Publications by authors named "Wojciech Polak"

108 Publications

Full-left-full-right split liver transplantation for adult recipients: A systematic review and meta-analysis.

Transpl Int 2021 Nov 13. Epub 2021 Nov 13.

Liver Unit, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham, United Kingdom.

Background: Full-left-full-right split liver transplantation (FSLT) for adult recipients, may increase availability of liver grafts, reduce waitlist time, and benefit recipients with below-average body weight. However, FSLT may lead to impaired graft and patient survival. This study aims to assess outcomes after FSLT.

Methods: Five databases were searched to identify studies concerning FSLT. Incidences of complications, graft- and patient survival were assessed. Discrete data were pooled with random-effect models. Graft and patient survival after FSLT were compared to whole liver transplantation (WLT) according to the inverse variance method.

Results: Vascular complications were reported in 25/273 patients after FSLT (Pooled proportion: 6.9%, 95%CI: 3.1-10.7%, I : 36%). Biliary complications were reported in 84/308 patients after FSLT (Pooled proportion: 25.6%, 95%CI: 19-32%, I : 44%). Pooled proportions of graft and patient survival after 3 years follow-up were 72.8% (95%CI: 67.2-78.5, n=231) and 77.3% (95%CI: 66.7-85.8, n=331), respectively. Compared to WLT, FSLT was associated with increased graft loss (pooled HR: 2.12, 95%CI: 1.24-3.61, P=0.006, n=189) and patient mortality (pooled HR: 1.81, 95%CI: 1.17-2.81, P=0.008, n=289).

Conclusion: FSLT was associated with high incidences of vascular and biliary complications. Nevertheless, long-term patient and graft survival appear acceptable and justify transplant benefit in selected patients.
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http://dx.doi.org/10.1111/tri.14160DOI Listing
November 2021

European Liver Transplant Registry: donor and transplant surgery aspects of 16,641 liver transplantations in children.

Hepatology 2021 Nov 1. Epub 2021 Nov 1.

Dept. of Pediatrics, University Medical Center Groningen, University of Groningen, Hospital, Groningen, The Netherlands.

Background & Aims: The European Liver Transplant Registry (ELTR) has collected data on liver transplant procedures performed in Europe since 1968.

Approach & Results: Over a 50 years period (1968 - 2017), clinical and laboratory data were collected from 133 transplant centers and analyzed retrospectively (16,641 liver transplants in 14,515 children). Data were analyzed according to 3 successive periods (A: before 2000, B: 2000 to 2009, and C: since 2010), studying donor and graft characteristics, and graft outcome. The use of living donors steadily increased from A to C [A: n=296 (7%), B: n=1131 (23%) and C: n=1985 (39%); P=0.0001]. Overall, the 5-year graft survival rate has improved from 65% in group A to 75% in group B (p<0.0001), and to 79% in group C (B vs C, p<0.0001). Graft half-life was 31 years, overall; it was 41 years for children who survived the first year after transplant. The late annual graft loss rate in teen-agers is higher than children aged < 12 years, and similar to that of young adults. No evidence for accelerated graft loss after age 18 year was found.

Conclusions: Pediatric liver transplantation has reached a high efficacy as a cure, or treatment, for severe liver disease in infants and children. Grafts that survived the first year had a half-life time similar to standard human half-life. Transplantation before or after puberty may be the pivot-point for lower long-term outcome in children. Further studies are necessary to re-visit some old concepts regarding transplant benefit (survival time) for small children, the role of recipient pathophysiology versus graft aging, and risk at transition to adult age.
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http://dx.doi.org/10.1002/hep.32223DOI Listing
November 2021

A multicentre outcome analysis to define global benchmarks for donation after circulatory death liver transplantation.

J Hepatol 2021 Oct 13. Epub 2021 Oct 13.

Hepatobiliary Unit, Careggi University Hospital, University of Florence, Florence, Italy.

Background: To identify the best possible outcomes in liver transplantation from donation after circulatory death donors (DCD) and to propose outcome values, which serve as reference for individual liver recipients or patient groups.

Methods: Based on 2219 controlled DCD liver transplantations, collected from 17 centres in North America and Europe, we identified 1012 low-risk, primary, adult liver transplantations with a laboratory MELD of ≤20points, receiving a DCD liver with a total donor warm ischemia time of ≤30minutes and asystolic donor warm ischemia time of ≤15minutes. Clinically relevant outcomes were selected and complications were reported according to the Clavien-Dindo-Grading and the Comprehensive Complication Index (CCI). Corresponding benchmark cut-offs were based on median values of each centre, where the 75-percentile was considered.

Results: Benchmark cases represented between 19.7% and 75% of DCD transplantations in participating centers. The one-year retransplant and mortality rate was 5.23% and 9.01%, respectively. Within the first year of follow-up, 51.1% of recipients developed at least one major complication (≥Clavien-Dindo-Grade-III). Benchmark cut-offs were ≤3days and ≤16days for ICU and hospital stay, ≤66% for severe recipient complications (≥Grade-III), ≤16.8% for ischemic cholangiopathy, and ≤38.9CCI points at one-year posttransplant. Comparisons with higher risk groups showed more complications and impaired graft survival, outside the benchmark cut-offs. Organ perfusion techniques reduced the complications to values below benchmark cut-offs, despite higher graft risk.

Conclusions: Despite excellent 1-year survival, morbidity in benchmark cases remains high with more than half of recipients developing severe complications during 1-year follow-up. Benchmark cut-offs targeting morbidity parameters offer a valid tool to assess the protective value of new preservation technologies in higher risk groups, and provide a valid comparator cohort for future clinical trials.

