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Gadour E. Lesson learnt from 60 years of liver transplantation: Advancements, challenges, and future directions. World J Transplant 2025; 15:93253. [PMID: 40104199 PMCID: PMC11612893 DOI: 10.5500/wjt.v15.i1.93253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Revised: 09/06/2024] [Accepted: 09/14/2024] [Indexed: 11/26/2024] Open
Abstract
Over the past six decades, liver transplantation (LT) has evolved from an experimental procedure into a standardized and life-saving intervention, reshaping the landscape of organ transplantation. Driven by pioneering breakthroughs, technological advancements, and a deepened understanding of immunology, LT has seen remarkable progress. Some of the most notable breakthroughs in the field include advances in immunosuppression, a revised model for end-stage liver disease, and artificial intelligence (AI)-integrated imaging modalities serving diagnostic and therapeutic roles in LT, paired with ever-evolving technological advances. Additionally, the refinement of transplantation procedures, resulting in the introduction of alternative transplantation methods, such as living donor LT, split LT, and the use of marginal grafts, has addressed the challenge of organ shortage. Moreover, precision medicine, guiding personalized immunosuppressive strategies, has significantly improved patient and graft survival rates while addressing emergent issues, such as short-term complications and early allograft dysfunction, leading to a more refined strategy and enhanced post-operative recovery. Looking ahead, ongoing research explores regenerative medicine, diagnostic tools, and AI to optimize organ allocation and post-transplantation car. In summary, the past six decades have marked a transformative journey in LT with a commitment to advancing science, medicine, and patient-centered care, offering hope and extending life to individuals worldwide.
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Affiliation(s)
- Eyad Gadour
- Department of Gastroenterology and Hepatology, King Abdulaziz National Guard Hospital, Ahsa 36428, Saudi Arabia
- Internal Medicine, Zamzam University College, Khartoum 11113, Sudan
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Semash K, Dzhanbekov T, Akbarov M, Mirolimov M, Usmonov A, Razzokov N, Primov Z, Gaybullaev T, Yigitaliev S. Implementation of a living donor liver transplantation program in the Republic of Uzbekistan: a report of the first 40 cases. CLINICAL TRANSPLANTATION AND RESEARCH 2024; 38:116-127. [PMID: 38895775 PMCID: PMC11228380 DOI: 10.4285/ctr.24.0013] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Revised: 05/01/2024] [Accepted: 05/05/2024] [Indexed: 06/21/2024]
Abstract
BACKGROUND Living donor liver transplantation (LDLT) is an effective treatment for patients with end-stage liver disease. This study was performed to evaluate the outcomes of the initial series of LDLT procedures performed in the Republic of Uzbekistan and to demonstrate that liver transplantation is viable under the conditions in this country. METHODS Between October 2021 and December 2023, we performed 40 LDLTs. We evaluated both immediate and long-term outcomes. RESULTS Thrombosis of the hepatic artery developed in one case (2.5%). Arterial anastomotic stenoses were diagnosed in three cases (7.5%) and were successfully treated with endovascular balloon vasodilation. Splenic artery steal syndrome arose in three patients (7.5%) and was managed with endovascular embolization of the splenic artery. One patient (2.5%) developed portal vein thrombosis. Portal vein stenosis occurred in two patients (5%) at 10 months posttransplantation and was addressed with endovascular balloon angioplasty, yielding good clinical outcomes. Biliary complications were observed in 45% of the cases, with bile leakages accounting for 89% of these issues and strictures of the biliary anastomoses for 11%. The in-hospital mortality rate was 12.5%. CONCLUSIONS Our research findings and analysis of complications align with the international literature, and the results are deemed acceptable during this implementation phase of the liver transplantation program. Accordingly, liver transplantation is feasible in the Republic of Uzbekistan; however, improvements in surgical and therapeutic methods are necessary to minimize the development of both early and late postoperative complications.
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Affiliation(s)
- Konstantin Semash
- Department of HPB Surgery and Liver Transplantation #1, Republican Specialized Scientific and Practical Medical Center for Surgery named after Academician V. Vakhidov, Tashkent, Uzbekistan
- Department of Faculty and Hospital Surgery and Transplantation, Tashkent Medical Academy, Tashkent, Uzbekistan
- Department of Minimally Invasive Pediatric Surgery, National Children’s Medical Center, Tashkent, Uzbekistan
| | - Timur Dzhanbekov
- Department of HPB Surgery and Liver Transplantation #1, Republican Specialized Scientific and Practical Medical Center for Surgery named after Academician V. Vakhidov, Tashkent, Uzbekistan
- Department of Faculty and Hospital Surgery and Transplantation, Tashkent Medical Academy, Tashkent, Uzbekistan
- Department of Minimally Invasive Pediatric Surgery, National Children’s Medical Center, Tashkent, Uzbekistan
| | - Mirshavkat Akbarov
- Department of HPB Surgery and Liver Transplantation #1, Republican Specialized Scientific and Practical Medical Center for Surgery named after Academician V. Vakhidov, Tashkent, Uzbekistan
- Department of Faculty and Hospital Surgery and Transplantation, Tashkent Medical Academy, Tashkent, Uzbekistan
| | - Miraziz Mirolimov
- Department of HPB Surgery and Liver Transplantation #1, Republican Specialized Scientific and Practical Medical Center for Surgery named after Academician V. Vakhidov, Tashkent, Uzbekistan
| | - Azimjon Usmonov
- Department of HPB Surgery and Liver Transplantation #1, Republican Specialized Scientific and Practical Medical Center for Surgery named after Academician V. Vakhidov, Tashkent, Uzbekistan
| | - Navruz Razzokov
- Department of HPB Surgery and Liver Transplantation #1, Republican Specialized Scientific and Practical Medical Center for Surgery named after Academician V. Vakhidov, Tashkent, Uzbekistan
| | - Ziyodulla Primov
- Department of HPB Surgery and Liver Transplantation #1, Republican Specialized Scientific and Practical Medical Center for Surgery named after Academician V. Vakhidov, Tashkent, Uzbekistan
| | - Temurbek Gaybullaev
- Department of HPB Surgery and Liver Transplantation #1, Republican Specialized Scientific and Practical Medical Center for Surgery named after Academician V. Vakhidov, Tashkent, Uzbekistan
- Department of Faculty and Hospital Surgery and Transplantation, Tashkent Medical Academy, Tashkent, Uzbekistan
| | - Sardor Yigitaliev
- Department of HPB Surgery and Liver Transplantation #1, Republican Specialized Scientific and Practical Medical Center for Surgery named after Academician V. Vakhidov, Tashkent, Uzbekistan
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Iakovleva V, Wuestefeld A, Ong ABL, Gao R, Kaya NA, Lee MY, Zhai W, Tam WL, Dan YY, Wuestefeld T. Mfap4: a promising target for enhanced liver regeneration and chronic liver disease treatment. NPJ Regen Med 2023; 8:63. [PMID: 37935709 PMCID: PMC10630300 DOI: 10.1038/s41536-023-00337-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 10/11/2023] [Indexed: 11/09/2023] Open
Abstract
The liver has a remarkable regenerative capacity. Nevertheless, under chronic liver-damaging conditions, this capacity becomes exhausted, allowing the accumulation of fibrotic tissue and leading to end-stage liver disease. Enhancing the endogenous regenerative capacity by targeting regeneration breaks is an innovative therapeutic approach. We set up an in vivo functional genetic screen to identify such regeneration breaks. As the top hit, we identified Microfibril associated protein 4 (Mfap4). Knockdown of Mfap4 in hepatocytes enhances cell proliferation, accelerates liver regeneration, and attenuates chronic liver disease by reducing liver fibrosis. Targeting Mfap4 modulates several liver regeneration-related pathways including mTOR. Our research opens the way to siRNA-based therapeutics to enhance hepatocyte-based liver regeneration.
