Safety and efficacy of irreversible electroporation treatment in hepatobiliary and pancreatic tumours: a single-centre experience.

AIM: To report initial experience with irreversible electroporation (IRE) in a single tertiary oncology centre and to describe its role in the management of liver and pancreatic tumours. MATERIALS AND METHODS: The present study was a retrospective review of the technical success rate, complications, and treatment efficacy of patients who had undergone IRE treatment for hepatobiliary and pancreatic tumours between February 2014 to January 2020. The patients were divided into two cohorts: first 30 patients (cohort A) and subsequent 70 patients (cohort B) after a change in protocol. RESULTS: One hundred IRE procedures (n=69 liver lesions; n=28 pancreatic lesions, n=3 nodal disease) were reviewed. The overall technical success rate was 99%. Early and immediate complications were 4% and 3%, respectively. In cohort A, the complete tumour ablation rate was 65% (13/20) for hepatic tumours, 20% (1/5) for locally advanced pancreatic adenocarcinoma, 50% (2/4) for pancreatic neuroendocrine tumours, and 0% (0/1) for nodal metastasis. For cohort B, the rate improved to 87.76% (43/49) for hepatic tumours, 28.57% (4/14) for locally advanced pancreatic adenocarcinoma, 80% (4/5) for pancreatic neuroendocrine, and 50% (1/2) for nodal metastasis. After the initial cohort A, cohort B showed a significant increase in the initial complete ablation rate in hepatic tumours (p=0.028). CONCLUSION: IRE is a complex technique with a steep learning curve. It is safe, effective, and is valuable in the treatment of liver tumours that are unsuitable or considered high risk for conventional thermal ablation. Its role in the management of pancreatic tumours is less clear and requires larger studies.

Short- and long-term mortality after liver transplantation in patients with and without hepatocellular carcinoma in the UK.

BACKGROUND: The increasing demand for liver transplantation has led to considerable changes in characteristics of donors and recipients. This study evaluated the short- and long-term mortality of recipients with and without hepatocellular carcinoma (HCC) in the UK between 1997 and 2016. METHODS: First-time elective adult liver transplant recipients in the UK were identified and four successive eras of transplantation were compared. Hazard ratios (HRs) comparing the impact of era on short-term (first 90 days) and longer-term (from 90 days to 5 years) mortality were estimated, with adjustment for recipient and donor characteristics. RESULTS: Some 1879 recipients with and 7661 without HCC were included. There was an increase in use of organs donated after circulatory death (DCD), from 0 per cent in era 1 to 35·2 per cent in era 4 for recipients with HCC, and from 0·2 to 24·1 per cent for non-HCC recipients. The 3-year mortality rate decreased from 28·3 per cent in era 1 to 16·9 per cent in era 4 (adjusted HR 0·47, 95 per cent c.i. 0·35 to 0·63) for recipients with HCC, and from 20·4 to 9·3 per cent (adjusted HR 0·44, 0·36 to 0·53) for those without HCC. Comparing era 4 with era 1, improvements were more marked in short-term than in long-term mortality, both for recipients with HCC (0-90 days: adjusted HR 0·20, 0·10 to 0·39; 90 days to 5 years: adjusted HR 0·52, 0·35 to 0·75; P = 0·043) and for non-HCC recipients (0-90 days: adjusted HR 0·32, 0·24 to 0·42; 90 days to 5 years: adjusted HR 0·52, 0·40 to 0·67; P = 0·024). CONCLUSION: In the past 20 years, the mortality rate after liver transplantation has more than halved, despite increasing use of DCD donors. Improvements in overall survival can be explained by decreases in short-term and longer-term mortality.

