Liver Transplantation for Primary Sclerosing Cholangitis (PSC) With or Without Inflammatory Bowel Disease (IBD)-A European Society of Organ Transplantation (ESOT) Consensus Statement.

Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD) and a lead indication for liver transplantation (LT) in the western world. In this article, we present a Consensus Statement on LT practice, developed by a dedicated Guidelines' Taskforce of the European Society of Organ Transplantation (ESOT). The overarching goal is to provide practical guidance on commonly debated topics, including indications and timing of LT, management of bile duct stenosis in patients on the transplant waiting list, technical aspects of transplantation, immunosuppressive strategies post-transplant, timing and extension of intestinal resection and futility criteria for re-transplantation.

Simulated model of RAPID concept: highlighting innate inflammation and liver regeneration.

BACKGROUND: The resection and partial liver segment II/III transplantation with delayed total hepatectomy (RAPID) concept is a novel transplantation technique for removal of non-resectable liver tumours. The aim of this study was to establish a simulated RAPID model to explore the mechanism involved in the liver regeneration. METHODS: A RAPID model was created in rats involving cold ischaemia and reperfusion of the selected future liver remnant (FLR), portal vein ligation, followed by resection of the deportalized lobes in a second step. Histology, liver regeneration and inflammatory markers in RAPID-treated rats were compared with those in controls that underwent 70 per cent hepatectomy with the same FLR size. The effects of interleukin (IL) 6 and macrophage polarization on hepatocyte viability were evaluated in an in vitro co-culture system of macrophages and BRL hepatocytes. RESULTS: The survival rate in RAPID and control hepatectomy groups was 100 per cent. The regeneration rate was higher in the RAPID-treated rats, with higher levels of IL-6 and M1 macrophage polarization (P < 0·050). BRL hepatocytes co-cultured with M1 macrophages showed a higher proliferation rate through activation of the IL-6/signal transducer and activator of transcription 3/extracellular signal-regulated kinase pathway. This enhancement of proliferation was inhibited by tocilizumab or gadolinium trichloride (P < 0·050). CONCLUSION: The surgical model provides a simulation of RAPID that can be used to study the liver regeneration profile. Surgical Relevance The mechanisms sustaining liver regeneration are a relevant field of research to reduce the 'small for size' liver syndrome when the future liver remnant is not adequate. Several surgical strategies have been introduced both for liver resection and transplant surgery, mostly related to this issue and to the scarcity of grafts, among these the RAPID concept involving the use of an auxiliary segment II/III donor liver that expands to a sufficient size until a safe second-stage hepatectomy can be performed. Understanding the mechanisms and pitfalls of the liver regeneration profile may help in tailoring surgical strategies and in selecting patients. In this experimental model the authors investigated liver histology, regeneration and inflammatory markers in RAPID-treated rats.

ANTECEDENTES: La asociación de la resección y el trasplante de los segmentos 2/3 hepáticos antes de completar, de forma diferida, una hepatectomía total (Resection And Partial Liver Segment 2/3 Transplantation With Delayed Total Hepatectomy, RAPID) es una nueva técnica de trasplante que permite extirpar tumores hepáticos inicialmente no resecables. El objetivo de este estudio fue simular un modelo RAPID para estudiar los mecanismos involucrados en la regeneración hepática. MÉTODOS: Se desarrolló un modelo RAPID en ratas mediante isquemia fría y reperfusión del futuro remanente hepático (future liver remnant, FLR) y ligadura de la vena porta, seguido de resección de los lóbulos deportalizados (ligadura portal previa). Se comparó la histología, la regeneración hepática y los marcadores inflamatorios en las ratas tratadas con RAPID frente a un grupo control, en el que se realizó una hepatectomía del 70% del mismo tamaño del FLR. Se evaluaron los efectos sobre la IL-6 y la polarización de los macrófagos para la viabilidad hepatocitaria mediante un sistema de cocultivo in vitro de macrófagos y hepatocitos BRL. RESULTADOS: La tasa de supervivencia tras el modelo RAPID y en la hepatectomía control fue del 100%. La tasa de regeneración fue mayor en las ratas tratadas con RAPID con niveles más elevados de IL-6 y mayor polarización de macrófagos M1 (P < 0,05). Los hepatocitos BRL cocultivados con macrófagos M1 mostraron una tasa de proliferación mayor mediada a través de la activación de la vía IL-6/STAT3/ERK, mientras que tocilizumab o GdCl3 inhibieron la respuesta proliferativa (P < 0,05). CONCLUSIÓN: Este modelo quirúrgico proporciona una aproximación a la técnica RAPID que permite estudiar la regeneración hepática.

