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Lee J, Kim IW, Hong SK, Han N, Suh KS, Oh JM. Development and Clinical Validation of Model-Informed Precision Dosing for Everolimus in Liver Transplant Recipients. ACS Pharmacol Transl Sci 2025; 8:216-224. [PMID: 39816805 PMCID: PMC11729436 DOI: 10.1021/acsptsci.4c00581] [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: 10/07/2024] [Revised: 11/24/2024] [Accepted: 11/28/2024] [Indexed: 01/18/2025]
Abstract
Everolimus presents significant dosing challenges due to between- and within-patient pharmacokinetic variabilities. This study aimed to develop and validate a model-informed precision dosing strategy for everolimus in liver transplant recipients. The dosing strategy was initially developed using retrospective data, employing nonlinear mixed-effects modeling. The model included readily measurable covariates, body surface area, albumin, and tacrolimus trough concentration. The dosing strategy was subsequently validated in a prospective trial, recommending 1 to 1.75 mg dosages every 12 h, depending on covariates. Lower dosages were recommended for patients with lower body surface area and albumin with adjustments based on tacrolimus trough concentration. The estimated pharmacokinetic parameters (typical value ± standard error), apparent clearance (CL/F: 15.0 ± 0.5 L/h), and apparent volume of distribution (Vd/F: 862 ± 79.3 L) were refined using prospective clinical data from 20 patients, reducing interindividual variations. This research successfully developed and validated a population pharmacokinetic model for everolimus. The developed "dosE" web-based platform translates our pharmacokinetic model into a practical tool for healthcare providers, exemplifying the application of pharmaceutical research in clinical practice and potentially improving therapeutic outcomes in liver transplantation.
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Affiliation(s)
- Jeayoon Lee
- College
of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea
| | - In-Wha Kim
- College
of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea
| | - Suk Kyun Hong
- Department
of Surgery, Seoul National University College
of Medicine, Seoul 03080, Republic
of Korea
| | - Nayoung Han
- College
of Pharmacy and Research Institute of Pharmaceutical Sciences, Jeju National University, Jeju, Special Self-Governing Province 63243, Republic
of Korea
| | - Kyung-Suk Suh
- Department
of Surgery, Seoul National University College
of Medicine, Seoul 03080, Republic
of Korea
| | - Jung Mi Oh
- College
of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea
- College
of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 08826, Republic of Korea
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Nacif LS, Galvão F, Kubrusly MS, Zanini LYK, Espinoza P, Waisberg DR, Pinheiro RSN, da Silva AB, Rocha-Santos V, Alves VAF, Carneiro-D’Albuquerque L, Andraus W. Nuclear factor kappa-light-chain-enhancer of activated B cells gene expression involvement in porcine liver transplant experimental model. Acta Cir Bras 2024; 39:e392724. [PMID: 38958304 PMCID: PMC11216529 DOI: 10.1590/acb392724] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Accepted: 04/02/2024] [Indexed: 07/04/2024] Open
Abstract
PURPOSE Gene expressions of vascular Endothelial Growth Factor Alpha (VEGFa), Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B cells (NFkB) and cytokines could be useful for identifying potential therapeutic targets to alleviate ischemia-reperfusion injury after liver transplantation. Cytokine gene expressions, VEGFa and NFkB were investigated in a preclinical swine model of liver transplantation. METHODS A total of 12 pigs were used as donors and recipients in liver transplantation without venovenous bypass or aortic clamping. NFkB, IL-6, IL-10, VEGFa and Notch1 gene expression were assessed. These samples were collected in two specific times: group 1 (n= 6) - control, samples were collected before recipient's total hepatectomy and group 2 - liver transplantation group (n=6), where the samples were collected one hour after graft reperfusion. RESULTS Liver transplantation was successfully performed in all recipients. Liver enzymes were elevated in the transplantation group. NFkB gene expression was significantly decreased in the transplantation group in comparison with the control group (0.62±0.19 versus 0.39±0.08; p= 0.016). No difference was observed between groups Interleucine 6 (IL-6), interleucine 10 (IL-10), VEGFa and Notch homolog 1 (Notch1). CONCLUSIONS In this survey a decreased NFkB gene expression in a porcine model of liver transplantation was observed.
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Affiliation(s)
- Lucas Souto Nacif
- Universidade de São Paulo – School of Medicine – Liver and Gastrointestinal Transplant Division – São Paulo (SP), Brazil
| | - Flávio Galvão
- Universidade de São Paulo – School of Medicine – Liver and Gastrointestinal Transplant Division – São Paulo (SP), Brazil
| | - Márcia Saldanha Kubrusly
- Universidade de São Paulo – School of Medicine – Liver and Gastrointestinal Transplant Division – São Paulo (SP), Brazil
| | - Leonardo Yuri Kasputis Zanini
- Universidade de São Paulo – School of Medicine – Liver and Gastrointestinal Transplant Division – São Paulo (SP), Brazil
| | - Paola Espinoza
- Universidade de São Paulo – School of Medicine – Liver and Gastrointestinal Transplant Division – São Paulo (SP), Brazil
| | - Daniel Reis Waisberg
- Universidade de São Paulo – School of Medicine – Liver and Gastrointestinal Transplant Division – São Paulo (SP), Brazil
| | - Rafael Soares Nunes Pinheiro
- Universidade de São Paulo – School of Medicine – Liver and Gastrointestinal Transplant Division – São Paulo (SP), Brazil
| | - Amadeo Batista da Silva
- Universidade de São Paulo – School of Medicine – Liver and Gastrointestinal Transplant Division – São Paulo (SP), Brazil
| | - Vinicius Rocha-Santos
- Universidade de São Paulo – School of Medicine – Liver and Gastrointestinal Transplant Division – São Paulo (SP), Brazil
| | | | - Luiz Carneiro-D’Albuquerque
- Universidade de São Paulo – School of Medicine – Liver and Gastrointestinal Transplant Division – São Paulo (SP), Brazil
| | - Wellington Andraus
- Universidade de São Paulo – School of Medicine – Liver and Gastrointestinal Transplant Division – São Paulo (SP), Brazil
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Yoshizumi T, Mori M. Portal flow modulation in living donor liver transplantation: review with a focus on splenectomy. Surg Today 2019; 50:21-29. [PMID: 31555908 PMCID: PMC6949207 DOI: 10.1007/s00595-019-01881-y] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Accepted: 09/08/2019] [Indexed: 01/10/2023]
Abstract
Small-for-size graft (SFSG) syndrome after living donor liver transplantation (LDLT) is the dysfunction of a small graft, characterized by coagulopathy, cholestasis, ascites, and encephalopathy. It is a serious complication of LDLT and usually triggered by excessive portal flow transmitted to the allograft in the postperfusion setting, resulting in sinusoidal congestion and hemorrhage. Portal overflow injures the liver directly through nutrient excess, endothelial activation, and sinusoidal shear stress, and indirectly through arterial vasoconstriction. These conditions may be attenuated with portal flow modulation. Attempts have been made to control excessive portal flow to the SFSG, including simultaneous splenectomy, splenic artery ligation, hemi-portocaval shunt, and pharmacological manipulation, with positive outcomes. Currently, a donor liver is considered a SFSG when the graft-to-recipient weight ratio is less than 0.8 or the ratio of the graft volume to the standard liver volume is less than 40%. A strategy for transplanting SFSG safely into recipients and avoiding extensive surgery in the living donor could effectively address the donor shortage. We review the literature and assess our current knowledge of and strategies for portal flow modulation in LDLT.