Lay Summary: The best possible outcomes after liver transplantation of grafts donated after circulatory death (DCD) were defined using the concept of benchmarking. These were based on 2219 liver transplantations following controlled DCD donation in 17 centres worldwide. The following benchmark cut-offs for the most relevant outcome parameters were developed: ICU and hospital stay: ≤3 and ≤16 days; primary non function: ≤2.5%; renal replacement therapy: ≤9.6%; ischemic cholangiopathy: ≤16.8% and anastomotic strictures ≤28.4%. One-year graft loss and mortality were defined as ≤14.4% and 9.6%, respectively. Donor and recipient combinations with higher risk had significantly worse outcomes. The use of novel organ perfusion technology achieved similar, good results in this high-risk group with prolonged donor warm ischemia time, when compared to the benchmark cohort.
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http://dx.doi.org/10.1016/j.jhep.2021.10.004DOI Listing
October 2021

Global impact of the first wave of COVID-19 on liver transplant centers: A multi-society survey (EASL-ESOT/ELITA-ILTS).

J Hepatol 2021 Oct 12. Epub 2021 Oct 12.

Department of Surgery, Division of HPB and Transplant Surgery, Erasmus MC Transplant Institute, University Medical Centre, Rotterdam, the Netherlands.

Background And Aims: The global impact of SARS-CoV-2 on liver transplantation (LT) practices across the world is unknown. The goal of this survey was to assess the impact of the pandemic on global LT practices.

Method: A prospective web-based survey (available online from 7 September 2020 to 31 December 2020) was proposed to the active members of the EASL-ESOT/ELITA-ILTS in the Americas (including North, Central, and South America) (R1), Europe (R2), and the rest of the world (R3). The survey comprised four parts concerning the transplant processes, therapy, living donor, and organ procurement.

Results: Of the 470 transplant centers reached, 128 answered each part of the survey, 29 centers (23%), 64 centers (50%), and 35 centers (27%) from R1, R2, and R3, respectively. When we compared the practices during the first six months of the pandemic in 2020 with that a year earlier in 2019, statistically significant differences were found in the number of patients added to the waiting list (WL), the number of WL mortality, and the number of transplantations. At the regional level, we found that in R2 the number of LTs was significantly higher in 2019 (p < 0.01), while R3 had more patients listed, higher WL mortality, and more LTs performed before the pandemic. Countries severely affected by the pandemic ("hit" countries) had a lower number of WL patients (p = 0.009) and LT (p = 0.002) during the pandemic. Interestingly, WL mortality was higher in the pandemic in "non-hit" countries (p = 0.022) compared to 2019.

Conclusion: The first wave of the pandemic differentially impacted LT across the world, especially with detrimental effects on the "hit" countries. The modifications in the policies for recipient and donor selection, organ retrieval, and postoperative recipient management were adopted at a regional or national level.

Lay Summary: The health emergency caused by the Coronavirus has dramatically changed clinical practice during the pandemic. The first wave of pandemic impacted Liver Transplantation across the world differently, especially with detrimental effects on the hit countries. The resilience of the entire transplant network has enabled the support of organ donations and transplants to ultimately improve the lives of patients with end-stage liver disease.
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http://dx.doi.org/10.1016/j.jhep.2021.09.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8511875PMC
October 2021

Effects of the COVID-19 Pandemic on Solid Organ Transplantation During 2020 in Poland Compared with Countries in Western Europe, Asia, and North America: A Review.

Med Sci Monit 2021 Sep 4;27:e932025. Epub 2021 Sep 4.

Department of General and Transplantation Surgery, Medical University of Warsaw, Warsaw, Poland.

The coronavirus disease 2019 (COVID-19) pandemic, due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which began in March 2020, affected organ donor acceptance and rates of heart, lung, kidney, and liver transplants worldwide. According to data reported to POLTRANSPLANT, the number of solid organ transplants decreased by over 35% and the number of patients enlisted de novo for organ transplantation was reduced to 70% of its pre-COVID-19 volume in Poland. Most transplant centers in Western Europe and the USA have also drastically reduced their activity when compared to the pre-pandemic era. Areas of high SARS-CoV-2 infection incidence, like Italy, Spain, and France, were most affected. Significant decreases in organ donation and number of transplant procedures and increase in waitlist deaths have been noted due to overload of the healthcare system as well as uncertainty of donor SARS-CoV-2 status. Intensive care unit bed shortages and less intensive care resources available for donor management are major factors limiting access to organ procurement. The impact of the COVID-19 outbreak on transplant activities was not so adverse in Asia, as a result of a strategy based on experience gained during a previous SARS pandemic. This review aims to compare the effects of the COVID-19 pandemic on solid organ transplantation during 2020 in Poland with countries in Western Europe, North America, and Asia.
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http://dx.doi.org/10.12659/MSM.932025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425269PMC
September 2021

The Treatment Effect of Liver Transplantation versus Liver Resection for HCC: A Review and Future Perspectives.

Cancers (Basel) 2021 Jul 24;13(15). Epub 2021 Jul 24.

Department of Surgery Division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, Erasmus MC, University Medical Centre Rotterdam, 3015AA Rotterdam, The Netherlands.

For patients presenting with hepatocellular carcinoma within the Milan criteria, either liver resection or liver transplantation can be performed. However, to what extent either of these treatment options is superior in terms of long-term survival is unknown. Obviously, the comparison of these treatments is complicated by several selection processes. In this article, we comprehensively review the current literature with a focus on factors accounting for selection bias. Thus far, studies that did not perform an intention-to-treat analysis conclude that liver transplantation is superior to liver resection for early-stage hepatocellular carcinoma. In contrast, studies performing an intention-to-treat analysis state that survival is comparable between both modalities. Furthermore, all studies demonstrate that disease-free survival is longer after liver transplantation compared to liver resection. With respect to the latter, implications of recurrences for survival are rarely discussed. Heterogeneous treatment effects and logical inconsistencies indicate that studies with a higher level of evidence are needed to determine if liver transplantation offers a survival benefit over liver resection. However, randomised controlled trials, as the golden standard, are believed to be infeasible. Therefore, we suggest an alternative research design from the causal inference literature. The rationale for a regression discontinuity design that exploits the natural experiment created by the widely adopted Milan criteria will be discussed. In this type of study, the analysis is focused on liver transplantation patients just within the Milan criteria and liver resection patients just outside, hereby ensuring equal distribution of confounders.
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http://dx.doi.org/10.3390/cancers13153730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345205PMC
July 2021

Perihilar Cholangiocarcinoma - Novel Benchmark Values for Surgical and Oncological Outcomes From 24 Expert Centers.