Immediate and long-term impact of the COVID-19 pandemic on delivery of surgical services.

BACKGROUND: The ongoing pandemic is having a collateral health effect on delivery of surgical care to millions of patients. Very little is known about pandemic management and effects on other services, including delivery of surgery. METHODS: This was a scoping review of all available literature pertaining to COVID-19 and surgery, using electronic databases, society websites, webinars and preprint repositories. RESULTS: Several perioperative guidelines have been issued within a short time. Many suggestions are contradictory and based on anecdotal data at best. As regions with the highest volume of operations per capita are being hit, an unprecedented number of operations are being cancelled or deferred. No major stakeholder seems to have considered how a pandemic deprives patients with a surgical condition of resources, with patients disproportionally affected owing to the nature of treatment (use of anaesthesia, operating rooms, protective equipment, physical invasion and need for perioperative care). No recommendations exist regarding how to reopen surgical delivery. The postpandemic evaluation and future planning should involve surgical services as an essential part to maintain appropriate surgical care for the population during an outbreak. Surgical delivery, owing to its cross-cutting nature and synergistic effects on health systems at large, needs to be built into the WHO agenda for national health planning. CONCLUSION: Patients are being deprived of surgical access, with uncertain loss of function and risk of adverse prognosis as a collateral effect of the pandemic. Surgical services need a contingency plan for maintaining surgical care in an ongoing or postpandemic phase.

ANTECEDENTES: La pandemia en curso tiene un efecto colateral sobre la salud en la prestación de atención quirúrgica a millones de pacientes. Se sabe muy poco sobre el manejo de la pandemia y sus efectos colaterales en otros servicios, incluida la prestación de servicios quirúrgicos. MÉTODOS: Se ha realizado una revisión de alcance de toda la literatura disponible relacionada con COVID-19 y cirugía utilizando bases de datos electrónicas, páginas web de sociedades, seminarios online y repositorios de pre-publicaciones. RESULTADOS: Se han publicado varias guías perioperatorias en un corto período de tiempo. Muchas recomendaciones son contradictorias y, en el mejor de los casos, se basan en datos anecdóticos. A medida que las regiones con el mayor volumen de operaciones per cápita se ven afectadas, se cancela o difiere un número sin precedentes de operaciones. Ninguna de las principales partes interesadas parece haber considerado cómo una pandemia priva de recursos a los pacientes que necesitan una intervención quirúrgica, con pacientes afectados de manera desproporcionada debido a la naturaleza del tratamiento (uso de anestesia, quirófanos, equipo de protección, contacto físico y necesidad de atención perioperatoria). No existen recomendaciones sobre cómo reanudar la actividad quirúrgica. La evaluación tras la pandemia y la planificación futura deben incluir a los servicios quirúrgicos como una parte esencial para mantener la atención quirúrgica adecuada para la población también durante un brote epidémico. La prestación de servicios quirúrgicos, debido a su naturaleza transversal y a sus efectos sinérgicos en los sistemas de salud en general, debe incorporarse a la agenda de la OMS para la planificación nacional de la salud. CONCLUSIÓN: Los pacientes se ven privados de acceso a la cirugía con una pérdida de función incierta y riesgo de un pronóstico adverso como efecto colateral de la pandemia. Los servicios quirúrgicos necesitan un plan de contingencia para mantener la atención quirúrgica durante la pandemia y en la fase post-pandemia.

Liver transplantation for unresectable colorectal liver metastases in patients and donors with extended criteria (SECA-II arm D study).