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Affiliation(s)
- Viktoriia Iakovleva
- Laboratory of In Vivo Genetics and Gene Therapy, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Singapore, 138672, Republic of Singapore
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, Republic of Singapore
- Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Republic of Singapore
| | - Anna Wuestefeld
- Laboratory of In Vivo Genetics and Gene Therapy, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Singapore, 138672, Republic of Singapore
| | - Agnes Bee Leng Ong
- Laboratory of In Vivo Genetics and Gene Therapy, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Singapore, 138672, Republic of Singapore
| | - Rong Gao
- Laboratory of In Vivo Genetics and Gene Therapy, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Singapore, 138672, Republic of Singapore
| | - Neslihan Arife Kaya
- Laboratory of Translational Cancer Biology, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Singapore, 138672, Republic of Singapore
| | - May Yin Lee
- Laboratory of Translational Cancer Biology, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Singapore, 138672, Republic of Singapore
| | - Weiwei Zhai
- Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China
- Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, 650223, China
| | - Wai Leong Tam
- Laboratory of Translational Cancer Biology, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Singapore, 138672, Republic of Singapore
- Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Republic of Singapore
| | - Yock Young Dan
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, Republic of Singapore
- Division of Gastroenterology and Hepatology, National University Health System, Singapore, 119074, Republic of Singapore
| | - Torsten Wuestefeld
- Laboratory of In Vivo Genetics and Gene Therapy, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Singapore, 138672, Republic of Singapore.
- School of Biological Science, Nanyang University of Singapore, Singapore, 637551, Republic of Singapore.
- National Cancer Centre, Singapore, 169610, Republic of Singapore.
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Sharma S, Saner FH, Bezinover D. A brief history of liver transplantation and transplant anesthesia. BMC Anesthesiol 2022; 22:363. [PMID: 36435747 PMCID: PMC9701388 DOI: 10.1186/s12871-022-01904-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Accepted: 11/13/2022] [Indexed: 11/28/2022] Open
Abstract
In this review, we describe the major milestones in the development of organ transplantation with a specific focus on hepatic transplantation. For many years, the barriers preventing successful organ transplantation in humans seemed insurmountable. Although advances in surgical technique provided the technical ability to perform organ transplantation, limited understanding of immunology prevented successful organ transplantation. The breakthrough to success was the result of several significant discoveries between 1950 and 1980 involving improved surgical techniques, the development of effective preservative solutions, and the suppression of cellular immunity to prevent graft rejection. After that, technical innovations and laboratory and clinical research developed rapidly. However, these advances alone could not have led to improved transplant outcomes without parallel advances in anesthesia and critical care. With increasing organ demand, it proved necessary to expand the donor pool, which has been achieved with the use of living donors, split grafts, extended criteria organs, and organs obtained through donation after cardiac death. Given this increased access to organs and organ resources, the number of transplantations performed every year has increased dramatically. New regulatory organizations and transplant societies provide critical oversight to ensure equitable organ distribution and a high standard of care and also perform outcome analyses. Establishing dedicated transplant anesthesia teams results in improved organ transplantation outcomes and provides a foundation for developing new standards for other subspecialties in anesthesiology, critical care, and medicine overall. Through a century of discovery, the success we enjoy at the present time is the result of the work of well-organized multidisciplinary teams following standardized protocols and thereby saving thousands of lives worldwide each year. With continuing innovation, the future is bright.
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Affiliation(s)
- Sonal Sharma
- Department of Anesthesiology and Perioperative Medicine, Pennsylvania State University, Milton S. Hershey Medical Center, 500 University Dr, Hershey, PA, 17033, USA
| | - Fuat H Saner
- Department of General, Visceral, and Transplant Surgery, Medical Center University Essen, Hufeland 55, 45147, Essen, Germany
| | - Dmitri Bezinover
- Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce St, Philadelphia, PA, 19104, USA.
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Alqahtani SA, Gurakar A, Tamim H, Schiano TD, Bonder A, Fricker Z, Kazimi M, Eckhoff DE, Curry MP, Saberi B. Regional and National Trends of Adult Living Donor Liver Transplantation in the United States Over the Last Two Decades. J Clin Transl Hepatol 2022; 10:814-824. [PMID: 36304492 PMCID: PMC9547266 DOI: 10.14218/jcth.2021.00538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 01/26/2022] [Accepted: 02/15/2022] [Indexed: 12/04/2022] Open
Abstract
Background and Aims Liver organ shortage remains a major health burden in the US, with more patients being waitlisted than the number of liver transplants (LTs) performed. This study investigated US national and regional trends in living donor LT (LDLT) and identified factors associated with recipient survival. Methods We retrospectively analyzed LDLT recipients and donors from the United Network Organ Sharing/Organ Procurement Transplant Network database from 1998 until 2019 for clinical characteristics, demographic differences, and survival rate. National and regional trends in LDLT, recipient outcomes, and predictors of survival were analyzed. Results Of the 223,571 candidates listed for an LT, 57.5% received an organ, of which only 4.2% were LDLTs. Annual adult LDLTs first peaked at 412 in 2001 but experienced a significant decline to 168 by 2009. LDLTs then gradually increased to 445 in 2019. Region 2 had the highest LDLT numbers (n =919), while region 1 had the highest proportion (11.1%). Overall, post-LT mortality was 21.4% among LDLT recipients. Post-LDLT survival rates after 1-, 5-, and 10-years were 92%, 87%, and 70%, respectively. Interval analysis (2004–2019) showed that patients undergoing LDLT in recent years had lower mortality than in earlier years (hazard ratio=0.81, 95% confidence interval=0.75–0.88). Conclusions Following a substantial decline after a peak in 2001, the number of adult LDLTs steadily increased from 2011 to 2019. However, LDLTs still constitute the minority of the transplant pool in the US. Life-saving policies to increase the use of LDLTs, particularly in regions of high organ demand, should be implemented.
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Affiliation(s)
- Saleh A. Alqahtani
- Johns Hopkins University, Division of Gastroenterology and Hepatology, Baltimore, MD, USA
| | - Ahmet Gurakar
- Johns Hopkins University, Division of Gastroenterology and Hepatology, Baltimore, MD, USA
| | - Hani Tamim
- American University of Beirut, Department of Internal Medicine, Beirut, Lebanon
| | - Thomas D. Schiano
- Icahn School of Medicine at Mount Sinai, Division of Liver Diseases, New York, NY, USA
| | - Alan Bonder
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Zachary Fricker
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Marwan Kazimi
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Devin E. Eckhoff
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Michael P. Curry
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Behnam Saberi
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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Recipient Age Predicts 20-Year Survival in Pediatric Liver Transplant. Can J Gastroenterol Hepatol 2022; 2022:1466602. [PMID: 36164664 PMCID: PMC9509270 DOI: 10.1155/2022/1466602] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 07/12/2022] [Accepted: 08/25/2022] [Indexed: 11/18/2022] Open
Abstract
INTRODUCTION Pediatric liver transplant recipients have demonstrated excellent long-term survival. The purpose of this analysis is to investigate factors associated with 20-year survival to identify areas for improvement in patient care. METHODS Kaplan-Meier with log-rank test as well as univariate and multivariate logistic regression methods were used to retrospectively analyze 4,312 liver transplant recipients under the age of 18 between September 30, 1987 and March 9, 1998. Our primary endpoint was 20-year survival among one-year survival. RESULTS Logistic regression analysis identified recipient age as a significant risk factor, with recipients below 5 years old having a higher 20-year survival rate (p < 0.001). A preoperative primary diagnosis of a metabolic dysfunction was found to be protective compared to other diagnoses (OR 1.64, CI 1.20-2.25). African-American ethnicity (OR 0.71, CI 0.58-0.87) was also found to be a risk factor for mortality. Technical variant allografts (neither living donor nor cadaveric) were not associated with increased or decreased rates of 20-year survival. CONCLUSIONS Our analysis suggests that long-term survival is inversely correlated with recipient age following pediatric liver transplant. If validated with further studies, this conclusion may have profound implications on the timing of pediatric liver transplantation.