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Affiliation(s)
- Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
| | - Masaki Mori
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
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A novel and simple formula to predict liver mass in porcine experimental models. Sci Rep 2019; 9:12459. [PMID: 31462673 PMCID: PMC6713746 DOI: 10.1038/s41598-019-48781-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Accepted: 08/07/2019] [Indexed: 02/05/2023] Open
Abstract
A primary limitation in hepatic surgery is leaving a remnant liver of adequate size and function. Experimental models have been designed to study processes of liver injury and regeneration in this context, yet a formula to accurately calculate liver mass in an animal model is lacking. This study aims to create a novel and simple formula to estimate the mass of the native liver in a species of pigs commonly used in experimental liver surgery protocols. Using data from 200 male weanling Landrace-Large White hybrid pigs, multiple linear regression analysis is used to generate the formula. Clinical features used as variables for the predictive model are body mass and length. The final formula for pig liver mass is as follows: Liver mass (g) = 26.34232 * Body mass (kg) - 1.270629 * Length (cm) + 163.0076; R2 = 0.7307. This formula for porcine liver mass is simple to use and may be helpful in studies using animals of similar characteristics to evaluate restoration of liver mass following major hepatectomy.
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Navarro JG, Choi GH, Kim MS, Jung YB, Lee JG. Right anterior section graft for living-donor liver transplantation: A case report. Medicine (Baltimore) 2019; 98:e15212. [PMID: 31083154 PMCID: PMC6531230 DOI: 10.1097/md.0000000000015212] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
RATIONALE In living-donor liver transplantation (LDLT), the right lobe graft is commonly utilized to prevent small-for-size syndrome, despite the considerable donor morbidity. Conversely, the feasibility of the left lobe graft and the right posterior section graft in smaller-sized recipients is now commonly employed with comparable outcomes to right lobe grafts. The efficacy of the right anterior section graft has rarely been reported. PATIENT CONCERNS A 56-year-old man, a heavy alcoholic beverage drinker for 20 years, presented in the emergency department with massive ascites and lethargy. He was previously admitted twice due to bleeding esophageal varices. DIAGNOSIS He was diagnosed with hepatic encephalopathy coma due to alcoholic liver cirrhosis. The Child-Turcotte-Pugh score was 11 (class C), and the Model for End-stage Liver Disease score was 21.62. INTERVENTION A LDTL was offered to the patient as the best treatment option available. The patient's 26-year-old son was found to be the only donor-compatible candidate for the LDTL.Preoperatively, the right lobe of the donor occupied 76.2% of the total liver volume exposing the donor to a small residual liver volume. The right posterior section and left lobe volumes were insufficient, providing a graft-to-recipient weight ratio of 0.42% and 0.38%, respectively. However, the right anterior section could fulfill an acceptable GRWR of 0.83%. Thus, a living donor right anterior sectionectomy was performed. OUTCOMES Clinical signs and symptoms and liver function improved following anterior section graft transplantation without complications. LESSON The procurement of anterior section graft is technically feasible in selected patients, especially in high-volume liver centers.
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Shoreem H, Gad EH, Soliman H, Hegazy O, Saleh S, Zakaria H, Ayoub E, Kamel Y, Abouelella K, Ibrahim T, Marawan I. Small for size syndrome difficult dilemma: Lessons from 10 years single centre experience in living donor liver transplantation. World J Hepatol 2017; 9:930-944. [PMID: 28824744 PMCID: PMC5545138 DOI: 10.4254/wjh.v9.i21.930] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2016] [Revised: 04/14/2017] [Accepted: 06/19/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To analyze the incidence, risk factors, prevention, treatment and outcome of small for size syndrome (SFSS) after living donor liver transplantation (LDLT). METHODS Through-out more than 10 years: During the period from April 2003 to the end of 2013, 174 adult-to-adults LDLT (A-ALDLT) had been performed at National Liver Institute, Menoufiya University, Shibin Elkoom, Egypt. We collected the data of those patients to do this cohort study that is a single-institution retrospective analysis of a prospectively collected database analyzing the incidence, risk factors, prevention, treatment and outcome of SFSS in a period started from the end of 2013 to the end of 2015. The median period of follow-up reached 40.50 m, range (0-144 m). RESULTS SFSS was diagnosed in 20 (11.5%) of our recipients. While extra-small graft [small for size graft (SFSG)], portal hypertension, steatosis and left lobe graft were significant predictors of SFSS in univariate analysis (P = 0.00, 0.04, 0.03, and 0.00 respectively); graft size was the only independent predictor of SFSS on multivariate analysis (P = 0.03). On the other hand, there was lower incidence of SFSS in patients with SFSG who underwent splenectomy [4/10 (40%) SFSS vs 3/7 (42.9%) no SFSS] but without statistical significance, However, there was none significant lower incidence of the syndrome in patients with right lobe (RL) graft when drainage of the right anterior and/or posterior liver sectors by middle hepatic vein, V5, V8, and/or right inferior vein was done [4/10 (28.6%) SFSS vs 52/152 (34.2%) no SFSS]. The 6-mo, 1-, 3-, 5-, 7- and 10-year survival in patients with SFSS were 30%, 30%, 25%, 25%, 25% and 25% respectively, while, the 6-mo, 1-, 3-, 5-, 7- and 10-year survival in patients without SFSS were 70.1%, 65.6%, 61.7%, 61%, 59.7%, and 59.7% respectively, with statistical significant difference (P = 0.00). CONCLUSION SFSG is the independent and main factor for occurrence of SFSS after A-ALDLT leading to poor outcome. However, the management of this catastrophe depends upon its prevention (i.e., selecting graft with proper size, splenectomy to decrease portal venous inflow, and improving hepatic vein outflow by reconstructing large draining veins of the graft).