ANTECEDENTES: La creciente demanda de trasplante hepático ha determinado cambios considerables en las características de los donantes y receptores. En este estudio, se evaluó la mortalidad a corto y a largo plazo de los receptores de trasplante hepático por carcinoma hepatocelular (hepatocelular carcinoma, HCC) y no-HCC en el Reino Unido entre 1997 y 2016. MÉTODOS: Se identificaron los receptores adultos de un primer trasplante hepático electivo en el Reino Unido y se compararon cuatro eras sucesivas de trasplante. Se estimaron los cocientes de riesgos instantáneos ajustados (adjusted hazard ratio, aHR) que comparaban el impacto de la era en la mortalidad a corto plazo (primeros 90 días) y a largo plazo (de 90 días a 5 años) ajustando por las características del receptor y del donante. RESULTADOS: Se incluyeron 1.879 receptores HCC y 7.661 receptores no-HCC. Hubo un aumento en el uso de donantes después de parada cardíaca (donors following circulatory death, DCD) del 0% en la era 1 al 35,2% en la era 4 para los receptores HCC y del 0,2% al 24,1% para los receptores no-HCC. La mortalidad a los 3 años disminuyó de 28,3% en la era 1 a 16,9% en la era 4 (aHR 0,47, i.c. del 95% 0,35-0,63) para receptores HCC y de 20,4% a 9,3% (aHR 0,44, 0,36-0,53) para receptores no-HCC. Comparando la era 1 y la era 4, las mejoras en la mortalidad a corto plazo fueron más marcadas que en la mortalidad a largo plazo, tanto para receptores HCC (aHR 0-90 días 0,20, 0,10-0,39; 90 días-5 años 0,52, 0,35-0,75; P =舁0,04) como para receptores no-HCC (aHR 0-90 días 0,32, 0,24-0,42; 90 días-5 años 0,52, 0,40-0,67; P =舁0,02). CONCLUSIÓN: En los últimos 20 años, la mortalidad después del trasplante de hígado se ha reducido a más de la mitad, a pesar del uso cada vez mayor de donantes DCD. Las mejoras en la supervivencia global pueden explicarse por la disminución de la mortalidad a corto y largo plazo.

Liver transplantation outcomes after transarterial chemotherapy for hepatocellular carcinoma.

BACKGROUND: Transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) awaiting liver transplantation is widespread, although evidence that it improves outcomes is lacking and there exist concerns about morbidity. The impact of TACE on outcomes after transplantation was evaluated in this study. METHODS: Patients with HCC who had liver transplantation in the UK were identified, and stratified according to whether they received TACE between 2006 and 2016. Cox regression methods were used to estimate hazard ratios (HRs) for death and graft failure after transplantation adjusted for donor and recipient characteristics. RESULTS: In total, 385 of 968 patients (39·8 per cent) received TACE. Five-year patient survival after transplantation was similar in those who had or had not received TACE: 75·2 (95 per cent c.i. 68·8 to 80·5) and 75·0 (70·5 to 78·8) per cent respectively. After adjustment for donor and recipient characteristics, there were no differences in mortality (HR 0·96, 95 per cent c.i. 0·67 to 1·38; P = 0·821) or graft failure (HR 1·01, 0·73 to 1·40; P = 0·964). The number of TACE treatments (2 or more versus 1: HR 0·97, 0·61 to 1·55; P = 0·903) or the time of death after transplantation (within or after 90 days; P = 0·291) did not alter the outcome. The incidence of hepatic artery thrombosis was low in those who had or had not received TACE (1·3 and 2·4 per cent respectively; P = 0·235). CONCLUSION: TACE delivered to patients with HCC before liver transplant did not affect complications, patient death or graft failure after transplantation.

