Liver Preservation Techniques for Transplantation

The development of optimal methods for preservation is important for the advancement of liver transplantation. This study compares hypothermic storage (HS) and hypothermic pulsatile perfusion (HPP) with various solutions, using an isolated normothermic perfusion model (LIPM). Canine livers were removed from mongrel dogs without warm ischemia and flushed with either heparinized Ringer's lactate (control and HPP-preserved groups) or the solution used for hypothermic storage (TP-V or modified Collins). The type of preservation and solution for each of the experimental groups was as follows: group I (n = 7), no preservation, fresh; group II (n = 7), 24-h HS with TP-V (a hyperosmolar colloid solution containing sucrose, dextrose, and ATP-MgCl2); group III (n = 7), 24-h HS with modified Collins (C-2), an intracellular crystalloid solution; group IV (n = 5), 24-h HP with TP-V; group V (n = 6), 24-h HPP with Belzer solution, containing ATP-MgCl2; group VI (n = 3), 24-h HPP with albumin. After the preservation period, livers were placed on HPP at 37 degrees C with albumin-mannitol solution for 3-h testing in an LIPM. Perfusate samples were taken at 1-h intervals to assess liver function. LDH, SGOT, alkaline phosphatase, lactic acid, LAP, GGT, pO2, pCO2, pH, osmolarity, AMP, ADP, and ATP were studied. Histologic studies were performed, as were representative HIDA scans. Using the LIPM, livers preserved by HS and HPP with TP-V solution appeared to be superior to those preserved with modified Collins, Belzer, and albumin solutions. In these non-TP-V groups, the greatest cellular and organ damage was observed. TP-V HPP appeared to give the best overall liver functional response and histologic results and is recommended as the preferred method for 24-h liver preservation.     

Liver Transplantation for HCC: A Review

Hepatocellular carcinoma (HCC) often occurs in patients with chronic liver disease or cirrhosis. Liver transplantation for hepatocellular carcinoma has the potential to eliminate both the tumor as well as the underlying cirrhosis and is the ideal treatment for HCC in cirrhotic liver as well as massive HCC in noncirrhotic liver. Limitations in organ availability, necessitate stringent selection of patients who would likely to derive most benefit. Selection criteria have considered tumor size, number, volume as well as biological features. The Milan criteria set the benchmark for tumors that would benefit from liver transplantation but were found to be excessively restrictive. Modest expansion in criteria has also been shown to be associated with equivalent survival. Microvascular invasion is the single most important adverse prognostic factor for survival. Living donor liver transplantation has expanded donor options and has the advantage of lower waiting period and not impacting the non-HCC waiting list. Acceptable outcomes have been obtained with living donor liver transplantation for larger and more numerous tumors in the absence of microvascular invasion. Downstaging of tumors to prevent progression while waiting for an organ or for reduction in size to allow enrolment for transplantation has met with variable success.     

Bone Disease and Liver Transplantation: A Review

Liver transplantation is currently the most effective and almost routine treatment for chronic and acute liver diseases. The survival of transplanted patients has increased exponentially, which has led to more knowledge of the long-term complications secondary to the underlying pathology or the various treatments that must be followed. Bone metabolic disease is a chronic complication of liver transplantation that inhibits quality of life. The factors that contribute to the development of bone disease are different according to the various etiologies of liver damage. All patients should be examined for osteoporosis risk factors because the incidence of new fractures in transplant patients is higher during the first year after transplantation, reflecting the greater bone loss during this time. This article outlines a proposal for a treatment algorithm; we propose that pharmacologic therapy in patients post liver transplant should first consider the diagnosis of osteoporosis by bone mineral density, the patient's personal and family history of spine and femoral neck fractures, and the use glucocorticoids (dose and time) until a tool is available that allows the best estimation of the fracture risk in this population of patients.     

Pregnancy Outcomes After Liver Transplantation: A Systematic Review

Purpose

Liver transplantation (LT) constitutes a major therapeutic option for a number of patients suffering from liver pathologies. Pregnancy outcomes in patients who have undergone LT are assessed by a number of studies. The aim of our systematic review was to present the currently available evidence concerning the results of pregnancy in patients with LT.