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Affiliation(s)
- Hany Shoreem
- Hany Shoreem, Emad Hamdy Gad, Hosam Soliman, Osama Hegazy, Sherif Saleh, Hazem Zakaria, Eslam Ayoub, Kalid Abouelella, Tarek Ibrahim, Ibrahim Marawan, Hepatobiliary Surgery Department, National Liver Institute, Menoufiya University, Shibin El-Koum 32817, Egypt
| | - Emad Hamdy Gad
- Hany Shoreem, Emad Hamdy Gad, Hosam Soliman, Osama Hegazy, Sherif Saleh, Hazem Zakaria, Eslam Ayoub, Kalid Abouelella, Tarek Ibrahim, Ibrahim Marawan, Hepatobiliary Surgery Department, National Liver Institute, Menoufiya University, Shibin El-Koum 32817, Egypt
| | - Hosam Soliman
- Hany Shoreem, Emad Hamdy Gad, Hosam Soliman, Osama Hegazy, Sherif Saleh, Hazem Zakaria, Eslam Ayoub, Kalid Abouelella, Tarek Ibrahim, Ibrahim Marawan, Hepatobiliary Surgery Department, National Liver Institute, Menoufiya University, Shibin El-Koum 32817, Egypt
| | - Osama Hegazy
- Hany Shoreem, Emad Hamdy Gad, Hosam Soliman, Osama Hegazy, Sherif Saleh, Hazem Zakaria, Eslam Ayoub, Kalid Abouelella, Tarek Ibrahim, Ibrahim Marawan, Hepatobiliary Surgery Department, National Liver Institute, Menoufiya University, Shibin El-Koum 32817, Egypt
| | - Sherif Saleh
- Hany Shoreem, Emad Hamdy Gad, Hosam Soliman, Osama Hegazy, Sherif Saleh, Hazem Zakaria, Eslam Ayoub, Kalid Abouelella, Tarek Ibrahim, Ibrahim Marawan, Hepatobiliary Surgery Department, National Liver Institute, Menoufiya University, Shibin El-Koum 32817, Egypt
| | - Hazem Zakaria
- Hany Shoreem, Emad Hamdy Gad, Hosam Soliman, Osama Hegazy, Sherif Saleh, Hazem Zakaria, Eslam Ayoub, Kalid Abouelella, Tarek Ibrahim, Ibrahim Marawan, Hepatobiliary Surgery Department, National Liver Institute, Menoufiya University, Shibin El-Koum 32817, Egypt
| | - Eslam Ayoub
- Hany Shoreem, Emad Hamdy Gad, Hosam Soliman, Osama Hegazy, Sherif Saleh, Hazem Zakaria, Eslam Ayoub, Kalid Abouelella, Tarek Ibrahim, Ibrahim Marawan, Hepatobiliary Surgery Department, National Liver Institute, Menoufiya University, Shibin El-Koum 32817, Egypt
| | - Yasmin Kamel
- Hany Shoreem, Emad Hamdy Gad, Hosam Soliman, Osama Hegazy, Sherif Saleh, Hazem Zakaria, Eslam Ayoub, Kalid Abouelella, Tarek Ibrahim, Ibrahim Marawan, Hepatobiliary Surgery Department, National Liver Institute, Menoufiya University, Shibin El-Koum 32817, Egypt
| | - Kalid Abouelella
- Hany Shoreem, Emad Hamdy Gad, Hosam Soliman, Osama Hegazy, Sherif Saleh, Hazem Zakaria, Eslam Ayoub, Kalid Abouelella, Tarek Ibrahim, Ibrahim Marawan, Hepatobiliary Surgery Department, National Liver Institute, Menoufiya University, Shibin El-Koum 32817, Egypt
| | - Tarek Ibrahim
- Hany Shoreem, Emad Hamdy Gad, Hosam Soliman, Osama Hegazy, Sherif Saleh, Hazem Zakaria, Eslam Ayoub, Kalid Abouelella, Tarek Ibrahim, Ibrahim Marawan, Hepatobiliary Surgery Department, National Liver Institute, Menoufiya University, Shibin El-Koum 32817, Egypt
| | - Ibrahim Marawan
- Hany Shoreem, Emad Hamdy Gad, Hosam Soliman, Osama Hegazy, Sherif Saleh, Hazem Zakaria, Eslam Ayoub, Kalid Abouelella, Tarek Ibrahim, Ibrahim Marawan, Hepatobiliary Surgery Department, National Liver Institute, Menoufiya University, Shibin El-Koum 32817, Egypt
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7
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Small for size syndrome difficult dilemma: Lessons from 10 years single centre experience in living donor liver transplantation. World J Hepatol 2017. [PMID: 28824744 DOI: 10.4254/wjh.v9.i21.930.] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
AIM To analyze the incidence, risk factors, prevention, treatment and outcome of small for size syndrome (SFSS) after living donor liver transplantation (LDLT). METHODS Through-out more than 10 years: During the period from April 2003 to the end of 2013, 174 adult-to-adults LDLT (A-ALDLT) had been performed at National Liver Institute, Menoufiya University, Shibin Elkoom, Egypt. We collected the data of those patients to do this cohort study that is a single-institution retrospective analysis of a prospectively collected database analyzing the incidence, risk factors, prevention, treatment and outcome of SFSS in a period started from the end of 2013 to the end of 2015. The median period of follow-up reached 40.50 m, range (0-144 m). RESULTS SFSS was diagnosed in 20 (11.5%) of our recipients. While extra-small graft [small for size graft (SFSG)], portal hypertension, steatosis and left lobe graft were significant predictors of SFSS in univariate analysis (P = 0.00, 0.04, 0.03, and 0.00 respectively); graft size was the only independent predictor of SFSS on multivariate analysis (P = 0.03). On the other hand, there was lower incidence of SFSS in patients with SFSG who underwent splenectomy [4/10 (40%) SFSS vs 3/7 (42.9%) no SFSS] but without statistical significance, However, there was none significant lower incidence of the syndrome in patients with right lobe (RL) graft when drainage of the right anterior and/or posterior liver sectors by middle hepatic vein, V5, V8, and/or right inferior vein was done [4/10 (28.6%) SFSS vs 52/152 (34.2%) no SFSS]. The 6-mo, 1-, 3-, 5-, 7- and 10-year survival in patients with SFSS were 30%, 30%, 25%, 25%, 25% and 25% respectively, while, the 6-mo, 1-, 3-, 5-, 7- and 10-year survival in patients without SFSS were 70.1%, 65.6%, 61.7%, 61%, 59.7%, and 59.7% respectively, with statistical significant difference (P = 0.00). CONCLUSION SFSG is the independent and main factor for occurrence of SFSS after A-ALDLT leading to poor outcome. However, the management of this catastrophe depends upon its prevention (i.e., selecting graft with proper size, splenectomy to decrease portal venous inflow, and improving hepatic vein outflow by reconstructing large draining veins of the graft).
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8
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Osman AMA, Hosny AA, El-Shazli MA, Uemoto S, Abdelaziz O, Helmy AS. A portal pressure cut-off of 15 versus a cut-off of 20 for prevention of small-for-size syndrome in liver transplantation: A comparative study. Hepatol Res 2017; 47:293-302. [PMID: 27084787 DOI: 10.1111/hepr.12727] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2015] [Revised: 04/12/2016] [Accepted: 04/13/2016] [Indexed: 02/08/2023]
Abstract
AIM Portal hypertension has recently been implicated in the pathogenesis of small-for-size syndrome (SFSS) in adult-to-adult living-donor liver transplantation (A-LDLT). The aim of our study is to compare the portal venous pressure (PVP) cut-off values of 15 mmHg and 20 mmHg in terms of prevention of SFSS in A-LDLT. METHODS Seventy-six patients underwent A-LDLT. A PVP <20 mmHg at the end of the operation was targeted using graft inflow modulation. Patients were divided into two groups: group A, final PVP <15 mmHg; and group B, final PVP 15-19 mmHg. Peak serum bilirubin and peak international normalized ratio in the first month after A-LDLT, as well as hepatic encephalopathy, SFSS, 90-day morbidity, and mortality were observed in both groups. RESULTS Final PVP was well controlled below 20 mmHg in all patients (group A, n = 39; group B, n = 37). Six patients suffered SFSS in group B (16.2%) compared to one patient (2.6%) in group A (P = 0.04). Nine patients died in group B (24.3%), four of whom died of SFSS, compared to three patients in group A (7.7%) (P = 0.047). CONCLUSION A PVP cut-off of 15 mmHg seems to be a more appropriate target level than a cut-off of 20 mmHg for prevention of postoperative SFSS in A-LDLT.