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Liang C, Takahashi K, Furuya K, Ohkohchi N, Oda T. Dualistic role of platelets in living donor liver transplantation: Are they harmful? World J Gastroenterol 2022; 28:897-908. [PMID: 35317052 PMCID: PMC8908284 DOI: 10.3748/wjg.v28.i9.897] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Revised: 07/04/2021] [Accepted: 01/27/2022] [Indexed: 02/06/2023] Open
Abstract
Platelets are anucleate fragments mainly involved in hemostasis and thrombosis, and there is emerging evidence that platelets have other nonhemostatic potentials in inflammation, angiogenesis, regeneration and ischemia/reperfusion injury (I/R injury), which are involved in the physiological and pathological processes during living donor liver transplantation (LDLT). LDLT is sometimes associated with impaired regeneration and severe I/R injury, leading to postoperative complications and decreased patient survival. Recent studies have suggested that perioperative thrombocytopenia is associated with poor graft regeneration and postoperative morbidity in the short and long term after LDLT. Although it is not fully understood whether thrombocytopenia is the cause or result, increasing platelet counts are frequently suggested to improve posttransplant outcomes in clinical studies. Based on rodent experiments, previous studies have identified that platelets stimulate liver regeneration after partial hepatectomy. However, the role of platelets in LDLT is controversial, as platelets are supposed to aggravate I/R injury in the liver. Recently, a rat model of partial liver transplantation (LT) was used to demonstrate that thrombopoietin-induced thrombocytosis prior to surgery accelerated graft regeneration and improved the survival rate after transplantation. It was clarified that platelet-derived liver regeneration outweighed the associated risk of I/R injury after partial LT. Clinical strategies to increase perioperative platelet counts, such as thrombopoietin, thrombopoietin receptor agonist and platelet transfusion, may improve graft regeneration and survival after LDLT.
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Affiliation(s)
- Chen Liang
- Gastrointestinal and Hepatobiliary-Pancreatic Surgery, University of Tsukuba, Tsukuba 3058575, Ibaraki, Japan
| | - Kazuhiro Takahashi
- Gastrointestinal and Hepatobiliary-Pancreatic Surgery, University of Tsukuba, Tsukuba 3058575, Ibaraki, Japan
| | - Kinji Furuya
- Gastrointestinal and Hepatobiliary-Pancreatic Surgery, University of Tsukuba, Tsukuba 3058575, Ibaraki, Japan
| | - Nobuhiro Ohkohchi
- Gastrointestinal and Hepatobiliary-Pancreatic Surgery, University of Tsukuba, Tsukuba 3058575, Ibaraki, Japan
| | - Tatsuya Oda
- Gastrointestinal and Hepatobiliary-Pancreatic Surgery, University of Tsukuba, Tsukuba 3058575, Ibaraki, Japan
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Akarca US, Akhan O, Bilgiç S, Bozkurt MF, Cantaşdemir M, Çermik TF, Çakaloğlu Y, Er Ö, Ilgıt E, Çapa Kaya G, Küçük NÖ, Numan F, Parıldar M, Türkmen C. The position of transarterial chemoembolization with drug-eluting beads and yttrium-90 transarterial radioembolization in patients with hepatocellular carcinoma: Consensus statements from a Delphi-method expert panel in Turkey. DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY (ANKARA, TURKEY) 2021; 27:732-739. [PMID: 34792027 DOI: 10.5152/dir.2021.201089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
PURPOSE Clinical studies conducted in different geographic regions using different methods to compare transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) have demonstrated discordant results. Meta-analyses in this field indicate comparable overall survival (OS) with TACE and TARE, while reporting a longer time to progression and a higher downstaging effect with TARE treatment. In terms of isolated procedure costs, treatment with TARE is 2 to 3 times more, and in some countries even more, expensive than TACE. However, relevant literature indicates that TARE is more advantageous compared to TACE regarding the need for repeat procedures, costs of complication management, total hospital stay and quality of life. Heterogeneity of hepatocellular carcinoma (HCC) patients as well as the shortcomings of clinical classifications, randomized clinical trials and cost-effectiveness studies make it difficult to choose between treatment alternatives in this field. As in other countries, these challenges lead to differences in treatment choice across different centers in Turkey. METHODS The present expert panel used two round modified Delphi method to investigate the resources and clinical parameters referenced while selecting patients for drug-eluting beads (DEB)-TACE and TARE treatment modalities in Turkish clinical practice. The cost-effectiveness parameters and comparisons of these treatments have also been evaluated at a prediction level. RESULTS The panelists stated that they most commonly use the BCLC staging system for the management of HCC patients in Turkey. However, they did not find any of the staging systems or treatment guidelines sufficient enough for their clinical practice in terms of covering the down-staging intent of treatments. Since living donor transplant preference is higher in Turkey than the rest of the Western countries, down-staging treatments are thought to be more prioritized in Turkey than that in other Western countries. The panelists reached a consensus that TARE may provide improved OS and reduce the number of repeat procedures compared to DEB-TACE in intermediate-stage patients with a single tumor spanning a diameter above 5 cm who experience recurrence after previous treatment with TACE and most TACE-naïve patient groups in intermediate stage. CONCLUSION Based on the consensus on OS and the number of procedures, the panelists assumed that TARE would be more cost-effective than DEB-TACE in most groups of TACE-naïve patients in intermediate stage and in those with a single tumor spanning a diameter above 5 cm. It was also stated that the predicted cost-effectiveness advantage of TARE could be more pronounced in patients with a tumor diameter greater than 7 cm.
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Affiliation(s)
- Ulus Salih Akarca
- From the Department of Gastroenterology, Ege University Faculty of Medicine, İzmir, Turkey
| | - Okan Akhan
- Department of Radiology, Ege University Faculty of Medicine, İzmir, Turkey
| | - Sadık Bilgiç
- Department of Radiology Ankara University Medical School, Ankara, Turkey
| | - Murat Fani Bozkurt
- Department of Radiology, Ankara University Faculty of Medicine, Ankara, Turkey
| | - Murat Cantaşdemir
- Department of Nuclear Medicine , Ankara University Faculty of Medicine, Ankara, Turkey
| | - Tevfik Fikret Çermik
- Department of Radiology, İstanbul University Cerrahpasa Faculty of Medicine, İstanbul
| | - Yılmaz Çakaloğlu
- Department of Gastroenterology and Hepatology, Memorial Şişli Hastanesi, İstanbul, Turkey
| | - Özlem Er
- Department of Oncology, Acibadem Maslak Hospital, İstanbul, Turkey
| | - Erhan Ilgıt
- Department of Radiology, Gazi University School of Medicine, Ankara, Turkey
| | - Gamze Çapa Kaya
- Department of Nuclear Medicine, Dokuz Eylül University Faculty of Medicine, İzmir, Turkey
| | - Nuriye Özlem Küçük
- Department of Nuclear Medicine ,İstanbul University Cerrahpasa Faculty of Medicine, İstanbul
| | - Furuzan Numan
- Department of Radiology, İstanbul University Cerrahpasa Faculty of Medicine, İstanbul
| | - Mustafa Parıldar
- Department of Radiology, Ege University School of Medicine, İzmir, Turkey
| | - Cüneyt Türkmen
- Department of Radiology, İstanbul University Cerrahpasa Faculty of Medicine, İstanbul
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Ordin YS, Karayurt Ö, Aksu Kul G, Kılıç M, Taylor LA. Exploration Into Donor-Recipient Relationship After Living-Donor Liver Transplantation Using Gift-Exchange Theory. Florence Nightingale Hemsire Derg 2021; 29:150-157. [PMID: 34263233 PMCID: PMC8245026 DOI: 10.5152/fnjn.2021.20065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Accepted: 01/08/2021] [Indexed: 11/22/2022] Open
Abstract
AIM This qualitative study aimed to explore the donor-recipient relationships following living-donor liver transplantation. METHOD A 1-time cross-sectional qualitative interview was conducted with liver transplant recipients (n = 17) and living liver donors (n = 11) post-transplant. The interviews were transcribed verbatim and analyzed manually by using thematic content analysis. RESULTS The mean age of the recipients and the donors was 54.41 ± 8.0 (range 39-71) and 36.6 ± 7.69 (range 28-57) years, respectively. Following the interviews, 2 overarching themes emerged: (1) Became care providers, and (2) differentiation in relationships after transplantation. A total of 3 sub-themes were explained under "differentiation in relationships after transplantation;" feeling guilty, becoming closer and more intense owing to a feeling of indebtedness, and putting some distance owing to a feeling of indebtedness. CONCLUSION The study focused on the reciprocation stage according to gift-exchange theory. During reciprocation, although recipients expressed positive feelings such as gratitude, closer relationships, and special bonds; they also reported negative feelings like guilt and indebtedness resulting in a purposeful distancing from their donors. Most donors understood what the recipients felt, but they wanted their relationship to return to normal. Married female donors had worse experiences, such as divorce or a weakened marital relationship after donation.