Liver Transplantation for Giant Hepatic Hemangioma: A Systematic Review

Introduction

Despite their benign nature, liver hemangiomas (LH) are lesions that can cause major complications requiring intervention. Liver transplantation (LT) has been suggested as an effective treatment option in selected patients with giant LHs causing severe symptoms and cannot be treated otherwise. The aim of our study was to investigate the indications, aspects and post-operative outcomes of patients with a LH who underwent LT.

Mixed Hepatocellular Cholangiocarcinoma: A Review of Long-Term Outcomes Following Liver Transplantation

Introduction

Mixed hepatocellular cholangiocarcinoma (HCC-CC) represents a rare hepatic tumor, which demonstrates histological features of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). HCC-CC can be an unexpected finding in patients undergoing liver transplantation (LT) for HCC. The objective of our review was to review and evaluate long-term outcomes in patients undergoing LT for mixed HCC-CC.

Biliary Complications Following Deceased and Living Donor Liver Transplantation: A Review

Introduction

Biliary complications are the most important source of complications after liver transplantation, and an important cause of morbidity and mortality. With the evolution of surgical transplantation techniques, including living donor and split-liver transplants, the complexity of these problems is increasing. Many studies have shown a higher incidence of biliary tract complications in living donor liver transplantation (LDLT) compared with deceased donor liver transplantation (DDLT). This article reviews biliary complications after liver transplantation and correlations with LDLT and DDLT.

Objective

Provide an overview of biliary complications among LDLT and DDLT.

Results

The incidence of biliary complications is higher among LDLT (28.7%) when compared with DDLT (15.5%). Bile leaks were the most common complication due to LDLT (17.1%); however, stricture was the most common complication due to DDLT (7.5%).     

Amphiregulin Stimulates Liver Regeneration After Small‐for‐Size Mouse Liver Transplantation

This study investigated whether amphiregulin (AR), a ligand of the epidermal growth factor receptor (EGFR), improves liver regeneration after small‐for‐size liver transplantation. Livers of male C57BL/6 mice were reduced to ～50% and ～30% of original sizes and transplanted. After transplantation, AR and AR mRNA increased in 50% but not in 30% grafts. 5‐Bromodeoxyuridine (BrdU) labeling, proliferating cell nuclear antigen (PCNA) expression and mitotic index increased substantially in 50% but not 30% grafts. Hyperbilirubinemia and hypoalbuminemia occurred and survival decreased after transplantation of 30% but not 50% grafts. AR neutralizing antibody blunted regeneration in 50% grafts whereas AR injection (5 μg/mouse, iv) stimulated liver regeneration, improved liver function and increased survival after transplantation of 30% grafts. Phosphorylation of EGFR and its downstream signaling molecules Akt, mTOR, p70S6K, ERK and JNK increased markedly in 50% but not 30% grafts. AR stimulated EGFR phosphorylation and its downstream signaling pathways. EGFR inhibitor PD153035 suppressed regeneration of 50% grafts and largely abrogated stimulation of regeneration of 30% grafts by AR. AR also increased cyclin D1 and cyclin E expression in 30% grafts. Together, liver regeneration is suppressed in small‐for‐size grafts, as least in part, due to decreased AR formation. AR supplementation could be a promising therapy to stimulate regeneration of partial liver grafts.     

Incisional Hernia After Orthotopic Liver Transplantation: A Systematic Review and Meta-analysis

BackgroundIncisional hernia (IH) is a well-known complication of orthotopic liver transplantation. Despite wide recognition of the impact of this problem, the incidence remains imprecisely known.MethodsThe MEDLINE, EMBASE, Cochrane Central Register of Clinical Trials and Cochrane Database of Systematic Reviews databases were searched from their inception to November 2017 for abstracts documenting IH after orthotropic liver transplantation (OLT). The primary endpoint of this study was incidence of IH, secondary endpoints were time to hernia and recurrence. Three reviewers independently graded abstracts for inclusion in this review. Heterogeneity in combining data was assumed prior to pooling. Random-effects meta-analyses were performed to estimate percentages and 95% CIs.ResultsAfter a review of 77 abstracts, 18 studies were graded as relevant. The methodological quality of studies was assessed with a minimum Oxford Centre for Evidence-Based Medicine level of 2B. These represent a cohort of 981 patients with IH after OLT reported in the literature. A meta-analysis of studies meeting inclusion criteria shows mean incidence of 15.1% (CI 12.1%-18.2%). Aggregate recurrence rate reported in the literature is 12.4% (CI 4.3%-20.5%). Overall reported time to IH after OLT was 42.9 months.ConclusionsAlthough reported incidences of IH after OLT vary widely across studies, an overall incidence of 15.1% is reported. This is a relatively late complication after transplantation. Recurrence of hernia after initial repair is 12.4% within this patient population.     