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Affiliation(s)
- Ayman M A Osman
- Department of General Surgery, Unit of Hepatobiliary Surgery, Faculty of Medicine, Cairo University, Egypt
| | - Adel A Hosny
- Department of General Surgery, Unit of Hepatobiliary Surgery, Faculty of Medicine, Cairo University, Egypt
| | - Mostafa A El-Shazli
- Department of General Surgery, Unit of Hepatobiliary Surgery, Faculty of Medicine, Cairo University, Egypt
| | - Shinji Uemoto
- Department of Surgery, Division of Hepato-Pancreatico-Biliary Surgery and Transplantation, Graduate School of Medicine, Kyoto University, Japan
| | - Omar Abdelaziz
- Department of Diagnostic and Interventional Radiology, Faculty of Medicine, Cairo University, Egypt
| | - Ayman S Helmy
- Department of General Surgery, Unit of Hepatobiliary Surgery, Faculty of Medicine, Cairo University, Egypt
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Zhang W, Tan Y, Shen S, Jiang L, Yan L, Yang J, Li B, Wen T, Zeng Y, Wang W, Xu M. Adult to adult right lobe living donor liver transplantation: does biological relationship matter? Medicine (Baltimore) 2017; 96:e4139. [PMID: 28121912 PMCID: PMC5287936 DOI: 10.1097/md.0000000000004139] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
The influence of the biological relationship between the donor and the recipient is rarely discussed in living donor liver transplantation (LDLT), although it is believed to be an important risk factor in other types of organ transplantations. A total of 272 consecutive patients undergoing adult to adult right lobe LDLT were retrospectively analyzed and stratified into a nonbiologically related (NBR) group (69 patients) and a biologically related (BR) group (203 patients). The preoperative data and postoperative outcomes of both recipients and donors were evaluated.More than two-thirds of the recipients had histories of HBV infection, and hepatocellular carcinoma (HCC) was the main reason for the patients undergoing LDLT in both groups. The percentage of female donors in the NBR group was more than the percentage in the BR group (P = 0.000). There were no differences between the groups in postoperative laboratory testing or daily immunosuppression dose, and the complication rates in both the recipient and donor surgeries showed no significant differences. For patients with benign diseases, the cumulative 1-, 3-, 5-, and 10-year survival rate were 92.9% in the 4 periods in the NBR group and 89.1%, 87.6%, 83.7%, and 83.7%, respectively, in BR group, while for the patients diagnosed as HCC, if patients exceeding the Milan criteria were involved, the 5-year survival rate was 41.2%, compared to 82% for patients within the Milan criteria, which was nearly the same as for those with the benign disease. In conclusion, our findings suggested that the biological relationship between the donor and the recipient in adult to adult LDLT was not associated with the short- and long-term outcomes of recipients diagnosed with benign liver diseases and early stage HCC. Moreover, the criteria for patients diagnosed with HCC to undergo LDLT should be restrictively selected.
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10
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Mohkam K, Darnis B, Mabrut JY. Porcine models for the study of small-for-size syndrome and portal inflow modulation: literature review and proposal for a standardized nomenclature. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2016; 23:668-680. [DOI: 10.1002/jhbp.396] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/08/2016] [Accepted: 09/01/2016] [Indexed: 12/21/2022]
Affiliation(s)
- Kayvan Mohkam
- Department of General Surgery and Liver Transplantation, Hospices Civils de Lyon; Croix-Rousse University Hospital; Lyon France
- Interdisciplinary Doctoral School of Science and Health ED205, Research Unit EMR3738; Lyon 1 Claude-Bernard University; Lyon France
| | - Benjamin Darnis
- Department of General Surgery and Liver Transplantation, Hospices Civils de Lyon; Croix-Rousse University Hospital; Lyon France
- Interdisciplinary Doctoral School of Science and Health ED205, Research Unit EMR3738; Lyon 1 Claude-Bernard University; Lyon France
| | - Jean-Yves Mabrut
- Department of General Surgery and Liver Transplantation, Hospices Civils de Lyon; Croix-Rousse University Hospital; Lyon France
- Interdisciplinary Doctoral School of Science and Health ED205, Research Unit EMR3738; Lyon 1 Claude-Bernard University; Lyon France
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Gyoten K, Mizuno S, Kato H, Murata Y, Tanemura A, Azumi Y, Kuriyama N, Kishiwada M, Usui M, Sakurai H, Isaji S. A Novel Predictor of Posttransplant Portal Hypertension in Adult-To-Adult Living Donor Liver Transplantation: Increased Estimated Spleen/Graft Volume Ratio. Transplantation 2016; 100:2138-2145. [PMID: 27472097 PMCID: PMC5120765 DOI: 10.1097/tp.0000000000001370] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2015] [Revised: 05/26/2016] [Accepted: 05/31/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND In adult living donor liver transplantation (ALDLT), graft-to-recipient weight ratio of less than 0.8 is incomplete for predicting portal hypertension (>20 mm Hg) after reperfusion. We aimed to identify preoperative factors contributing to portal venous pressure (PVP) after reperfusion and to predict portal hypertension, focusing on spleen volume-to-graft volume ratio (SVGVR). METHODS In 73 recipients with ALDLT between 2002 and 2013, first we analyzed survival according to PVP of 20 mm Hg as the threshold, evaluating the efficacy of splenectomy. Second, we evaluated various preoperative factors contributing to portal hypertension after reperfusion. RESULTS All of the recipients with PVP greater than 20 mm Hg (n = 19) underwent PVP modulation by splenectomy, and their overall survival was favorable compared with 54 recipients who did not need splenectomy (PVP ≤ 20 mm Hg). Graft-to-recipient weight ratio had no correlation with PVP.Multivariate analysis revealed that estimated graft and spleen volume were significant factors contributing to PVP after reperfusion (P < 0.0001 and P < 0.0001, respectively). Furthermore, estimated SVGVR showed a significant negative correlation to PVP after reperfusion (R = 0.652), and the best cutoff value for portal hypertension was 0.95. CONCLUSIONS In ALDLT, preoperative assessment of SVGVR is a good predictor of portal hypertension after reperfusion can be used to indicate the need for splenectomy before reperfusion.
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Affiliation(s)
- Kazuyuki Gyoten
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University School of Medicine, Tsu, Mie, Japan
| | - Shugo Mizuno
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University School of Medicine, Tsu, Mie, Japan
| | - Hiroyuki Kato
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University School of Medicine, Tsu, Mie, Japan
| | - Yasuhiro Murata
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University School of Medicine, Tsu, Mie, Japan
| | - Akihiro Tanemura
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University School of Medicine, Tsu, Mie, Japan
| | - Yoshinori Azumi
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University School of Medicine, Tsu, Mie, Japan
| | - Naohisa Kuriyama
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University School of Medicine, Tsu, Mie, Japan
| | - Masashi Kishiwada
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University School of Medicine, Tsu, Mie, Japan
| | - Masanobu Usui
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University School of Medicine, Tsu, Mie, Japan
| | - Hiroyuki Sakurai
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University School of Medicine, Tsu, Mie, Japan
| | - Shuji Isaji
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University School of Medicine, Tsu, Mie, Japan
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12
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Kinaci E, Kayaalp C. Portosystemic Shunts for “Too Small-for-Size Syndrome” After Liver Transplantation: A Systematic Review. World J Surg 2016; 40:1932-40. [DOI: 10.1007/s00268-016-3518-x] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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13
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Liu C, Song JL, Lu WS, Yang JY, Jiang L, Yan LN, Zhang JY, Lu Q, Wen TF, Xu MQ, Wang WT. Hepatic Arterial Buffer Response Maintains the Homeostasis of Graft Hemodynamics in Patient Receiving Living Donor Liver Transplantation. Dig Dis Sci 2016; 61:464-473. [PMID: 26441282 DOI: 10.1007/s10620-015-3881-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2015] [Accepted: 09/10/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND In living donor liver transplantation (LDLT), the hepatic hemodynamics plays important roles in graft regeneration, and the hepatic blood inflows are associated with graft size. However, the data of interplay between the hepatic arterial buffer response (HABR) and graft-to-recipient weight ratio (GRWR) in clinical LDLT are lacking. AIMS To identify the effect of the HABR on the hepatic hemodynamics and recovery of graft function and to evaluate the safe lower limit of the GRWR in carefully selected recipients. METHODS Portal venous and hepatic arterial blood flow was measured in recipients with ultrasonography, and the graft functional recovery, various complications, and survive states after LDLT were compared. RESULTS In total, 246 consecutive patients underwent LDLT with right lobe grafts. In total, 26 had a GRWR < 0.7 % (A), 29 had a GRWR between 0.7 and 0.8 % (B), and 181 had a GRWR > 0.8 % (C). For small-for-size syndrome, there was no significant difference (P = 0.176). Graft survival rates at 1, 3, and 5 year were not different (P = 0.710). The portal vein flow and portal vein flow per 100 g graft weight peaks were significantly higher in the A. Hepatic arterial velocity and hepatic arterial flow decreased in all the three groups on postoperative day 1; however, the hepatic arterial flow per 100 g graft weight was close to healthy controls. CONCLUSIONS HABR played important roles not only in the homeostasis of hepatic afferent blood supply but also in maintaining enough hepatic perfusion to the graft.
