Ahmer M. Hameed

Significant elevations of serum lipase not caused by pancreatitis: a systematic review

BACKGROUND Many authors advocate lipase as the preferred serological test for the diagnosis of pancreatitis and a cut-off level of three or more times the upper limit of normal (ULN) is often quoted. The literature contains no systematic review that explores alternative causes of a lipase level over three times as high as the ULN. Such a review was therefore the objective of this study. METHODS The EMBASE and MEDLINE databases (1985 to August 2013) were searched for all eligible articles. Predetermined data were extracted and independently analysed by two reviewers. RESULTS In total, data from 58 studies were included in the final analysis. The following causes other than pancreatitis of lipase levels exceeding three times the ULN were found: reduced clearance of lipase caused by renal impairment or macrolipase formation; other hepatobiliary, gastroduodenal, intestinal and neoplastic causes; critical illness, including neurosurgical pathology; alternative pancreatic diagnoses, such as non-pathological pancreatic hyperenzymaemia, and miscellaneous causes such as diabetes, drugs and infections. CONCLUSIONS A series of differential diagnoses for significant serum lipase elevations (i.e. exceeding three times the ULN) has been provided by this study. Clinicians should utilize this knowledge in the interpretation and management of patients who have lipase levels over three times as high as the ULN, remaining vigilant for an alternative diagnosis to pancreatitis. The medical officer should be aware of the possibility of incorrect diagnosis in the asymptomatic patient.

Maximizing kidneys for transplantation using machine perfusion: from the past to the future

Background:The two main options for renal allograft preservation are static cold storage (CS) and machine perfusion (MP). There has been considerably increased interest in MP preservation of kidneys, however conflicting evidence regarding its efficacy and associated costs have impacted its scale of clinical uptake. Additionally, there is no clear consensus regarding oxygenation, and hypo- or normothermia, in conjunction with MP, and its mechanisms of action are also debated. The primary aims of this article were to elucidate the benefits of MP preservation with and without oxygenation, and/or under normothermic conditions, when compared with CS prior to deceased donor kidney transplantation. Methods:Clinical (observational studies and prospective trials) and animal (experimental) articles exploring the use of renal MP were assessed (EMBASE, Medline, and Cochrane databases). Meta-analyses were conducted for the comparisons between hypothermic MP (hypothermic machine perfusion [HMP]) and CS (human studies) and normothermic MP (warm (normothermic) perfusion [WP]) compared with CS or HMP (animal studies). The primary outcome was allograft function. Secondary outcomes included graft and patient survival, acute rejection and parameters of tubular, glomerular and endothelial function. Subgroup analyses were conducted in expanded criteria (ECD) and donation after circulatory (DCD) death donors. Results:A total of 101 studies (63 human and 38 animal) were included. There was a lower rate of delayed graft function in recipients with HMP donor grafts compared with CS kidneys (RR 0.77; 95% CI 0.69–0.87). Primary nonfunction (PNF) was reduced in ECD kidneys preserved by HMP (RR 0.28; 95% CI 0.09–0.89). Renal function in animal studies was significantly better in WP kidneys compared with both HMP (standardized mean difference [SMD] of peak creatinine 1.66; 95% CI 3.19 to 0.14) and CS (SMD of peak creatinine 1.72; 95% CI 3.09 to 0.34). MP improves renal preservation through the better maintenance of tubular, glomerular, and endothelial function and integrity. Conclusions:HMP improves short-term outcomes after renal transplantation, with a less clear effect in the longer-term. There is considerable room for modification of the process to assess whether superior outcomes can be achieved through oxygenation, perfusion fluid manipulation, and alteration of perfusion temperature. In particular, correlative experimental (animal) data provides strong support for more clinical trials investigating normothermic MP.

Advances in organ preservation for transplantation

Organ transplantation provides the best available therapy for a myriad of medical conditions, including end‐stage renal disease, hepatic failure and type I diabetes mellitus. The current clinical reality is, however, that there is a significant shortage of organs available for transplantation with respect to the number of patients on organ waiting lists. As such, methods to increase organ supply have been instituted, including improved donor management, organ procurement and preservation strategies, living organ donation, transplantation education and the increased utilization of donation after circulatory death and expanded criteria donors. In particular, especially over the last decade, we have witnessed a significant change in the way donor organs are preserved, away from static cold storage methods to more dynamic techniques centred on machine perfusion (MP). This review highlights the current state and future of organ preservation for transplantation, focusing on both abdominal and thoracic organs. In particular, we focus on MP preservation of renal, hepatic, pancreatic, cardiac and lung allografts, also noting relevant advances in Australasia. MP of organs after procurement holds considerable promise, and has the potential to significantly improve graft viability and function post‐transplantation, especially in donors in whom acceptance criteria have been expanded.

