Lawrence Yuen

Outcomes From Pancreatic Transplantation in Donation After Cardiac Death: A Systematic Review and Meta-analysis

Background Pancreas transplantation remains the gold standard for treatment for type I diabetes providing an insulin-independent, normoglycemic state. Increasingly, donation after cardiac death (DCD) donors are used in view of the organ donor shortage. We aimed to systematically review recipient outcomes from DCD donors and where possible compared these with donor after brain death (DBD) donors. Methods We searched the databases MEDLINE via PubMed, EMBASE, and The Cochrane Library from inception to March 2015, for studies reporting the outcome of DCD pancreas transplants. We appraised studies using the Newcastle-Ottawa scale and meta-analyzed using a random effects model. Results We identified 18 studies, 4 retrospective and 6 prospective cohort studies and 8 case reports. Our bias assessment revealed that although studies were well conducted, some studies had potential confounding factors and absence of comparator groups. Eight of the 18 studies included a DBD comparison group comprising 23 609 transplant recipients. Importantly, there was no significant difference in allograft survival up to 10 years (hazard ratio, 0.98; 95% confidence interval [95% CI], 0.74-1.31; P = 0.92), or patient survival (hazard ratio, 1.31; 95% CI, 0.62-2.78; P = 0.47) between DCD and DBD pancreas transplants. We estimated that the odds of graft thrombosis was 1.67 times higher in DCD organs (95% CI, 1.04-2.67; P = 0.006). However, subgroup analysis found thrombosis was not higher in recipients whose DCD donors were given antemortem heparin (P = 0.62). Conclusions Using current DCD criteria, pancreas transplantation is a viable alternative to DBD transplantation, and antemortem interventions including heparinization may be beneficial. This potential benefit of DCD pancreas donation warrants further study.

Use of the harmonic scalpel in cold phase recovery of the pancreas for transplantation: the westmead technique.

Dear Editors, Pancreatic transplantation for the treatment of type I diabetes offers the current gold standard treatment for a previously incurable disease [1]. During our extensive experience with en bloc liver and pancreas recoveries, we noted the time-consuming nature of individually dividing vessels along the greater curvature of the stomach, in addition to dissection of the superior mesenteric pedicle close to the root of the small bowel mesentery. Additionally, small vessels around the pancreatic graft borders are often missed during cold phase dissection and are thus likely sources of blood loss during organ reperfusion in the recipient [2]. The ultrasonically activated Harmonic Scalpel (Smithfield, RI, USA) uses high-frequency ultrasound vibrations to cut and coagulate tissue [3]. The mechanical energy at the tip of the shear results in the denaturation of proteins, which then form a coagulum to produce haemostasis [3]. Direct comparisons between the Harmonic Scalpel (HS) and electrocautery have shown that the HS is associated with reduced operative time and bleeding [4,5]. Herein, we describe easily adaptable modifications to the en bloc technique incorporating pancreas recovery using the HS that allows for more timely and effective procurement of the organ; to our knowledge, the use of the HS has not yet been described for this procedure. The standard technique for procurement of the pancreas for transplantation has been described in detail previously [6–8]. Our HS modification [the modified (Westmead) technique] to the standard recovery technique can be divided into in situ and ex situ phases. In situ, the instrument is used for dissection around the greater curvature of the stomach, including division of the short gastric vessels. The HS is further utilized in mobilizing the splenic flexure of the colon, which is often surrounded by diffuse fatty and vascular tissue. This enables almost bloodless dissection down onto the pancreas and lower pole of the spleen and facilitates rapid skeletonization of the pancreas to allow its mobilization to the midline. Following perfusion within the cold phase of dissection, the HS allows the sealing of small jejunal branches, facilitating the rapid and safe creation of a more defined superior mesenteric artery (SMA) and vein (SMV) pedicle inferior to the pancreatic head (Fig. 1a). This pedicle can then be easily and safely ligated with the single deployment of a vascular stapler, while ensuring minimal vessel leakage in the recipient. Complete en bloc removal of the liver–pancreas block then proceeds in a standard fashion. Ex situ, the HS can also effectively be employed on the back-table for further clearing of extraneous tissues from the pancreas. We first use the device to separate the pancreas from the spleen via division of the splenorenal ligament. The splenic artery and vein are individually ligated with sutures, having skeletonized the vessels using the HS technique. It is then utilized for the removal of any remaining/excess fatty tissue around the body and tail of the pancreas, such that there is no further adherent tissue requiring removal at the recipient centre. We believe that the quality of the final recovered organ is significantly superior compared to cases when the HS is not employed