BACKGROUND: Patients with metastatic colorectal cancer receiving palliative chemotherapy have a 5-year survival rate of approximately 10 per cent. Liver transplantation using strict selection criteria in patients with colorectal cancer and unresectable liver-only disease will result in a 5-year survival rate of 56-83 per cent. The aim of this study was to evaluate survival of patients with colorectal liver metastases (CRLM) after liver transplantation using extended criteria for both patients and donors. METHODS: This was a prospective single-arm study. Patients with synchronous unresectable CRLM who were not suitable for arms A, B or C of the SEcondary CAncer (SECA) II study who had undergone radical resection of the primary tumour and received chemotherapy were included; they underwent liver transplantation with extended criteria donor grafts. Patients who had resectable pulmonary metastases were eligible for inclusion. The main exclusion criteria were BMI above 30 kg/m2 and liver metastases larger than 10 cm. Survival was estimated using Kaplan-Meier analysis. RESULTS: Ten patients (median age 54 years; 3 women) were included. They had an extensive liver tumour load with a median of 20 (range 1-45) lesions; the median size of the largest lesion was 59 (range 15-94) mm. Eight patients had (y)pN2 disease, six had poorly differentiated or signet ring cell-differentiated primary tumours, and five had primary tumour in the ascending colon. The median Fong clinical risk score was 3 (range 2-5) and the median Oslo score was 1 (range 1-4). The median plasma carcinoembryonic antigen level was 4·3 (range 2-4346) µg/l. Median disease-free and overall survival was 4 and 18 months respectively. CONCLUSION: Patients with unresectable liver-only CRLM undergoing liver transplantation with extended patient and donor criteria have relatively short overall survival.

ANTECEDENTES: Los pacientes con cáncer colorrectal metastásico (metastatic colorectal c¡ncer, CRC) que reciben quimioterapia paliativa presentan aproximadamente una supervivencia a los 5 años del 10%. El trasplante de hígado utilizando criterios de selección estrictos en pacientes con CRC y enfermedad localizada hepática no resecable presenta una supervivencia a los 5 años del 56-83%. El objetivo de este estudio fue evaluar la supervivencia de pacientes con metástasis hepáticas CRC no resecables (non-resectable CRC liver metastases, CRLM) después del trasplante hepático utilizando criterios extendidos para pacientes y donantes. MÉTODOS: Se ha realizado un estudio prospectivo de un solo brazo. A los pacientes con CRLM sincrónicas no resecables que no eran adecuados para ser incluidos en los brazos A, B o C del estudio SECA-II, con resección quirúrgica radical previa del tumor primario y que recibieron quimioterapia, se les realizó un trasplante de hígado con injerto de donante con criterios extendidos. Los pacientes con metástasis pulmonares resecables también podían ser incluidos. Los principales criterios de exclusión principales fueron el índice de masa corporal > 30 y metástasis hepáticas > 10 cm. La supervivencia se estimó utilizando el método de Kaplan-Meier. RESULTADOS: Diez pacientes (mediana de edad de 54 años, 3 varones) incluidos en el estudio tenían una carga tumoral hepática extensa con una mediana de 20 lesiones (rango 1-45) y un tamaño mediano de la lesión más grande de 59 mm (rango 15-94 mm). Ocho pacientes tenían (y) pN2, seis tenían tumores primarios pobremente diferenciados/células de anillo de sello y cinco tenían tumor primario en colon ascendente. La mediana del Fong Clinical Risk Score fue 3 (rango 2-5). La mediana del Oslo Score fue 1 (rango 1-4). La mediana del nivel de CEA en plasma fue 4 µg/L (rango 2-4346). La mediana de supervivencia libre de enfermedad y supervivencia global fue de 4 y 18 meses, respectivamente. CONCLUSIÓN: Los pacientes con CRLM no resecables localizadas en el hígado que se someten a un trasplante de hígado con criterios extendidos de pacientes y donantes tienen una supervivencia global relativamente corta.

Long-term quality of life after liver transplantation for non-resectable colorectal metastases confined to the liver.

Background: Liver transplantation for patients with non-resectable colorectal liver metastases offers increased survival, with median overall survival of more than 5 years. The aim of this study was to compare quality of life before and up to 3 years after liver transplantation for colorectal liver metastases. Methods: Quality of life was assessed using the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire version 3.0. The patients received the questionnaire before and up to 3 years after liver transplantation. Results: Some 23 patients were included in the analysis. Three months after liver transplantation they reported reduced quality of life (global health status scale), physical function and role function, and increased dyspnoea. At 6 months, global health status, physical function and role function had returned to pretransplant values. Three years after liver transplantation all symptom and function scores were comparable to baseline values. Patients with high scores for fatigue, pain and appetite loss at baseline had reduced 3-year overall survival. Conclusion: Patients with non-resectable colorectal liver-only metastases receiving liver transplantation had good long-term quality of life. Patients with high symptom scores before transplantation had reduced 3-year overall survival.