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Affiliation(s)
- Chang Liu
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
- Center of Interventional Radiology, West China Hospital, Sichuan University, Chengdu, 610041, China.
| | - Jiu-lin Song
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
| | - Wu-sheng Lu
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
| | - Jia-yin Yang
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
| | - Li Jiang
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
| | - Lu-nan Yan
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
| | - Jing-yi Zhang
- Department of Ultrasound, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
| | - Qiang Lu
- Department of Ultrasound, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
| | - Tian-fu Wen
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
| | - Ming-qing Xu
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
| | - Wen-tao Wang
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
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14
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Fondevila C. A bridge too far: We have not overstepped the line for extended deceased donors. Liver Transpl 2014; 20 Suppl 2:S9-13. [PMID: 25220866 DOI: 10.1002/lt.24000] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Accepted: 09/12/2014] [Indexed: 01/06/2023]
Affiliation(s)
- Constantino Fondevila
- Hepatobiliary Surgery & Liver Transplant, Hospital Clínic, University of Barcelona, Barcelona, Spain
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15
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Hessheimer AJ, Escobar B, Muñoz J, Flores E, Gracia-Sancho J, Taurá P, Fuster J, Rimola A, García-Valdecasas JC, Fondevila C. Somatostatin therapy protects porcine livers in small-for-size liver transplantation. Am J Transplant 2014; 14:1806-16. [PMID: 24935350 DOI: 10.1111/ajt.12758] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2013] [Revised: 03/17/2014] [Accepted: 03/25/2014] [Indexed: 01/25/2023]
Abstract
Small-for-size (SFS) injury occurs in partial liver transplantation due to several factors, including excessive portal inflow and insufficient intragraft responses. We aim to determine the role somatostatin plays in reducing portal hyperperfusion and preventing the cascade of deleterious events produced in small grafts. A porcine model of 20% liver transplantation is performed. Perioperatively treated recipients receive somatostatin and untreated controls standard intravenous fluids. Recipients are followed for up to 5 days. In vitro studies are also performed to determine direct protective effects of somatostatin on hepatic stellate cells (HSC) and sinusoidal endothelial cells (SEC). At reperfusion, portal vein flow (PVF) per gram of tissue increased fourfold in untreated animals versus approximately threefold among treated recipients (p = 0.033). Postoperatively, markers of hepatocellular, SEC and HSC injury were improved among treated animals. Hepatic regeneration occurred in a slower but more orderly fashion among treated grafts; functional recovery was also significantly better. In vitro studies revealed that somatostatin directly reduces HSC activation, though no direct effect on SEC was found. In SFS transplantation, somatostatin reduces PVF and protects SEC in the critical postreperfusion period. Somatostatin also exerts a direct cytoprotective effect on HSC, independent of changes in PVF.
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Affiliation(s)
- A J Hessheimer
- Department of Surgery, Institut de Malalties Digestives I Metabòliques (IMDiM), Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain
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16
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The safe minimally ischemic liver remnant for small-for-size syndrome in porcine hepatectomy. Transplant Proc 2014; 45:2419-24. [PMID: 23953558 DOI: 10.1016/j.transproceed.2012.12.034] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2012] [Accepted: 12/30/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND The minimal functional remnant liver mass or graft after an ischemic injury in hepatectomy or living donor liver transplantation (LDLT) is not clear. This study sought to determine the minimal remnant liver (MRL) size after 20 minutes hepatic inflow occlusion (HIO) and the maximal portal flow with which the liver remnant can sustain in a porcine model. METHODS Twenty pigs that underwent massive hepatectomy were randomly divided into 3 groups: 30% group, the remnant constituted about 30% of total liver volume (TLV); 35%+O group, the remnant constitute about 35% of TLV with 20 minutes HIO, and 30%+O group, the remnant constituted about 30% of TLV with 20 minutes of HIO. We evaluated survival rates, kinetic portal vein pressures (PVP), hemodynamics, hepatocyte metabolism, and injury. RESULTS The 14-day survival rate in the 30%+O group was significantly reduced compared with that of either the 30% group or the 35%+O group: l00% versus 28.6% versus 85.7% respectively (P = .009). The tissue, serum analyses, and PVP in the 30%+O group were significantly different compared with the measurements among the other groups (P < .05), revealing that the liver remnant in 30%+O group could not sustain more than 3 times baseline portal flow, whereas in 35%+O group it could sustain 2.8 times baseline portal flow. CONCLUSIONS Intraoperative ischemia can injure the sinusoidal endothelium, decreasing its ability to regulate portal hyperperfusion, causing less than 30% to 35% of TLV to show small-for-size syndrome or postoperative liver failure.
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17
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Asencio JM, García Sabrido JL, Olmedilla L. How to expand the safe limits in hepatic resections? JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2014; 21:399-404. [DOI: 10.1002/jhbp.97] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Affiliation(s)
- José Manuel Asencio
- General Surgery III Department and Liver Transplant Unit; Hospital General Universitario Gregorio Marañón; c/ Doctor Esquerdo 46 Madrid 28007 Spain
| | - José Luis García Sabrido
- General Surgery III Department and Liver Transplant Unit; Hospital General Universitario Gregorio Marañón; c/ Doctor Esquerdo 46 Madrid 28007 Spain
| | - Luis Olmedilla
- Department of Anesthesiology; Hospital General Universitario Gregorio Marañón; Madrid Spain
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18
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Chen PX, Yan LN, Wang WT. Outcome of patients undergoing right lobe living donor liver transplantation with small-for-size grafts. World J Gastroenterol 2014; 20:282-289. [PMID: 24415883 PMCID: PMC3886020 DOI: 10.3748/wjg.v20.i1.282] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2013] [Revised: 10/06/2013] [Accepted: 11/03/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the outcome of living donor liver transplantation (LDLT) recipients transplanted with small-for-size grafts (SFSGs).