ANTECEDENTES: La quimioembolización transarterial (transarterial chemoembolization, TACE) en pacientes con carcinoma hepatocelular (hepatocellular carcinoma, HCC) se utiliza como puente al trasplante hepático, aunque falta evidencia de que mejore los resultados y la morbilidad relacionada es motivo de preocupación. En este estudio se evaluó el impacto de la TACE en los resultados tras el trasplante para analizar las complicaciones. MÉTODOS: Se identificaron los receptores de trasplante hepático por HCC en el Reino Unido y se estratificaron según si habían recibido TACE entre 2006 y 2016. Se utilizó el método de regresión de Cox para estimar los cocientes de riesgos instantáneos (hazard ratio, HR) para la mortalidad post-trasplante y el fallo del injerto ajustados por las características del donante y del receptor. RESULTADOS: En total, 385 (39,8%) de 968 pacientes recibieron TACE, observándose similar supervivencia del paciente a los 5 años después del trasplante: 75,2% (i.c. del 95%: 68,8% a 80,5%) con TACE y 75,0% (70,5% a 78,8 %) sin TACE. Después de ajustar según las características del donante y del receptor, no hubo diferencias en la mortalidad (HR: 0,96, 0,67 a 1,38; P = 0,82) o en el fallo del injerto (HR: 1,01, 0,73 a 1,40; P = 0,96). El número de tratamientos con TACE (≥ 2 tratamientos TACE HR: 0,97, 0,61 a 1,55; P = 0,90) o el período de tiempo después del trasplante (mortalidad del paciente antes o después de 90 días; P = 0,29) no alteró el resultado. La incidencia de trombosis de la arteria hepática fue baja en aquellos que recibieron TACE o no (1,3% y 2,5%, respectivamente; P = 0,23). El fallo del injerto debido a eventos oclusivos fue similar en el grupo de pacientes que recibieron TACE (8,0% o 11/137) o que no la recibieron (6,7% o 5/75) TACE (P = 0,74). CONCLUSIÓN: La administración de TACE en pacientes con HCC antes del trasplante hepático no influyó en las complicaciones post-trasplante, la mortalidad del paciente o el fallo del injerto.

Congenital portosystemic venous shunt.

Congenital portosystemic venous shunts are rare developmental anomalies resulting in diversion of portal flow to the systemic circulation and have been divided into extra- and intrahepatic shunts. They occur during liver and systemic venous vascular embryogenesis and are associated with other congenital abnormalities. They carry a higher risk of benign and malignant liver tumors and, if left untreated, can result in significant medical complications including systemic encephalopathy and pulmonary hypertension. CONCLUSION: This article reviews the various types of congenital portosystemic shunts and their anatomy, pathogenesis, symptomatology, and timing and options of treatment. What is Known: • The natural history and basic management of this rare congenital anomaly are presented. What is New: • This paper is a comprehensive review; highlights important topics in pathogenesis, clinical symptomatology, and treatment options; and proposes an algorithm in the management of congenital portosystemic shunt disease in order to provide a clear idea to a pediatrician. An effort has been made to emphasize the indications for treatment in the children population and link to the adult group by discussing the consequences of lack of treatment or delayed diagnosis.

Improving the Diagnostic Criteria for Primary Liver Graft Nonfunction in Adults Utilizing Standard and Transportable Laboratory Parameters: An Outcome-Based Analysis.

Current diagnostic criteria for primary nonfunction (PNF) of liver grafts are based on clinical experience rather than statistical methods. A retrospective, single-center study was conducted of all adults (n = 1286) who underwent primary liver transplant (LT) 2000-2008 in our center. Laboratory variables during the first post LT week were analyzed. Forty-two patients (3.7%) had 2-week graft failure. Transplant albumin, day-1 aspartate aminotransferase (AST), day-1 lactate, day-3 bilirubin, day-3 international normalized ratio (INR), and day-7 AST were independently associated with PNF on multivariate logistic regression. PNF score =(0.000280*D1AST)+ (0.361*D1 Lactate)+(0.00884*D3 Bilirubin)+(0.940*D3 INR)+(0.00153*D7 AST)-(0.0972*TxAlbumin)-4.5503. Receiver operating curve analysis showed the model area under receiver operating curve (AUROC) of 0.912 (0.889-0.932) was superior to the current United Kingdom (UK) PNF criteria of 0.669 (0.634-0.704, p < 0.0001). When applied to a validation cohort (n = 386, 34.4% patients), the model had AUROC of 0.831 (0.789-0.867) compared to the UK early graft dysfunction criteria of 0.674 (0.624-0.721). The new model performed well after exclusion of patients with marginal grafts and when modified to include variables from the first three post-LT days only (AUROC of 0.818, 0.776-0.856, p = 0.001). This model is superior to the current UK PNF criteria and is based on statistical methods. The model is also applicable to recipients of all types of grafts (marginal and nonmarginal).