Ann Surg 2021 11;274(5):780-788

Multi-Organ Transplant and HPB Surgical Oncology, Division of General Surgery, University Health Network, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.

Objective: The aim of this study was to define robust benchmark values for the surgical treatment of perihilar cholangiocarcinomas (PHC) to enable unbiased comparisons.

Background: Despite ongoing efforts, postoperative mortality and morbidity remains high after complex liver surgery for PHC. Benchmark data of best achievable results in surgical PHC treatment are however still lacking.

Methods: This study analyzed consecutive patients undergoing major liver surgery for PHC in 24 high-volume centers in 3 continents over the recent 5-year period (2014-2018) with a minimum follow-up of 1 year in each patient. Benchmark patients were those operated at high-volume centers (≥50 cases during the study period) without the need for vascular reconstruction due to tumor invasion, or the presence of significant co-morbidities such as severe obesity (body mass index ≥35), diabetes, or cardiovascular diseases. Benchmark cutoff values were derived from the 75th or 25th percentile of the median values of all benchmark centers.

Results: Seven hundred eight (39%) of a total of 1829 consecutive patients qualified as benchmark cases. Benchmark cut-offs included: R0 resection ≥57%, postoperative liver failure (International Study Group of Liver Surgery): ≤35%; in-hospital and 3-month mortality rates ≤8% and ≤13%, respectively; 3-month grade 3 complications and the CCI: ≤70% and ≤30.5, respectively; bile leak-rate: ≤47% and 5-year overall survival of ≥39.7%. Centers operating mostly on complex cases disclosed better outcome including lower post-operative liver failure rates (4% vs 13%; P = 0.002). Centers from Asia disclosed better outcomes.

Conclusion: Surgery for PHC remains associated with high morbidity and mortality with now the availability of benchmark values covering 21 outcome parameters, which may serve as key references for comparison in any future analyses of individuals, group of patients or centers.
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http://dx.doi.org/10.1097/SLA.0000000000005103DOI Listing
November 2021

2020 position statement and recommendations of the European Liver and Intestine Transplantation Association (ELITA): management of hepatitis B virus-related infection before and after liver transplantation.

Aliment Pharmacol Ther 2021 09 19;54(5):583-605. Epub 2021 Jul 19.

Valencia, Spain.

Background: Prophylaxis of HBV recurrence is critical after liver transplantation in HBV patients. Despite new prophylactic schemes, most European LT centres persist on a conservative approach combining hepatitis B immunoglobulin (HBIG) and nucleos(t)ides analogues (NA).

Aim: This setting prompted the European Liver Intestine Transplantation Association (ELITA) to look for a consensus on the prevention of HBV recurrence.

Methods: Based on a 4-round Delphi process, ELITA investigated 16 research questions and established 50 recommendations.

Results: Prophylaxis should be driven according to 3 simplified risk groups: Low and high virological risk patients, with undetectable and detectable HBV DNA pre-LT, respectively, and special populations (HDV, HCC, poorly adherent patients). In low-risk patients, short-term (4 weeks) combination of third-generation NA+ HBIG, or third generation NA monotherapy can be considered as prophylactic options. In high-risk patients, HBIG can be discontinued once HBV DNA undetectable. Combined therapy for 1 year is advised. HBV-HCC patients should be treated according to their virological risk. In HDV/HBV patients, indefinite dual prophylaxis remains the gold standard. Full withdrawal of HBV prophylaxis following or not HBV vaccination should only be attempted in the setting of clinical trials. Organs from HBsAg+ve donors may be considered after assessment of risks, benefits, and patient consent. They should not be used if HDV is present. In poorly adherent patients, dual long-term prophylaxis is recommended. Budget impact analysis should be taken into account to drive prophylactic regimen.

Conclusions: These ELITA recommendations should stimulate a more rational and homogeneous approach to HBV prophylaxis across LT programs.
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http://dx.doi.org/10.1111/apt.16374DOI Listing
September 2021

COVID-19 in liver transplant candidates: pretransplant and post-transplant outcomes - an ELITA/ELTR multicentre cohort study.

Gut 2021 10 19;70(10):1914-1924. Epub 2021 Jul 19.

Department of Gastroenterology, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Lombardia, Italy.

Objective: Explore the impact of COVID-19 on patients on the waiting list for liver transplantation (LT) and on their post-LT course.

Design: Data from consecutive adult LT candidates with COVID-19 were collected across Europe in a dedicated registry and were analysed.

Results: From 21 February to 20 November 2020, 136 adult cases with laboratory-confirmed SARS-CoV-2 infection from 33 centres in 11 European countries were collected, with 113 having COVID-19. Thirty-seven (37/113, 32.7%) patients died after a median of 18 (10-30) days, with respiratory failure being the major cause (33/37, 89.2%). The 60-day mortality risk did not significantly change between first (35.3%, 95% CI 23.9% to 50.0%) and second (26.0%, 95% CI 16.2% to 40.2%) waves. Multivariable Cox regression analysis showed Laboratory Model for End-stage Liver Disease (Lab-MELD) score of ≥15 (Model for End-stage Liver Disease (MELD) score 15-19, HR 5.46, 95% CI 1.81 to 16.50; MELD score≥20, HR 5.24, 95% CI 1.77 to 15.55) and dyspnoea on presentation (HR 3.89, 95% CI 2.02 to 7.51) being the two negative independent factors for mortality. Twenty-six patients underwent an LT after a median time of 78.5 (IQR 44-102) days, and 25 (96%) were alive after a median follow-up of 118 days (IQR 31-170).

Conclusions: Increased mortality in LT candidates with COVID-19 (32.7%), reaching 45% in those with decompensated cirrhosis (DC) and Lab-MELD score of ≥15, was observed, with no significant difference between first and second waves of the pandemic. Respiratory failure was the major cause of death. The dismal prognosis of patients with DC supports the adoption of strict preventative measures and the urgent testing of vaccination efficacy in this population. Prior SARS-CoV-2 symptomatic infection did not affect early post-transplant survival (96%).
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http://dx.doi.org/10.1136/gutjnl-2021-324879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300535PMC
October 2021

The Liver Retransplantation Risk Score: a prognostic model for survival after adult liver retransplantation.