METHODS: Between November 2001 and December 2010, 196 patients underwent LDLT with right lobe liver grafts at our center. Recipients were divided into 2 treatment groups: group A with an actuarial graft-to-recipient weight ratio (aGRWR) < 0.8% (n = 45) and group B with an aGRWR ≥ 0.8% (n = 151). We evaluated serum liver function markers within 4 wk after transplantation. We also retrospectively evaluated the outcomes of these patients for potential effects related to the recipients, the donors and the transplantation procedures based upon a review of their medical records.
RESULTS: Small-for-size syndrome (SFSS) developed in 7 of 45 patients (15.56%) in group A and 9 of 151 patients (5.96%) in group B (P = 0.080). The levels of alanine aminotransferase and aspartate aminotransferase in group A were higher than those in group B during early period after transplantation, albeit not significantly. The cumulative 1-, 3- and 5-year liver graft survival rates were 82.22%, 71.11% and 71.11% for group A and 81.46%, 76.82%, and 75.50% for group B patients, respectively (P = 0.623). However, univariate analysis of risk factors associated with graft survival in group A demonstrated that the occurrence of SFSS after LDLT was the only significant risk factor affecting graft survival (P < 0.001). Furthermore, multivariate analysis of our data did not identify any additional significant risk factors accounting for poor graft survival.
CONCLUSION: Our study suggests that LDLT recipients with an aGRWR < 0.8% may have liver graft outcomes comparable to those who received larger size grafts. Further studies are required to ascertain the safety of using SFSGs.
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Yoichi T, Takayashiki T, Shimizu H, Yoshidome H, Ohtsuka M, Kato A, Yoshitomi H, Furukawa K, Kuboki S, Okamura D, Suzuki D, Nakajima M, Miyazaki M. Protective effects of simultaneous splenectomy on small-for-size liver graft injury in rat liver transplantation. Transpl Int 2013; 27:106-13. [DOI: 10.1111/tri.12223] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2013] [Revised: 04/20/2013] [Accepted: 10/20/2013] [Indexed: 12/17/2022]
Affiliation(s)
- Takuya Yoichi
- Department of General Surgery; Graduate School of Medicine; Chiba University; Chiba Japan
| | - Tsukasa Takayashiki
- Department of General Surgery; Graduate School of Medicine; Chiba University; Chiba Japan
| | - Hiroaki Shimizu
- Department of General Surgery; Graduate School of Medicine; Chiba University; Chiba Japan
| | - Hiroyuki Yoshidome
- Department of General Surgery; Graduate School of Medicine; Chiba University; Chiba Japan
| | - Masayuki Ohtsuka
- Department of General Surgery; Graduate School of Medicine; Chiba University; Chiba Japan
| | - Atsushi Kato
- Department of General Surgery; Graduate School of Medicine; Chiba University; Chiba Japan
| | - Hideyuki Yoshitomi
- Department of General Surgery; Graduate School of Medicine; Chiba University; Chiba Japan
| | - Katsunori Furukawa
- Department of General Surgery; Graduate School of Medicine; Chiba University; Chiba Japan
| | - Satoshi Kuboki
- Department of General Surgery; Graduate School of Medicine; Chiba University; Chiba Japan
| | - Daiki Okamura
- Department of General Surgery; Graduate School of Medicine; Chiba University; Chiba Japan
| | - Daisuke Suzuki
- Department of General Surgery; Graduate School of Medicine; Chiba University; Chiba Japan
| | - Masayuki Nakajima
- Department of General Surgery; Graduate School of Medicine; Chiba University; Chiba Japan
| | - Masaru Miyazaki
- Department of General Surgery; Graduate School of Medicine; Chiba University; Chiba Japan
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20
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Strategies to optimize donor safety with smaller grafts for adult-to-adult living donor liver transplantation. Curr Opin Organ Transplant 2013; 17:230-4. [PMID: 22569511 DOI: 10.1097/mot.0b013e32835365b2] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE OF REVIEW To describe our current understanding of adult-to-adult living donor liver transplantation (AA-LDLT) in terms of graft size. RECENT FINDINGS Improved outcomes of small liver graft with the use of portal vein pressure (PVP) modulation. SUMMARY AA-LDLT is viewed as a viable alternative to whole liver transplantation on the treatment of end-stage liver disease. Over the past two decades, right lobe AA-LDLT has been the standard because of concerns related to graft size. Small-for-size syndrome (SFSS) is an entity that presents in recipients of small grafts. It negatively affects patient and graft survival and recipients of grafts with a graft weight-to-recipient weight ratio (GW/RW) lower than 1.0 are at the highest risk. Over the last decade, our understanding of SFSS has identified PVP as a major determinant in the development of SFSS. Direct or indirect surgical PVP modulation has demonstrated a way to prevent the development of SFSS in recipients of small grafts and has improved the survival outcomes of small grafts. These improved outcomes coupled with concerns for donor safety have led to the renaissance of the use of left lobe grafts. Based on the current clinical data, the use of small grafts GW/RW greater than 0.6 is viewed as well tolerated when PVP is modulated to achieve a target PVP less than 15 mmHg after reperfusion and the left lobe is currently viewed as the ideal graft for AA-LDLT.
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21
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Fu WY, Yan JQ, Shi MM, Ma D, Peng CH, Li HW. Suppression of liver regeneration affects hepatic graft survival in small-for-size liver transplantation in rats. Hepatol Res 2013; 43:300-10. [PMID: 22882432 DOI: 10.1111/j.1872-034x.2012.01071.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
AIM Small-for-size liver transplantation (SFSLT) often results in hepatic graft failure and decreased survival. The present study was aimed to investigate the possible mechanism of hepatic graft failure in SFSLT in rats. METHODS Rat models of full-size orthotopic liver transplantation, 50% partial liver transplantation and 30% partial liver transplantation were established. Proliferative responses of the hepatic graft were evaluated by immunohistochemical staining and western blotting. Apoptosis-, inflammatory-, anti-inflammatory- and growth factor-related genes were screened by quantitative reverse transcription polymerase chain reaction. Activities of transcription factors of AP-1 and nuclear factor (NF)-κB were analyzed by electrophoretic mobility shift assay. RESULTS A 30% partial liver transplant not only resulted in marked structural damages to the hepatic graft, but also showed the lowest 7-day survival rate. In addition, sup pressed expressions of proliferating cell nuclear antigen (PCNA) and cyclin D1 by immunohistochemical staining and decreased expressions of cyclin D1 and p-c-Jun by western blotting were detected. Downregulated expressions of Bcl-2, Bcl-XL, interleukin (IL)-6, IL-10, IP-10 and CXCR2, upregulated expression of tumor necrosis factor-α, and decreased levels of AP-1 and NF-κB were also found following 30% partial liver transplantation after reperfusion. CONCLUSION Liver regeneration is remarkably suppressed in SFSLT. The significant changes of intra-graft gene expression described above indicated that ischemia reperfusion injury would be severe in 30% partial liver transplantation. The capability of liver regeneration secondary to ischemia reperfusion injury might determine hepatic graft survival in SFSLT.
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Affiliation(s)
- Wen-Yi Fu
- Department of Surgery, Ruijin Hospital, Medical School of Shanghai Jiaotong University, Shanghai, China
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22
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Abstract
The characteristics of the hepatic macrocirculation, i.e., the parallel portal-venous and arterial blood supply, is of utmost relevance for liver surgery. With extended hepatectomy or transplantation of a reduced-size liver the remaining or transplanted liver tissue is overperfused because the liver fails to regulate the portal-venous inflow. This portal hyperperfusion is responsible for the initiation of liver cell proliferation but represents at the same time one of the substantial events in the pathogenesis of the small-for-size syndrome. Portal-venous hyperperfusion, the so-called hepatic arterial buffer response, which describes the semi-reciprocal relationship between the portal-venous and hepatic arterial blood flows, leads to an arterial hypoperfusion of the small-for-size liver. In this article experimental and clinical data are discussed which underline the high but so far overseen relevance of this arterial underperfusion in the development of a small-for-size syndrome.