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Affiliation(s)
- Yaprak Sarıgöl Ordin
- Department of Surgical Nursing, Dokuz Eylül University, Faculty of Nursing, İzmir, Turkey
| | - Özgül Karayurt
- Department of Nursing, İzmir University of Economics, Faculty of Health Science, İzmir, Turkey
| | - Gülay Aksu Kul
- Department of Nursing, İzmir University of Economics, Faculty of Health Science, İzmir, Turkey
| | - Murat Kılıç
- Department of Nursing, İzmir University of Economics, Faculty of Health Science, İzmir, Turkey
| | - Laura A Taylor
- Adult Gerontology Clinical Nurse Specialist Program, Uniformed Services University of Health Sciences Daniel K. Inouye Graduate School of Nursing, Bethesda, USA
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Shono Y, Kushida Y, Wakao S, Kuroda Y, Unno M, Kamei T, Miyagi S, Dezawa M. Protection of liver sinusoids by intravenous administration of human Muse cells in a rat extra-small partial liver transplantation model. Am J Transplant 2021; 21:2025-2039. [PMID: 33350582 PMCID: PMC8248424 DOI: 10.1111/ajt.16461] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 11/22/2020] [Accepted: 12/11/2020] [Indexed: 01/25/2023]
Abstract
Small-for-size syndrome (SFSS) has a poor prognosis due to excessive shear stress and sinusoidal microcirculatory disturbances in the acute phase after living-donor liver transplantation (LDLT). Multilineage-differentiating stress enduring (Muse) cells are reparative stem cells found in various tissues and currently under clinical trials. These cells selectively home to damaged sites via the sphingosine-1-phosphate (S1P)-S1P receptor 2 system and repair damaged tissue by pleiotropic effects, including tissue protection and damaged/apoptotic cell replacement by differentiating into tissue-constituent cells. The effects of intravenously administered human bone marrow-Muse cells and -mesenchymal stem cells (MSCs) (4 × 105 ) on liver sinusoidal endothelial cells (LSECs) were examined in a rat SFSS model without immunosuppression. Compared with MSCs, Muse cells intensively homed to the grafted liver, distributed to the sinusoids and vessels, and delivered improved blood chemistry and Ki-67(+) proliferative hepatocytes and -LSECs within 3 days. Tissue clearing and three-dimensional imaging by multiphoton laser confocal microscopy revealed maintenance of the sinusoid continuity, organization, and surface area, as well as decreased sinusoid interruption in the Muse group. Small-interfering RNA-induced knockdown of hepatocyte growth factor and vascular endothelial growth factor-A impaired the protective effect of Muse cells on LSECs. Intravenous injection of Muse cells might be a feasible approach for LDLT with less recipient burden.
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Affiliation(s)
- Yoshihiro Shono
- Department of SurgeryTohoku University Graduate School of MedicineSendaiMiyagiJapan
| | - Yoshihiro Kushida
- Department of Stem Cell Biology and HistologyTohoku University Graduate School of MedicineSendaiMiyagiJapan
| | - Shohei Wakao
- Department of Stem Cell Biology and HistologyTohoku University Graduate School of MedicineSendaiMiyagiJapan
| | - Yasumasa Kuroda
- Department of Stem Cell Biology and HistologyTohoku University Graduate School of MedicineSendaiMiyagiJapan
| | - Michiaki Unno
- Department of SurgeryTohoku University Graduate School of MedicineSendaiMiyagiJapan
| | - Takashi Kamei
- Department of SurgeryTohoku University Graduate School of MedicineSendaiMiyagiJapan
| | - Shigehito Miyagi
- Department of SurgeryTohoku University Graduate School of MedicineSendaiMiyagiJapan
| | - Mari Dezawa
- Department of Stem Cell Biology and HistologyTohoku University Graduate School of MedicineSendaiMiyagiJapan
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11
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Comparison of the Quality of Life and Emotional Responses in Kidney Transplant Recipients from Living and Deceased Donors in Nephrology Clinics. Nephrourol Mon 2021. [DOI: 10.5812/numonthly.100728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Background: Quality of life (QoL) is one of the essential measures in assessing a patient's status after kidney transplant, and emotional response is an important factor in evaluating the patient’s compatibility with the transplant. Also, emotional response affects a patient’s QoL. Objectives: This study aimed to compare the QoL and emotional responses of kidney recipients from deceased and living donors. Methods: This descriptive comparative study randomly selected 118 kidney transplant patients (67 recipients from living donors and 51 recipients from deceased) referred to the Nephrology Clinic of Tehran University of Medical Sciences for a post-surgery follow-up. The QoL questionnaire for patients with renal transplants introduced by Laupacis et al. and the emotional response questionnaire (ERQ) by Ziegelmann et al. were used in this study. For data analysis, Mann-Whitney, independent t-test, and Pearson’s correlation tests were used. All the analyses were performed using SPSS software version 20. Results: The kidney recipients from living donors had significantly higher QoL score (especially emotionally) compared with kidney recipients from deceased donors (P=0.04). The score of emotional response was higher in recipients from a living donor, which is related to feeling guilty, transplant disclosure. Furthermore, recipients from a living donor felt guiltier and were unwilling to disclose their transplant compared with recipients from deceased donors. Conclusions: Feeling of guilt and being anxious about transplant disclosure were higher in recipients from living donors. A significant difference was observed in the QoL and emotional response between the two groups of kidney recipients. Therefore, it is important to involve the transplant team, specifically nurses, in the identification of emotional response and planning accordingly to improve the patients’ QoL, especially in recipients from a living donor.
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12
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So J, Kim M, Lee SH, Ko S, Lee DA, Park H, Azuma M, Parsons MJ, Prober D, Shin D. Attenuating the Epidermal Growth Factor Receptor-Extracellular Signal-Regulated Kinase-Sex-Determining Region Y-Box 9 Axis Promotes Liver Progenitor Cell-Mediated Liver Regeneration in Zebrafish. Hepatology 2021; 73:1494-1508. [PMID: 32602149 PMCID: PMC7769917 DOI: 10.1002/hep.31437] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Revised: 06/02/2020] [Accepted: 06/03/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIMS The liver is a highly regenerative organ, but its regenerative capacity is compromised in severe liver injury settings. In chronic liver diseases, the number of liver progenitor cells (LPCs) correlates proportionally to disease severity, implying that their inefficient differentiation into hepatocytes exacerbates the disease. Moreover, LPCs secrete proinflammatory cytokines; thus, their prolonged presence worsens inflammation and induces fibrosis. Promoting LPC-to-hepatocyte differentiation in patients with advanced liver disease, for whom liver transplantation is currently the only therapeutic option, may be a feasible clinical approach because such promotion generates more functional hepatocytes and concomitantly reduces inflammation and fibrosis. APPROACH AND RESULTS Here, using zebrafish models of LPC-mediated liver regeneration, we present a proof of principle of such therapeutics by demonstrating a role for the epidermal growth factor receptor (EGFR) signaling pathway in differentiation of LPCs into hepatocytes. We found that suppression of EGFR signaling promoted LPC-to-hepatocyte differentiation through the mitogen-activated ERK kinase (MEK)-extracellular signal-regulated kinase (ERK)-sex-determining region Y-box 9 (SOX9) cascade. Pharmacological inhibition of EGFR or MEK/ERK promoted LPC-to-hepatocyte differentiation as well as genetic suppression of the EGFR-ERK-SOX9 axis. Moreover, Sox9b overexpression in LPCs blocked their differentiation into hepatocytes. In the zebrafish liver injury model, both hepatocytes and biliary epithelial cells contributed to LPCs. EGFR inhibition promoted the differentiation of LPCs regardless of their origin. Notably, short-term treatment with EGFR inhibitors resulted in better liver recovery over the long term. CONCLUSIONS The EGFR-ERK-SOX9 axis suppresses LPC-to-hepatocyte differentiation during LPC-mediated liver regeneration. We suggest EGFR inhibitors as a proregenerative therapeutic drug for patients with advanced liver disease.