Late cytomegalovirus infection in children: High incidence of allograft rejection and hepatitis in donor negative and seropositive liver transplant recipients.

The complications and outcome associated with late CMV infection and disease on the graft are poorly characterized in PLT recipients. We studied the overall incidence, risk factors, and outcome of late CMV infection and disease (infection 6 months after transplant) in 180 PLT recipients admitted between 2008 and 2011 at the King's College Hospital. Antiviral prophylaxis of intravenous ganciclovir was given only to the D+R- group starting at day 7 post-transplant. The remaining groups (D-R+, D+R+, and D-R-) received pre-emptive therapy when they have CMV viremia above cut-off value and treatment for symptomatic CMV infection. The overall incidence of late CMV infection and disease was 9.4% (19/180) and 14.5% (19/130) in D+R-, D-R+, D+R- groups. The D-R+ group had the highest incidence of hepatitis (37.5%) and significantly increased incidence of CMV disease, and single and multiple acute rejection episodes when compared to the D+R- group, which received prophylaxis. The late CMV infection and disease in pediatric LT recipients was comparable to adult LT recipients despite variable duration of antiviral prophylaxis. Our results show that D-R+ group had highest rate of hepatitis and rejection episodes, associated with high morbidity, and should be considered for antiviral prophylaxis.

Liver Transplantation After Ex Vivo Normothermic Machine Preservation: A Phase 1 (First-in-Man) Clinical Trial.

The number of donor organs suitable for liver transplantation is restricted by cold preservation and ischemia-reperfusion injury. We present the first patients transplanted using a normothermic machine perfusion (NMP) device that transports and stores an organ in a fully functioning state at 37°C. In this Phase 1 trial, organs were retrieved using standard techniques, attached to the perfusion device at the donor hospital, and transported to the implanting center in a functioning state. NMP livers were matched 1:2 to cold-stored livers. Twenty patients underwent liver transplantation after NMP. Median NMP time was 9.3 (3.5-18.5) h versus median cold ischaemia time of 8.9 (4.2-11.4) h. Thirty-day graft survival was similar (100% NMP vs. 97.5% control, p = 1.00). Median peak aspartate aminotransferase in the first 7 days was significantly lower in the NMP group (417 IU [84-4681]) versus (902 IU [218-8786], p = 0.03). This first report of liver transplantation using NMP-preserved livers demonstrates the safety and feasibility of using this technology from retrieval to transplantation, including transportation. NMP may be valuable in increasing the number of donor livers and improving the function of transplantable organs.

Meta-analysis of benefits of portal-superior mesenteric vein resection in pancreatic resection for ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma has a poor prognosis without surgery. No standard treatment has yet been accepted for patients with portal-superior mesenteric vein (PV-SMV) infiltration. The present meta-analysis aimed to compare the results of pancreatic resection with PV-SMV resection for suspected infiltration with the results of surgery without PV-SMV resection. METHODS: A systematic search was performed of PubMed, Embase and the Cochrane Library in accordance with PRISMA guidelines from the time of inception to 2013. The inclusion criteria were comparative studies including patients who underwent pancreatic resection with or without PV-SMV resection. One, 3- and 5-year survival were the primary outcomes. RESULTS: Twenty-seven studies were identified involving a total of 9005 patients (1587 in PV-SMV resection group). Patients undergoing PV-SMV resection had an increased risk of postoperative mortality (risk difference (RD) 0.01, 95 per cent c.i. 0.00 to 0.03; P = 0.2) and of R1/R2 resection (RD 0.09, 0.06 to 0.13; P < 0.001) compared with those undergoing standard surgery. One-, 3- and 5-year survival were worse in the PV-SMV resection group: hazard ratio 1.23 (95 per cent c.i. 1.07 to 1.43; P = 0.005), 1.48 (1.14 to 1.91; P = 0.004) and 3.18 (1.95 to 5.19; P < 0.001) respectively. Median overall survival was 14.3 months for patients undergoing pancreatic resection with PV-SMV resection and 19.5 months for those without vein resection (P = 0.063). Neoadjuvant therapies recently showed promising results. CONCLUSION: This meta-analysis showed increased postoperative mortality, higher rates of non-radical surgery and worse survival after pancreatic resection with PV-SMV resection. This may be related to more advanced disease in this group.