Cost-effectiveness of liver transplantation in patients with colorectal metastases confined to the liver.

BACKGROUND: Patients with non-resectable colorectal metastases are currently treated with chemotherapy. However, liver transplantation can increase the 5-year survival rate from 9 to 56 per cent if the cancer is confined to the liver. The aim of this study was to estimate the cost-effectiveness of liver transplantation for colorectal liver metastases. METHODS: A Markov model with a lifetime perspective was developed to estimate the life-years, quality-adjusted life-years (QALYs), direct healthcare costs and cost-effectiveness for patients with non-resectable colorectal liver metastases who received liver transplantation or chemotherapy alone. RESULTS: In non-selected cohorts, liver transplantation increased patients' life expectancy by 3·12 life-years (2·47 QALYs), at an additional cost of €209 143, giving an incremental cost-effectiveness ratio (ICER) of €67 140 per life-year (€84 667 per QALY) gained. In selected cohorts (selection based on tumour diameter, time since primary cancer, carcinoembryonic antigen levels and response to chemotherapy), the effect of liver transplantation increased to 4·23 life-years (3·41 QALYs), at a higher additional cost (€230 282), and the ICER decreased to €54 467 per life-year (€67 509 per QALY) gained. Given a willingness to pay of €70 500, the likelihood of transplantation being cost-effective was 0·66 and 0·94 (0·23 and 0·67 QALYs) for non-selected and selected cohorts respectively. CONCLUSION: Liver transplantation was cost-effective but only for highly selected patients. This might be possible in countries with good access to grafts and low waiting list mortality.

Natural killer T cells mediate inflammation in the bile ducts.

Cholangiocytes function as antigen-presenting cells with CD1d-dependent activation of natural killer T (NKT) cells in vitro. NKT cells may act both pro- and anti-inflammatory in liver immunopathology. We explored this immune pathway and the antigen-presenting potential of NKT cells in the bile ducts by challenging wild-type and Cd1d-/- mice with intrabiliary injection of the NKT cell activating agent oxazolone. Pharmacological blocking of CD1d-mediated activation was performed with a monoclonal antibody. Intrabiliary oxazolone injection in wild-type mice caused acute cholangitis with significant weight loss, elevated serum levels of alanine transaminase, aspartate transaminase, alkaline phosphatase and bilirubin, increased histologic grade of cholangitis and number of T cells, macrophages, neutrophils and myofibroblasts per portal tract after 7 days. NKT cells were activated after intrabiliary injection of oxazolone with upregulation of activation markers. Cd1d-/- and wild-type mice pretreated with antibody blocking of CD1d were protected from disease. These findings implicate that cells in the bile ducts function as antigen-presenting cells in vivo and activate NKT cells in a CD1d-restricted manner. The elucidation of this biliary immune pathway opens up for potentially new therapeutic approaches for cholangiopathies.

Survival following liver transplantation for liver-only colorectal metastases compared with hepatocellular carcinoma.

BACKGROUND: Liver transplantation is considered the standard of care for patients with hepatocellular carcinoma (HCC) within the Milan criteria. Liver transplantation in patients with unresectable colorectal cancer with liver-only disease has been shown to be associated with a 5-year overall survival rate of 56 per cent, compared with 9 per cent in patients receiving standard palliative chemotherapy. The aim of the present study was to compare disease-free (DFS) and overall (OS) survival after liver transplantation in patients with HCC and those with colorectal metastases. METHODS: Data were collected from the SEcondary CAncer (SECA) study database and an institutional (national) database of patients undergoing liver transplantation for HCC; all liver-transplanted patients were included. Patients with colorectal metastases treated by liver transplantation were divided into high- and low-risk groups for mortality based on carcinoembryonic antigen levels, response to chemotherapy, largest lesion at time of transplantation and time from primary surgery to transplantation. RESULTS: Patients with colorectal metastases had a median of 8 lesions, compared with 1 in patients with HCC within the Milan criteria. DFS was shorter in both the high-risk and the low-risk colorectal cancer groups compared with that in patients with HCC. The 5-year OS rate in the low-risk colorectal cancer group was 75 per cent, compared with 76 per cent in patients with HCC within the Milan criteria. The 5-year OS rate in patients with HCC beyond the Milan criteria was 56 per cent. CONCLUSION: The low-risk group of patients with colorectal cancer and unresectable liver-only disease had a 5-year OS rate following liver transplantation similar to that of patients with HCC with lesions within the Milan criteria.

