38 results on '"de Kleine RHJ"'
Search Results
2. Algorithm-based care versus usual care for the early recognition and management of complications after pancreatic resection in the Netherlands: an open-label, nationwide, stepped-wedge cluster-randomised trial
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Smits, F Jasmijn, primary, Henry, Anne Claire, additional, Besselink, Marc G, additional, Busch, Olivier R, additional, van Eijck, Casper H, additional, Arntz, Mark, additional, Bollen, Thomas L, additional, van Delden, Otto M, additional, van den Heuvel, Daniel, additional, van der Leij, Christiaan, additional, van Lienden, Krijn P, additional, Moelker, Adriaan, additional, Bonsing, Bert A, additional, Borel Rinkes, Inne H, additional, Bosscha, Koop, additional, van Dam, Ronald M, additional, Derksen, Wouter J M, additional, den Dulk, Marcel, additional, Festen, Sebastiaan, additional, Groot Koerkamp, Bas, additional, de Haas, Robbert J, additional, Hagendoorn, Jeroen, additional, van der Harst, Erwin, additional, de Hingh, Ignace H, additional, Kazemier, Geert, additional, van der Kolk, Marion, additional, Liem, Mike, additional, Lips, Daan J, additional, Luyer, Misha D, additional, de Meijer, Vincent E, additional, Mieog, J Sven, additional, Nieuwenhuijs, Vincent B, additional, Patijn, Gijs A, additional, te Riele, Wouter W, additional, Roos, Daphne, additional, Schreinemakers, Jennifer M, additional, Stommel, Martijn W J, additional, Wit, Fennie, additional, Zonderhuis, Babs A, additional, Daamen, Lois A, additional, van Werkhoven, C Henri, additional, Molenaar, I Quintus, additional, van Santvoort, Hjalmar C, additional, Blomjous, JG, additional, de Boer, MT, additional, van den Boezem, P, additional, Bouwense, S, additional, Bruijnen, R, additional, Buis, CI, additional, del Chiaro, M, additional, Coene, PP, additional, Coolsen, M, additional, Daams, F, additional, Dejong, K, additional, Draaisma, W, additional, Eker, HH, additional, Elsen, AH, additional, Gerhards, MF, additional, Hartog, H, additional, Hoogwater, FJ, additional, Imani, F, additional, Jenniskens, S, additional, de Jong, KP, additional, Karsten, TM, additional, Klaase, JM, additional, de Kleine, RHJ, additional, van Laarhoven, CJ, additional, van der Lelij, H, additional, Manusama, ER, additional, Meerdink, M, additional, Meijerink, M, additional, Nederend, J, additional, Nijkamp, MW, additional, Nota, CL, additional, Porte, RJ, additional, Reef, J, additional, de Reuver, P, additional, van Rijswijk, C, additional, Romkens, T, additional, Rupert, C, additional, van der Schelling, GP, additional, Serafino, JP, additional, Vos, LD, additional, Vriens, MR, additional, Beers-Vural, E, additional, Wagtenberg, JM, additional, Wijsman, JH, additional, de Wilde, RF, additional, Wolfgang, CL, additional, and Zeh, HJ, additional
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- 2022
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3. Prevalence, management and efficacy of treatment in portal vein obstruction after paediatric liver transplantation: protocol of the retrospective international multicentre PORTAL registry.
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Alfares BA, van der Doef HPJ, Wildhaber BE, Casswall T, Nowak G, Delle M, Aldrian D, Berchtold V, Vogel GF, Kaliciński P, Markiewicz-Kijewska M, Kolesnik A, Bernabeu JQ, Hally MM, Larrarte K M, Marra P, Bravi M, Pinelli D, Kasahara M, Sakamoto S, Uchida H, Mali V, Aw M, Franchi-Abella S, Gonzales E, Guérin F, Cervio G, Minetto J, Sierre S, de Santibañes M, Ardiles V, Uno JW, Evans H, Duncan D, McCall J, Hartleif S, Sturm E, Patel J, Mtegha M, Prasad R, Ferreira CT, Nader LS, Farina M, Jaramillo C, Rodriguez-Davalos MI, Feola P, Shah AA, Wood PM, Acord MR, Fischer RT, Mullapudi B, Hendrickson RJ, Khanna R, Pamecha V, Mukund A, Sharif K, Gupte G, McGuirk S, Porta G, Spada M, Alterio T, Maggiore G, Hardikar W, Beretta M, Dierckx R, de Kleine RHJ, and Bokkers RPH
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- Humans, Child, Portal Vein, Retrospective Studies, Prevalence, Registries, Observational Studies as Topic, Multicenter Studies as Topic, Liver Transplantation adverse effects, Liver Diseases, Vascular Diseases epidemiology, Vascular Diseases etiology, Vascular Diseases surgery
- Abstract
Introduction: Portal vein obstruction (PVO) consists of anastomotic stenosis and thrombosis, which occurs due to a progression of the former. The aim of this large-scale international study is to assess the prevalence, current management practices and efficacy of treatment in patients with PVO., Methods and Analysis: The Portal vein Obstruction Revascularisation Therapy After Liver transplantation registry will facilitate an international, retrospective, multicentre, observational study, with 25 centres around the world already actively involved. Paediatric patients (aged <18 years) with a diagnosed PVO between 1 January 2001 and 1 January 2021 after liver transplantation will be eligible for inclusion. The primary endpoints are the prevalence of PVO, primary and secondary patency after PVO intervention and current management practices. Secondary endpoints are patient and graft survival, severe complications of PVO and technical success of revascularisation techniques., Ethics and Dissemination: Medical Ethics Review Board of the University Medical Center Groningen has approved the study (METc 2021/072). The results of this study will be disseminated via peer-reviewed publications and scientific presentations at national and international conferences., Trial Registration Number: Netherlands Trial Register (NL9261)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2023
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4. Minimally invasive versus open distal pancreatectomy for resectable pancreatic cancer (DIPLOMA): an international randomised non-inferiority trial.
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Korrel M, Jones LR, van Hilst J, Balzano G, Björnsson B, Boggi U, Bratlie SO, Busch OR, Butturini G, Capretti G, Casadei R, Edwin B, Emmen AMLH, Esposito A, Falconi M, Groot Koerkamp B, Keck T, de Kleine RHJ, Kleive DB, Kokkola A, Lips DJ, Lof S, Luyer MDP, Manzoni A, Marudanayagam R, de Pastena M, Pecorelli N, Primrose JN, Ricci C, Salvia R, Sandström P, Vissers FLIM, Wellner UF, Zerbi A, Dijkgraaf MGW, Besselink MG, and Abu Hilal M
- Abstract
Background: The oncological safety of minimally invasive surgery has been questioned for several abdominal cancers. Concerns also exist regarding the use of minimally invasive distal pancreatectomy (MIDP) in patients with resectable pancreatic cancer as randomised trials are lacking., Methods: In this international randomised non-inferiority trial, we recruited adults with resectable pancreatic cancer from 35 centres in 12 countries. Patients were randomly assigned to either MIDP (laparoscopic or robotic) or open distal pancreatectomy (ODP). Both patients and pathologists were blinded to the assigned approach. Primary endpoint was radical resection (R0, ≥1 mm free margin) in patients who had ultimately undergone resection. Analyses for the primary endpoint were by modified intention-to-treat, excluding patients with missing data on primary endpoint. The pre-defined non-inferiority margin of -7% was compared with the lower limit of the two-sided 90% confidence interval (CI) of absolute difference in the primary endpoint. This trial is registered with the ISRCTN registry (ISRCTN44897265)., Findings: Between May 8, 2018 and May 7, 2021, 258 patients were randomly assigned to MIDP (131 patients) or ODP (127 patients). Modified intention-to-treat analysis included 114 patients in the MIDP group and 110 patients in the ODP group. An R0 resection occurred in 83 (73%) patients in the MIDP group and in 76 (69%) patients in the ODP group (difference 3.7%, 90% CI -6.2 to 13.6%; p
non-inferiority = 0.039). Median lymph node yield was comparable (22.0 [16.0-30.0] vs 23.0 [14.0-32.0] nodes, p = 0.86), as was the rate of intraperitoneal recurrence (41% vs 38%, p = 0.45). Median follow-up was 23.5 (interquartile range 17.0-30.0) months. Other postoperative outcomes were comparable, including median time to functional recovery (5 [95% CI 4.5-5.5] vs 5 [95% CI 4.7-5.3] days; p = 0.22) and overall survival (HR 0.99, 95% CI 0.67-1.46, p = 0.94). Serious adverse events were reported in 23 (18%) of 131 patients in the MIDP group vs 28 (22%) of 127 patients in the ODP group., Interpretation: This trial provides evidence on the non-inferiority of MIDP compared to ODP regarding radical resection rates in patients with resectable pancreatic cancer. The present findings support the applicability of minimally invasive surgery in patients with resectable left-sided pancreatic cancer., Funding: Medtronic Covidien AG, Johnson & Johnson Medical Limited, Dutch Gastroenterology Society., Competing Interests: Tobias Keck is a member of the advisory board for Olympus, Medtronic, and Dexter. Daan Lips received a proctoring grant by 10.13039/100010477Intuitive Surgical. Marc Besselink and Mohammad Abu Hilal received Investigator Initiated Research grants by Medtronic (DIPLOMA trial), Ethicon (DIPLOMA trial and E-MIPS registry), and Intuitive Surgical (E-MIPS registry) and proctoring grants for Dutch and European training programs in robotic pancreatoduodenectomy by Intuitive Surgical. The other authors have no conflicts of interest., (© 2023 The Authors.)- Published
- 2023
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5. Correction: Doppler Ultrasound of Vascular Complications After Pediatric Liver Transplantation: Incidence, Time of Detection, and Positive Predictive Value.