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Affiliation(s)
- Juhoon So
- Department of Developmental Biology, McGowan Institute for Regenerative Medicine, Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA 15260, USA
| | - Minwook Kim
- Department of Developmental Biology, McGowan Institute for Regenerative Medicine, Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA 15260, USA
| | - Seung-Hoon Lee
- Department of Developmental Biology, McGowan Institute for Regenerative Medicine, Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA 15260, USA
| | - Sungjin Ko
- Department of Developmental Biology, McGowan Institute for Regenerative Medicine, Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA 15260, USA
- Present address: Division of Experimental Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
| | - Daniel A. Lee
- Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA
| | - Hyewon Park
- Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA
| | - Mizuki Azuma
- Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA
| | - Michael J. Parsons
- Department of Developmental and Cell Biology, University of California Irvine, Irvine, CA 92697, USA
| | - David Prober
- Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA
| | - Donghun Shin
- Department of Developmental Biology, McGowan Institute for Regenerative Medicine, Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA 15260, USA
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13
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Raza MH, Kim MH, Ding L, Fong TL, Romero C, Genyk Y, Sher L, Emamaullee J. Long-Term Financial, Psychosocial, and Overall Health-Related Quality of Life After Living Liver Donation. J Surg Res 2020; 253:41-52. [PMID: 32320896 PMCID: PMC8351216 DOI: 10.1016/j.jss.2020.03.025] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 03/13/2020] [Accepted: 03/16/2020] [Indexed: 01/14/2023]
Abstract
BACKGROUND To assess the impact of living liver donation (LD) in a diverse and aging population up to 20 y after donation, particularly with regard to medical, financial, psychosocial, and overall health-related quality of life (HRQOL). METHODS Patients undergoing LD between 1999 and 2009 were recruited to respond to the Short-Form 36 and a novel Donor Quality of Life Survey at two time points (2010 and 2018). RESULTS Sixty-eight living liver donors (LLDs) completed validated surveys, with a mean follow-up of 11.5 ± 5.1 y. Per Donor Quality of Life Survey data, physical activity or strength was not impacted by LD in most patients. All respondents returned to school or employment, and 82.4% reported that LD had no impact on school or work performance. LD did not impact health insurability in 95.6% of donors, and only one patient experienced difficulty obtaining life insurance. Overall, 97.1% of respondents did not regret LD. Short-Form 36 survey-measured outcomes were similar between LLDs and the general U.S. POPULATION LLDs who responded in both 2010 and 2018 were followed for an overall average of 15.4 ± 2.4 y and HRQOL outcomes in these donors also remained statistically equivalent to U.S. population norms. CONCLUSIONS This study represents the longest postdonation follow-up and offers unique insight related to HRQOL in a highly diverse patient population. Although LLDs continue to maintain excellent HRQOL outcomes up to 20 y after donation, continued lifetime follow-up is required to accurately provide young, healthy potential donors with an accurate description of the risks that they may incur on aging.
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Affiliation(s)
- Muhammad H Raza
- Keck School of Medicine, University of Southern California, Los Angeles, California
| | - Michelle H Kim
- Keck School of Medicine, University of Southern California, Los Angeles, California; Division of Hepatobiliary and Abdominal Transplant Surgery, Department of Surgery, University of Southern California, Los Angeles, California
| | - Li Ding
- Department of Preventive Medicine, University of Southern California, Los Angeles, California
| | - Tse-Ling Fong
- Keck School of Medicine, University of Southern California, Los Angeles, California; Department of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, California
| | - Christian Romero
- Department of Surgery, University of Southern California, Los Angeles, California
| | - Yuri Genyk
- Keck School of Medicine, University of Southern California, Los Angeles, California; Division of Hepatobiliary and Abdominal Transplant Surgery, Department of Surgery, University of Southern California, Los Angeles, California
| | - Linda Sher
- Keck School of Medicine, University of Southern California, Los Angeles, California; Division of Hepatobiliary and Abdominal Transplant Surgery, Department of Surgery, University of Southern California, Los Angeles, California
| | - Juliet Emamaullee
- Keck School of Medicine, University of Southern California, Los Angeles, California; Division of Hepatobiliary and Abdominal Transplant Surgery, Department of Surgery, University of Southern California, Los Angeles, California.
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14
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So J, Kim A, Lee SH, Shin D. Liver progenitor cell-driven liver regeneration. Exp Mol Med 2020; 52:1230-1238. [PMID: 32796957 PMCID: PMC8080804 DOI: 10.1038/s12276-020-0483-0] [Citation(s) in RCA: 70] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 06/08/2020] [Accepted: 06/17/2020] [Indexed: 12/28/2022] Open
Abstract
The liver is a highly regenerative organ, but its regenerative capacity is compromised in severe liver diseases. Hepatocyte-driven liver regeneration that involves the proliferation of preexisting hepatocytes is a primary regeneration mode. On the other hand, liver progenitor cell (LPC)-driven liver regeneration that involves dedifferentiation of biliary epithelial cells or hepatocytes into LPCs, LPC proliferation, and subsequent differentiation of LPCs into hepatocytes is a secondary mode. This secondary mode plays a significant role in liver regeneration when the primary mode does not effectively work, as observed in severe liver injury settings. Thus, promoting LPC-driven liver regeneration may be clinically beneficial to patients with severe liver diseases. In this review, we describe the current understanding of LPC-driven liver regeneration by exploring current knowledge on the activation, origin, and roles of LPCs during regeneration. We also describe animal models used to study LPC-driven liver regeneration, given their potential to further deepen our understanding of the regeneration process. This understanding will eventually contribute to developing strategies to promote LPC-driven liver regeneration in patients with severe liver diseases.
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Affiliation(s)
- Juhoon So
- Department of Developmental Biology, McGowan Institute for Regenerative Medicine, Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA, 15260, USA.
| | - Angie Kim
- Department of Developmental Biology, McGowan Institute for Regenerative Medicine, Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA, 15260, USA
| | - Seung-Hoon Lee
- Department of Developmental Biology, McGowan Institute for Regenerative Medicine, Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA, 15260, USA
| | - Donghun Shin
- Department of Developmental Biology, McGowan Institute for Regenerative Medicine, Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA, 15260, USA.
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15
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A Systematic Review of Opt-out Versus Opt-in Consent on Deceased Organ Donation and Transplantation (2006-2016). World J Surg 2020; 43:3161-3171. [PMID: 31428836 DOI: 10.1007/s00268-019-05118-4] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Significant numbers of patients in the USA and UK die while waiting for solid organ transplant. Only 1-2% of deaths are eligible as donors with a fraction of the deceased donating organs. The form of consent to donation may affect the organs available. Forms of consent include: opt-in, mandated choice, opt-out, and organ conscription. Opt-in and opt-out are commonly practiced. A systematic review was conducted to determine the effect of opt-in versus opt-out consent on the deceased donation rate (DDR) and deceased transplantation rate (DTR). METHODS Literature searches of PubMed and EMBASE between 2006 and 2016 were performed. Research studies were selected based on certain inclusion criteria which include USA, UK, and Spain; compare opt-in versus opt-out; primary data analysis; and reported DDR or DTR. Modeled effect on US transplant activity was conducted using public data from Organ Procurement and Transplantation Network and Centers for Disease Control WONDER from 2006 to 2015. RESULTS A total of 2400 studies were screened and six studies were included. Four studies reported opt-out consent increases DDR by 21-76% over 5-14 years. These studies compared 13-25 opt-out countries versus 9-23 opt-in countries. Three studies reported opt-out consent increases DTR by 38-83% over 11-13 years. These studies compared 22-25 opt-out versus 22-28 opt-in countries. Modeled opt-out activity on the USA resulted in 4753-17,201 additional transplants annually. CONCLUSION Opt-out consent increases DDR and DTR and may be useful in decreasing deaths on the waiting list in the USA and other countries. REGISTRATION NUMBER PROSPERO CRD42019098759.