Decreasing incidence of cancer after liver transplantation-A Nordic population-based study over 3 decades.

Cancer remains one of the most serious long-term complications after liver transplantation (LT). Data for all adult LT patients between 1982 and 2013 were extracted from the Nordic Liver Transplant Registry. Through linkage with respective national cancer-registry data, we calculated standardized incidence ratios (SIRs) based on country, sex, calendar time, and age-specific incidence rates. Altogether 461 cancers were observed in 424 individuals of the 4246 LT patients during a mean 6.6-year follow-up. The overall SIR was 2.22 (95% confidence interval [CI], 2.02-2.43). SIRs were especially increased for colorectal cancer in recipients with primary sclerosing cholangitis (4.04) and for lung cancer in recipients with alcoholic liver disease (4.96). A decrease in the SIR for cancers occurring within 10 years post-LT was observed from the 1980s: 4.53 (95%CI, 2.47-7.60), the 1990s: 3.17 (95%CI, 2.70-3.71), to the 2000s: 1.76 (95%CI, 1.51-2.05). This was observed across age- and indication-groups. The sequential decrease for the SIR of non-Hodgkin lymphoma was 25.0-12.9-7.53, and for nonmelanoma skin cancer 80.0-29.7-10.4. Cancer risk after LT was found to be decreasing over time, especially for those cancers that are strongly associated with immunosuppression. Whether immunosuppression minimization contributed to this decrease merits further study.

Growth rates of pulmonary metastases after liver transplantation for unresectable colorectal liver metastases.

BACKGROUND: The previously reported SECA study demonstrated a dramatic 5-year survival improvement in patients with unresectable colorectal liver metastases (CLM) treated with liver transplantation (LT) compared with chemotherapy. The objective of this study was to assess whether immunosuppressive therapy accelerates the growth of pulmonary metastases in patients transplanted for unresectable CLM. METHODS: Chest CT scans from 11 patients in the SECA study resected for 18 pulmonary metastases were reviewed retrospectively. Tumour diameter, volume and CT characteristics were registered and tumour volume doubling time was calculated. Findings in the SECA group were compared with those of a control group consisting of 12 patients with non-transplanted rectal cancer resected for 26 pulmonary metastases. Disease-free survival (DFS) and overall survival (OS) after first pulmonary resection were determined. RESULTS: Median doubling time based on tumour diameter and volume in the SECA and control groups were 125 and 130 days (P = 0·658) and 110 and 129 days (P = 0·632) respectively. The metastases in both groups were distributed to all lung lobes and were mostly peripheral. Median DFS after LT in the SECA group and after primary pelvic surgery in the control group was 17 (range 6-42) and 18 (2-57) months respectively (P = 0·532). In the SECA group, estimated 5-year DFS and OS rates after first pulmonary resection were 39 and 51 per cent respectively. CONCLUSION: Patients treated by LT for unresectable CLM have a good prognosis following resection of pulmonary metastases. Doubling time did not appear to be worse with the immunosuppression used after LT.

Trends in indications, complications and outcomes for venous resection during pancreatoduodenectomy.

BACKGROUND: Pancreatoduodenectomy with superior mesenteric-portal vein resection has become a common procedure in pancreatic surgery. The aim of this study was to compare standard pancreatoduodenectomy with pancreatoduodenectomy plus venous resection at a high-volume centre, and to examine trends in management and outcome over a decade for the latter procedure. METHODS: This retrospective observational study included all patients undergoing pancreatoduodenectomy with or without venous resection at Oslo University Hospital between January 2006 and December 2015. Trends were evaluated by assessing preoperative clinical and radiological characteristics, as well as perioperative outcomes in three time intervals (early, intermediate and late). RESULTS: A total of 784 patients had a pancreatoduodenectomy, of whom 127 (16·2 per cent) underwent venous resection. Venous resection resulted in a longer operating time (median 422 versus 312 min; P = 0·001) and greater estimated blood loss (EBL) (median 700 versus 500 ml; P = 0·004) than standard pancreatoduodenectomy. The rate of severe complications was significantly higher for pancreatoduodenectomy with venous resection (37·0 versus 26·3 per cent; P = 0·014). The overall burden of complications, evaluated using the Comprehensive Complication Index (CCI), did not differ (median score 8·7 versus 8·7; P = 0·175). Trends in venous resection over time showed a significant reduction in EBL (median 1050 versus 375 ml; P = 0·001) and duration of hospital stay (median 14 versus 9 days; P = 0·011) between the early and late periods. However, despite an improvement in the intermediate period, severe complication rates returned to baseline in the late period (18 of 43 versus 9 of 42 versus 20 of 42 patients in early, intermediate and late periods respectively; P = 0·032), as did CCI scores (median 20·9 versus 0 versus 20·9; P = 0·041). CONCLUSION: Despite an initial improvement in severe complications for venous resection during pancreatoduodenectomy, this was not maintained over time. Every fourth patient with venous resection needed relaparotomy, most frequently for bleeding.