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Verhagen MV, de Kleine RHJ, van der Doef HPJ, Kwee TC, and de Haas RJ
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[This corrects the article DOI: 10.1055/a-1961-9100.]., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)
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- 2023
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6. Waitlist mortality of young patients with biliary atresia: Impact of allocation policy and living donor liver transplantation.
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Esmati H, van Rosmalen M, van Rheenen PF, de Boer MT, van den Berg AP, van der Doef HPJ, Rayar M, de Kleine RHJ, Porte RJ, de Meijer VE, and Verkade HJ
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- Humans, Living Donors, Cohort Studies, Risk Assessment, Retrospective Studies, Treatment Outcome, Liver Transplantation adverse effects, Biliary Atresia surgery
- Abstract
Patients with biliary atresia (BA) below 2 years of age in need of a transplantation largely rely on partial grafts from deceased donors (deceased donor liver transplantation [DDLT]) or living donors (living donor liver transplantation [LDLT]). Because of high waitlist mortality in especially young patients with BA, the Eurotransplant Liver Intestine Advisory Committee (ELIAC) has further prioritized patients with BA listed before their second birthday for allocation of a deceased donor liver since 2014. We evaluated whether this Eurotransplant (ET) allocation prioritization changed the waitlist mortality of young patients with BA. We used a pre-post cohort study design with the implementation of the new allocation rule between the two periods. Participants were patients with BA younger than 2 years who were listed for liver transplantation in the ET database between 2001 and 2018. Competing risk analyses were performed to assess waitlist mortality in the first 2 years after listing. We analyzed a total of 1055 patients with BA, of which 882 had been listed in the preimplementation phase (PRE) and 173 in the postimplementation phase (POST). Waitlist mortality decreased from 6.7% in PRE to 2.3% in POST ( p = 0.03). Interestingly, the proportion of young patients with BA undergoing DDLT decreased from 32% to 18% after ET allocation prioritization ( p = 0.001), whereas LDLT increased from 55% to 74% ( p = 0.001). The proportional increase in LDLT decreased the median waitlist duration of transplanted patients from 1.5 months in PRE to 0.85 months in POST ( p = 0.003). Since 2014, waitlist mortality in young patients with BA has strongly decreased in the ET region. Rather than associated with prioritized allocation of deceased donor organs, the decreased waitlist mortality was related to a higher proportion of patients undergoing LDLT., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2023
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7. Anti-IFC antibodies in a patient with CHAPLE syndrome: Implications for blood management.
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Minović I, Schipperus MR, Mäkelburg ABU, Meijer K, Lukens MV, Kootstra-Ros JE, van der Heide F, Abbasova I, de Kleine RHJ, Meekers JH, and Mulder AB
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- Humans, Syndrome, Autoantibodies
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- 2023
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8. Doppler Ultrasound of Vascular Complications After Pediatric Liver Transplantation: Incidence, Time of Detection, and Positive Predictive Value.
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Verhagen MV, de Kleine RHJ, van der Doef HPJ, Kwee TC, and de Haas RJ
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Purpose Doppler ultrasound (DUS) is widely used to detect vascular complications after pediatric liver transplantation (LT). This study aimed to assess the moment of first detection of vascular complications with DUS, and to determine the positive predictive value (PPV) of DUS. Materials and Methods Patients aged 0-18 years who underwent LT between 2015 and 2019 were retrospectively included. 92 LTs in 83 patients were included (median age: 3.9 years, interquartile range: 0.7-10.5). Patients underwent perioperative (intra-operative and immediately postoperative) and daily DUS surveillance during the first postoperative week, and at 1, 3, and 12 months. Vascular complications were categorized for the hepatic artery, portal vein, and hepatic veins. DUS findings were compared to surgical or radiological findings during the 1-year follow-up. Results 52 vascular complications were diagnosed by DUS in 35/92 LTs (38%). 15 out of 52 (28.8%) were diagnosed perioperatively, 29/52 (55.8%) were diagnosed on postoperative days 1-7, and 8/52 (15.4%) after day 7. The PPV for all vascular complications diagnosed with DUS was 92.3%. During the 1-year follow-up, 18/19 (94.7%) hepatic artery complications, 19/26 (73.1%) portal vein complications, and 7/7 (100%) hepatic vein complications were diagnosed perioperatively or during the first week. Conclusion The majority of vascular complications during the first year after pediatric LT were diagnosed by DUS perioperatively or during the first week, with a high PPV. Our findings provide important information regarding when to expect different types of vascular complications on DUS, which might improve DUS post-LT surveillance protocols., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)
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- 2022
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9. Risk factors for complications after surgery for pancreatic neuroendocrine tumors.
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van Beek DJ, Takkenkamp TJ, Wong-Lun-Hing EM, de Kleine RHJ, Walenkamp AME, Klaase JM, Nijkamp MW, Valk GD, Molenaar IQ, Hagendoorn J, van Santvoort HC, Borel Rinkes IHM, Hoogwater FJH, and Vriens MR
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- Cohort Studies, Humans, Pancreatectomy adverse effects, Risk Factors, Multiple Endocrine Neoplasia Type 1 complications, Neuroendocrine Tumors pathology, Pancreatic Neoplasms
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Background: Surgical resection is the only potentially curative treatment for pancreatic neuroendocrine tumors. The choice for the type of procedure is influenced by the expected oncological benefit and the anticipated risk of procedure-specific complications. Few studies have focused on complications in these patients. This cohort study aimed to assess complications and risk factors after resections of pancreatic neuroendocrine tumors., Methods: Patients undergoing resection of a pancreatic neuroendocrine tumor were identified within 2 centers of excellence. Complications were assessed according to the Clavien-Dindo classification and the comprehensive complication index. Logistic regression was performed to compare surgical procedures with adjustment for potential confounders (Clavien-Dindo ≥3)., Results: The cohort comprised 123 patients, including 12 enucleations, 50 distal pancreatectomies, 51 pancreatoduodenectomies, and 10 total/combined pancreatectomies. Mortality was 0.8%, a severe complication occurred in 41.5%, and the failure-to-rescue rate was 2.0%. The median comprehensive complication index was 22.6 (0-100); the comprehensive complication index increased after more extensive resections. After adjustment, a pancreatoduodenectomy, as compared to a distal pancreatectomy, increased the risk for a severe complication (odds ratio 3.13 [95% confidence interval 1.32-7.41]). Of the patients with multiple endocrine neoplasia type 1 or von Hippel-Lindau, 51.9% developed a severe complication vs 38.5% with sporadic disease. After major resections, morbidity was significantly higher in patients with multiple endocrine neoplasia type 1/von Hippel-Lindau (comprehensive complication index 45.1 vs 28.9, P = .029)., Conclusion: Surgery for pancreatic neuroendocrine tumors is associated with a high rate of complications but low failure-to-rescue in centers of excellence. Complications are procedure-specific. Major resections in patients with multiple endocrine neoplasia type 1/von Hippel-Lindau appear to increase the risk of complications., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2022
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10. Sequential hypothermic and normothermic machine perfusion enables safe transplantation of high-risk donor livers.
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van Leeuwen OB, Bodewes SB, Lantinga VA, Haring MPD, Thorne AM, Brüggenwirth IMA, van den Berg AP, de Boer MT, de Jong IEM, de Kleine RHJ, Lascaris B, Nijsten MWN, Reyntjens KMEM, de Meijer VE, and Porte RJ
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- Hemoglobins, Humans, Liver, Living Donors, Organ Preservation methods, Oxygen, Perfusion methods, Prospective Studies, Liver Transplantation methods
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Ex situ normothermic machine perfusion (NMP) is increasingly used for viability assessment of high-risk donor livers, whereas dual hypothermic oxygenated machine perfusion (DHOPE) reduces ischemia-reperfusion injury. We aimed to resuscitate and test the viability of initially-discarded, high-risk donor livers using sequential DHOPE and NMP with two different oxygen carriers: an artificial hemoglobin-based oxygen carrier (HBOC) or red blood cells (RBC). In a prospective observational cohort study of 54 livers that underwent DHOPE-NMP, the first 18 procedures were performed with a HBOC-based perfusion solution and the subsequent 36 procedures were performed with an RBC-based perfusion solution for the NMP phase. All but one livers were derived from extended criteria donation after circulatory death donors, with a median donor risk index of 2.84 (IQR 2.52-3.11). After functional assessment during NMP, 34 livers (63% utilization), met the viability criteria and were transplanted. One-year graft and patient survival were 94% and 100%, respectively. Post-transplant cholangiopathy occurred in 1 patient (3%). There were no significant differences in utilization rate and post-transplant outcomes between the HBOC and RBC group. Ex situ machine perfusion using sequential DHOPE-NMP for resuscitation and viability assessment of high-risk donor livers results in excellent transplant outcomes, irrespective of the oxygen carrier used., (© 2022 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)
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- 2022
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11. Unusual Long Absence of Isolated Biliary Atresia in COVID Lockdown: Coincidence or Association?
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Nomden M, de Kleine RHJ, Bruggink JLM, Verkade HJ, Burgerhof JGM, and Hulscher JBF
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- Communicable Disease Control, Humans, Infant, SARS-CoV-2, Biliary Atresia complications, Biliary Atresia surgery, COVID-19
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- 2022
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12. Pancreatic resection in the pediatric, adolescent and young adult population: nationwide analysis on complications.