Imaging modalities in the diagnosis of pancreatic adenocarcinoma: A systematic review and meta-analysis of sensitivity, specificity and diagnostic accuracy

BACKGROUND Pancreatic cancer, primarily pancreatic ductal adenocarcinoma (PDAC), accounts for 2.4% of cancer diagnoses and 5.8% of cancer death annually. Early diagnoses can improve 5-year survival in PDAC. The aim of this systematic review was to determine the sensitivity, specificity and diagnostic accuracy values for MRI, CT, PET&PET/CT, EUS and transabdominal ultrasound (TAUS) in the diagnosis of PDAC. METHODS A systematic review was undertaken to identify studies reporting sensitivity, specificity and/or diagnostic accuracy for the diagnosis of PDAC with MRI, CT, PET, EUS or TAUS. Proportional meta-analysis was performed for each modality. RESULTS A total of 5399 patients, 3567 with PDAC, from 52 studies were included. The sensitivity, specificity and diagnostic accuracy were 93% (95% CI=88-96), 89% (95% CI=82-94) and 90% (95% CI=86-94) for MRI; 90% (95% CI=87-93), 87% (95% CI=79-93) and 89% (95% CI=85-93) for CT; 89% (95% CI=85-93), 70% (95% CI=54-84) and 84% (95% CI=79-89) for PET; 91% (95% CI=87-94), 86% (95% CI=81-91) and 89% (95% CI=87-92) for EUS; and 88% (95% CI=86-90), 94% (95% CI=87-98) and 91% (95% C=87-93) for TAUS. CONCLUSION This review concludes all modalities, except for PET, are equivalent within 95% confidence intervals for the diagnosis of PDAC.

Dual kidney transplant techniques: A systematic review

Dual kidney transplantation (DKT) was developed to improve outcomes from transplantation of extended criteria donors (ECD). This study examined which surgical techniques have been reported for DKT and whether any technique had superior patient and graft survival.

A National Registry Analysis of Aortic versus Dual in Situ Perfusion for Retrieval of the DBD Liver

Introduction In situ perfusion of preservation fluid during donation after brain death (DBD) liver retrieval can be conducted via the aorta alone, or aorta and portal vein (dual perfusion). There is considerable disagreement in the literature with regards to the comparative efficacy of each perfusion route for both normal and expanded criteria liver donors, and the few existing studies are disadvantaged by low patient numbers and short periods of follow-up. Materials/Methods DBD whole liver transplants (initial) in Australia were included from 2007-2016, and stratified by aortic (n = 957) or dual (n = 425) perfusion routes. Data points were obtained from the Australia and New Zealand (ANZ) Liver Transplant Registry, the ANZ Organ Donation Registry, and a national survey of senior donor surgeons. University of Wisconsin (UW) solution was given via the aorta and/or portal vein, followed by organ transport in the same fluid. Missing data was handled by multiple imputations. Graft and patient survival were compared using Kaplan-Meier curves and Cox proportional hazards. Causes of graft loss, including primary non-function (PNF), hepatic artery (HAT) and portal vein thrombosis (HAT), biliary complications (BC) and acute rejection (AR) were compared using logistic regression. Results Baseline characteristics between study groups were similar, except for a lower mean cold ischemic time (CIT; 6.3 vs 7.0 hrs), mean secondary warm ischemic time (SWIT; 37.8 vs 45.4 mins), and median recipient MELD score (14 vs 18) in the dual-perfused patient cohort compared to the aortic-only perfusion group (p < 0.001). Actuarial 5-year graft and patient survivals in aortic and dual perfusion cohorts were 80.1% vs 84.6% (p = 0.066, univariate log-rank test), and 82.6% vs 87.8% (p = 0.026, univariate log-rank test), respectively. Multivariate Cox proportion hazards models, accounting for CIT, SWIT, MELD, and other donor/recipient factors with a p-value < 0.1 in univariate analyses, showed that graft survival after aortic vs dual perfusion was not significantly different (HR 0.81, 95% CI 0.60-1.11, p = 0.188). Similarly, overall patient survival was not different between the aortic and dual groups (HR 0.74, 95% CI 0.52-1.05, p = 0.087). There were no significant differences between aortic and dual perfusion groups with respect to causes of graft loss, including PNF, HAT, PVT, BC, and AR. Discussion After accounting for confounders, there were no significant differences in causes of graft loss, graft survival, and patient survival between liver transplants performed after aortic-only or dual in situ liver perfusion at retrieval. Subgroup analyses will need to be conducted to compare high-risk donors. Conclusion The retrieval technique employed does not impact outcomes for standard risk donors. Future RCTs should focus on the efficacy of either technique in liver donors with a high donor risk index, and also consider the impact on other organs, in particular the pancreas. Royal Australasian College of Surgeons.

