Liver transplant outcomes after ex vivo machine perfusion: a meta-analysis

Background: The pressure on liver-transplant programmes has expanded the usage of extended-criteria allografts. Machine perfusion may be better than conventional static cold storage (SCS) in alleviating ischaemia-reperfusion injury in this setting. Recipient outcomes with hypothermic or normothermic machine perfusion were assessed against SCS here. Methods: A search in MEDLINE, EMBASE and Scopus was conducted in February 2021. Primary studies investigating ex vivo machine perfusion were assessed for the following outcomes: morbidity, ICU and hospital stay, graft and patient survival rates and relative costs. Meta-analysis was performed to obtain pooled summary measures. Results: Thirty-four articles involving 1742 patients were included, of which 20 were used for quantitative synthesis. Odds ratios favoured hypothermic machine perfusion (over SCS) with less early allograft dysfunction, ischaemic cholangiopathy, non-anastomotic strictures and graft loss. Hypothermic machine perfusion was associated with a shorter hospital stay and normothermic machine perfusion with reduced graft injury. Two randomized clinical trials found normothermic machine perfusion reduced major complication risks. Conclusion: Machine perfusion assists some outcomes with potential cost savings

Delayed dynamic abdominal wall closure following multi-visceral transplantation

INTRODUCTION: Primary closure of the abdominal wall following intestinal transplantation or multivisceral transplantation could become a challenging problem in a significant number of patients. PRESENTATION OF CASE: A 38-year-old woman with familial adenomatous polyposis (FAP) underwent a multi-visceral transplantation for short gut syndrome. She subsequently developed acute graft rejection that proved resistant to conventional treatment. She was relisted and underwent re-transplantation along with kidney transplantation. Abdominal wall closure could not be achieved because of the large size of the graft and bowel oedema. The wound was initially managed with laparostomy followed by insertion of the delayed dynamic abdominal closure (DDAC) device (Abdominal Retraction Anchor – ABRA® system). Continuous dynamic traction to the wound edges resulted in gradual approximation and complete closure of the abdominal wound was achieved within 3 weeks. DISCUSSION: Successful abdominal closure after multivisceral transplantation or isolated intestinal transplantation often requires biological mesh, vascularised flaps or abdominal wall transplantation. DDAC eliminated the need for a prosthetic mesh or skin graft and provided an excellent cosmetic result. Adjustment of the dynamic traction at the bedside minimised the need for multiple returns to the operating theatre. It resulted in a well-healed linear scar without a hernia. CONCLUSION: Dynamic traction allows delayed closure of laparotomy resulting in strong and cosmetically sound wound healing with native tissue

Outcomes of primary arteriovenous fistulas in patients older than 70 years.

BACKGROUND: The population of elderly hemodialysis patients is increasing, yet the most suitable approach for providing permanent hemodialysis access remains unclear. Here we report outcomes using an approach aimed predominantly at creating radiocephalic (RC) fistulas. METHODS: A single-center retrospective cohort study was performed in which access outcomes for primary arteriovenous fistulas created between January 1, 2005, and December 31, 2012, in patients aged 70 years or older were compared. RESULTS: During the study period, 204 RC, 1 brachiobasilic, and 9 brachiocephalic (BC) primary fistulas were created initially for patients requiring dialysis. Immediate failure rates for RC fistulas were lower than for BC fistulas but not significantly so (12% vs 22%; Fisher's exact text, P = .319). One-year primary and secondary patency for RC fistulas was 54% and 66%, respectively, and similar for those created in patients between 70 and 80 years old and in those older than 80 years. The secondary patency rate at 1 year for RC fistulas using cephalic vein of diameter 2.5 mm (49% vs 72%; log-rank test, P = .005). Creation of a BC fistula was associated with a significantly higher incidence of steal syndrome than with an RC fistula (10% vs 2%; Fisher's exact text, P = .009). CONCLUSIONS: RC fistulas formed in the elderly carry a lower risk of steal syndrome than BC fistulas and offer the potential for further revision surgery, such that acceptable secondary patency is achieved for RC fistulas formed using even small (<2.5 mm) cephalic veins.This work was supported in part by the NIHR Cambridge Biomedical Research Centre.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.jvs.2015.12.04

Phlebotonics for haemorrhoids

BACKGROUND Haemorrhoids are variceal dilatations of the anal and perianal venous plexus and often develop secondary to the persistently elevated venous pressure within the haemorrhoidal plexus. Phlebotonics are a heterogenous class of drugs consisting of plant extracts (i.e. flavonoids) and synthetic compounds (i.e. calcium dobesilate). Although their precise mechanism of action has not been fully established, they are known to improve venous tone, stabilize capillary permeability and increase lymphatic drainage. They have been used to treat a variety of conditions including chronic venous insufficiency, lymphoedema and haemorrhoids. OBJECTIVE The aim of this review was to investigate the efficacy of phlebotonics in alleviating the signs, symptoms and severity of haemorrhoidal disease and verify their effect post-haemorrhoidectomy. METHODS Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library 2011 issue 9, MEDLINE (1950 to September 2011) and EMBASE (1974 to September 2011). Selection criteria: Only randomized controlled trials evaluating the use of phlebotonics in treating haemorrhoidal disease were used. No cross-over or cluster-randomized trials were included for analysis and any trial which had a quasi-random method of allocation was excluded. Data collection and analysis: Two authors independently extracted the data and analyzed the eligibility of the data for inclusion. Disagreements were resolved by meaningful discussion. MAIN RESULTS We considered twenty-four studies for inclusion in the final analysis. Twenty of these studies (enrolling a total of 2344 participants) evaluated the use of phlebotonics versus a control intervention. One of these twenty studies evaluated the use of phlebotonics with a medical intervention and another study with rubber band ligation. AUTHORS' CONCLUSIONS The evidence suggests that there is a potential benefit in using phlebotonics in treating haemorrhoidal disease as well as a benefit in alleviating post-haemorrhoidectomy symptoms. Outcomes such as bleeding and overall symptom improvement show a statistically significant beneficial effect and there were few concerns regarding their overall safety from the evidence presented in the clinical trials.Only randomized controlled trials evaluating the use of phlebotonics in treating haemorrhoidal disease were used. No cross-over or cluster-randomized trials were included for analysis and any trial which had a quasi-random method of allocation was excluded