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Pranger BK, van Dam JL, Groen JV, van Eijck CH, Koerkamp BG, Bonsing BA, Mieog JSD, Besselink MG, Busch OR, Kazemier G, de Jong KP, de Kleine RHJ, Molenaar IQ, Stommel MWJ, Gerhards MF, Coolsen MME, van Santvoort HC, van der Harst E, Klaase JM, and de Meijer VE
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- Adolescent, Child, Humans, Pancreas, Pancreatectomy adverse effects, Pancreaticoduodenectomy adverse effects, Postoperative Complications etiology, Retrospective Studies, Treatment Outcome, Young Adult, Exocrine Pancreatic Insufficiency, Pancreatic Neoplasms surgery
- Abstract
Background: The aim of this study was to determine pancreatic surgery specific short- and long-term complications of pediatric, adolescent and young adult (PAYA) patients who underwent pancreatic resection, as compared to a comparator cohort of adults., Methods: A nationwide retrospective cohort study was performed in PAYA patients who underwent pancreatic resection between 2007 and 2016. PAYA was defined as all patients <40 years at time of surgery. Pancreatic surgery-specific complications were assessed according to international definitions and textbook outcome was determined., Results: A total of 230 patients were included in the PAYA cohort (112 distal pancreatectomies, 99 pancreatoduodenectomies), and 2526 patients in the comparator cohort. For pancreatoduodenectomy, severe morbidity (29.3% vs. 28.6%; P = 0.881), in-hospital mortality (1% vs. 4%; P = 0.179) and textbook outcome (62% vs. 58%; P = 0.572) were comparable between the PAYA and the comparator cohort. These outcomes were also similar for distal pancreatectomy. After pancreatoduodenectomy, new-onset diabetes mellitus (8% vs. 16%) and exocrine pancreatic insufficiency (27% vs. 73%) were lower in the PAYA cohort when compared to adult literature., Conclusion: Pancreatic surgery-specific complications were comparable with patients ≥40 years. Development of endocrine and exocrine insufficiency in PAYA patients who underwent pancreatoduodenectomy, however, was substantially lower compared to adult literature., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2021
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13. Machine Perfusion of Donation After Circulatory Death Liver and Lungs Before Combined Liver-lung Transplantation.
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van Leeuwen OB, Brüggenwirth IMA, de Kleine RHJ, van den Berg AP, Verschuuren EAM, Erasmus ME, and Porte RJ
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Shortage of deceased donor organs for transplantation has led to the increased use of organs from donation after circulatory death (DCD) donors. There are currently no reports describing outcomes after multiorgan transplantation with DCD livers. The use of DCD organs for multiorgan transplantation can be enhanced if the detrimental effects of prolonged cold ischemia and subsequent ischemia-reperfusion injury are overcome. We present a case in which the liver and lungs of a DCD donor were preserved using ex situ machine perfusion for combined liver-lung transplantation. The recipient was a 19-year-old male patient requiring bilateral lung transplantation for severe progressive pleural parenchymal fibroelastosis and portal hypertension with portal vein thrombosis. The donor liver was preserved with dual hypothermic oxygenated machine perfusion, whereas the lungs were perfused using ex vivo lung perfusion. With ex vivo lung perfusion, total preservation time of right and left lung reached 17 and 21 h, respectively. Now, 2 y after transplantation, liver function is normal and lung function is improving. To conclude, we suggest that combined transplantation of DCD liver and lungs is feasible when cold ischemia is reduced with ex situ machine perfusion preservation., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)
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- 2021
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14. Ex Situ Dual Hypothermic Oxygenated Machine Perfusion for Human Split Liver Transplantation.
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Thorne AM, Lantinga V, Bodewes S, de Kleine RHJ, Nijkamp MW, Sprakel J, Hartog H, Polak WG, Porte RJ, and de Meijer VE
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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
2 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., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2021 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)- Published
- 2021
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15. Human extrahepatic and intrahepatic cholangiocyte organoids show region-specific differentiation potential and model cystic fibrosis-related bile duct disease.
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Verstegen MMA, Roos FJM, Burka K, Gehart H, Jager M, de Wolf M, Bijvelds MJC, de Jonge HR, Ardisasmita AI, van Huizen NA, Roest HP, de Jonge J, Koch M, Pampaloni F, Fuchs SA, Schene IF, Luider TM, van der Doef HPJ, Bodewes FAJA, de Kleine RHJ, Spee B, Kremers GJ, Clevers H, IJzermans JNM, Cuppen E, and van der Laan LJW
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- Adolescent, Bile Duct Diseases pathology, Bile Ducts, Intrahepatic pathology, Cystic Fibrosis pathology, Humans, Male, Organoids pathology, Bile Duct Diseases metabolism, Bile Ducts, Intrahepatic metabolism, Cell Differentiation, Cystic Fibrosis metabolism, Organoids metabolism
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The development, homeostasis, and repair of intrahepatic and extrahepatic bile ducts are thought to involve distinct mechanisms including proliferation and maturation of cholangiocyte and progenitor cells. This study aimed to characterize human extrahepatic cholangiocyte organoids (ECO) using canonical Wnt-stimulated culture medium previously developed for intrahepatic cholangiocyte organoids (ICO). Paired ECO and ICO were derived from common bile duct and liver tissue, respectively. Characterization showed both organoid types were highly similar, though some differences in size and gene expression were observed. Both ECO and ICO have cholangiocyte fate differentiation capacity. However, unlike ICO, ECO lack the potential for differentiation towards a hepatocyte-like fate. Importantly, ECO derived from a cystic fibrosis patient showed no CFTR channel activity but normal chloride channel and MDR1 transporter activity. In conclusion, this study shows that ECO and ICO have distinct lineage fate and that ECO provide a competent model to study extrahepatic bile duct diseases like cystic fibrosis.
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- 2020
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16. Body Composition of Infants With Biliary Atresia: Anthropometric Measurements and Computed Tomography-based Body Metrics.
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Grutters LA, Pennings JP, Bruggink JLM, Viddeleer AR, Verkade HJ, de Kleine RHJ, and de Haas RJ
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- Arm, Benchmarking, Body Composition, Cross-Sectional Studies, Humans, Infant, Infant, Newborn, Retrospective Studies, Tomography, X-Ray Computed, Biliary Atresia complications, Biliary Atresia diagnostic imaging
- Abstract
Objectives: Biliary atresia (BA) causes neonatal cholestasis that requires hepatoportoenterostomy or liver transplantation (LT) for long-term survival. Nutritional optimization is necessary as sarcopenia and sarcopenic obesity have been associated with adverse clinical outcome. Currently, mid upper arm circumference (MUAC) is considered the most accurate indicator. The aim of the study was to determine computed tomography (CT)-based body metrics in infants with BA and to evaluate its correlation with MUAC., Methods: We retrospectively analyzed all BA infants below 2 years of age who underwent CT as part of LT screening at our hospital between 2006 and 2019. Measured variables were indexed with length and included: MUAC, total psoas muscle surface area (tPMSA), cross-sectional skeletal muscle area (CSMA), and total abdominal fat area. Intraclass correlation coefficients and Pearson coefficients were calculated. CSMA-to-abdominal fat area ratio was divided in quartiles, the lowest quartile group was considered sarcopenic obese., Results: Eighty infants with a median age of 4.6 months at LT screening were included. Intraclass correlation coefficients were: tPMSA = 0.94, CSMA = 0.92, and total abdominal fat area = 0.99. Correlation between MUAC z-score and indices of tPMSA, CSMA, and total abdominal fat area were r = 0.02, r = 0.06, and r = 0.43, respectively. The cut-off for sarcopenic obesity was CSMA-to-abdominal fat area ratio below 0.93., Conclusions: In BA infants, it is possible to determine CT-based body metrics during LT screening with very strong interobserver agreement. Poor correlation between CT-based body metrics and MUAC suggests that CT-based body metrics provide additional information on body composition in BA infants, such as relative muscle mass.
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- 2020
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17. In Vitro Evaluation of Pro- and Anticoagulant Drugs in Children with End-Stage Liver Disease Undergoing Liver Transplantation.
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Werner MJM, Adelmeijer J, de Meijer VE, de Kleine RHJ, Scheenstra R, Bontemps STH, Reyntjens KMEM, Hulscher JBF, Porte RJ, and Lisman T
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- Anticoagulants therapeutic use, Blood Coagulation Factors pharmacology, Blood Coagulation Factors therapeutic use, Child, Child, Preschool, Dabigatran pharmacology, Dabigatran therapeutic use, End Stage Liver Disease blood, Female, Hemostatics therapeutic use, Heparin pharmacology, Heparin therapeutic use, Humans, Male, Rivaroxaban pharmacology, Rivaroxaban therapeutic use, Anticoagulants pharmacology, Blood Coagulation drug effects, End Stage Liver Disease therapy, Hemostatics pharmacology, Liver Transplantation
- Abstract
Background: Pro- and anticoagulant drugs are commonly used in pediatric liver transplantation to prevent and treat thrombotic and bleeding complications. However, the combination of baseline hemostatic changes in children with liver disease and additional changes induced by transplantation makes this very challenging. This study aimed to analyze the efficacy of clinically available pro- and anticoagulant drugs in plasma from children undergoing liver transplantation., Methods: In vitro effects of pro- and anticoagulant drugs on thrombin generation capacity were tested in plasma samples of 20 children (≤ 16 years) with end-stage liver disease undergoing liver transplantation, and compared with 30 age-matched healthy controls., Results: Addition of pooled normal plasma had no effect in patients or controls, while 4-factor prothrombin complex concentrate increased thrombin generation in both patients and controls, with enhanced activity in patients. At start of transplantation, dabigatran and unfractionated heparin had a higher anticoagulant potency in patients, whereas 30 days after transplantation low molecular weight heparin was slightly less effective in patients. Effects of rivaroxaban were comparable between patients and controls., Conclusion: This study revealed important differences in efficacy of commonly used pro- and anticoagulant drugs in children with end-stage liver disease undergoing liver transplantation. Therefore, dose adjustments of these drugs may be required. The results of this study may be helpful in the development of urgently needed protocols for strategies to prevent and treat bleeding and thrombotic complications in pediatric liver transplantation., Competing Interests: None declared., (Thieme. All rights reserved.)