Transpl Int 2021 Oct 16;34(10):1928-1937. Epub 2021 Jul 16.

Division of HPB Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

High-risk combinations of recipient and graft characteristics are poorly defined for liver retransplantation (reLT) in the current era. We aimed to develop a risk model for survival after reLT using data from the European Liver Transplantation Registry, followed by internal and external validation. From 2006 to 2016, 85 067 liver transplants were recorded, including 5581 reLTs (6.6%). The final model included seven predictors of graft survival: recipient age, model for end-stage liver disease score, indication for reLT, recipient hospitalization, time between primary liver transplantation and reLT, donor age, and cold ischemia time. By assigning points to each variable in proportion to their hazard ratio, a simplified risk score was created ranging 0-10. Low-risk (0-3), medium-risk (4-5), and high-risk (6-10) groups were identified with significantly different 5-year survival rates ranging 56.9% (95% CI 52.8-60.7%), 46.3% (95% CI 41.1-51.4%), and 32.1% (95% CI 23.5-41.0%), respectively (P < 0.001). External validation showed that the expected survival rates were closely aligned with the observed mortality probabilities. The Retransplantation Risk Score identifies high-risk combinations of recipient- and graft-related factors prognostic for long-term graft survival after reLT. This tool may serve as a guidance for clinical decision-making on liver acceptance for reLT.
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http://dx.doi.org/10.1111/tri.13956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8518385PMC
October 2021

A comparison between combined liver kidney transplants to liver transplants alone: A systematic review and meta-analysis.

Transplant Rev (Orlando) 2021 12 1;35(4):100633. Epub 2021 Jun 1.

Department of Surgery, Division of HPB & Transplant Surgery, Erasmus MC University Transplant Institute, Rotterdam, the Netherlands. Electronic address:

Background: Since the introduction of the Model for End-stage Liver disease criteria in 2002, more combined liver kidney transplants are performed. Until 2017, no standard allocation policy for combined liver kidney transplant (CLKT) was available and each transplant center decided eligibility for CLKT or liver transplant alone (LTA) on a case-by-case basis. The aim of this systematic review was to compare the clinical outcomes of CLKT compared to LTA in patients with renal dysfunction.

Methods: Databases were systematically searched for studies published between January 2010 and March 2021. Outcomes were expressed as risk ratios and pooled with a random-effects model. The primary outcome was patient survival.

Results: Four studies were included. No differences were observed for mortality risk at 1 year (risk ratio (RR) 1.03 [confidence interval (CI) 0.97-1.09], 3 years (RR 1.06 [CI 0.99-1.13]) and 5 years (RR 1.08 [CI 0.98-1.19]). The risk of graft loss was similar in the first year (RR 1.10 [CI 0.93-1.30], while 3-year risk of graft loss was significantly lower in CLKT patients (RR 1.15 [CI 1.08-1.24]).

Conclusions: CLKT has similar short-term graft and patient survival as LTA in patients with renal dysfunction. More data is needed to decide from which KDIGO stage patients benefit the most from CLKT.
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http://dx.doi.org/10.1016/j.trre.2021.100633DOI Listing
December 2021

Recurrence of primary sclerosing cholangitis after liver transplantation - analysing the European Liver Transplant Registry and beyond.

Transpl Int 2021 Aug 28;34(8):1455-1467. Epub 2021 Jun 28.

Department of Gastroenterology and Hepatology, Erasmus MC Transplant Institute, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.

Liver transplantation for primary sclerosing cholangitis (PSC) can be complicated by recurrence of PSC (rPSC). This may compromise graft survival but the effect on patient survival is less clear. We investigated the effect of post-transplant rPSC on graft and patient survival in a large European cohort. Registry data from the European Liver Transplant Registry regarding all first transplants for PSC between 1980 and 2015 were supplemented with detailed data on rPSC from 48 out of 138 contributing transplant centres, involving 1,549 patients. Bayesian proportional hazards models were used to investigate the impact of rPSC and other covariates on patient and graft survival. Recurrence of PSC was diagnosed in 259 patients (16.7%) after a median follow-up of 5.0 years (quantile 2.5%-97.5%: 0.4-18.5), with a significant negative impact on both graft (HR 6.7; 95% CI 4.9-9.1) and patient survival (HR 2.3; 95% CI 1.5-3.3). Patients with rPSC underwent significantly more re-transplants than those without rPSC (OR 3.6, 95% CI 2.7-4.8). PSC recurrence has a negative impact on both graft and patient survival, independent of transplant-related covariates. Recurrence of PSC leads to higher number of re-transplantations and a 33% decrease in 10-year graft survival.
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http://dx.doi.org/10.1111/tri.13925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456806PMC
August 2021

A review of brachytherapy physical phantoms developed over the last 20 years: clinical purpose and future requirements.

J Contemp Brachytherapy 2021 Feb 18;13(1):101-115. Epub 2021 Feb 18.

Department of Mechanical Engineering, Faculty of Technology University of Portsmouth, Portsmouth, United Kingdom.

Within the brachytherapy community, many phantoms are constructed in-house, and less commercial development is observed as compared to the field of external beam. Computational or virtual phantom design has seen considerable growth; however, physical phantoms are beneficial for brachytherapy, in which quality is dependent on physical processes, such as accuracy of source placement. Focusing on the design of physical phantoms, this review paper presents a summary of brachytherapy specific phantoms in published journal articles over the last twenty years (January 1, 2000 - December 31, 2019). The papers were analyzed and tabulated by their primary clinical purpose, which was deduced from their associated publications. A substantial body of work has been published on phantom designs from the brachytherapy community, but a standardized method of reporting technical aspects of the phantoms is lacking. In-house phantom development demonstrates an increasing interest in magnetic resonance (MR) tissue mimicking materials, which is not yet reflected in commercial phantoms available for brachytherapy. The evaluation of phantom design provides insight into the way, in which brachytherapy practice has changed over time, and demonstrates the customised and broad nature of treatments offered.
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http://dx.doi.org/10.5114/jcb.2021.103593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117707PMC
February 2021

Primary and secondary liver failure after major liver resection for perihilar cholangiocarcinoma.