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Affiliation(s)
- C Eipel
- Institut für Experimentelle Chirurgie, Universität Rostock, Schillingallee 69a, 18055, Rostock, Deutschland.
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23
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Abstract
Partial liver transplantation, including reducedsize liver transplantation, split liver transplantation, and living donor liver transplantation, has been developed with several innovative techniques because of donor shortage. Reduced-size liver transplantation is based on Couinaud's anatomical classification, benefiting children and small adult recipients but failing to relieve the overall donor shortage. Split liver transplantation provides chances to two or even more recipients when only one liver graft is available. The splitting technique must follow stricter anatomical and physiological criteria either ex situ or in situ to ensure long-term quality. The first and most important issue involving living donor liver transplantation is donor safety. Before surgery, a series of donor evaluations-including anatomical, liver volume, and liver function evaluations-is indispensable, followed by ethnic agreement. At different recipient conditions, auxiliary liver transplantation and auxiliary partial orthotopic liver transplantation, which employ piggyback techniques, are good alternatives. Partial liver transplantation enriches the practice and knowledge of the transplant society.
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24
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Improved preservation and microcirculation with POLYSOL after partial liver transplantation in rats. J Surg Res 2011; 167:e375-83. [PMID: 21392801 DOI: 10.1016/j.jss.2010.12.040] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2010] [Revised: 12/06/2010] [Accepted: 12/28/2010] [Indexed: 12/16/2022]
Abstract
BACKGROUND Due to the severe shortage of deceased donors, demand for living-donor liver transplantation (LDLT) has increased worldwide. Here, we compared POLYSOL, a recently developed low-viscosity preservation solution, and histidine-tryptophan-ketoglutarate (HTK) for cold storage of partial liver graft in this study. METHODS Partial liver transplantations with 30% of the native liver were performed in Lewis rats. The graft livers were flushed with either HTK or POLYSOL (n = 25, respectively) and stored in the respective solution for 3 h at 5°C. Graft function was evaluated regarding ischemia-reperfusion injury and regeneration at 1, 3, 24, and 168 h after reperfusion. RESULTS POLYSOL preservation resulted in improvement of portal venous flow (HTK versus POLYSOL; mean ± SEM: 16.8 ± 2.2 versus 21.6 ± 2.1 mL/min; P = 0.005), microcirculation (383 ± 63 versus 532 ± 64 Flux; P = 0.045), ALT (310.2 ± 56.1 versus 181.8 ± 17.0 IU/L; P = 0.0262), LDH (4052.4 ± 764.4 versus 2494.1 ± 410.0 IU/L; P = 0.0215), total bilirubin (21.6 ± 14.2 versus 4.0 ± 0.6 IU/L; P = 0.0236), malondialdehyde (100.0 ± 4.3 versus 69.2 ± 4.0 nmol/mL; P = 0.0015), as well histologic findings at 24 h. Liver regeneration was improved in POLYSOL with regards to liver weight (4.0 ± 0.2 versus 4.3 ± 0.3 g; P = 0.038) and Ki-67 labeling index (9.67 ± 2.17 versus 1.10 ± 0.14%; P < 0.0001) at 24 h with higher up-regulation of portal VEGF (31.55 ± 5.78 versus 91.94 ± 9.27 pg/mL; P = 0.0052). CONCLUSIONS This study showed that POLYSOL improves microcirculation and thus improves the preservation quality of partial liver transplantation.
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25
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Mikami K, Matsuoka N, Maekawa T, Yamauchi Y, Noritomi T, Hoshino S, Shinohara T, Takahashi Y, Noda N, Yamashita Y. Impact of short hepatic vein reconstruction in living donor adult liver transplantation using a left liver plus caudate lobe graft. Asian J Surg 2010; 33:8-13. [PMID: 20497876 DOI: 10.1016/s1015-9584(10)60002-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/24/2009] [Indexed: 10/19/2022] Open
Abstract
OBJECTIVE To investigate the impact of short hepatic vein reconstruction in the transplanted left liver plus caudate lobe graft. METHODS Six left liver plus caudate lobe grafts used for living donor adult liver transplantation were included in this study. The liver grafts were divided into two groups: those with (V1 group; n = 4) or without (control group; n = 2) short hepatic vein reconstruction. The changes in the transplanted left lobe (segments II-IV) and caudate lobe were compared between the two groups at 1 month after transplantation. RESULTS The addition of the caudate lobe increased the graft volume by 15 mL, which corresponded to a 4.3% gain of graft volume at the time of transplantation. Although the graft volume/standard liver volume ratio of the whole grafts after transplantation showed no difference between the two groups, the regeneration rate of the caudate lobe in the V1 group was significantly greater than that in the control group (p= 0.04). CONCLUSION Although no definite advantage from the V1 reconstruction was demonstrated, hepatic vein reconstruction with a significantly-sized short hepatic vein might provide an additional margin of safety for marginally-sized liver grafts during the early phase of graft regeneration.
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Affiliation(s)
- Koji Mikami
- Department of Surgery, Fukuoka University Chikushi Hospital, Fukuoka, Japan
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26
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Sutaria R, Adams DH. Efforts to expand the donor pool for liver transplantation. F1000 MEDICINE REPORTS 2010; 2. [PMID: 20948842 PMCID: PMC2950055 DOI: 10.3410/m2-42] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
Liver transplantation has become a victim of its own success in that there are no longer enough suitable livers for transplantation while at the same time the indications for transplantation increase. Efforts to expand the number of recipients who benefit from this life-saving procedure are being made, in particular through the use of split grafts and live donors. However, such grafts are associated with increased morbidity and mortality related to their reduced size.
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Affiliation(s)
- Rupesh Sutaria
- Centre for Liver Research, 5th Floor, Institute of Biomedical Research, University of BirminghamWolfson Drive, Edgbaston, Birmingham, B15 2TTUK
- National Institute for Health Research (NIHR) Biomedical Research Unit in Liver Disease, Queen Elizabeth HospitalEdgbaston, Birmingham, B15 2TTUK
| | - David H Adams
- Centre for Liver Research, 5th Floor, Institute of Biomedical Research, University of BirminghamWolfson Drive, Edgbaston, Birmingham, B15 2TTUK
- National Institute for Health Research (NIHR) Biomedical Research Unit in Liver Disease, Queen Elizabeth HospitalEdgbaston, Birmingham, B15 2TTUK
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27
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Kwak MS, Lee JH, Kim YJ, Yoon JH, Lee HS. Development of Spontaneous Bacterial Peritonitis after Extended Hepatic Resection in a Patient without Evidence of Liver Cirrhosis. Gut Liver 2010; 4:129-34. [PMID: 20479927 DOI: 10.5009/gnl.2010.4.1.129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2009] [Accepted: 09/15/2009] [Indexed: 11/04/2022] Open
Abstract
Hilar cholangiocarcinomas are often treated with liver resections. Hepatic dysfunction and infection are common postoperative complications. Although secondary bacterial peritonitis due to abdominal abscess or perforation is common, we report herein the first case of spontaneous bacterial peritonitis after hepatic resection. A 61-year-old male patient without underlying liver disease was diagnosed as having a Klatskin tumor, and a right trisectionectomy with caudate lobectomy was performed. From postoperative days 18-28, the patient gained 4.1 kg as ascites developed, and showed evidence of hepatic insufficiency with prolonged prothrombin time and jaundice. Computed tomography, performed at postoperative day 28 when fever had developed, showed only ascites without bowel perforation or abscess. When paracentesis was performed, the serum-ascites albumin gradient was 2.3 g/dL, indicating portal hypertension, and the ascites' polymorphonuclear cell count was 1,156/mm(3). Since the clinical, laboratory, and image findings were compatible with spontaneous bacterial peritonitis, we started empirical antibiotics without additional intervention. Follow-up analysis of the ascites after 48 hours revealed that the polymorphonuclear cell count had decreased markedly to 108/mm(3); the fever and leukocytosis had also improved. After 2 weeks of antibiotic treatment, the patient recovered well, and was discharged without any problem.