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- 2020
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18. A Preoperative Clinical Risk Score Including C-Reactive Protein Predicts Histological Tumor Characteristics and Patient Survival after Surgery for Sporadic Non-Functional Pancreatic Neuroendocrine Neoplasms: An International Multicenter Cohort Study.
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Primavesi F, Andreasi V, Hoogwater FJH, Partelli S, Wiese D, Heidsma C, Cardini B, Klieser E, Marsoner K, Fröschl U, Thalhammer S, Fischer I, Göbel G, Hauer A, Kiesslich T, Ellmerer P, Klug R, Neureiter D, Wundsam H, Sellner F, Kornprat P, Függer R, Öfner D, Nieveen van Dijkum EJM, Bartsch DK, de Kleine RHJ, Falconi M, and Stättner S
- Abstract
Background: Oncological survival after resection of pancreatic neuroendocrine neoplasms (panNEN) is highly variable depending on various factors. Risk stratification with preoperatively available parameters could guide decision-making in multidisciplinary treatment concepts. C-reactive Protein (CRP) is linked to inferior survival in several malignancies. This study assesses CRP within a novel risk score predicting histology and outcome after surgery for sporadic non-functional panNENs. Methods: A retrospective multicenter study with national exploration and international validation. CRP and other factors associated with overall survival (OS) were evaluated by multivariable cox-regression to create a clinical risk score (CRS). Predictive values regarding OS, disease-specific survival (DSS), and recurrence-free survival (RFS) were assessed by time-dependent receiver-operating characteristics. Results: Overall, 364 patients were included. Median CRP was significantly higher in patients >60 years, G3, and large tumors. In multivariable analysis, CRP was the strongest preoperative factor for OS in both cohorts. In the combined cohort, CRP (cut-off ≥0.2mg/dL; hazard-ratio (HR):3.87), metastases (HR:2.80), and primary tumor size ≥3.0cm (HR:1.83) showed a significant association with OS. A CRS incorporating these variables was associated with postoperative histological grading, T category, nodal positivity, and 90-day morbidity/mortality. Time-dependent area-under-the-curve at 60 months for OS, DSS, and RFS was 69%, 77%, and 67%, respectively (all p < 0.001), and the inclusion of grading further improved the predictive potential (75%, 84%, and 78%, respectively). Conclusions: CRP is a significant marker of unfavorable oncological characteristics in panNENs. The proposed internationally validated CRS predicts histological features and patient survival.
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- 2020
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19. Evidence for a rebalanced hemostatic system in pediatric liver transplantation: A prospective cohort study.
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Werner MJM, de Meijer VE, Adelmeijer J, de Kleine RHJ, Scheenstra R, Bontemps STH, Reyntjens KMEM, Hulscher JBF, Lisman T, and Porte RJ
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- Adult, Blood Coagulation Tests, Child, Hemostasis, Humans, Prospective Studies, Hemostatics, Liver Transplantation adverse effects
- Abstract
In adults with end-stage liver disease concurrent changes in pro- and antihemostatic pathways result in a rebalanced hemostasis. Children though, have a developing hemostatic system, different disease etiologies, and increased risk of thrombosis. This study aimed to assess the hemostatic state of children during and after liver transplantation. Serial blood samples were obtained from 20 children (≤16 years) undergoing primary liver transplantation (September 2017-October 2018). Routine hemostasis tests, thrombomodulin-modified thrombin generation, clot lysis times, and hemostatic proteins were measured. Reference values were established using an age-matched control group of 30 children. Thrombocytopenia was present in study patients. Von Willebrand factors were doubled and ADAMTS13 levels decreased during and after transplantation up until day 30, when platelet count had normalized. Whereas prothrombin time and activated partial thromboplastin time were prolonged during transplantation, thrombin generation was within normal ranges, except during perioperative heparin administration. Fibrinogen, factor VIII levels, and clot lysis time were elevated up until day 30. In conclusion, children with end-stage liver disease are in tight hemostatic balance. During transplantation a temporary heparin-dependent hypocoagulable state is present, which rapidly converts to a hemostatic balance with distinct hypercoagulable features that persist until at least day 30. This hypercoagulable state may contribute to the risk of posttransplant thrombosis., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)
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- 2020
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20. Routine Postoperative Antithrombotic Therapy in Pediatric Liver Transplantation: Impact on Bleeding and Thrombotic Complications.
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Werner MJM, de Kleine RHJ, de Boer MT, de Meijer VE, Scheenstra R, Verkade HJ, Bodewes FAJA, Bontemps STH, Reyntjens KMEM, Dikkers R, Lisman T, and Porte RJ
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- Biliary Atresia epidemiology, Biliary Atresia mortality, Child, Child, Preschool, Cohort Studies, Female, Hemorrhage etiology, Humans, Incidence, Infant, Male, Netherlands epidemiology, Retrospective Studies, Risk Factors, Survival Analysis, Thrombosis etiology, Treatment Outcome, Biliary Atresia therapy, Fibrinolytic Agents therapeutic use, Hemorrhage prevention & control, Hepatic Artery pathology, Liver Transplantation, Portal Vein pathology, Postoperative Complications prevention & control, Thrombosis prevention & control
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Background: Hepatic artery thrombosis (HAT) and portal vein thrombosis (PVT) are serious causes of morbidity and mortality after pediatric liver transplantation. To reduce thrombotic complications, routine antithrombotic therapy consisting of 1 week heparin followed by 3 months acetylsalicylic acid, was implemented in our pediatric liver transplant program in 2003. This study aimed to evaluate incidences of bleeding and thrombotic complications since the implementation of routine antithrombotic therapy and to identify risk factors for these complications., Methods: This retrospective cohort study includes 200 consecutive pediatric primary liver transplantations performed between 2003 and 2016. Uni- and multivariate logistic regression analysis, Kaplan-Meier method, and Cox regression analysis were used to evaluate recipient outcome., Results: HAT occurred in 15 (7.5%), PVT in 4 (2.0%), and venous outflow tract thrombosis in 2 (1.0%) recipients. Intraoperative vascular interventions (odds ratio [OR] 14.45 [95% confidence interval [CI] 3.75-55.67]), low recipient age (OR 0.81 [0.69-0.95]), and donor age (OR 0.96 [0.93-0.99]) were associated with posttransplant thrombosis. Clinically relevant bleeding occurred in 37%. Risk factors were high recipient age (OR 1.08 [1.02-1.15]), high Child-Pugh scores (OR 1.14 [1.02-1.28]), and intraoperative blood loss in mL/kg (OR 1.003 [1.001-1.006]). Both posttransplant thrombotic (hazard ratio [HR] 3.38 [1.36-8.45]; p = 0.009) and bleeding complications (HR 2.50 [1.19-5.24]; p = 0.015) significantly increased mortality., Conclusion: In 200 consecutive pediatric liver transplant recipients receiving routine postoperative antithrombotic therapy, we report low incidences of posttransplant vascular complications. Posttransplant antithrombotic therapy seems to be a valuable strategy in pediatric liver transplantation. Identified risk factors for bleeding and thrombotic complications might facilitate a more personalized approach in antithrombotic therapy., Competing Interests: None declared., (Georg Thieme Verlag KG Stuttgart · New York.)
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- 2020
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21. Long-Term Neurodevelopmental Outcomes in Children with Biliary Atresia.
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Rodijk LH, den Heijer AE, Hulscher JBF, Alizadeh BZ, de Kleine RHJ, Verkade HJ, and Bruggink JLM
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- Adolescent, Biliary Atresia surgery, Child, Female, Follow-Up Studies, Humans, Incidence, Liver Transplantation, Male, Netherlands epidemiology, Neurodevelopmental Disorders epidemiology, Neurodevelopmental Disorders psychology, Prognosis, Time Factors, Biliary Atresia complications, Cognition physiology, Motor Skills physiology, Neurodevelopmental Disorders etiology
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Objective: To assess long-term neurodevelopmental outcomes in school-aged children with biliary atresia., Study Design: All Dutch children (6-12 years of age) diagnosed with biliary atresia were invited to participate in this study. We used validated neurodevelopmental tests to assess motor skills and cognition, and questionnaires to assess behavior. Scores were compared with the Dutch norm population, by means of 1-sample tests. Results are given as number and percentage or mean ± SD., Results: We included 46 children, with a median age of 11 years (range, 6-13 years); 36 children had undergone a liver transplantation (78%). Twelve children (26%) received special education (vs 2.4% in the norm population; P < .01). Motor outcomes were significantly affected compared with the norm population (P < .01), with 25% normal (vs 85%), 25% borderline (vs 10%), and 50% low scores (vs 5%). Total IQ was lower in patients with biliary atresia, compared with the norm population (91 ± 18 vs 100 ± 15; P < .01). There were no significant differences in test scores between children with native liver and after liver transplantation., Conclusions: School-aged children with biliary atresia show neurodevelopmental impairments compared with the norm population, especially in motor skills. Our data strongly warrant evaluation of neurodevelopmental intervention programs to assess whether long-term outcomes could be improved., (Copyright © 2019 Elsevier Inc. All rights reserved.)