Outcomes for adults with type 1 diabetes referred with severe hypoglycaemia and/or referred for islet transplantation to a specialist hypoglycaemia service.

Islet transplantation alone (ITA) is indicated for patients with type 1 diabetes (T1D) with disabling severe hypoglycaemia (SH) despite optimised medical therapy. We examined outcomes for patients referred to an islet transplant unit with recurrent SH. Retrospective case note audit of 45 patients with ≥1 SH per year who were referred to our ITA unit between 2009-2012; 36 patients attended follow-up appointments. The cohort was 52.8% male, mean (± SD) age 43.9 (± 11.4) years, and duration of diabetes 26.5 (± 12.9) years. Baseline HbA1c was 8.3% (± 1.7) (67.2 mmol/mol), median (IQR) frequency of SH was 6.0 (2.0-24.0) per/patient/year and 83.3% had impaired awareness of hypoglycaemia (IAH). 80.6% of patients were referred from other secondary diabetes services, 22.2% had completed structured education, and 30.6% were using continuous subcutaneous insulin infusion (CSII). Seventeen patients were optimised with conventional therapy; SH reduced from 2.0 (1.5-9.0) to 0.0 (0.0-0.5) episodes/patient/year; p<0.001, and there was concurrent improvement in HbA1c (8.1-7.7%; 65.0 vs. 60.7 mmol/mol; p=0.072). Ten patients were listed for transplantation as they were not optimised despite structured education, CSII, and continuous glucose monitoring (CGM). The remaining 9 had a reduction in SH [7.0 (4.8-40.5) to 4.0 (2.5-6.3) episodes/patient/year; p=0.058] and either left the service (n=5) or are still being optimised (n=4). In conclusion, 47.2% of patients presenting with problematic hypoglycaemia resolved with optimal medical therapy, with a further 25% achieving clinically relevant improvement, however 27.8% required transplantation despite access to all therapies. Provision of expertise in hypoglycaemia management is essential to focus limited transplant resources on those who need it most.

Modification of human islet preparation: an effective approach to improve graft outcome after islet transplantation?

Revascularisation of transplanted islets is an essential prerequisite for graft survival and function. However, current islet isolation procedures deprive the islets of endothelial tubulets. This may have a detrimental effect on the revascularisation process of islets following transplantation. We hypothesise that modification of the isolation procedure that preserves islet endothelial vessels may improve the islet revascularisation process following transplantation. Here, we present a modified islet isolation method by which a substantial amount of endothelial cells still attached to the islets could be preserved. The islets with preserved endothelial cells isolated by this method were revascularised within 3 days, not observed in islets isolated by standard methods. Further, we observed that grafts of islets isolated by standard methods had more patches of dead tissue than islet grafts obtained by the modified method, indicating that attached endothelial cells may play an important role in the islet revascularisation process and potentially help to improve the transplantation outcome.

Hemagglutinin stalk-based universal vaccine constructs protect against group 2 influenza A viruses.

Current influenza virus vaccines contain H1N1 (phylogenetic group 1 hemagglutinin), H3N2 (phylogenetic group 2 hemagglutinin), and influenza B virus components. These vaccines induce good protection against closely matched strains by predominantly eliciting antibodies against the membrane distal globular head domain of their respective viral hemagglutinins. This domain, however, undergoes rapid antigenic drift, allowing the virus to escape neutralizing antibody responses. The membrane proximal stalk domain of the hemagglutinin is much more conserved compared to the head domain. In recent years, a growing collection of antibodies that neutralize a broad range of influenza virus strains and subtypes by binding to this domain has been isolated. Here, we demonstrate that a vaccination strategy based on the stalk domain of the H3 hemagglutinin (group 2) induces in mice broadly neutralizing anti-stalk antibodies that are highly cross-reactive to heterologous H3, H10, H14, H15, and H7 (derived from the novel Chinese H7N9 virus) hemagglutinins. Furthermore, we demonstrate that these antibodies confer broad protection against influenza viruses expressing various group 2 hemagglutinins, including an H7 subtype. Through passive transfer experiments, we show that the protection is mediated mainly by neutralizing antibodies against the stalk domain. Our data suggest that, in mice, a vaccine strategy based on the hemagglutinin stalk domain can protect against viruses expressing divergent group 2 hemagglutinins.