Surgery 2021 10 18;170(4):1024-1030. Epub 2021 May 18.

Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands; Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands. Electronic address:

Background: The aim of this study was to investigate the incidence and risk factors of primary and secondary liver failure after major liver resection for perihilar cholangiocarcinoma.

Methods: All patients who underwent a major liver resection for presumed perihilar cholangiocarcinoma between 2000 and 2020 at 2 tertiary-referral hospitals were included. Liver failure was defined according to the International Study Group for Liver Surgery criteria, and only grade B/C was considered clinically relevant. Primary liver failure was defined as failure without any underlying postoperative cause, and secondary liver failure was defined as liver failure with an onset after an underlying postoperative complication as a cause.

Results: The incidence of liver failure and 90-day mortality were 20.9% and 17.0% in the 253 included patients, respectively. The incidences of primary liver failure was 9.1% and secondary liver failure was 11.9%. Abdominal sepsis, portal vein thrombosis, and arterial thrombosis were the most frequent causes. The absence of preoperative remnant liver assessment and blood loss were independent risk factors for primary liver failure. Independent risk factors for secondary liver failure were Eastern Cooperative Oncology group performance status, percutaneous biliary drainage, and preoperative cholangitis.

Conclusion: Liver failure after major liver resection for perihilar cholangiocarcinoma occurred in 1 of every 5 patients. The proposed subdivision into primary and secondary liver failure could help to understand differences in outcomes between centers and help to reduce liver failure.
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http://dx.doi.org/10.1016/j.surg.2021.04.013DOI Listing
October 2021

Liver transplantation for patients with acute-on-chronic liver failure (ACLF) in Europe: Results of the ELITA/EF-CLIF collaborative study (ECLIS).

J Hepatol 2021 09 2;75(3):610-622. Epub 2021 May 2.

Department of Hepatogastroenterology, Hepatology and Liver Transplantation Unit, HCL Hopital de la Croix-Rousse, Lyon, France.

Background & Aims: Liver transplantation (LT) has been proposed as an effective salvage therapy even for the sickest patients with acute-on-chronic liver failure (ACLF). This large collaborative study was designed to assess the current clinical practice and outcomes of patients with ACLF who are wait-listed for LT in Europe.

Methods: This was a retrospective study including 308 consecutive patients with ACLF, listed in 20 centres across 8 European countries, from January 2018 to June 2019.

Results: A total of 2,677 patients received a LT: 1,216 (45.4%) for decompensated cirrhosis. Of these, 234 (19.2%) had ACLF at LT: 58 (4.8%) had ACLF-1, 78 (6.4%) had ACLF-2, and 98 (8.1%) had ACLF-3. Wide variations were observed amongst countries: France and Germany had high rates of ACLF-2/3 (27-41%); Italy, Switzerland, Poland and the Netherlands had medium rates (9-15%); and the United Kingdom and Spain had low rates (3-5%) (p <0.0001). The 1-year probability of survival after LT for patients with ACLF was 81% (95% CI 74-87). Pre-LT arterial lactate levels >4 mmol/L (hazard ratio [HR] 3.14; 95% CI 1.37-7.19), recent infection from multidrug resistant organisms (HR 3.67; 95% CI 1.63-8.28), and renal replacement therapy (HR 2.74; 95% CI 1.37-5.51) were independent predictors of post-LT mortality. During the same period, 74 patients with ACLF died on the waiting list. In an intention-to-treat analysis, 1-year survival of patients with ACLF on the LT waiting list was 73% for ACLF-1 or -2 and 50% for ACLF-3.

Conclusion: The results reveal wide variations in the listing of patients with ACLF in Europe despite favourable post-LT survival. Risk factors for mortality were identified, enabling a more precise prognostic assessment of patients with ACLF.

Lay Summary: Acute-on-chronic liver failure (ACLF) is a severe clinical condition for which liver transplantation is an effective therapeutic option. This study has demonstrated that in Europe, referral and access to liver transplantation (LT) for patients with ACLF needs to be harmonised to avoid inequities. Post-LT survival for patients with ACLF was >80% after 1 year and some factors have been identified to help select patients with favourable outcomes.
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http://dx.doi.org/10.1016/j.jhep.2021.03.030DOI Listing
September 2021

Surgical morbidity in the first year after resection for perihilar cholangiocarcinoma.

HPB (Oxford) 2021 Oct 20;23(10):1607-1614. Epub 2021 Apr 20.

Erasmus MC Cancer Institute, Rotterdam, the Netherlands; Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands. Electronic address:

Background: Surgery for perihilar cholangiocarcinoma (pCCA) is associated with high morbidity and mortality rates. The impact of surgery for pCCA may affect patients after discharge. The aim of this study was to investigate all morbidity and mortality during the first year after surgery for pCCA.

Methods: All consecutive liver resections for suspected pCCA between 2000 and 2019 at two tertiary referral centers were included. All morbidity and mortality until one year after surgery was collected retrospectively, including readmissions and reinterventions. All recurrences within the first year were scored to calculate disease-free survival.

Results: In 250 patients, the major morbidity rate was 61% (152/250), in-hospital mortality was 15% (37/250) and 90-day mortality was 16% (40/250). In the 213 discharged patients, 98 patients (46%) suffered 260 surgical complications. These complications required 185 readmissions in 92 patients (43%) and 400 reinterventions in 110 patients (52%), including 330 radiological (83%), 61 endoscopic (15%) and 9 surgical reinterventions (2%). One-year overall survival was 77% and one-year disease-free survival was 70%. Out of the 20 patients who died within the first year after discharge, 15 died of recurrent disease and 3 due to surgery related complications and 2 of unknown causes.