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- 2020
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22. Transplantation of High-risk Donor Livers After Ex Situ Resuscitation and Assessment Using Combined Hypo- and Normothermic Machine Perfusion: A Prospective Clinical Trial.
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van Leeuwen OB, de Vries Y, Fujiyoshi M, Nijsten MWN, Ubbink R, Pelgrim GJ, Werner MJM, Reyntjens KMEM, van den Berg AP, de Boer MT, de Kleine RHJ, Lisman T, de Meijer VE, and Porte RJ
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- Adult, Aged, Aged, 80 and over, Donor Selection, Female, Graft Rejection, Graft Survival, Hepatectomy methods, Humans, Kaplan-Meier Estimate, Liver Transplantation adverse effects, Living Donors, Male, Middle Aged, Patient Safety, Perfusion methods, Prognosis, Prospective Studies, Resuscitation methods, Risk Assessment, Statistics, Nonparametric, Survival Analysis, Treatment Outcome, Cold Ischemia methods, Liver Transplantation methods, Organ Preservation methods, Reperfusion Injury prevention & control, Tissue and Organ Procurement, Warm Ischemia methods
- Abstract
Objective: The aim of this study was to evaluate sequential hypothermic and normothermic machine perfusion (NMP) as a tool to resuscitate and assess viability of initially declined donor livers to enable safe transplantation., Summary Background Data: Machine perfusion is increasingly used to resuscitate and test the function of donor livers. Although (dual) hypothermic oxygenated machine perfusion ([D]HOPE) resuscitates livers after cold storage, NMP enables assessment of hepatobiliary function., Methods: In a prospective clinical trial, nationwide declined livers were subjected to ex situ NMP (viability assessment phase), preceded by 1-hour DHOPE (resuscitation phase) and 1 hour of controlled oxygenated rewarming (COR), using a perfusion fluid containing an hemoglobin-based oxygen carrier. During the first 2.5 hours of NMP, hepatobiliary viability was assessed, using predefined criteria: perfusate lactate <1.7 mmol/L, pH 7.35 to 7.45, bile production >10 mL, and bile pH >7.45. Livers meeting all criteria were accepted for transplantation. Primary endpoint was 3-month graft survival., Results: Sixteen livers underwent DHOPE-COR-NMP. All livers were from donors after circulatory death, with median age of 63 (range 42-82) years and median Eurotransplant donor risk index of 2.82. During NMP, all livers cleared lactate and produced sufficient bile volume, but in 5 livers bile pH remained <7.45. The 11 (69%) livers that met all viability criteria were successfully transplanted, with 100% patient and graft survival at 3 and 6 months. Introduction of DHOPE-COR-NMP increased the number of deceased donor liver transplants by 20%., Conclusions: Sequential DHOPE-COR-NMP enabled resuscitation and safe selection of initially declined high-risk donor livers, thereby increasing the number of transplantable livers by 20%., Trial Registration: www.trialregister.nl; NTR5972.
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- 2019
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23. Transplantation of high-risk donor livers after resuscitation and viability assessment using a combined protocol of oxygenated hypothermic, rewarming and normothermic machine perfusion: study protocol for a prospective, single-arm study (DHOPE-COR-NMP trial).
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de Vries Y, Berendsen TA, Fujiyoshi M, van den Berg AP, Blokzijl H, de Boer MT, van der Heide F, de Kleine RHJ, van Leeuwen OB, Matton APM, Werner MJM, Lisman T, de Meijer VE, and Porte R
- Subjects
- Blood Substitutes, Graft Survival, Hemoglobins, Hepatic Artery, Humans, Hypothermia, Induced, Infusion Pumps, Portal Vein, Prospective Studies, Resuscitation, Rewarming, Tissue and Organ Harvesting, Liver Transplantation methods, Organ Preservation methods, Organ Preservation Solutions, Tissue Survival
- Abstract
Introduction: Extended criteria donor (ECD) livers are increasingly accepted for transplantation in an attempt to reduce the gap between the number of patients on the waiting list and the available number of donor livers. ECD livers; however, carry an increased risk of developing primary non-function (PNF), early allograft dysfunction (EAD) or post-transplant cholangiopathy. Ischaemia-reperfusion injury (IRI) plays an important role in the development of these complications. Machine perfusion reduces IRI and allows for reconditioning and subsequent evaluation of liver grafts. Single or dual hypothermic oxygenated machine perfusion (DHOPE) (4°C-12°C) decreases IRI by resuscitation of mitochondria. Controlled oxygenated rewarming (COR) may further reduce IRI by preventing sudden temperature shifts. Subsequent normothermic machine perfusion (NMP) (37°C) allows for ex situ viability assessment to facilitate the selection of ECD livers with a low risk of PNF, EAD or post-transplant cholangiopathy., Methods and Analysis: This prospective, single-arm study is designed to resuscitate and evaluate initially nationwide declined ECD livers. End-ischaemic DHOPE will be performed for the initial mitochondrial and graft resuscitation, followed by COR of the donor liver to a normothermic temperature. Subsequently, NMP will be continued to assess viability of the liver. Transplantation into eligible recipients will proceed if all predetermined viability criteria are met within the first 150 min of NMP. To facilitate machine perfusion at different temperatures, a perfusion solution containing a haemoglobin-based oxygen carrier will be used. With this protocol, we aim to transplant extra livers. The primary endpoint is graft survival at 3 months after transplantation., Ethics and Dissemination: This protocol was approved by the medical ethical committee of Groningen, METc2016.281 in August 2016 and registered in the Dutch Trial registration number TRIAL REGISTRATION NUMBER: NTR5972, NCT02584283., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)
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- 2019
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24. Reversal of secondary protein-losing enteropathy after surgical revision of a jejunal Roux-en-Y loop in a patient after liver transplantation.
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Holvast A, Kats-Ugurlu G, Bodewes FAJA, de Kleine RHJ, Porte RJ, Brouwers AH, and van der Doef HPJ
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- Brain Diseases pathology, Humans, Hyperammonemia pathology, Infant, Male, Prognosis, Protein-Losing Enteropathies etiology, Protein-Losing Enteropathies pathology, Recovery of Function, Anastomosis, Roux-en-Y methods, Brain Diseases surgery, Hyperammonemia surgery, Liver Transplantation adverse effects, Protein-Losing Enteropathies surgery
- Abstract
Secondary protein-losing enteropathy (PLE) is a rare complication following pediatric liver transplantation (LT), mostly related to venous outflow obstruction of the liver. Here, we discuss a thus far unknown cause of secondary PLE following pediatric LT. A 7-month-old boy underwent LT with biliary anastomosis using a Roux-en-Y jejunal loop. Eleven months later he developed PLE. Routine diagnostic workup was negative. No hepatic outflow obstruction was detected during catheterization. Although the hepatic venous pressure gradient was slightly increased (10 mm Hg), there were no clinical signs of portal hypertension. Albumin scintigraphy with specific early recordings suggested focal albumin intestinal entry in the jejunal Roux-en-Y loop. Local bacterial overgrowth or local lymphangiectasia, possibly due to (venous) congestion, was considered. Treatment with metronidazole did not improve albumin loss. Next, surgical revision of the jejunal Roux-en-Y loop was performed. The explanted loop contained a small abnormal area with a thin hyperemic mucosa, near the former anastomosis. Histopathological analysis showed changes both in the blood vessels and the lymphatic vessels with focal deeper chronic active inflammation resulting in congestion of vessels, hampering lymphatic outflow leading to lymphangiectasia and patchy distortion of lymphatic vessels. Following surgical revision, secondary PLE disappeared, up to now, 1.5 year post revision., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)
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- 2019
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25. Biliary Bicarbonate, pH, and Glucose Are Suitable Biomarkers of Biliary Viability During Ex Situ Normothermic Machine Perfusion of Human Donor Livers.
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Matton APM, de Vries Y, Burlage LC, van Rijn R, Fujiyoshi M, de Meijer VE, de Boer MT, de Kleine RHJ, Verkade HJ, Gouw ASH, Lisman T, and Porte RJ
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- Bile Ducts pathology, Bile Ducts transplantation, Biomarkers metabolism, Biopsy, Humans, Hydrogen-Ion Concentration, Liver Transplantation adverse effects, Liver Transplantation instrumentation, Predictive Value of Tests, Reproducibility of Results, Time Factors, Tissue Survival, Bicarbonates metabolism, Bile metabolism, Bile Ducts metabolism, Donor Selection, Glucose metabolism, Liver Transplantation methods, Perfusion adverse effects, Perfusion instrumentation
- Abstract
Background: Ex situ normothermic machine perfusion (NMP) can be used to assess viability of suboptimal donor livers before implantation. Our aim was to assess the diagnostic accuracy of bile biochemistry for the assessment of bile duct injury (BDI)., Methods: In a preclinical study, 23 human donor livers underwent 6 hours of end-ischemic NMP to determine biomarkers of BDI. Livers were divided into groups with low or high BDI, based on a clinically relevant histological grading system. During NMP, bile was analyzed biochemically and potential biomarkers were correlated with the degree of BDI. Receiver operating characteristics curves were generated to determine optimal cutoff values. For clinical validation, identified biomarkers were subsequently included as viability criteria in a clinical trial (n = 6) to identify transplantable liver grafts with low BDI., Results: Biliary bicarbonate and pH were significantly higher and biliary glucose was significantly lower in livers with low BDI, compared with high BDI. The following cutoff values were associated with low BDI: biliary bicarbonate greater than 18 mmol/L (P = 0.002), biliary pH greater than 7.48 (P = 0.019), biliary glucose less than 16 mmol/L (P = 0.013), and bile/perfusate glucose ratio less than 0.67 (P = 0.013). In the clinical trial, 4 of 6 livers met these criteria and were transplanted, and none developed clinical evidence of posttransplant cholangiopathy., Conclusions: Biliary bicarbonate, pH, and glucose during ex situ NMP of liver grafts are accurate biomarkers of BDI and can be easily determined point of care, making them suitable for the pretransplant assessment of bile duct viability. This may improve graft selection and decrease the risk of posttransplant cholangiopathy.