Experimental evaluation of liver regeneration patterns and liver function following ALPPS.

BACKGROUND: The underlying mechanism of liver regeneration after Associating Liver Partition and Portal vein ligation (PVL) for Staged hepatectomy (ALPPS) is still unclear. The aim of this study was to evaluate the relationship between future liver remnant (FLR) volume, liver regeneration characteristics and restoration of function in an experimental model of ALPPS. METHODS: An ALPPS model in rats was developed with selective PVL, parenchymal transection and partial hepatectomy (step 1), followed by resection of the liver (step 2). Three different ALPPS groups with FLR sizes of 30, 20 and 10 per cent of total liver volume were compared with sham-operated controls and animals undergoing resection of left lateral lobe and 90 per cent PVL with respect to morbidity, mortality, liver regeneration and function. RESULTS: Three of 15 animals that had ALPPS with 10 per cent FLR (ALPPS10) died after step 1. Ascites developed in two of five rats that had ALPPS with 20 per cent FLR and in three of four animals in the ALPPS10 group after step 2. Although the relative increments in FLR size and growth rates were highest in the ALPPS groups, small FLR size was associated with a sustained increase in levels of serum aminotransferases and bilirubin, a lower albumin concentration, severe sinusoidal injury, increased expression of proliferation markers and increased activation of hepatic progenitor cells after step 2. CONCLUSION: There is discordance between FLR volume increase and functional restoration after the ALPPS procedure.

Treatment options in hepatocellular carcinoma today.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer related death worldwide. As over 90% of HCCs arise in cirrhotic livers preventive methods and surveillance policies have been adopted in most countries with high prevalence of hepatitis B or C infected people. Poor prognosis of HCC has shown some improvement during the last years. Targeted therapy with radiofrequency ablation (RFA), hepatic resection (HR), liver transplantation (LT), and transcatheter arterial chemoembolisation (TACE) seems to have an influence on this development. The heterogeneity of cirrhotic patients with HCC is still a big challenge. A patient with a small tumour in a cirrhotic liver may have a worse prognosis than a patient with a large tumor in a relatively preserved liver after "curative" HR. The choice of the treatment modality depends on the size and the number of tumours, the stage and the cause of cirrhosis and finally on the availability of various modalities in each centre.

The association of early post-transplant glucose levels with long-term mortality.

AIMS/OBJECTIVE: We aimed to assess the long-term effects of post-transplant glycaemia on long-term survival after renal transplantation. METHODS: Study participants were 1,410 consecutive transplant recipients without known diabetes who underwent an OGTT 10 weeks post-transplant and were observed for a median of 6.7 years (range 0.3-13.8 years). The HRs adjusted for age, sex, traditional risk factors and transplant-related risk factors were estimated. RESULTS: Each 1 mmol/l increase in fasting plasma glucose (fPG) or 2 h plasma glucose (2hPG) was associated with 11% (95% CI -1%, 24%) and 5% (1%, 9%) increments in all-cause mortality risk and 19% (1%, 39%) and 6% (1%, 12%) increments in cardiovascular (CV) mortality risk, respectively. Including both fPG and 2hPG in the multi-adjusted model the HR for 2hPG remained unchanged, while the HR for fPG was attenuated (1.05 [1.00, 1.11] and 0.97 [0.84, 1.14]). Compared with recipients with normal glucose tolerance, patients with post-transplant diabetes mellitus had higher all-cause and CV mortality (1.54 [1.09, 2.17] and 1.80 [1.10, 2.96]), while patients with impaired glucose tolerance (IGT) had higher all-cause, but not CV mortality (1.39 [1.01, 1.91] and 1.04 [0.62, 1.74]). Conversely, impaired fasting glucose was not associated with increased all-cause or CV mortality (0.79 [0.52, 1.23] and 0.76 [0.39, 1.49]). Post-challenge hyperglycaemia predicted death from any cause and infectious disease in the multivariable analyses (1.49 [1.15, 1.95] and 1.91 [1.09, 3.33]). CONCLUSIONS/INTERPRETATION: For predicting all-cause and CV mortality, 2hPG is superior to fPG after renal transplantation. Also, early post-transplant diabetes, IGT and post-challenge hyperglycaemia were significant predictors of death. Future studies should determine whether an OGTT helps identify renal transplant recipients at increased risk of premature death.