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16
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Abu Rmilah AA, Zhou W, Nyberg SL. Hormonal Contribution to Liver Regeneration. Mayo Clin Proc Innov Qual Outcomes 2020; 4:315-338. [PMID: 32542223 PMCID: PMC7283948 DOI: 10.1016/j.mayocpiqo.2020.02.001] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Revised: 02/01/2020] [Accepted: 02/07/2020] [Indexed: 02/07/2023] Open
Abstract
An understanding of the molecular basis of liver regeneration will open new horizons for the development of novel therapies for chronic liver failure. Such therapies would solve the drawbacks associated with liver transplant, including the shortage of donor organs, long waitlist time, high medical costs, and lifelong use of immunosuppressive agents. Regeneration after partial hepatectomy has been studied in animal models, particularly fumarylacetoacetate hydrolase-deficient (FAH -/-) mice and pigs. The process of regeneration is distinctive, complex, and well coordinated, and it depends on the interplay among several signaling pathways (eg, nuclear factor κβ, Notch, Hippo), cytokines (eg, tumor necrosis factor α, interleukin 6), and growth factors (eg, hepatocyte growth factor, epidermal growth factor, vascular endothelial growth factor), and other components. Furthermore, endocrinal hormones (eg, norepinephrine, growth hormone, insulin, thyroid hormones) also can influence the aforementioned pathways and factors. We believe that these endocrinal hormones are important hepatic mitogens that strongly induce and accelerate hepatocyte proliferation (regeneration) by directly and indirectly triggering the activity of the involved signaling pathways, cytokines, growth factors, and transcription factors. The subsequent induction of cyclins and associated cyclin-dependent kinase complexes allow hepatocytes to enter the cell cycle. In this review article, we comprehensively summarize the current knowledge regarding the roles and mechanisms of these hormones in liver regeneration. Articles used for this review were identified by searching MEDLINE and EMBASE databases from inception through June 1, 2019.
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Key Words
- CDK, cyclin-dependent kinase
- EGF, epidermal growth factor
- EGFR, EGF receptor
- ERK, extracellular signal-regulated kinase
- FAH, fumarylacetoacetate hydrolase
- GH, growth hormone
- Ghr-/-, growth hormone receptor gene knockout
- HGF, hepatocyte growth factor
- HNF, hepatocyte nuclear factor
- HPC, hepatic progenitor cell
- IGF, insulinlike growth factor
- IL, interleukin
- IR, insulin receptor
- InsP3, inositol 1,4,5-trisphosphate
- JNK, JUN N-terminal kinase
- LDLT, living donor liver transplant
- LRP, low-density lipoprotein-related protein
- MAPK, mitogen-activated protein kinase
- NF-κβ, nuclear factor κβ
- NOS, nitric oxide synthase
- NTBC, 2-nitro-4-trifluoro-methyl-benzoyl-1,3-cyclohexanedione
- PCNA, proliferating cell nuclear antigen
- PCR, polymerase chain reaction
- PH, partial hepatectomy
- PI3K, phosphatidylinositol-4,5-bisphosphate 3-kinase
- PKB, protein kinase B
- PTU, 6-n-propyl-2-thiouracil
- ROS, reactive oxygen species
- STAT, signal transducer and activator of transcription
- T3, triiodothyronine
- TGF, transforming growth factor
- TNF, tumor necrosis factor
- TR, thyroid receptor
- hESC, human embryonic stem cell
- hiPSC, human induced pluripotent stem cells
- mRNA, messenger RNA
- mTOR, mammalian target of rapamycin
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Affiliation(s)
| | - Wei Zhou
- Division of Transplantation Surgery, Mayo Clinic, Rochester, MN.,First Affiliated Hospital of China, Medical University, Department of Hepatobiliary Surgery, Shenyang, China
| | - Scott L Nyberg
- Division of Transplantation Surgery, Mayo Clinic, Rochester, MN
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17
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Huang V, Chen CL, Lin YH, Lin TS, Lin CC, Wang SH, Yong CC, Chen CY, Cheng YF. Bilateral proficiency over time leads to reduced donor morbidity in living donor hepatectomy. Hepatobiliary Surg Nutr 2019; 8:459-469. [PMID: 31673535 DOI: 10.21037/hbsn.2019.03.12] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Background Although left-lobe donation is considered safer, right-sided donor hepatectomy predominates in adult living donor liver transplantation (LDLT). We hypothesized that bilateral proficiency with donor hepatectomy reduces overall donor complications. Methods A retrospective review of 834 adult LDLT donors (221 left lobes) from January 2004 to December 2014 was performed, dividing cases into two eras based on left-graft experience. Donor complications within 6 months were investigated, focusing on graft side and surgical era. Results The overall complication rate was 17.6%, and was higher in right-lobe donors. In Era 2, during which left-lobe donation rates were three times higher, total complications decreased (14.7% vs. 20.9%, P=0.02). A significant reduction in postoperative ascites accounted for the lower overall complication rate. The proportion of major biliary complications (BCs) was halved from 62.5% to 25.0%. Right-lobe donor complications also decreased significantly (15.8% vs. 22.9%, P=0.032), demonstrating that it was not only increased left-lobe donations leading to lowered complication rates, but also greater experience with donor hepatectomy in general. Conclusions Accumulating experience with bilateral donor hepatectomy leads to decreased donor morbidity and comparable outcomes for right and left lobes, further enhancing the goal of donor safety while balancing recipient needs.
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Affiliation(s)
- Viola Huang
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.,Department of General Surgery, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire, USA
| | - Chao-Long Chen
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Yu-Hung Lin
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Tsan-Shiun Lin
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chih-Che Lin
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Shih-Ho Wang
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chee-Chien Yong
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chih-Yi Chen
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Yu-Fan Cheng
- Liver Transplantation Center and Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
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18
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Zidan A, Sturdevant M, Alkhail FA, Alabbad S, Boehnert MU, Broering D. The first two cases of living donor liver transplantation using dual grafts in Saudi Arabia. Ann Saudi Med 2019; 39:118-123. [PMID: 30955020 PMCID: PMC6464670 DOI: 10.5144/0256-4947.2019.118] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2018] [Accepted: 07/02/2018] [Indexed: 01/05/2023] Open
Abstract
The concept of dual-graft liver transplantation was introduced to overcome the discrepancy between liver transplantation demand and liver donation. Dual-graft transplantation also mitigates cumulative family risk by decreasing individual donor risk through minimization of the resected liver volume from each donor. Here, we describe the first two cases performed in Saudi Arabia wherein a dual-graft living donor liver transplantation was facilitated by the use of one left lobe graft and one left lateral segment in both cases. These are the first two cases of dual-graft liver transplantation reported from Saudi Arabia and the Middle East. SIMILAR CASES PUBLISHED: Nine on the same subject in other parts of the world (Korea, Japan, Germany, China, and Brazil).
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Affiliation(s)
- Ahmed Zidan
- Dr. Ahmed Zidan Liver Transplantation,, King Faisal Specialist Hospital and Research Centre,, PO Box 3544, Riyadh 11211, Saudi Arabia, T: 966550390905, , ORCID: https://orcid.org/00000002-2423-8246
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19
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Blackford SJ, Ng SS, Segal JM, King AJ, Austin AL, Kent D, Moore J, Sheldon M, Ilic D, Dhawan A, Mitry RR, Rashid ST. Validation of Current Good Manufacturing Practice Compliant Human Pluripotent Stem Cell-Derived Hepatocytes for Cell-Based Therapy. Stem Cells Transl Med 2019; 8:124-137. [PMID: 30456803 PMCID: PMC6344902 DOI: 10.1002/sctm.18-0084] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Revised: 08/22/2018] [Accepted: 09/25/2018] [Indexed: 01/04/2023] Open
Abstract
Recent advancements in the production of hepatocytes from human pluripotent stem cells (hPSC-Heps) afford tremendous possibilities for treatment of patients with liver disease. Validated current good manufacturing practice (cGMP) lines are an essential prerequisite for such applications but have only recently been established. Whether such cGMP lines are capable of hepatic differentiation is not known. To address this knowledge gap, we examined the proficiency of three recently derived cGMP lines (two hiPSC and one hESC) to differentiate into hepatocytes and their suitability for therapy. hPSC-Heps generated using a chemically defined four-step hepatic differentiation protocol uniformly demonstrated highly reproducible phenotypes and functionality. Seeding into a 3D poly(ethylene glycol)-diacrylate fabricated inverted colloid crystal scaffold converted these immature progenitors into more advanced hepatic tissue structures. Hepatic constructs could also be successfully encapsulated into the immune-privileged material alginate and remained viable as well as functional upon transplantation into immune competent mice. This is the first report we are aware of demonstrating cGMP-compliant hPSCs can generate cells with advanced hepatic function potentially suitable for future therapeutic applications. Stem Cells Translational Medicine 2019;8:124&14.