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- 2019
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26. Robot-Assisted Laparoscopic Resection of a Todani Type II Choledochal Malformation.
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Ten Hove A, de Kleine RHJ, Nijkamp MW, Gouw ASH, Koopman T, and Klaase JM
- Abstract
Choledochal malformation (CM) comprise various congenital cystic dilatations of the extrahepatic and/or intrahepatic biliary tree. CM is classified into five different types. Our case describes a 58-year-old man presenting with acute abdominal pain. Further examination showed a Todani type II CM. Treatment for type II is complete cyst excision without the need for an extrahepatic bile duct resection. A robot-assisted laparoscopic resection of the CM was performed and the patient recovered without complications. Pathology results showed a Todani type II malformation in which complete squamous metaplasia has occurred. In this paper, we report, to the best of our knowledge, the first description of a robot-assisted laparoscopic resection of a type II CM.
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- 2019
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27. First report of successful transplantation of a pediatric donor liver graft after hypothermic machine perfusion.
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Werner MJM, van Leeuwen OB, de Jong IEM, Bodewes FAJA, Fujiyoshi M, Luhker OC, Scheenstra R, de Vries Y, de Kleine RHJ, and Porte RJ
- Subjects
- Adolescent, Alanine Transaminase metabolism, Aspartate Aminotransferases metabolism, Cholestasis, Intrahepatic surgery, Female, Graft Survival, Humans, Liver Transplantation methods, Oxygen metabolism, Pediatrics, Postoperative Period, Prothrombin Time, Tissue and Organ Procurement methods, Treatment Outcome, Liver surgery, Liver Transplantation instrumentation, Organ Preservation instrumentation, Organ Preservation methods, Perfusion
- Abstract
One of the main limiting factors in pediatric liver transplantation is donor availability. For adults, DCD liver grafts are increasingly used to expand the donor pool. To improve outcome after DCD liver transplantation, ex situ machine perfusion is used as an alternative organ preservation strategy, with the supplemental value of providing oxygen to the graft during preservation. We here report the first successful transplantation of a pediatric DCD liver graft after hypothermic oxygenated machine perfusion. The full-size liver graft was derived from a 13-year-old, female DCD donor and was end-ischemic pretreated with dual hypothermic oxygenated machine perfusion. Arterial and portal pressures were set at 18 and 4 mm Hg, slightly lower than protocolized settings for adult livers. During 2 hours of machine perfusion, portal and arterial flows increased from 100 to 210 mL/min and 30 to 63 mL/min, respectively. The pretreated liver graft was implanted in a 16-year-old girl with progressive familial intrahepatic cholestasis type 2. Postoperative AST, ALT, and prothrombin time normalized within a week. The recipient quickly recovered and was discharged from the hospital after 18 days. One year after transplantation, she is in excellent condition with a completely normal liver function and histology. This case is the first report of successful transplantation of a pediatric DCD liver graft after hypothermic oxygenated machine perfusion and illustrates the potential role of ex situ machine perfusion in expanding the donor pool and improving outcome after pediatric liver transplantation., (© 2019 The Authors. Pediatric Transplantation Published by Wiley Periodicals, Inc.)
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- 2019
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28. Pretransplant sequential hypo- and normothermic machine perfusion of suboptimal livers donated after circulatory death using a hemoglobin-based oxygen carrier perfusion solution.
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de Vries Y, Matton APM, Nijsten MWN, Werner MJM, van den Berg AP, de Boer MT, Buis CI, Fujiyoshi M, de Kleine RHJ, van Leeuwen OB, Meyer P, van den Heuvel MC, de Meijer VE, and Porte RJ
- Subjects
- Adult, Cold Ischemia, Humans, Middle Aged, Solutions, Warm Ischemia, Hemoglobins metabolism, Liver Transplantation methods, Oxygen metabolism, Perfusion, Shock
- Abstract
Ex situ dual hypothermic oxygenated machine perfusion (DHOPE) and normothermic machine perfusion (NMP) of donor livers may have a complementary effect when applied sequentially. While DHOPE resuscitates the mitochondria and increases hepatic adenosine triphosphate (ATP) content, NMP enables hepatobiliary viability assessment prior to transplantation. In contrast to DHOPE, NMP requires a perfusion solution with an oxygen carrier, for which red blood cells (RBC) have been used in most series. RBC, however, have limitations and cannot be used cold. We, therefore, established a protocol of sequential DHOPE, controlled oxygenated rewarming (COR), and NMP using a new hemoglobin-based oxygen carrier (HBOC)-based perfusion fluid (DHOPE-COR-NMP trial, NTR5972). Seven livers from donation after circulatory death (DCD) donors, which were initially declined for transplantation nationwide, underwent DHOPE-COR-NMP. Livers were considered transplantable if perfusate pH and lactate normalized, bile production was ≥10 mL and biliary pH > 7.45 within 150 minutes of NMP. Based on these criteria five livers were transplanted. The primary endpoint, 3-month graft survival, was a 100%. In conclusion, sequential DHOPE-COR-NMP using an HBOC-based perfusion fluid offers a novel method of liver machine perfusion for combined resuscitation and viability testing of suboptimal livers prior to transplantation., (© 2018 The Authors American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)
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- 2019
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29. Opposite acute potassium and sodium shifts during transplantation of hypothermic machine perfused donor livers.
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Burlage LC, Hessels L, van Rijn R, Matton APM, Fujiyoshi M, van den Berg AP, Reyntjens KMEM, Meyer P, de Boer MT, de Kleine RHJ, Nijsten MW, and Porte RJ
- Subjects
- Humans, Perfusion, Hypothermia, Induced, Liver Transplantation, Potassium metabolism, Sodium metabolism, Tissue Donors
- Abstract
Liver transplantation is frequently associated with hyperkalemia, especially after graft reperfusion. Dual hypothermic oxygenated machine perfusion (DHOPE) reduces ischemia/reperfusion injury and improves graft function, compared to conventional static cold storage (SCS). We examined the effect of DHOPE on ex situ and in vivo shifts of potassium and sodium. Potassium and sodium shifts were derived from balance measurements in a preclinical study of livers that underwent DHOPE (n = 6) or SCS alone (n = 9), followed by ex situ normothermic reperfusion. Similar measurements were performed in a clinical study of DHOPE-preserved livers (n = 10) and control livers that were transplanted after SCS only (n = 9). During DHOPE, preclinical and clinical livers released a mean of 17 ± 2 and 34 ± 6 mmol potassium and took up 25 ± 9 and 24 ± 14 mmol sodium, respectively. After subsequent normothermic reperfusion, DHOPE-preserved livers took up a mean of 19 ± 3 mmol potassium, while controls released 8 ± 5 mmol potassium. During liver transplantation, blood potassium levels decreased upon reperfusion of DHOPE-preserved livers while levels increased after reperfusion of SCS-preserved liver, delta potassium levels were -0.77 ± 0.20 vs. +0.64 ± 0.37 mmol/L, respectively (P = .002). While hyperkalemia is generally anticipated during transplantation of SCS-preserved livers, reperfusion of hypothermic machine perfused livers can lead to decreased blood potassium or even hypokalemia in the recipient., (© 2018 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)
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- 2019
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30. Prognosis of Biliary Atresia After 2-year Survival With Native Liver: A Nationwide Cohort Analysis.
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Witt M, van Wessel DBE, de Kleine RHJ, Bruggink JLM, Hulscher JBF, and Verkade HJ
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- Adolescent, Adult, Biliary Atresia physiopathology, Biliary Atresia surgery, Child, Child, Preschool, Databases, Factual, Female, Follow-Up Studies, Humans, Liver physiopathology, Male, Netherlands, Prognosis, Registries, Retrospective Studies, Survival Rate, Time Factors, Young Adult, Biliary Atresia mortality, Portoenterostomy, Hepatic mortality
- Abstract
Objectives: The aim of the study is to determine the prognosis of patients with biliary atresia after 2 years of native liver survival (NLS) and to identify prognostic factors for continued NLS after 2 years of age., Methods: We retrospectively analyzed perioperative, laboratory, and outcome parameters of all biliary atresia patients in The Netherlands between January 1987 and June 2015 with NLS of at least 2 years. We compared parameters between patients who continued to have their native liver (NLS+) to those who did not, either by transplant or death (NLS-)., Results: We included 100 patients. Upon a median follow-up of 16.4 years, NLS ended in 37% by liver transplantation (LTx) and in 6% by (pre-transplant) mortality. NLS rates at 5, 10, 15, 18 years of age were 89%, 72%, 60%, 54%, respectively. Corresponding overall survival rates were 98%, 90%, 87%, 87%, respectively. Six months post-Kasai, NLS+ patients had higher clearance of jaundice (COJ) rate, significantly lower total and direct serum bilirubin, aspartate-aminotransferase and alkaline phosphatase levels, compared with NLS- patients (each P < 0.05). Cox regression could only assess a significant effect of COJ on continued NLS. Main indications for LTx after the age of 2 were irreversible jaundice and portal hypertension., Conclusions: Eighty-seven percent of patients with 2-year NLS reach adult age and more than 50% with their native liver. A pre-transplant mortality of 6%, however, exists among patients who reach the age of 2 years with their native livers. Early life parameters, other than COJ, did not have a significant effect on continued NLS after 2 years of age.