Genome-wide transcription profile of endothelial cells after cardiac transplantation in the rat.

Transcriptome analyses of organ transplants have until now usually focused on whole tissue samples containing activation profiles from different cell populations. Here, we enriched endothelial cells from rat cardiac allografts and isografts, establishing their activation profile at baseline and on days 2, 3 and 4 after transplantation. Modulated transcripts were assigned to three categories based on their regulation profile in allografts and isografts. Categories A and B contained the majority of transcripts and showed similar regulation in both graft types, appearing to represent responses to surgical trauma. By contrast, category C contained transcripts that were partly allograft-specific and to a large extent associated with interferon-gamma-responsiveness. Several transcripts were verified by immunohistochemical analysis of graft lesions, among them the matricellular protein periostin, which was one of the most highly upregulated transcripts but has not been associated with transplantation previously. In conclusion, the majority of the differentially expressed genes in graft endothelial cells are affected by the transplantation procedure whereas relatively few are associated with allograft rejection.

EULID project: European living donation and public health.

The choice of transplantation from a living donor offers advantages over a deceased donor. However, it also carries disadvantages related to donor risks in terms of health and safety. Furthermore, there are several controversial ethical aspects to be taken into account. Several national and international institutions and the scientific community have stated standards that have great influence on professional codes and legislations. Living organ donation and transplantation are to some extent regulated by parliamentary acts in most European countries. It is necessary to take a step forward to develop a legal framework to regulate all of these processes to guarantee the quality and to prevent illegal and nonethical practices. It is also necessary to develop and implement living donor protection practices not only in terms of physical health, but also to minimize potential impacts on the psychological, social, and economic spheres. Finally, an additional effort should be made to create a database model with recommendations for registration practices as part of the standardized follow-up care for the living donor. The European Living Donation (EULID) project's (http://www.eulivingdonor.eu/) main objective was to contribute to a European consensus to set standards and recommendations about legal, ethical, and living donor protection practices to guarantee the health and safety of living donors.

Double-balloon enteroscopy for endoscopic retrograde cholangiography in patients with a Roux-en-Y anastomosis.

BACKGROUND AND STUDY AIMS: Double-balloon enteroscopy (DBE) has been proved to be effective for deep intubation of the small bowel. Patients with a Roux-en-Y enteroanastomosis and biliary problems have been a challenge in gastrointestinal practice because of the lack of endoscopic access to the biliary anastomosis. We report on the first case series of patients with Roux-en-Y anatomy who have been examined using DBE. PATIENTS AND METHODS: Between September 2005 and May 2006, 18 endoscopic retrograde cholangiography procedures were performed in 13 patients (median age 53, range 2 - 81 years) using the DBE technique at our hospital. Most of the cases (10/13) had had a liver transplant for primary sclerosing cholangitis. The Fujinon T-series DBE system was used in all cases. RESULTS: The entero-enteric anastomosis was reached easily in all 18 procedures, and the end of the Roux limb was reached in 17/18 procedures. The mean intubation time was 40 minutes (range 5 - 120 minutes). Adequate imaging was achieved in all but two cases, one of whom had a native papilla. Biliary stenting was performed in two patients, stent removal in three patients, and removal of a small stone in one patient. CONCLUSIONS: Endoscopic access and biliary cannulation in the setting of Roux-en-Y anatomy is safe and feasible using the new DBE system for enteral intubation. Adaptation of accessories would further improve the utility of the procedure.