Human liver regeneration is characterized by the coordinated expression of distinct microRNA governing cell cycle fate.

In the absence of adequate compensatory regeneration, overwhelming liver damage can cause acute liver failure (ALF) and death without emergent liver transplantation (LT). Auxiliary LT produces satisfactory outcomes in this setting, with the prospect of native liver regeneration sustaining long-term survival. Since animal models only partially recapitulate human liver regeneration, we investigated the molecular mechanisms controlling it in this unique LT setting, as an exemplar of human liver regeneration. We demonstrate coordinated changes in expression of microRNA (miRNA) during regeneration that drive proliferation, innate immunity and angiogenesis. In contrast, failed regeneration in a similar cohort is associated with distinct miRNA enforcing cell cycle inhibition and DNA methylation. The miRNA expression associated with successful or failed regeneration when recapitulated in vitro, triggered expression of cardinal regeneration-linked genes promoting cell cycle entry or inhibition, respectively. Furthermore, inhibition of miRNA 150, 663 and 503, whose downregulation is associated with successful regeneration, induced cell proliferation which a key determinant of successful regeneration. Our data indicate that human liver regeneration may be orchestrated by distinct miRNA controlling key regeneration-linked processes including hepatocyte proliferation. To our knowledge this is the first characterization of molecular processes associated with human liver regeneration.

Patient perception of skin-cancer prevention and risk after liver transplantation.

INTRODUCTION: Sun exposure is a major risk factor for the development of skin cancer. This is particularly relevant in immunosuppressed liver-transplant recipients (LTRs). Preventative strategies may help minimize the skin-cancer risk in this patient group. METHODS: We assessed 670 patients in our post-transplant clinic, using questionnaires. Patient data were collected, and we assessed whether patients had received education (such as formal talks or information from transplant coordinators or from hepatologists) on skin, sun exposure and skin cancer. In a subset of 280 of the LTRs who responded, we recorded their recall of sun-protection advice and assessed the level of patient adherence to such advice. RESULTS: The response rate was 57.5% (349/607), with a mean responder age of 51.1 years (range 19-84) and an average post-transplant time of 7.1 years (range 0-27). In the recall assessment, 37.2% reported that they were given advice about their skin, while 18.1% were seen by a dermatologist, and education on sun exposure and the risks of skin cancer was given to 65.6% and 47.9%, respectively. Over three-quarters (78%; 185/280) of the patients used mechanical sun protection (i.e. hats/clothing), while 66% reported using sunscreen; 31.8% of these used a sunscreen of the recommended sun protection factor (SPF) of > 30. Twelve patients had developed squamous cell carcinoma after a mean of 10.9 years (1-23) post-transplant; half of these had used either no sunscreen or one with an SPF of < 15. CONCLUSIONS: Despite the fact that LTRs are given information on sun-exposure and SC before and after transplantation, recall of such advice and use of sun-protection methods was only moderate, indicating that regular reinforcement of SC education is needed.

Predictors of recurrence following laparoscopic minor hepatectomy for hepatocellular carcinoma in the UK.