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- 2018
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31. Neurodevelopmental Outcomes in Children With Liver Diseases: a Systematic Review.
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Rodijk LH, den Heijer AE, Hulscher JBF, Verkade HJ, de Kleine RHJ, and Bruggink JLM
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- Child, Humans, Developmental Disabilities complications, Liver Diseases complications, Nervous System growth & development
- Abstract
Objective: The aim of the study was to determine the neurodevelopmental outcomes of children with liver diseases based on a systematical review of the literature., Method: A literature search according to the PRISMA statement was conducted using predefined search terms in PubMed, Cochrane Library, and PsycINFO. The inclusion criterion was studies published from 2000 onwards that reported on the neurodevelopmental outcomes of term-born children with liver diseases. A narrative synthesis was done to appraise the studies., Results: Twenty-five studies were included (1913 children), 19 of which described children after liver transplantation (LTx; 1372 children). Sixty-seven percentage of the studies on children with liver diseases who survived with their native livers showed low-average or abnormal scores on specific subscales of cognitive and behavioral measures. In studies on children after LTx, this was 82%. After LTx, 83% of studies demonstrated impaired outcomes on behavior, whereas 42% of children received special education. Motor development was impaired in 82% of studies in children with native liver and after LTx., Limitations: Studies were heterogenic because of sample sizes, etiology of liver disease and type of assessment tools used., Conclusions: More than two-third of included studies showed neurodevelopmental deficits in children with liver diseases, affecting all neurodevelopmental areas. Knowledge on risk factors for impaired neurodevelopment is limited and lack of long-term follow-up is worrying, especially considering the increasing survival rates, resulting in more at-risk patients. Studying early predictors and risk factors of abnormal developmental trajectories of children with liver diseases is indicated to assess strategies to improve their long-term neurodevelopmental outcomes.
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- 2018
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32. Hypothermic oxygenated machine perfusion reduces bile duct reperfusion injury after transplantation of donation after circulatory death livers.
- Author
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van Rijn R, van Leeuwen OB, Matton APM, Burlage LC, Wiersema-Buist J, van den Heuvel MC, de Kleine RHJ, de Boer MT, Gouw ASH, and Porte RJ
- Subjects
- Adult, Biopsy, Common Bile Duct pathology, Common Bile Duct Diseases etiology, Common Bile Duct Diseases pathology, Female, Humans, Liver Transplantation adverse effects, Male, Middle Aged, Necrosis, Netherlands, Organ Preservation adverse effects, Organ Preservation instrumentation, Perfusion adverse effects, Perfusion instrumentation, Reperfusion Injury etiology, Reperfusion Injury pathology, Risk Factors, Time Factors, Treatment Outcome, Cold Temperature, Common Bile Duct transplantation, Common Bile Duct Diseases prevention & control, Donor Selection, Liver Transplantation methods, Organ Preservation methods, Perfusion methods, Reperfusion Injury prevention & control
- Abstract
Dual hypothermic oxygenated machine perfusion (DHOPE) of the liver has been advocated as a method to reduce ischemia/reperfusion injury (IRI). This study aimed to determine whether DHOPE reduces IRI of the bile ducts in donation after circulatory death (DCD) liver transplantation. In a recently performed phase 1 trial, 10 DCD livers were preserved with DHOPE after static cold storage (SCS; www.trialregister.nl NTR4493). Bile duct biopsies were obtained at the end of SCS (before DHOPE; baseline) and after graft reperfusion in the recipient. Histological severity of biliary injury was graded according to an established semiquantitative grading system. Twenty liver transplantations using DCD livers not preserved with DHOPE served as controls. Baseline characteristics and the degree of bile duct injury at baseline (end of SCS) were similar between both groups. In controls, the degree of stroma necrosis (P = 0.002) and injury of the deep peribiliary glands (PBG; P = 0.02) increased after reperfusion compared with baseline. In contrast, in DHOPE-preserved livers, the degree of bile duct injury did not increase after reperfusion. Moreover, there was less injury of deep PBG (P = 0.04) after reperfusion in the DHOPE group compared with controls. In conclusion, this study suggests that DHOPE reduces IRI of bile ducts after DCD liver transplantation. Liver Transplantation 24 655-664 2018 AASLD., (© 2018 The Authors Liver Transplantation published by Wiley Periodicals, Inc. on behalf of American Association for the Study of Liver Diseases.)
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- 2018
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33. Meta-analysis of risk of developing malignancy in congenital choledochal malformation.
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Ten Hove A, de Meijer VE, Hulscher JBF, and de Kleine RHJ
- Subjects
- Global Health, Humans, Incidence, Risk Factors, Biliary Tract Neoplasms diagnosis, Biliary Tract Neoplasms epidemiology, Biliary Tract Neoplasms etiology, Choledochal Cyst complications, Choledochal Cyst diagnosis, Choledochal Cyst surgery, Common Bile Duct abnormalities
- Abstract
Background: Choledochal malformations comprise various congenital cystic dilatations of the extrahepatic and/or intrahepatic biliary tree. Choledochal malformation is generally considered a premalignant condition, but reliable data on the risk of malignancy and optimal surgical treatment are lacking. The objective of this systematic review was to assess the prevalence of malignancy in patients with choledochal malformation and to differentiate between subtypes. In addition, the risk of malignancy following cystic drainage versus complete cyst excision was assessed., Methods: A systematic review of PubMed and Embase databases was performed in accordance with the PRISMA statement. A meta-analysis of the risk of malignancy following cystic drainage versus complete cyst excision was undertaken in line with MOOSE guidelines. Prevalence of malignancy was defined as the rate of biliary cancer before resection, and malignant transformation as new-onset biliary cancer after surgery., Results: Eighteen observational studies were included, reporting a total of 2904 patients with a median age of 36 years. Of these, 312 in total developed a malignancy (10·7 per cent); the prevalence of malignancy was 7·3 per cent and the rate of malignant transformation was 3·4 per cent. Patients with types I and IV choledochal malformation had an increased risk of malignancy (P = 0·016). Patients who underwent cystic drainage had an increased risk of developing biliary malignancy compared with those who had complete cyst excision, with an odds ratio of 3·97 (95 per cent c.i. 2·40 to 6·55)., Conclusion: The risk of developing malignancy among patients with choledochal malformation was almost 11 per cent. The malignancy risk following cystic drainage surgery was four times higher than that after complete cyst excision. Complete surgical resection is recommended in patients with choledochal malformation., (© 2018 The Authors. BJS published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.)
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- 2018
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34. Early and Late Complications After Surgery for MEN1-related Nonfunctioning Pancreatic Neuroendocrine Tumors.
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Nell S, Borel Rinkes IHM, Verkooijen HM, Bonsing BA, van Eijck CH, van Goor H, de Kleine RHJ, Kazemier G, Nieveen van Dijkum EJ, Dejong CHC, Valk GD, and Vriens MR
- Subjects
- Adult, Aged, Databases, Factual, Female, Follow-Up Studies, Humans, Logistic Models, Male, Middle Aged, Retrospective Studies, Multiple Endocrine Neoplasia Type 1 surgery, Pancreatectomy, Pancreatic Neoplasms surgery, Pancreaticoduodenectomy, Postoperative Complications epidemiology
- Abstract
Objective: To estimate short and long-term morbidity after pancreatic surgery for multiple endocrine neoplasia type 1 (MEN1)-related nonfunctioning pancreatic neuroendocrine tumors (NF-pNETs)., Background: Fifty percent of the MEN1 patients harbor multiple NF-pNETs. The decision to proceed to NF-pNET surgery is a balance between the risk of disease progression versus the risk of surgery-related morbidity. Currently, there are insufficient data on the surgical complications after MEN1 NF-pNET surgery., Methods: MEN1 patients diagnosed with a NF-pNET who underwent surgery were selected from the DutchMEN1 study group database, including >90% of the Dutch MEN1 population. Early postoperative complications, new-onset diabetes mellitus, and exocrine pancreatic insufficiency were captured., Results: Sixty-one patients underwent NF-pNET surgery at 1 of the 8 Dutch academic centers. Patients were young (median age 41 years) with low American Society of Anesthesiologists scores. Median NF-pNET size on imaging was 22 mm (3-157). Thirty-three percent (19/58) of the patients developed major early-Clavien-Dindo grade III to IV-complications mainly consisting International Study Group of Pancreatic Surgery grade B/C pancreatic fistulas. Twenty-three percent of the patients (14/61) developed endocrine or exocrine pancreas insufficiency. The development of major early postoperative complications was independent of the NF-pNET tumor size. Twenty-one percent of the patients (12/58) developed multiple major early complications., Conclusions: MEN1 NF-pNET surgery is associated with high rates of major short and long-term complications. Current findings should be taken into account in the shared decision-making process when MEN1 NF-pNET surgery is considered.