Aortic versus Dual Perfusion for Retrieval of the DBD Liver – a National Registry Analysis

There is lack of consensus in the literature regarding the comparative efficacy of in situ aortic‐only compared with dual (aortic and portal venous) perfusion for retrieval and transplantation of the liver. Recipient outcomes from the Australia/New Zealand Liver Transplant Registry (2007‐2016), including patient and graft survival and causes of graft loss, were stratified by perfusion route. Subgroup analyses were conducted for higher‐risk donors. A total of 1382 liver transplantation recipients were analyzed (957 aortic‐only; 425 dual perfusion). There were no significant differences in 5‐year graft and patient survivals between the aortic‐only and dual cohorts (80.1% versus 84.6% and 82.6% versus 87.8%, respectively) or in the odds ratios of primary nonfunction, thrombotic graft loss, or graft loss secondary to biliary complications or acute rejection. When analyzing only higher‐risk donors (n = 369), multivariate graft survival was significantly less in the aortic‐only cohort (hazard ratio, 0.49; 95% confidence interval, 0.26‐0.92). Overall, there was a trend toward improved outcomes when dual perfusion was used, which became significant when considering higher‐risk donors alone. Inferences into the ideal perfusion technique in multiorgan procurement will require further investigation by way of a randomized controlled trial, and outcomes after the transplantation of other organs will also need to be considered.

Extra-corporeal normothermic machine perfusion of the porcine kidney: working towards future utilization in Australasia: Normothermic machine perfusion system development

The ongoing supply‐demand gap with respect to donor kidneys for transplantation necessitates the increased use of higher kidney donor profile index and/or donation after circulatory death (DCD) kidneys. Machine perfusion (MP) preservation has become increasingly popular as a means to preserve such organs. Human data regarding normothermic kidney MP (NMP) is in its infancy, and such a system has not been established in the Australasian clinical setting.

Is the Glucose Handling Profile of Recipients With Donation After Cardiac Death (DCD) Pancreas Transplants Comparable to those With Donation After Brain Death (DBD) Transplants

Introduction The routine culture of organ donor transport media (ODTM) is yet to become standard policy at all transplant centers. This is possibly due to most previous studies finding it is characterized by low culture rates and unclear clinical utility. Our aim was to review our data from bacterial cultures of all ODTM to identify key factors that may contribute to potential infections in transplant recipients. Methods We reviewed 457 recipients of kidney, pancreas or SPK transplants, of which 286 had cultures performed on ODTM, using sterile technique. 208 samples were transferred into standard culture pots and 95 into BACTEC culture pots. Culture results were reviewed and organisms classified by likely source (skin flora, enteric flora or respiratory/oral flora). We then reviewed the presence of any clinically significant infection at the transplant site in all recipients and characterized the organisms by likely source. Analysis with SPSS statistical package was performed to assess the rate of contamination by source for kidney or SPK transplants and ascertain the likelihood of correspondence in infection source. Results The sensitivity of BACTEC culture was significantly superior to standard culture (X2(1, 286) =74.06, p < 0.001), detecting contamination in 62.1% of samples. This was relative to 15.9% of samples in the standard culture. The increased rate of contamination in the kidney for SPK group over the kidney for kidney alone group was driven by the high rate of enteric flora contamination in the SPK group (26.5%, N = 9/34), over kidney for kidney alone transplant (9.8%, N = 6/61). This is particularly relevant given 38.5% (10/26) of recipients with enteric flora contamination of transport media had an infection of the transplant site caused by enteric flora. Only 25% (65/260) of recipients who did not have contamination with enteric flora had an infection of the transplant site caused by enteric flora. Conclusions BACTEC culture is significantly superior and should be adopted as the standard of culture at all transplant centers, to improve the utility of routine testing of ODTM. Evidence suggests transmissibility of enteric contamination of ODTM, and the SPK transplant group is particularly vulnerable in this regard.