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Affiliation(s)
- Min-Sun Kwak
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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28
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Mulligan D. Living donor liver transplantation and donor graft size: how small can we go to reduce risk to the donor and what is the cost to the recipient? Liver Transpl 2009; 15:1392-4. [PMID: 19877257 DOI: 10.1002/lt.21922] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Zhuang ZG, Qian LJ, Wang BX, Zhou Y, Li QG, Xu JR, Cheng YF. Computed tomography perfusion in living donor liver transplantation: an initial study of normal hemodynamic changes in liver grafts. Clin Transplant 2009; 23:692-9. [DOI: 10.1111/j.1399-0012.2009.00991.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
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Lu Q, Wu H, Fan YT, Luo Y, Zhang ZW. Sonographic evaluation of vessel grafts in living donor liver transplantation recipients of the right lobe. World J Gastroenterol 2009; 15:3550-3554. [PMID: 19630113 PMCID: PMC2715984 DOI: 10.3748/wjg.15.3550] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2009] [Revised: 06/19/2009] [Accepted: 06/26/2009] [Indexed: 02/07/2023] Open
Abstract
AIM To evaluate the vessel grafts (VG) used to reconstruct the middle hepatic vein (MHV) tributaries with ultrasonography. METHODS Twenty-four patients undergone living donor liver transplantation were enrolled in our study. MHV tributaries larger than 5 mm in diameter were reconstructed with interposition VG. Blood flow of the graft and interposition VG was checked by Doppler ultrasonography daily in the first 2 postoperative weeks and monthly followed up after discharge. The sensitivity of VG detected by ultrasonography was assessed using surgical records as references. Student's t test was used to compare the velocity of VG and occluded VG in chronic patents (> 3 mo). RESULTS Thirty-one VG were used to reconstruct the MHV tributaries. Ultrasonography identified 96.7% (30/31) of large MHV tributaries and 90.3% (28/31) of VG. The diameter of VG was 5.6 +/- 0.8 mm and the velocity of VG was 19.7 +/- 8.1 cm/s. Two VG (2/31, 6.5%) were occluded on the first postoperative day in one patient who suffered from persistent ascites and had a prolonged recovery of liver function. Twenty-six VG (26/31, 83.9%) were patent 2 wk after operation. Six (6/31, 19.4%) VG were patent over 3 mo after operation. Intrahepatic venous collaterals were detected in 29.2% (7/24) patients. The velocity of VG and occluded VG was 30.1 +/- 5.6 cm/s, 16.5 +/- 5.8 cm/s, respectively, in chronic patents. The difference between two groups was statistically significant (P < 0.001). CONCLUSION Our results indicate that most VG are patent in the first postoperative week while only a small portion with a higher velocity remains patent after 3 mo. Intrahepatic venous collaterals can be observed in some patients after occlusion of VG.
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Affiliation(s)
- Qiang Lu
- Department of Sonography, West China Hospital, Sichuan University, Chengdu 610041, China
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Abstract
For years splenectomy in hepatic disorders has been indicated only for the treatment of gastro-esophageal varices. However, with recent advances in medical and surgical treatments for chronic hepatic disorders, the use of splenectomy has been greatly expanded, such that splenectomy is used for reversing hypersplenism, for applying interferon treatment for hepatitis C, for treating hyperdynamic portal circulation associated with intractable ascites, and for controlling portal pressure during small grafts in living donor liver transplantation. Such experiences have shown the importance of portal hemodynamics, even in cirrhotic livers. Recent advances in surgical techniques have enabled surgeons to perform splenectomy more safely and less invasively, but the procedure still has considerable clinical outcomes. Splenectomy in hepatic disorders may become a more common procedure with expanded indications. However, it should also be noted that the long-term effects of splenectomy, in terms of improved hematological or hepatic function, is still not guaranteed. Moreover, the impact of splenectomy on immunologic status remains unclear and needs to be elucidated in both experimental and clinical settings.
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Affiliation(s)
- Toru Ikegami
- The Department of Surgery, the University of Tokushima, Tokushima, Japan
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Ikegami T, Shimada M, Imura S, Arakawa Y, Nii A, Morine Y, Kanemura H. Current concept of small-for-size grafts in living donor liver transplantation. Surg Today 2008; 38:971-82. [PMID: 18958553 DOI: 10.1007/s00595-008-3771-1] [Citation(s) in RCA: 66] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2007] [Accepted: 02/18/2008] [Indexed: 12/16/2022]
Abstract
The extended application of living donor liver transplantation (LDLT) has revealed the problem of graft size mismatching called "small-for-size (SFS) graft syndrome." The initial trials to resolve this problem involved increasing the procured graft size, from left to right, and even extension to include a right lobe graft. Clinical cases of living right lobe donations have been reported since then, drawing attention to the risks of increasing the liver volume procured from a living donor. However, not only other modes of increasing graft volume such as auxiliary or dual liver transplantation, but also control of the increased portal pressure caused by an SFS graft, such as a portosystemic shunt or splenectomy, have been trialed with some positive results. To establish an effective strategy for transplanting SFS grafts and preventing SFS graft syndrome, it is essential to have precise knowledge and tactics to evaluate graft quality and graft volume, when performing these LDLTs with portal pressure control. We reviewed the updated literature on the pathogenesis of and strategies for using SFS grafts.
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Affiliation(s)
- Toru Ikegami
- Department of Surgery, University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
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Ozden I, Imura S. Somatostatin and propranolol for the treatment of small-for-size syndrome after liver transplantation. ACTA ACUST UNITED AC 2008; 15:560-1. [PMID: 18836814 DOI: 10.1007/s00534-008-1375-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2008] [Accepted: 05/20/2008] [Indexed: 12/21/2022]
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Hwang S, Moon DB, Lee SG. Current Status and Perspectives of Living Donor Liver Transplantation. JOURNAL OF THE KOREAN MEDICAL ASSOCIATION 2008. [DOI: 10.5124/jkma.2008.51.8.700] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Affiliation(s)
- Shin Hwang
- Division of Liver Transplantation and Hepatobiliary Surgery, University of Ulsan College of Medicine, Korea.
| | - Deok-Bog Moon
- Division of Liver Transplantation and Hepatobiliary Surgery, University of Ulsan College of Medicine, Korea.
| | - Sung-Gyu Lee
- Division of Liver Transplantation and Hepatobiliary Surgery, University of Ulsan College of Medicine, Korea.
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