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Affiliation(s)
- Samuel J.I. Blackford
- Centre for Stem Cells and Regenerative MedicineKing's College LondonLondonUnited Kingdom
| | - Soon Seng Ng
- Centre for Stem Cells and Regenerative MedicineKing's College LondonLondonUnited Kingdom
| | - Joe M. Segal
- Centre for Stem Cells and Regenerative MedicineKing's College LondonLondonUnited Kingdom
| | - Aileen J.F. King
- Diabetes Research GroupFaculty of Life Sciences & Medicine, King's College LondonLondonUnited Kingdom
| | - Amazon L. Austin
- Diabetes Research GroupFaculty of Life Sciences & Medicine, King's College LondonLondonUnited Kingdom
| | - Deniz Kent
- Centre for Stem Cells and Regenerative MedicineKing's College LondonLondonUnited Kingdom
| | - Jennifer Moore
- RUCDR Infinite BiologicsRutgers UniversityNew BrunswickNew JerseyUSA
| | - Michael Sheldon
- RUCDR Infinite BiologicsRutgers UniversityNew BrunswickNew JerseyUSA
| | - Dusko Ilic
- Stem Cell Laboratory, Department of Women and Children's HealthFaculty of Life Sciences and Medicine, King's College LondonLondonUnited Kingdom
| | - Anil Dhawan
- Institute for Liver StudiesKing's College Hospital, King's College LondonLondonUnited Kingdom
| | - Ragai R. Mitry
- Institute for Liver StudiesKing's College Hospital, King's College LondonLondonUnited Kingdom
| | - S. Tamir Rashid
- Centre for Stem Cells and Regenerative MedicineKing's College LondonLondonUnited Kingdom
- Institute for Liver StudiesKing's College Hospital, King's College LondonLondonUnited Kingdom
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20
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Au KP, Chok KSH. Minimally invasive donor hepatectomy, are we ready for prime time? World J Gastroenterol 2018; 24:2698-2709. [PMID: 29991875 PMCID: PMC6034150 DOI: 10.3748/wjg.v24.i25.2698] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2018] [Revised: 05/25/2018] [Accepted: 06/09/2018] [Indexed: 02/06/2023] Open
Abstract
Minimally invasive surgery potentially reduces operative morbidities. However, pure laparoscopic approaches to donor hepatectomy have been limited by technical complexity and concerns over donor safety. Reduced-wound donor hepatectomy, either in the form of a laparoscopic-assisted technique or by utilizing a mini-laparotomy wound, i.e., hybrid approach, has been developed to bridge the transition to pure laparoscopic donor hepatectomy, offering some advantages of minimally invasive surgery. To date, pure laparoscopic donor left lateral sectionectomy has been validated for its safety and advantages and has become the standard in experienced centres. Pure laparoscopic approaches to major left and right liver donation have been reported for their technical feasibility in expert hands. Robotic-assisted donor hepatectomy also appears to be a valuable alternative to pure laparoscopic donor hepatectomy, providing additional ergonomic advantages to the surgeon. Existing reports derive from centres with tremendous experience in both laparoscopic hepatectomy and donor hepatectomy. The complexity of these procedures means an arduous transition from technical feasibility to reproducibility. Donor safety is paramount in living donor liver transplantation. Careful donor selection and adopting standardized techniques allow experienced transplant surgeons to safely accumulate experience and acquire proficiency. An international prospective registry will advance the understanding for the role and safety of pure laparoscopic donor hepatectomy.
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Affiliation(s)
- Kin Pan Au
- Department of Surgery, Queen Mary Hospital, Hong Kong, China
| | - Kenneth Siu Ho Chok
- Department of Surgery and State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China
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21
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Dar FS, Bhatti ABH, Qureshi AI, Khan NY, Eswani Z, Zia HH, Khan EU, Khan NA, Rana A, Shah NH, Salih M, Nazer R. Living Donor Liver Transplantation in South Asia: Single Center Experience on Intermediate-Term Outcomes. World J Surg 2018; 42:1111-1119. [PMID: 28936685 DOI: 10.1007/s00268-017-4259-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND There is paucity of data on intermediate-term post liver transplant outcomes from South Asia. The objective of this study was to determine survival outcomes in patients who underwent living donor liver transplantation (LDLT) in a busy liver transplant center in Pakistan. METHODS This study was a review of patients who underwent LDLT between 2012 and 2016. A total of 321 patients were included in this study. Early (within 90 days) and late (>90 days) morbidity and mortality was assessed. Estimated 1- and 4-year survival was determined. RESULTS Median age was 48 (18-73) years. Male to female ratio was 4.5:1. Out of total 346 complications, 184 (57.3%) patients developed 276 (79.7%) complications in early post-transplant period, whereas there were 70 (21.3%) late complications. Most common early complication was pleural effusion in 46 (16.6%) patients. Biliary complications were the most common late complication and were seen in 31/70 (44.2%) patients. Overall 21.4% patients had a biliary complication. The 3-month mortality was 14%. The estimated 1- and 4-year OS for a MELD cutoff of 30 was 84.5 versus 72 and 80 versus 57% (P = 0.01). There was no donor mortality. CONCLUSION Acceptable intermediate-term post-transplant outcomes were achieved with LDLT. There is a need to improve outcomes in high-MELD patients.
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Affiliation(s)
- Faisal S Dar
- Department of HPB Surgery and Liver Transplantation, Shifa International Hospital, Sector H-8/4, Pitras Bukhari Road, Islamabad, Pakistan
| | - Abu Bakar H Bhatti
- Department of HPB Surgery and Liver Transplantation, Shifa International Hospital, Sector H-8/4, Pitras Bukhari Road, Islamabad, Pakistan.
| | - Ammal I Qureshi
- Department of HPB Surgery and Liver Transplantation, Shifa International Hospital, Sector H-8/4, Pitras Bukhari Road, Islamabad, Pakistan
| | - Nusrat Y Khan
- Department of HPB Surgery and Liver Transplantation, Shifa International Hospital, Sector H-8/4, Pitras Bukhari Road, Islamabad, Pakistan
| | - Zahaan Eswani
- Department of HPB Surgery and Liver Transplantation, Shifa International Hospital, Sector H-8/4, Pitras Bukhari Road, Islamabad, Pakistan
| | - Haseeb H Zia
- Department of HPB Surgery and Liver Transplantation, Shifa International Hospital, Sector H-8/4, Pitras Bukhari Road, Islamabad, Pakistan
| | - Eitzaz U Khan
- Department of Anesthesiology, Shifa International Hospital, Islamabad, Pakistan
| | - Nasir A Khan
- Department of Anesthesiology, Shifa International Hospital, Islamabad, Pakistan
| | - Atif Rana
- Department of Radiology, Shifa International Hospital, Islamabad, Pakistan
| | - Najmul H Shah
- Department of Gastroenterology and Hepatology, Shifa International Hospital, Islamabad, Pakistan
| | - Mohammad Salih
- Department of Gastroenterology and Hepatology, Shifa International Hospital, Islamabad, Pakistan
| | - Rashid Nazer
- Department of Radiology, Shifa International Hospital, Islamabad, Pakistan
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22
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Liver transplantation for hepatocellular carcinoma: outcomes and novel surgical approaches. Nat Rev Gastroenterol Hepatol 2017; 14:203-217. [PMID: 28053342 DOI: 10.1038/nrgastro.2016.193] [Citation(s) in RCA: 322] [Impact Index Per Article: 40.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Liver transplantation for hepatocellular carcinoma (HCC) is the best treatment option for patients with early-stage tumours and accounts for ∼20-40% of all liver transplantations performed at most centres worldwide. The Milan criteria are the most common criteria to select patients with HCC for transplantation but they can be seen as too restrictive. Several proposals have been made for a moderate expansion of the criteria, which result in good outcomes but with an increase in the risk of tumour recurrence. In this Review, we provide a comprehensive overview of the outcomes after liver transplantation for HCC, focusing on tumour recurrence in terms of surveillance, prevention and treatment. Additionally, novel surgical techniques have been developed to increase the available pool of organs for liver transplantation (such as living donor liver transplantation, donation after circulatory death and split livers), but the effect of these techniques on patients with HCC is still under debate. Thus, we will describe these techniques and expose the benefits and disadvantages of each surgical approach. Finally, we will comment on the limitations of the current priority policies for liver transplantation and the need to further refine them to better serve the population.