Conclusion: Readmissions, reinterventions and complications are frequent throughout the first year after surgery for pCCA in tertiary referral hospitals. These adverse events warrants treatment of these complex patients in high expertise centers offering intensive perioperative care and close follow-up of patients after discharge.
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http://dx.doi.org/10.1016/j.hpb.2021.03.016DOI Listing
October 2021

Reply.

Gastroenterology 2021 Aug 20;161(2):731-732. Epub 2021 Apr 20.

Erasmus MC, Transplant Institute, University Medical Center Rotterdam, Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Rotterdam, The Netherlands.

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http://dx.doi.org/10.1053/j.gastro.2021.04.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055919PMC
August 2021

TIGIT and PD1 Co-blockade Restores ex vivo Functions of Human Tumor-Infiltrating CD8 T Cells in Hepatocellular Carcinoma.

Cell Mol Gastroenterol Hepatol 2021 27;12(2):443-464. Epub 2021 Mar 27.

Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands. Electronic address:

Background & Aims: TIGIT is a co-inhibitory receptor, and its suitability as a target for cancer immunotherapy in HCC is unknown. PD1 blockade is clinically effective in about 20% of advanced HCC patients. Here we aim to determine whether co-blockade of TIGIT/PD1 has added value to restore functionality of HCC tumor-infiltrating T cells (TILs).

Methods: Mononuclear leukocytes were isolated from tumors, paired tumor-free liver tissues (TFL) and peripheral blood of HCC patients, and used for flow cytometric phenotyping and functional assays. CD3/CD28 T-cell stimulation and antigen-specific assays were used to study the ex vivo effects of TIGIT/PD1 single or dual blockade on T-cell functions.

Results: TIGIT was enriched, whereas its co-stimulatory counterpart CD226 was down-regulated on PD1 CD8 TILs. PD1 TIGIT CD8 TILs co-expressed exhaustion markers TIM3 and LAG3 and demonstrated higher TOX expression. Furthermore, this subset showed decreased capacity to produce IFN-γ and TNF-α. Expression of TIGIT-ligand CD155 was up-regulated on tumor cells compared with hepatocytes in TFL. Whereas single PD1 blockade preferentially enhanced ex vivo functions of CD8 TILs from tumors with PD1 CD8 TILs (high PD1 expressers), co-blockade of TIGIT and PD1 improved proliferation and cytokine production of CD8 TILs from tumors enriched for PD1 CD8 TILs (low PD1 expressers). Importantly, ex vivo co-blockade of TIGIT/PD1 improved proliferation, cytokine production, and cytotoxicity of CD8 TILs compared with single PD1 blockade.

Conclusions: Ex vivo, co-blockade of TIGIT/PD1 improves functionality of CD8 TILs that do not respond to single PD1 blockade. Therefore co-blockade of TIGIT/PD1 could be a promising immune therapeutic strategy for HCC patients.
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http://dx.doi.org/10.1016/j.jcmgh.2021.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255944PMC
March 2021

Regulations and Procurement Surgery in DCD Liver Transplantation: Expert Consensus Guidance From the International Liver Transplantation Society.

Transplantation 2021 05;105(5):945-951

Edinburgh Transplant Center, Royal Infirmary of Edinburgh, United Kingdom.

Donation after circulatory death (DCD) donors are an increasingly more common source of livers for transplantation in many parts of the world. Events that occur during DCD liver recovery have a significant impact on the success of subsequent transplantation. This working group of the International Liver Transplantation Society evaluated current evidence as well as combined experience and created this guidance on DCD liver procurement. Best practices for the recovery and transplantation of livers arising through DCD after euthanasia and organ procurement with super-rapid cold preservation and recovery as well as postmortem normothermic regional perfusion are described, as are the use of adjuncts during DCD liver procurement.
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http://dx.doi.org/10.1097/TP.0000000000003729DOI Listing
May 2021

Impact of hypoxia and AMPK on CFTR-mediated bicarbonate secretion in human cholangiocyte organoids.

Am J Physiol Gastrointest Liver Physiol 2021 05 3;320(5):G741-G752. Epub 2021 Mar 3.

Department of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands.

Cholangiocytes express cystic fibrosis transmembrane conductance regulator (CFTR), which is involved in bicarbonate secretion for the protection against bile toxicity. During liver transplantation, prolonged hypoxia of the graft is associated with cholangiocyte loss and biliary complications. Hypoxia is known to diminish CFTR activity in the intestine, but whether it affects CFTR activity in cholangiocytes remains unknown. Thus, the aim of this study is to investigate the effect of hypoxia on CFTR activity in intrahepatic cholangiocyte organoids (ICOs) and test drug interventions to restore bicarbonate secretion. Fifteen different human ICOs were cultured as monolayers and ion channel [CFTR and anoctamin-1 (ANO1)] activity was determined using an Ussing chamber assay with or without AMP kinase (AMPK) inhibitor under hypoxic and oxygenated conditions. Bile toxicity was tested by apical exposure of cells to fresh human bile. Overall gene expression analysis showed a high similarity between ICOs and primary cholangiocytes. Under oxygenated conditions, both CFTR and ANO1 channels were responsible for forskolin and uridine-5'-triphosphate (UTP) UTP-activated anion secretion. Forskolin stimulation in the absence of intracellular chloride showed ion transport, indicating that bicarbonate could be secreted by CFTR. During hypoxia, CFTR activity significantly decreased ( = 0.01). Switching from oxygen to hypoxia during CFTR measurements reduced CFTR activity ( = 0.03). Consequently, cell death increased when ICO monolayers were exposed to bile during hypoxia compared with oxygen ( = 0.04). Importantly, addition of AMPK inhibitor restored CFTR-mediated anion secretion during hypoxia. ICOs provide an excellent model to study cholangiocyte anion channels and drug-related interventions. Here, we demonstrate that hypoxia affects cholangiocyte ion secretion, leaving cholangiocytes vulnerable to bile toxicity. The mechanistic insights from this model maybe relevant for hypoxia-related biliary injury during liver transplantation. The previously described liver-derived organoids resemble primary cholangiocytes and should be properly named intrahepatic cholangiocyte organoids (ICOs). ICOs have functional cholangiocyte ion channels (CFTR and ANO1). CFTR might be able to secrete bicarbonate directly into the bile duct lumen. Hypoxia inhibits CFTR and ANO1 functionality in ICOs, which can partially be restored by addition of an AMP kinase inhibitor. Hypoxia impairs cholangiocyte resistance against cytotoxic effects of bile, resulting in increased cell death.
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http://dx.doi.org/10.1152/ajpgi.00389.2020DOI Listing
May 2021

Hypothermic Machine Perfusion in Liver Transplantation - A Randomized Trial.