成人间肝活体肝移植的外科技术与创新

1989年巴西的Raia等首次对2例先天性胆管闭锁的患儿施行了亲体肝移植（liver—related liver transplantation，LRLT），但不幸2例患儿均未存活；而第1例成功的LRLT则在1990年由澳大利亚的Strong等完成；此后LRLT在亚洲迅速开展。     

Intraoperative Management of Liver Transplantation in Patients with Hypertrophic Cardiomyopathy: A Review

Hypertrophic cardiomyopathy (HCM) is a genetic disorder defined by the presence of a hypertrophied nondilated left ventricle in the absence of other known causes. Anatomic variants exist, and dynamic features of this disease process may include left ventricular outflow tract obstruction during systole, systolic anterior motion of the mitral valve, and mitral regurgitation. Patients with HCM are at higher risk for sudden cardiac death, stroke, atrial fibrillation, atrial reentrant tachycardia, syncope, and congestive heart failure (CHF). Few studies have evaluated the perioperative risk of noncardiac surgery in this patient population. However, there appears to be a relatively high incidence of perioperative adverse cardiac events, such as CHF, myocardial ischemia, stable and life-threatening arrhythmias, and transient hypotension. Interoperative challenges of patients with HCM are exacerbated in the setting of end-stage liver disease (ESLD) and liver transplantation. ESLD physiology includes relative hypovolemia, decreased systemic vascular resistance and arterial pressure, and hyperdynamic circulation characterized by increased cardiac output. General anesthesia, release of ascites, temporary occlusion of the inferior vena cava, and reperfusion of the donor liver can result in cardiovascular instability. Liver transplantation is associated with blood loss, hypovolemia, vasodilation, tachycardia, and hypotension. Anesthetic goals to limit the dynamic features of HCM include avoiding tachycardia and increased contractility, as well as maintaining preload and afterload. Transesophageal echocardiography (TEE) is an ideal monitoring technique for patients with HCM undergoing liver transplantation. Benefits of TEE include real-time visualization of cardiac function and structure, better indication of intravascular volume, and immediate evaluation of pharmacologic interventions.     

Surgical Techniques of Allogeneic Liver Transplantation in a Nonhuman Primate Model

Herein, we report our experience of performing allogeneic orthotopic liver transplantation (LT) in nonhuman primates. We designed an allogeneic ABO-compatible orthotopic LT model in monkeys in a manner similar to that used in humans. We applied almost the same surgical procedures used for human conventional deceased donor LT. A total of 6 monkeys underwent allogeneic LT. One cynomolgus monkey aged 45 months (3.4 kg) and 5 rhesus macaque monkeys aged 50.2 ± 14.8 months (5.40 ± 0.33 kg) were used as recipients. In the donor surgery, the liver was perfused in situ through the aorta using cold histidine-tryptophan-ketoglutarate solution. The portal vein (diameter, 5–10 mm), supra- and infra-hepatic inferior vena cava (IVC) (diameter, 12–15 mm), and common bile duct (diameter, 1.5–3.0 mm) were dissected out. The hepatic artery was kept in continuity with the celiac trunk and abdominal aorta up to the iliac bifurcation (diameter, 5–6 mm). The mean graft weight was 102.0 g (94.8–111.0 g). Recipient surgery was conducted in parallel. After recipient hepatectomy, the graft was implanted. The suprahepatic IVC and portal vein were anastomosed to those of the graft. After reperfusion, the infrahepatic IVC was anastomosed. The aorta conduit of the graft was anastomosed to the infrarenal aorta of the recipient in a retrocolic end-to-side manner. Biliary reconstruction was performed in a duct-to-duct anastomosis with cholecystectomy. Mean operative time was 107.0 minutes for donor and 198.2 minutes for recipient. There was one operative death due to unknown cause. In conclusion, for allogeneic orthotopic LT in nonhuman primate model, we can apply almost the same procedure used for human conventional deceased donor LT in a similar manner.     