A systematic review and meta‐analysis of cold in situ perfusion and preservation of the hepatic allograft: Working toward a unified approach

The efficacy of cold in situ perfusion and static storage of the liver is a possible determinant of transplantation outcomes. The aim of this study was to determine whether there is evidence to substantiate a preference for a particular perfusion route (aortic or dual) or perfusion/preservation solution in donation after brain death (DBD) liver transplantation. The Embase, MEDLINE, and Cochrane databases were used (1980‐2017). Random effects modeling was used to estimate effects on transplantation outcomes based on (1) aortic or dual in situ perfusion and (2) the use of University of Wisconsin (UW), histidine tryptophan ketoglutarate (HTK), Celsior, and/or Institut Georges Lopez–1 (IGL‐1) solutions for perfusion/preservation. A total of 22 articles were included (2294 liver transplants). The quality of evidence ranged from very low to moderate Grading of Recommendations, Assessment, Development and Evaluations score. Meta‐analyses were conducted for 14 eligible studies. Although there was no difference in the primary nonfunction (PNF) rate, a higher peak alanine aminotransferase (ALT) was recorded in dual compared with aortic‐only UW‐perfused livers (standardized mean difference, 0.24; 95% confidence interval, 0.01‐0.47); a back‐table portal venous flush was undertaken in the majority of aortic‐only perfused livers. There were no relevant differences in peak enzymes, PNF, thrombotic graft loss, biliary complications, or 1‐year graft survival in comparisons between dual‐perfused livers using UW, HTK, Celsior, or IGL‐1. In conclusion, there is no significant evidence that aortic‐only perfusion of the DBD liver compromises transplantation outcomes, and it may be favored because of its simplicity. However, there is currently insufficient evidence to advocate for the use of any particular perfusion/preservation fluid over the others. Liver Transplantation 23 1615–1627 2017 AASLD.

Hepatic resection for metastatic melanoma: a systematic review.

Melanoma metastatic to the liver has a very poor prognosis, and has traditionally been treated using systemic chemotherapy with limited efficacy. Surgery is increasingly being explored as a therapeutic option for melanoma liver metastases, with varying levels of success. A systematic review was undertaken to explore the short-term and long-term outcomes associated with hepatectomy for melanoma metastases, in addition to identifying prognostic factors favouring increased survival. All eligible studies were identified through an electronic search of Medline and Embase (January 1990–March 2013). Each study was independently analysed by two reviewers, with relevant data extracted and tabulated according to predetermined criteria. Thirteen studies were selected that fulfilled the selection criteria, with a total of 551 patients undergoing hepatic resection for melanoma metastases. Metastases to the liver occurred at a median interval of 54 months. The median perioperative morbidity and mortality were 10% (range 0–28.6%) and 0% (range 0–7.1%), respectively. The median overall survival for operative patients was 24 months, with median survival being greater in the R0 resection group (25 months; range 9.5–65.6 months) compared with the R1/2 resection group (16 months; range 11.7–29 months). Overall median 1-, 3- and 5-year survival rates were 70% (range 39–100%), 36% (range 10.2–53%) and 24% (range 3–53%), respectively. Positive prognostic factors may include single hepatic metastases, a longer time to development of hepatic metastases and R0 resection. Hepatic resection for metastatic melanoma might confer a distinct survival benefit in a select group of patients, although disease recurrence is the norm.

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

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.

A novel, customized 3D-printed perfusion chamber for normothermic machine perfusion of the kidney

Normothermic machine perfusion (NMP) prior to transplantation has gained significant prominence in the recent past, and has been clinically utilized in the setting of liver, heart, lung, and kidney transplantation. Nicholson and Hosgood were the first to report a series of kidney transplants following a brief period of pre-implantation NMP in 18 marginal donors; the success of this initial study and further investigations has led to a multi-center randomized control trial that is currently underway in the UK. This article is protected by copyright. All rights reserved.

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.