N Engl J Med 2021 04 24;384(15):1391-1401. Epub 2021 Feb 24.

From the Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation (R.R., Y.V., O.B.L., V.E.M., R.J.P.), the Departments of Gastroenterology and Hepatology (A.P.B.) and Radiology (R.J.H., J.J.G.S.), University of Groningen, University Medical Center Groningen, Groningen, the Departments of Surgery (I.J.S., W.G.P., J.J.) and Gastroenterology and Hepatology (S.D.M.), Erasmus University Medical Center, Rotterdam, and the Departments of Surgery (J.I.E., V.A.L.H.) and Gastroenterology and Hepatology (B.H.), Leiden University Medical Center, Leiden - all in the Netherlands; the Institute of Liver Studies, Kings College Hospital NHS Foundation Trust, London (M.C.C., N.H.); the Transplantation Research Group, the Department of Microbiology, Immunology, and Transplantation, Katholieke Universiteit Leuven, and the Department of Abdominal Transplantation Surgery and Coordination, University Hospitals Leuven, Leuven (N.G., I.J., D.M.), and the Department of Transplant Surgery, Ghent University Hospital, Ghent (R.I.T., A.V.) - both in Belgium.

Background: Transplantation of livers obtained from donors after circulatory death is associated with an increased risk of nonanastomotic biliary strictures. Hypothermic oxygenated machine perfusion of livers may reduce the incidence of biliary complications, but data from prospective, controlled studies are limited.

Methods: In this multicenter, controlled trial, we randomly assigned patients who were undergoing transplantation of a liver obtained from a donor after circulatory death to receive that liver either after hypothermic oxygenated machine perfusion (machine-perfusion group) or after conventional static cold storage alone (control group). The primary end point was the incidence of nonanastomotic biliary strictures within 6 months after transplantation. Secondary end points included other graft-related and general complications.

Results: A total of 160 patients were enrolled, of whom 78 received a machine-perfused liver and 78 received a liver after static cold storage only (4 patients did not receive a liver in this trial). Nonanastomotic biliary strictures occurred in 6% of the patients in the machine-perfusion group and in 18% of those in the control group (risk ratio, 0.36; 95% confidence interval [CI], 0.14 to 0.94; P = 0.03). Postreperfusion syndrome occurred in 12% of the recipients of a machine-perfused liver and in 27% of those in the control group (risk ratio, 0.43; 95% CI, 0.20 to 0.91). Early allograft dysfunction occurred in 26% of the machine-perfused livers, as compared with 40% of control livers (risk ratio, 0.61; 95% CI, 0.39 to 0.96). The cumulative number of treatments for nonanastomotic biliary strictures was lower by a factor of almost 4 after machine perfusion, as compared with control. The incidence of adverse events was similar in the two groups.

Conclusions: Hypothermic oxygenated machine perfusion led to a lower risk of nonanastomotic biliary strictures following the transplantation of livers obtained from donors after circulatory death than conventional static cold storage. (Funded by Fonds NutsOhra; DHOPE-DCD ClinicalTrials.gov number, NCT02584283.).
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http://dx.doi.org/10.1056/NEJMoa2031532DOI Listing
April 2021

Organ Donation After Euthanasia Starting at Home Is Feasible-Reply.

JAMA Surg 2021 May;156(5):502-503

Division of Hepato-Pancreato-Biliary and Transplant Surgery, Department of Surgery, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands.

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http://dx.doi.org/10.1001/jamasurg.2020.6680DOI Listing
May 2021

Ex Situ Dual Hypothermic Oxygenated Machine Perfusion for Human Split Liver Transplantation.

Transplant Direct 2021 Mar 4;7(3):e666. Epub 2021 Feb 4.

Department of Surgery, Section of HPB Surgery & Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Liver splitting allows the opportunity to share a deceased graft between 2 recipients but remains underutilized. We hypothesized that liver splitting during continuous dual hypothermic oxygenated machine perfusion (DHOPE) is feasible, with shortened total cold ischemia times and improved logistics. Here, we describe a left lateral segment (LLS) and extended right lobe (ERL) liver split procedure during continuous DHOPE preservation with subsequent transplantation at 2 different centers.

Methods: After transport using static cold storage, a 51-year-old brain death donor liver underwent end-ischemic DHOPE. During DHOPE, the donor liver was maintained <10 °C and oxygenated with a Po of >106 kPa. An ex situ ERL/LLS split was performed with continuing DHOPE throughout the procedure to avoid additional ischemia time.

Results: Total cold ischemia times for the LLS and ERL were 205 minutes and 468 minutes, respectively. Both partial grafts were successfully transplanted at 2 different transplant centers. Peak aspartate aminotransferase and alanine aminotransferase were 172 IU/L and 107 IU/L for the LLS graft, and 839 IU/L and 502 IU/L for the ERL graft, respectively. The recipient of the LLS experienced an episode of acute cellular rejection. The ERL transplantation was complicated by severe acute pancreatitis with jejunum perforation requiring percutaneous drainage and acute cellular rejection. No device-related adverse events were observed.

Conclusions: Liver splitting during continuous DHOPE preservation is feasible, has the potential to substantially shorten cold ischemia time and may optimize transplant logistics. Therefore liver splitting with DHOPE can potentially improve utilization of split liver transplantation.
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http://dx.doi.org/10.1097/TXD.0000000000001116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862033PMC
March 2021

Protective Role of Tacrolimus, Deleterious Role of Age and Comorbidities in Liver Transplant Recipients With Covid-19: Results From the ELITA/ELTR Multi-center European Study.