Defatting of donor transplant livers during normothermic perfusion—a randomised clinical trial: study protocol for the DeFat study

Abstract Background Liver disease is the third leading cause of premature death in the UK. Transplantation is the only successful treatment for end-stage liver disease but is limited by a shortage of suitable donor organs. As a result, up to 20% of patients on liver transplant waiting lists die before receiving a transplant. A third of donated livers are not suitable for transplant, often due to steatosis. Hepatic steatosis, which affects 33% of the UK population, is strongly associated with obesity, an increasing problem in the potential donor pool. We have recently tested defatting interventions during normothermic machine perfusion (NMP) in discarded steatotic human livers that were not transplanted. A combination of therapies including forskolin (NKH477) and L-carnitine to defat liver cells and lipoprotein apheresis filtration were investigated. These interventions resulted in functional improvement during perfusion and reduced the intrahepatocellular triglyceride (IHTG) content. We hypothesise that defatting during NMP will allow more steatotic livers to be transplanted with improved outcomes. Methods In the proposed multi-centre clinical trial, we will randomly assign 60 livers from donors with a high-risk of hepatic steatosis to either NMP alone or NMP with defatting interventions. We aim to test the safety and feasibility of the defatting intervention and will explore efficacy by comparing ex-situ and post-reperfusion liver function between the groups. The primary endpoint will be the proportion of livers that achieve predefined functional criteria during perfusion which indicate potential suitability for transplantation. These criteria reflect hepatic metabolism and injury and include lactate clearance, perfusate pH, glucose metabolism, bile composition, vascular flows and transaminase levels. Clinical secondary endpoints will include proportion of livers transplanted in the two arms, graft function; cell-free DNA (cfDNA) at follow-up visits; patient and graft survival; hospital and ITU stay; evidence of ischemia-reperfusion injury (IRI); non-anastomotic biliary strictures and recurrence of steatosis (determined on MRI at 6 months). Discussion This study explores ex-situ pharmacological optimisation of steatotic donor livers during NMP. If the intervention proves effective, it will allow the safe transplantation of livers that are currently very likely to be discarded, thereby reducing waiting list deaths. Trial registration ISRCTN ISRCTN14957538. Registered in October 2022. </jats:sec

Defatting of donor transplant livers during normothermic perfusion-a randomised clinical trial: study protocol for the DeFat study.

BACKGROUND: Liver disease is the third leading cause of premature death in the UK. Transplantation is the only successful treatment for end-stage liver disease but is limited by a shortage of suitable donor organs. As a result, up to 20% of patients on liver transplant waiting lists die before receiving a transplant. A third of donated livers are not suitable for transplant, often due to steatosis. Hepatic steatosis, which affects 33% of the UK population, is strongly associated with obesity, an increasing problem in the potential donor pool. We have recently tested defatting interventions during normothermic machine perfusion (NMP) in discarded steatotic human livers that were not transplanted. A combination of therapies including forskolin (NKH477) and L-carnitine to defat liver cells and lipoprotein apheresis filtration were investigated. These interventions resulted in functional improvement during perfusion and reduced the intrahepatocellular triglyceride (IHTG) content. We hypothesise that defatting during NMP will allow more steatotic livers to be transplanted with improved outcomes. METHODS: In the proposed multi-centre clinical trial, we will randomly assign 60 livers from donors with a high-risk of hepatic steatosis to either NMP alone or NMP with defatting interventions. We aim to test the safety and feasibility of the defatting intervention and will explore efficacy by comparing ex-situ and post-reperfusion liver function between the groups. The primary endpoint will be the proportion of livers that achieve predefined functional criteria during perfusion which indicate potential suitability for transplantation. These criteria reflect hepatic metabolism and injury and include lactate clearance, perfusate pH, glucose metabolism, bile composition, vascular flows and transaminase levels. Clinical secondary endpoints will include proportion of livers transplanted in the two arms, graft function; cell-free DNA (cfDNA) at follow-up visits; patient and graft survival; hospital and ITU stay; evidence of ischemia-reperfusion injury (IRI); non-anastomotic biliary strictures and recurrence of steatosis (determined on MRI at 6 months). DISCUSSION: This study explores ex-situ pharmacological optimisation of steatotic donor livers during NMP. If the intervention proves effective, it will allow the safe transplantation of livers that are currently very likely to be discarded, thereby reducing waiting list deaths. TRIAL REGISTRATION: ISRCTN ISRCTN14957538. Registered in October 2022