AIMS: Minor hepatectomy, which is increasingly carried out laparoscopically (LLR), is a cornerstone of curative treatment for hepatocellular carcinoma (HCC). The majority of relevant publications however originate from regions with endemic viral hepatitis. Although the incidence of HCC in the UK is increasing, little is known about outcomes following LLR. METHODS: Consecutive patients undergoing minor (involving ≤2 segments) LLR or open resection (OLR) at our institute between 2014 and 2021 were compared. Selection from a plethora of factors potentially impacting on overall (OS) and disease free survival (DFS) was optimised with Lasso regression. To enable analysis of patients having repeat resection, multivariate frailty modelling was utilised to calculate hazard ratios (HR). RESULTS: The analysis of 111 liver resections included 55 LLR and 56 OLR. LLR was associated with a shorter hospital stay (5 ± 2 vs. 7 ± 2 days; p < 0.001) and a lower comprehensive complication index (4.43 vs. 9.96; p = 0.006). Mean OS (52.3 ± 2.3 vs. 49.9 ± 3.0 months) and DFS (33.9 ± 3.4 vs. 36.5 ± 3.6 months; p = 0.59) were comparable between LLR and OLR, respectively (median not reached). Presence of mixed cholangiocarcinoma/HCC, satellite lesions and AFP level predicted OS and DFS. In addition tumour size was predictive of DFS. CONCLUSIONS: In the studied population minor LLR was associated with shorter hospital stay and fewer complications while offering non-inferior long-term outcomes. A number of predictors for disease free survival have been elucidated that may aid in identifying patients with a high risk of disease recurrence and need for further treatment.

Prediction models of donor arrest and graft utilization in liver transplantation from maastricht-3 donors after circulatory death.

Shortage of organs for transplantation has led to the renewed interest in donation after circulatory-determination of death (DCDD). We conducted a retrospective analysis (2001-2009) and a subsequent prospective validation (2010) of liver Maastricht-Category-3-DCDD and donation-after-brain-death (DBD) offers to our program. Accepted and declined offers were compared. Accepted DCDD offers were divided into donors who went on to cardiac arrest and those who did not. Donors who arrested were divided into those producing grafts that were transplanted or remained unused. Descriptive comparisons and regression analyses were performed to assess predictor models of donor cardiac arrest and graft utilization. Variables from the multivariate analysis were prospectively validated. Of 1579 DCDD offers, 621 were accepted, and of these, 400 experienced cardiac arrest after withdrawal of support. Of these, 173 livers were transplanted. In the DCDD group, donor age < 40 years, use of inotropes and absence of gag/cough reflexes were predictors of cardiac arrest. Donor age >50 years, BMI >30, warm ischemia time >25 minutes, ITU stay >7 days and ALT ≥ 4× normal rates were risk factors for not using the graft. These variables had excellent sensitivity and specificity for the prediction of cardiac arrest (AUROC = 0.835) and graft use (AUROC = 0.748) in the 2010 prospective validation. These models can feasibly predict cardiac arrest in potential DCDDs and graft usability, helping to avoid unnecessary recoveries and healthcare expenditure.

Should we retransplant a patient who is non-adherent? A literature review and critical reflection.

The majority of transplant centers around the world face an ethical debate whether to retransplant a young non-adherent patient. Non-adherence to lifelong immunosuppressants presents a significant risk for graft loss, yet rates remain consistently high. Despite a number of these patients presenting for retransplantation, there is little evidence to guide professionals in their decision-making. This paper aims to provide such guidance, by systematically reviewing the existing outcome data for retransplantation in patients who are known to be non-adherent to their immunosuppressants. This review searched for original papers that addressed retransplantation of a solid organ and included quantitative data on adherence or graft function. Only one original research paper was found to meet the inclusion criteria. This paper is reviewed, and details of the protocol to determine eligibility for retransplantation are summarized. The findings are discussed within the ethical context that transplant professionals work within, and the arguments for and against retransplantation are considered. The need for effective integration of adherence management into routine practice is highlighted, with an emphasis on reliable measurement of adherence throughout the patient's life. Examples of good practice are discussed, favoring prevention over cure.

Manganese-enhanced MRI predicts the histological grade of hepatocellular carcinoma in potential surgical candidates.