劈离式肝移植一供两受的报告

我院于 2 0 0 2年 7月 1 9日行劈离式肝移植治疗终末期肝硬化和Ｗｉｌｓｏｎ病 (肝豆状核变性 )各一例 ,现报告如下。临床资料　　 1 .供体手术　　供体血型Ａ型。按快速取肝法获取尸肝 ,采用双灌注方法 (即腹主动脉和门静脉 ) ,先以 0～ 4℃Ｃｏｌｌｉｎ液分别灌注含肝素 50 0 0 0ＩＵ的 2 50 0ｍｌ和 1 50 0ｍｌ,接着用 4℃的ＵＷ液经门静脉灌注 ,然后置肝脏于ＵＷ液中保存。热缺血时间为 6ｍｉｎ ,手术历时 35ｍｉｎ ,切取肝脏重量 1 0 80 ｇ。　　 2 .肝的分离和修整　　用ＣＵＳＡ沿肝脏镰状韧带的左侧劈离肝脏 ,一半为Ⅱ、Ⅲ段 ,重量 …     

Pancreas Transplantation After Liver Transplantation: A Case Report

Our aim was to describe the clinical indications, surgical technique, and clinical outcomes of a pancreas transplantation, performed 4 years after liver transplantation, as treatment for new-onset, uncontrolled diabetes mellitus in a 53-year-old man. Liver transplantation was performed for end-stage liver disease secondary to hepatitis B virus infection and hepatocellular carcinoma. The patient had no history of diabetes prior to the liver transplantation. The decision to proceed with a pancreas transplantation was made when the patient's blood sugar levels could not be normalized despite insulin doses >100 IU/d. A modified cadaveric transplantation technique was used, with the recipient's inferior vena cava dissected for anastomosis with the portal vein of the graft, using a diamond-shaped patch procedure. Moreover, the right common iliac artery was anastomosed with a Y-graft in the pancreas graft, and the duodenum remnant of the graft was anastomosed to the recipient's duodenum using a side-to-side procedure. The 6-month postoperative follow-up included repeated endoscopic biopsy of the graft duodenum, with no evidence of thrombosis or rejection of the graft, with glucose level within normal limits without requirement for diabetic drugs. To our knowledge, this is the first reported case of pancreas transplantation after liver transplantation.     

睾丸生精小管干细胞移植受体模型建立与移植技术改进

目的:探讨建立稳定的、适合干细胞睾丸生精小管移植的受体小鼠模型和移植技术改进。方法:将雄性ICR小鼠60只随机分为A、B、C、D4组,每组15只。A、B、C组注射白消安的剂量分别为15、30、40mg/kg体重,D组注射50%二甲亚砜作为对照。注射后常规饲养,观察小鼠死亡情况。于注射后4、8、12周称量各组小鼠的睾丸重量,制作睾丸石蜡切片,观察生精小管的中空率和生精上皮结构变化。自主设计干细胞移植装置,改进干细胞移植技术。该装置通过三通连接装置将口含端、注射器端及穿刺端连接在一起,口含端负责试探性的注射,注射器端负责抽吸细胞悬液和注射。结果:注射后只有C组出现1只小鼠死亡。4周时A、B、C组睾丸重量的变化,与作为对照的D组相比有显著性差异(P<0.05);8周时A组与D组无差异(P>0.05),而B、C组与D组差异仍有显著性(P<0.05);12周时各组与D组均无显著性差异(P>0.05)。4、8周时A组的生精小管中空率<50%,B、C组中空率都在50%以上,而D组无明显改变;12周时A、B、C组无显著性差异(P>0.05),恢复近正常状态。自主设计的三通式注射装置注射成功率高,可达90%以上;细胞浪费少,注射双侧睾丸所需细胞悬液量<50μl;所需时间短,注射一侧睾丸<10min。结论:雄性ICR小鼠腹腔内单次注射30mg/kg体重白消安,无小鼠死亡,且4周后生精小管的中空率高(均>50%),适合作为干细胞移植的模型。改进后的移植装置和方法,提高了移植的效率和成功率。为探讨干细胞向雄性配子发育研究提供了简单易学、适于推广的新技术。