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23
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Manzini G, Henne-Bruns D, Porzsolt F, Kremer M. Is there a standard for surgical therapy of hepatocellular carcinoma in healthy and cirrhotic liver? A comparison of eight guidelines. BMJ Open Gastroenterol 2017; 4:e000129. [PMID: 28405349 PMCID: PMC5372044 DOI: 10.1136/bmjgast-2016-000129] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2016] [Revised: 02/08/2017] [Accepted: 02/13/2017] [Indexed: 12/12/2022] Open
Abstract
Background and aims Liver resection (LR) and transplantation are the most reliable treatments for hepatocellular carcinoma (HCC). Aim was to compare different guidelines regarding indication for resection and transplantation because of HCC with and without underlying cirrhosis. Methods We compared the following guidelines published after 1 January 2010: American (American Association for the Study of Liver Diseases (AASLD)), Spanish (Sociedad Espanola de Oncologia Medica (SEOM)), European (European Association for the study of liver-European Organization for Research and Treatment of Cancer (EASL-EORTC) and European Society for Medical Oncology-European Society of Digestive Oncology (ESMO-ESDO)), Asian (Asian Pacific Association for the Study of Liver (APASL)), Japanese (Japan Society of Hepatology (JSH)), Italian (Associazione Italiana Oncologia Medica (AIOM)) and German (S3) guidelines. Results All guidelines recommend resection as therapy of choice in healthy liver. Guidelines based on the Barcelona Clinic Liver Cancer staging system recommend resection for single HCC<2 cm and Child-Pugh A cirrhosis and for HCC≤5 cm with normal bilirubin and portal pressure, whereas transplantation is recommended for multiple tumours between Milan criteria and for single tumours ≤5 cm and advanced liver dysfunction. Patients with HCC and Child-Pugh C cirrhosis are not candidates for transplantation. JSH guidelines recommend LR for patients with Child-Pugh A/B with HCC without tumour size restriction; APASL guidelines in general exclude patients with Child-Pugh A from transplantation. In patients with Child-Pugh B, transplantation is the second-line therapy, if resection is not possible for patients within Milan criteria. German and Italian guidelines recommend transplantation for all patients within Milan criteria. Conclusions Whereas resection is the standard therapy of HCC in healthy liver, a standard regarding the indication for LR and transplantation for HCC in cirrhotic liver does not exist, although nearly all guidelines claim to be evidence based. Surprisingly, despite European guidelines, Germany and Italy use their own national guidelines which partially differ from the European. Possible solutions of the problems are discussed.
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Affiliation(s)
- Giulia Manzini
- Department of General and Visceral Surgery , University of Ulm , Ulm , Germany
| | - Doris Henne-Bruns
- Department of General and Visceral Surgery , University of Ulm , Ulm , Germany
| | - Franz Porzsolt
- Health Care Research Group at the Hospital of General and Visceral Surgery, University Hospital of Ulm , Ulm , Germany
| | - Michael Kremer
- Department of General and Visceral Surgery , University of Ulm , Ulm , Germany
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24
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Rutkowski DR, Reeder SB, Fernandez LA, Roldán-Alzate A. Surgical planning for living donor liver transplant using 4D flow MRI, computational fluid dynamics and in vitro experiments. COMPUTER METHODS IN BIOMECHANICS AND BIOMEDICAL ENGINEERING-IMAGING AND VISUALIZATION 2017; 6:545-555. [PMID: 30094106 DOI: 10.1080/21681163.2017.1278619] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
This study used magnetic resonance imaging (MRI), computational fluid dynamics (CFD) modeling, and in vitro experiments to predict patient-specific alterations in hepatic hemodynamics in response to partial hepatectomy in living liver donors. 4D Flow MRI was performed on three donors before and after hepatectomy and models of the portal venous system were created. Virtual surgery was performed to simulate (1) surgical resection and (2) post-surgery vessel dilation. CFD simulations were conducted using in vivo flow data for boundary conditions. CFD results showed good agreement with in vivo data, and in vitro experimental values agreed well with imaging and simulation results. The post-surgery models predicted an increase in all measured hemodynamic parameters, and the dilated virtual surgery model predicted post-surgery conditions better than the model that only simulated resection. The methods used in this study have potential significant value for the surgical planning process for the liver and other vascular territories.
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Affiliation(s)
- David R Rutkowski
- Mechanical Engineering, University of Wisconsin-Madison Madison, WI, United States.,Radiology, University of Wisconsin-Madison Madison, WI, United States
| | - Scott B Reeder
- Radiology, University of Wisconsin-Madison Madison, WI, United States.,Medical Physics, University of Wisconsin-Madison Madison, WI, United States.,Biomedical Engineering, University of Wisconsin-Madison Madison, WI, United States.,Medicine, University of Wisconsin-Madison Madison, WI, United States.,Emergency Medicine, University of Wisconsin-Madison Madison, WI, United States
| | | | - Alejandro Roldán-Alzate
- Mechanical Engineering, University of Wisconsin-Madison Madison, WI, United States.,Radiology, University of Wisconsin-Madison Madison, WI, United States.,Biomedical Engineering, University of Wisconsin-Madison Madison, WI, United States
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25
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Elwir S, Thompson J, Amateau SK, Trikudanathan G, Attam R, Hassan M, Kandaswamy R, Pruett T, Lake J, Chinnakotla S, Freeman ML, Arain MA. Endoscopic Management of Biliary Leaks and Strictures After Living Donor Liver Transplantation: Optimizing Techniques for Successful Management. Dig Dis Sci 2017; 62:244-252. [PMID: 27866300 DOI: 10.1007/s10620-016-4367-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2016] [Accepted: 10/27/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Biliary complications (BCs) occur in up to 40% of living donor liver transplant (LDLT) recipients. The aim of this study was to evaluate the efficacy of endoscopic therapy in the management of LDLT-related BCs. METHODS A retrospective study of 100 LDLT recipients at a single transplant center over a 9-year period was conducted. BC was defined as a biliary leak and/or a stricture. Patient records were used to identify time to diagnosis, type of intervention, and time to resolution. RESULTS BCs occurred in 46 (46%) patients; median follow-up was 4.6 years (range 5 days-9.3 years); and median time to diagnosis was 37.5 days (range 1 day-3.5 years). BCs were classified as a leak in 6 (6%), stricture in 22 (22%), and a leak + stricture in 18 (18%). ERCP was the initial treatment modality in 43/46 (93%) patients and was completed in 42/43 (98%). Three (6.5%) patients with a leak underwent surgery as the primary treatment approach. The median time to resolution of BCs was 91.5 days (range 21-367). Thirteen patients had a recurrence which was managed with endoscopic therapy alone. CONCLUSIONS Endoscopic therapy was successful in almost all patients (98%) and ERCP alone resulted in successful treatment in a higher proportion of patients (93%) than traditionally reported. Advanced endoscopic techniques obviate the need for PTC and/or surgery and allow successful management in almost all LDLT recipients presenting with BC and in patients with recurrence of strictures.
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Affiliation(s)
- Saleh Elwir
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, 406 Harvard St. SE, MMC 36, Minneapolis, MN, 55455, USA
| | - Julie Thompson
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, 406 Harvard St. SE, MMC 36, Minneapolis, MN, 55455, USA
| | - Stuart K Amateau
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, 406 Harvard St. SE, MMC 36, Minneapolis, MN, 55455, USA
| | - Guru Trikudanathan
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, 406 Harvard St. SE, MMC 36, Minneapolis, MN, 55455, USA
| | - Rajeev Attam
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, 406 Harvard St. SE, MMC 36, Minneapolis, MN, 55455, USA
| | - Mohamed Hassan
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, 406 Harvard St. SE, MMC 36, Minneapolis, MN, 55455, USA
| | - Raja Kandaswamy
- Division of Solid Organ Transplant, University of Minnesota, Minneapolis, MN, USA
| | - Timothy Pruett
- Division of Solid Organ Transplant, University of Minnesota, Minneapolis, MN, USA
| | - John Lake
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, 406 Harvard St. SE, MMC 36, Minneapolis, MN, 55455, USA.,Division of Solid Organ Transplant, University of Minnesota, Minneapolis, MN, USA
| | - Srinath Chinnakotla
- Division of Solid Organ Transplant, University of Minnesota, Minneapolis, MN, USA
| | - Martin L Freeman
- Division of Solid Organ Transplant, University of Minnesota, Minneapolis, MN, USA
| | - Mustafa A Arain
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, 406 Harvard St. SE, MMC 36, Minneapolis, MN, 55455, USA.
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