 1.8 ± 0.2; P = NS) but was markedly increased during the 24-hour study (3.3 ± 0.1 at 24 hours), indicating a progressive loss of adenosine triphosphate tissue stores.

Conclusions

Young pig pancreata can be hypothermically stored for up to 12 hours without affecting islet yield and purity; however, islet viability is reduced. These data highlight the need for uniform shipping parameters to standardize islet quality, ideally with CIT <6 hours.     

Fast track surgery and preoperative optimization

Enhanced recovery pathways have been rapidly embraced by surgeons as a mechanism for improving patient care and driving down complications and costs. They seek to employ a holistic approach, reviewing all aspects of patient management, to improve care. Many components are dissimilar to traditional surgical teaching, involving early mobilization and enteral nutrition, as well as a strong emphasis on fluid balance and pain management. By addressing all components of the patient pathway from preoperative through to post-surgery, significant improvement in outcomes can be achieved for a range of surgical procedures.     

Clinical and Cost Effectiveness of Hexaminolevulinate-guided Blue-light Cystoscopy: Evidence Review and Updated Expert Recommendations

Context

Non–muscle-invasive bladder cancer (NMIBC) is associated with a high recurrence risk, partly because of the persistence of lesions following transurethral resection of bladder tumour (TURBT) due to the presence of multiple lesions and the difficulty in identifying the exact extent and location of tumours using standard white-light cystoscopy (WLC). Hexaminolevulinate (HAL) is an optical-imaging agent used with blue-light cystoscopy (BLC) in NMIBC diagnosis. Increasing evidence from long-term follow-up confirms the benefits of BLC over WLC in terms of increased detection and reduced recurrence rates.

Objective

To provide updated expert guidance on the optimal use of HAL-guided cystoscopy in clinical practice to improve management of patients with NMIBC, based on a review of the most recent data on clinical and cost effectiveness and expert input.

Evidence acquisition

PubMed and conference searches, supplemented by personal experience.

Evidence synthesis

Based on published data, it is recommended that BLC be used for all patients at initial TURBT to increase lesion detection and improve resection quality, thereby reducing recurrence and improving outcomes for patients. BLC is particularly useful in patients with abnormal urine cytology but no evidence of lesions on WLC, as it can detect carcinoma in situ that is difficult to visualise on WLC. In addition, personal experience of the authors indicates that HAL-guided BLC can be used as part of routine inpatient cystoscopic assessment following initial TURBT to confirm the efficacy of treatment and to identify any previously missed or recurrent tumours. Health economic modelling indicates that the use of HAL to assist primary TURBT is no more expensive than WLC alone and will result in improved quality-adjusted life-years and reduced costs over time.

Conclusions

HAL-guided BLC is a clinically effective and cost-effective tool for improving NMIBC detection and management, thereby reducing the burden of disease for patients and the health care system.

Patient summary

Blue-light cystoscopy (BLC) helps the urologist identify bladder tumours that may be difficult to see using standard white-light cystoscopy (WLC). As a result, the amount of tumour that is surgically removed is increased, and the risk of tumour recurrence is reduced. Although use of BLC means that the initial operation costs more than it would if only WLC were used, over time the total costs of managing bladder cancer are reduced because patients do not need as many additional operations for recurrent tumours.