AIM: To evaluate the role of manganese-enhanced magnetic resonance (Mn-MRI) in predicting tumour differentiation prior to liver transplant or resection for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The inclusion criteria were patients with HCC who underwent Mn-MRI prior to transplantation or resection from 2001-2008. T1-weighted MRI images were acquired at 0 and 24h after manganese dipyridoxal diphosphate (MnDPDP) intravenous contrast medium and reviewed prospectively. Manganese retention at 24h was correlated with tumour differentiation and disease-free survival. RESULTS: Eighty-six patients underwent Mn-MRI (transplantation 60, resection 26); 114/125 lesions (91%) that were arterialised as evidenced at computed tomography (CT) and had manganese uptake on MRI were HCC. There were 11 false positives (9%) that were regenerative nodules. Ten of fourteen non-manganese-retaining HCC (71%) were poorly differentiated, compared with only 13/114 manganese-retaining HCC (11%) (p<0.0001). Sensitivity, specificity, positive and negative predictive values of non-retention of MnDPDP in predicting poorly differentiated tumours were 0.43, 0.96, 0.71 and 0.88. Median disease-free survival of patients with non-manganese-retaining HCC was less than for patients with manganese-retaining HCC (14±5 months versus 39±3 months, log rank p=0.025). CONCLUSION: Non-manganese-retaining HCCs are likely to be poorly differentiated and have a poor prognosis. Manganese-enhanced MRI appears to have a role in preoperative assessment of HCC and warrants further evaluation.

Outcomes of severe pregnancy-related liver disease: refining the role of transplantation.

Severe liver disease in pregnancy is generally considered to have a favorable prognosis. The limited data available have not yielded disease-specific prognostic criteria or guidance on who should undergo liver transplantation (LT). We retrospectively evaluated 54 admissions with pregnancy-related liver disease to (1) evaluate if any admission parameters were associated with death and/or transplantation and (2) identify maternal complications. Eighteen had acute fatty liver of pregnancy and 32 had hypertension/eclampsia related disease. Seven patients (13%) died and four (7%) underwent LT. Survival rates were 43/48 if not listed for LT and 4/6 if listed. Of the four transplanted, three survived. Patients who died and/or underwent LT were more likely to have encephalopathy (p = 0.04) and hyperlactaemia (p = 0.03). Serum lactate was the best discriminant (ROC AUC 0.84). An admission lactate greater than 2.8mg/dL had 73% sensitivity and 75% specificity for predicting death or LT. The addition of encephalopathy to this parameter increased sensitivity and specificity to 90% and 86%, respectively. The King's College criteria were not effective in predicting outcome. This study confirms the overall favorable prognosis in pregnancy-related liver failure but indicates that elevated lactate levels in the presence of encephalopathy best identify patients at greatest risk of death or LT.

Safety and Efficacy of Inferior Vena Cava Reconstruction During Hepatic Resection.

BACKGROUND AND AIMS: Patients with liver tumors involving the inferior vena cava have a poor outcome without surgery. Liver resection en bloc with inferior vena cava resection and reconstruction is now performed in many centers. The purpose of this study is to investigate the safety and efficacy of inferior vena cava reconstruction during hepatic resection. MATERIALS AND METHODS: A review of 12 centers reporting 240 patients with combined hepatectomy and inferior vena cava resection and reconstruction for malignant tumors was performed. Sample size, patient characteristics, histological type of the tumor, method of reconstruction, complications, and long-term survival (1-, 2-, and 5-year survival) were evaluated. RESULTS: A total of 240 patients from 12 institutions (male 58%) with mean age 54 years underwent combined liver resection and inferior vena cava resection and reconstruction for colorectal liver metastases (43%), cholangiocarcinomas (26%), hepatocellular carcinomas (19%), leiomyosarcomas (4%), and other tumors (7.9%). Reconstruction included primary closure (35.8%), patch repair (13.3%), or interposition graft (50.8%) In-hospital mortality was 6.25% and overall morbidity was 42.1%. 1- and 10-year survival rates were 79.7% and 28.9%, respectively. CONCLUSION: Tumors arising in or extending to inferior vena cava that require liver resection should be considered for surgery as it can be performed with an acceptable mortality and morbidity in centers with liver transplantation and hepato-pancreato-biliary facilities.