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- 2018
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35. Choledochal Malformation in Children: Lessons Learned from a Dutch National Study.
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van den Eijnden MHA, de Kleine RHJ, de Blaauw I, Peeters PGJM, Koot BPG, Oomen MWN, Sloots CEJ, van Gemert WG, van der Zee DC, van Heurn LWE, Verkade HJ, Wilde JCH, and Hulscher JBF
- Subjects
- Adolescent, Anastomosis, Roux-en-Y methods, Biliary Tract Surgical Procedures methods, Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Laparoscopy methods, Male, Postoperative Complications etiology, Retrospective Studies, Choledochal Cyst surgery
- Abstract
Introduction: A choledochal malformation (CM) is a rare entity, especially in the Western world. We aimed to determine the incidence of CM in the Netherlands and the outcome of surgery for CM in childhood., Methods: All pediatric patients who underwent a surgical procedure for type I-IV CM between 1989 and 2014 were entered into the Netherlands Study group on choledochal cyst/malformation. Patients with type V CM were excluded from the present analysis. Symptoms, surgical details, short-term (<30 days) and long-term (>30 days) complications were studied retrospectively., Results: Between January 1989 and December 2014, 91 pediatric patients underwent surgery for CM at a median age of 2.1 years (0.0-17.7 years). All patients underwent resection of the extrahepatic biliary tree with restoration of the continuity via Roux-en-Y hepaticojejunostomy. Twelve patients (12%) were operated laparoscopically. Short-term complications, mainly biliary leakage and cholangitis, occurred in 20 patients (22%), without significant correlations with weight or age at surgery or surgical approach. Long-term postoperative complications were mainly cholangitis (13%) and anastomotic stricture (4%). Eight patients (9%) required radiological intervention or additional surgery. Surgery before 1 year of age (OR 9.3) and laparoscopic surgery (OR 4.4) were associated with more postoperative long-term complications. We did not observe biliary malignancies during treatment or follow-up., Conclusion: Surgery for CM carries a significant short- and long-term morbidity. Given the low incidence, we would suggest that (laparoscopic) hepatobiliary surgery for CM should be performed in specialized pediatric surgical centers with a wide experience in laparoscopy and hepatobiliary surgery.
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- 2017
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36. Preterm Infants With Biliary Atresia: A Nationwide Cohort Analysis From The Netherlands.
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van Wessel DBE, Boere T, Hulzebos CV, de Kleine RHJ, Verkade HJ, and Hulscher JBF
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- Biliary Atresia surgery, Child, Preschool, Female, Follow-Up Studies, Humans, Incidence, Infant, Infant, Newborn, Infant, Premature, Infant, Premature, Diseases surgery, Liver Transplantation, Male, Netherlands epidemiology, Portoenterostomy, Hepatic, Prognosis, Retrospective Studies, Survival Rate, Biliary Atresia epidemiology, Infant, Premature, Diseases epidemiology
- Abstract
Objectives: Biliary atresia (BA) occurs in 0.54 of 10.000 of overall live births in the Netherlands. BA has an unfavorable prognosis: <40% of patients are cleared of jaundice after Kasai portoenterostomy (KPE), 4-year transplant-free survival rate is 46% and the 4-year survival rate is ∼75%. Little is known on difficulties in diagnosis and the outcome of BA in preterm infants. We aimed to analyze the incidence and outcome of BA in preterm infants in the Netherlands., Methods: Retrospective study including Dutch preterm infants treated for BA. Parameters included gestational age, congenital anomalies, age at KPE, days between first symptoms, and KPE and referral interval (first hospital to KPE). Outcome parameters were clearance of jaundice (COJ) and (transplant-free) survival. Data are presented as medians (ranges)., Results: Included 28 preterm infants (13 boys/15 girls) between March 1988 and December 2015. The incidence of BA was 1.06 of 10.000 preterm live births. Gestational age was 34.8 (27.3-36.9) weeks. Congenital anomalies were present in 11 of 28 (39%) infants. Time between first symptoms and KPE was 57 (9-138) days. Referral interval was 28 (8-86) days. Age at KPE was 70 (35-145) days. COJ was achieved in 23% of cases. Four-year transplant-free survival rate was 21%. Four-year overall survival was 61%., Conclusions: BA has a higher incidence in the preterm population compared to the overall BA population. The outcome of BA in preterm infants is poor, regarding COJ and (transplant-free) survival. We speculate that timely recognition of BA-related signs and symptoms in preterm infants will improve prognosis.
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- 2017
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37. Dual hypothermic oxygenated machine perfusion in liver transplants donated after circulatory death.
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van Rijn R, Karimian N, Matton APM, Burlage LC, Westerkamp AC, van den Berg AP, de Kleine RHJ, de Boer MT, Lisman T, and Porte RJ
- Subjects
- Case-Control Studies, Feasibility Studies, Female, Graft Survival, Humans, Liver Function Tests, Male, Middle Aged, Oxygen, Perfusion methods, Prospective Studies, Treatment Outcome, Hypothermia, Induced methods, Liver Transplantation, Organ Preservation methods, Tissue and Organ Procurement
- Abstract
Background: Experimental studies have suggested that end-ischaemic dual hypothermic oxygenated machine perfusion (DHOPE) may restore hepatocellular energy status and reduce reperfusion injury in donation after circulatory death (DCD) liver grafts. The aim of this prospective case-control study was to assess the safety and feasibility of DHOPE in DCD liver transplantation., Methods: In consecutive DCD liver transplantations, liver grafts were treated with end-ischaemic DHOPE. Outcome was compared with that in a control group of DCD liver transplantations without DHOPE, matched for donor age, donor warm ischaemia time, and recipient Model for End-stage Liver Disease (MELD) score. All patients were followed for 1 year., Results: Ten transplantations involving liver grafts treated with DHOPE were compared with 20 control procedures. There were no technical problems. All 6-month and 1-year graft and patient survival rates were 100 per cent in the DHOPE group. Six-month graft survival and 1-year graft and patient survival rates in the control group were 80, 67 and 85 per cent respectively. During DHOPE, median (i.q.r.) hepatic adenosine 5'-triphosphate (ATP) content increased 11-fold, from 6 (3-10) to 66 (42-87) µmol per g protein (P = 0·005). All DHOPE-preserved livers showed excellent early function. At 1 week after transplantation peak serum alanine aminotransferase (ALT) and bilirubin levels were twofold lower in the DHOPE group than in the control group (ALT: median 966 versus 1858 units/l respectively, P = 0·006; bilirubin: median 1·0 (i.q.r. 0·7-1·4) versus 2·6 (0·9-5·1) mg/dl, P = 0·044). None of the ten DHOPE-preserved livers required retransplantation for non-anastomotic biliary stricture, compared with five of 20 in the control group (P = 0·140)., Conclusion: This clinical study of end-ischaemic DHOPE in DCD liver transplantation suggests that the technique restores hepatic ATP, reduces reperfusion injury, and is safe and feasible. RCTs with larger numbers of patients are warranted to assess the efficacy in reducing post-transplant biliary complications., (© 2017 The Authors. BJS published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.)
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- 2017
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38. [Liver transplantation in paediatric patients in the Netherlands; evolution over the past two decades].
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Werner MJM, de Kleine RHJ, Bodewes FAJA, de Boer MT, de Jong KP, de Meijer VE, Scheenstra R, Sieders E, Verkade HJJ, and Porte RJ
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- Academic Medical Centers, Child, Child, Preschool, Cohort Studies, Female, Humans, Infant, Male, Netherlands, Postoperative Complications epidemiology, Reoperation statistics & numerical data, Retrospective Studies, Survival Rate, Tissue Donors statistics & numerical data, Treatment Outcome, Liver Transplantation statistics & numerical data
- Abstract
Objective: To evaluate the results of the national paediatric liver transplantation programme in the University Medical Centre (UMC) Groningen in the Netherlands during the past two decades., Design: Retrospective cohort study., Method: We analysed data from paediatric patients who underwent liver transplantation at UMC Groningen in the period 1995-2016. We compared outcomes from children who had undergone a liver transplantation in the period 1995-2005 (cohort A; n = 126) and in the period 2006-2016 (cohort B; n = 169). We performed a subanalysis in cohort B between liver transplantations with deceased donor livers (n = 132) and living donor liver transplantations (LDLT; n = 37)., Results: In cohort A, almost all livers came from deceased donors (99%), whereas in cohort B, 37 LDLTs (22%) were performed. The median age of recipients was significantly higher in cohort A (4.4 vs. 2.5 years; p = 0.015). Postoperative complications were comparable for both cohorts. Re-transplantations within a year after transplantation were more often performed in cohort A than in cohort B (25% vs. 12%; p = 0.004). Following LDLT, there was 2 times (5.4%) an indication for re-transplantation. In cohort B the 5-year survival rate was better than in cohort A (83 vs. 71%; p = 0.014). In cohort B, 5-year survival was higher after LDLT than after transplantation with a deceased donor liver (95 vs. 81%; p = 0.025)., Conclusion: Outcomes after paediatric liver transplantation in the Netherlands have further improved during the past two decades. With an actuarial 5-year survival of 83% in the most recent cohort, and as high as 95% following LDLT, we can say that the UMC Groningen has a successful national paediatric liver transplant programme.
- Published
- 2017
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