Gastroenterology 2021 03 9;160(4):1151-1163.e3. Epub 2020 Dec 9.

Liver and Multi-organ Transplantation, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.

Background And Aims: Despite concerns that liver transplant (LT) recipients may be at increased risk of unfavorable outcomes from COVID-19 due the high prevalence of co-morbidities, immunosuppression and ageing, a detailed analysis of their effects in large studies is lacking.

Methods: Data from adult LT recipients with laboratory confirmed SARS-CoV2 infection were collected across Europe. All consecutive patients with symptoms were included in the analysis.

Results: Between March 1 and June 27, 2020, data from 243 adult symptomatic cases from 36 centers and 9 countries were collected. Thirty-nine (16%) were managed as outpatients while 204 (84%) required hospitalization including admission to the ICU (39 of 204, 19.1%). Forty-nine (20.2%) patients died after a median of 13.5 (10-23) days, respiratory failure was the major cause. After multivariable Cox regression analysis, age >70 (HR, 4.16; 95% CI, 1.78-9.73) had a negative effect and tacrolimus (TAC) use (HR, 0.55; 95% CI, 0.31-0.99) had a positive independent effect on survival. The role of co-morbidities was strongly influenced by the dominant effect of age where comorbidities increased with the increasing age of the recipients. In a second model excluding age, both diabetes (HR, 1.95; 95% CI, 1.06-3.58) and chronic kidney disease (HR, 1.97; 95% CI, 1.05-3.67) emerged as associated with death CONCLUSIONS: Twenty-five percent of patients requiring hospitalization for COVID-19 died, the risk being higher in patients older than 70 and with medical co-morbidities, such as impaired renal function and diabetes. Conversely, the use of TAC was associated with a better survival thus encouraging clinicians to keep TAC at the usual dose.
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http://dx.doi.org/10.1053/j.gastro.2020.11.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724463PMC
March 2021

Development of a novel and low-cost anthropomorphic pelvis phantom for 3D dosimetry in radiotherapy.

J Contemp Brachytherapy 2020 Oct 30;12(5):470-479. Epub 2020 Oct 30.

Department of Physics, University of Surrey, Guildford, United Kingdom.

Purpose: The aim of this study was to construct a low-cost, anthropomorphic, and 3D-printed pelvis phantom and evaluate the feasibility of its use to perform 3D dosimetry with commercially available bead thermoluminescent dosimeters (TLDs).

Material And Methods: A novel anthropomorphic female phantom was developed with all relevant pelvic organs to position the bead TLDs. Organs were 3D-printed using acrylonitrile butadiene styrene. Phantom components were confirmed to have mass density and computed tomography (CT) numbers similar to relevant tissues. To find out clinically required spatial resolution of beads to cause no perturbation effect, TLDs were positioned with 2.5, 5, and 7.5 mm spacing on the surface of syringe. After taking a CT scan and creating a 4-field conformal radiotherapy plan, 3 dose planes were extracted from the treatment planning system (TPS) at different depths. By using a 2D-gamma analysis, the TPS reports were compared with and without the presence of beads. Moreover, the bead TLDs were placed on the organs' surfaces of the pelvis phantom and exposed to high-dose-rate (HDR) Co source. TLDs' readouts were compared with the TPS calculated doses, and dose surface histograms (DSHs) of organs were plotted.

Results: 3D-printed phantom organs agreed well with body tissues regarding both their design and radiation properties. Furthermore, the 2D-gamma analysis on the syringe showed more than 99% points passed 3%- and 3-mm criteria at different depths. By calculating the integral dose of DSHs, the percentage differences were -1.5%, 2%, 5%, and 10% for uterus, rectum, bladder, and sigmoid, respectively. Also, combined standard uncertainty was estimated as 3.5% ( = 1).

Conclusions: A customized pelvis phantom was successfully built and assessed to confirm properties similar to body tissues. Additionally, no significant perturbation effect with different bead resolutions was presented by the external TPS, with 0.1 mm dose grid resolution.
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http://dx.doi.org/10.5114/jcb.2020.100380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701919PMC
October 2020

Donor diabetes mellitus is a risk factor for diminished outcome after liver transplantation: a nationwide retrospective cohort study.

Transpl Int 2021 01 5;34(1):110-117. Epub 2020 Nov 5.

Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

With the growing incidence of diabetes mellitus (DM), an increasing number of organ donors with DM can be expected. We sought to investigate the association between donor DM with early post-transplant outcomes. From a national cohort of adult liver transplant recipients (1996-2016), all recipients transplanted with a liver from a DM donor (n = 69) were matched 1:2 with recipients of livers from non-DM donors (n = 138). The primary end-point included early post-transplant outcome, such as the incidence of primary nonfunction (PNF), hepatic artery thrombosis (HAT), and 90-day graft survival. Cox regression analysis was used to analyze the impact of donor DM on graft failure. PNF was observed in 5.8% of grafts from DM donors versus 2.9% of non-DM donor grafts (P = 0.31). Recipients of grafts derived from DM donors had a higher incidence of HAT (8.7% vs. 2.2%, P = 0.03) and decreased 90-day graft survival (88.4% [70.9-91.1] vs. 96.4% [89.6-97.8], P = 0.03) compared to recipients of grafts from non-DM donors. The adjusted hazard ratio for donor DM on graft survival was 2.21 (1.08-4.53, P = 0.03). In conclusion, donor DM is associated with diminished outcome early after liver transplantation. The increased incidence of HAT after transplantation of livers from DM donors requires further research.
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http://dx.doi.org/10.1111/tri.13770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820994PMC
January 2021

Reply to Rodriguez-Peralvarez et al.

Transpl Int 2020 12 9;33(12):1825-1826. Epub 2020 Nov 9.

Medical Liver Transplant Unit and Liver Department, Henri Mondor Hospital AP-HP, Paris Est University, Champs-sur-Marne, France.

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http://dx.doi.org/10.1111/tri.13765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675308PMC
December 2020
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