Nobuhisa Akamatsu

Biliary reconstruction, its complications and management of biliary complications after adult liver transplantation: a systematic review of the incidence, risk factors and outcome

Biliary reconstruction remains common in postoperative complications after liver transplantation. A systematic search was conducted on the PubMed database and 61 studies of retrospective or prospective institutional data were eligible for this review. The study comprised a total of 14 359 liver transplantations. The overall incidence of biliary stricture was 13%; 12% among deceased donor liver transplantation (DDLT) patients and 19% among living donor liver transplantation (LDLT) recipients. The overall incidence of biliary leakage was 8.2%, 7.8% among DDLT patients and 9.5% among LDLT recipients. An endoscopic strategy is the first choice for biliary complications; 83% of patients with biliary stricture were treated by endoscopic modalities with a success rate of 57% and 38% of patients with leakage were indicated for endoscopic biliary drainage. T‐tube placement was not performed in 82% of duct‐to‐duct reconstruction. The incidence of biliary stricture was 10% with a T‐tube and 13% without a T‐tube and the incidence of leakage was 5% with a T‐tube and 6% without a T‐tube. A preceding bile leak and LDLT procedure are accepted risk factors for anastomotic stricture. Biliary complications remain common, which requires further investigation and the refinement of reconstruction techniques and management strategies.

Refinement of venous reconstruction using cryopreserved veins in right liver grafts

Short and direct vein anastomosis is generally performed in living donor liver transplantation using a right liver graft. The graft will regenerate, however, and might thus compress the anastomosis. We formulated a strategy for outflow reconstruction in right liver graft. When reconstruction of multiple short hepatic veins was necessary, a cryopreserved inferior vena cava graft was anastomosed with the hepatic veins of the graft in a basin. When there were no major short hepatic veins in the graft, a rectangular‐shaped vein graft was used to make a single orifice using the middle and right hepatic veins in the graft. When there were no tributaries of the middle hepatic vein to be reconstructed, a diamond‐shaped vein patch was anastomosed on the anterior wall of the right hepatic vein orifice of the graft. These techniques were satisfactorily applied in 40 patients with no torsion or tension at the anastomotic site of the hepatic venous reconstruction or other complications in outflow. The present strategy seemed to be technically feasible for outflow reconstruction in a right liver graft. (Liver Transpl 2004;10:541–547.)

Duct-to-duct biliary reconstruction in adult living-donor liver transplantation

Background. Bile duct-to-duct reconstruction is now used in living-donor liver transplantation (LDLT) for adult patients. Methods. The results of duct-to-duct reconstruction were retrospectively analyzed. The subjects were 81 adult patients who underwent LDLT at the University of Tokyo Hospital with a follow-up period of at least 1 year. The hilar plate of the recipient was dissected to at least the second-order branch of the bile ducts. Duct-to-duct anastomosis was performed with interrupted sutures, and an external stent tube was inserted from the orifice opposite the hilar plate. Results. During the observation period (median, 664 days), biliary complications were observed in 26 cases (32%). The complications included bile juice leakage at the anastomosis or dissection plane of the graft in 12 patients, anastomotic stenosis in 10 patients, and tube trouble in 6 patients. Two patients had bile juice leakage followed by stenosis. Of the 26 patients, 21 required surgical revision. Conclusions. The current technique did not reduce morbidity as expected. Further technical advancement and refinement are needed for better results.

Effects of middle hepatic vein reconstruction on right liver graft regeneration.

Background. A right liver graft without the middle hepatic vein (MHV) trunk is now commonly used in living-donor liver transplantation for adult patients. The significance of MHV reconstruction on regeneration or functional recovery of right liver grafts after living-donor liver transplantation, however, remains unclear. Methods. From 2000 to 2002 at the University of Tokyo Hospital in Tokyo, Japan, 56 adult patients received a right liver graft. The patients were divided into three groups by graft type: right liver graft without MHV trunk or MHV reconstruction (n=17); right liver graft without MHV trunk, but with MHV reconstruction (n=27); and extended right liver graft (n=12). Regeneration rate and postoperative liver function were compared among groups. Predictive factors associated with the graft regeneration were identified among clinical variables, including the graft type. Results. The regeneration rate of the right paramedian sector and the whole graft was lowest in the right liver grafts without the MHV trunk or MHV reconstruction. The regeneration rate of the lateral sector was highest in this type of graft, but the difference was not statistically significant. The factors that significantly correlated with the regeneration rate were preoperative graft volume and graft type. There was no significant difference among groups in any of the liver function parameters. Conclusions. In the present series, satisfactory outcome was independent of the type of graft used, which indicates that MHV reconstruction should not be omitted routinely but should be performed in selected patients.

Preemptive Treatment of Fungal Infection Based on Plasma (1 → 3)β-D-Glucan Levels after Liver Transplantation

Background:Invasive fungal infection remains a major challenge in liver transplantation and themortality rate is high. Early diagnosis and treatment are required for better results.Patients:We prospectively measured plasma (1 → 3)β-D-glucan (BDG) levels in 180 living donor liver transplant recipients for 1 year after surgery. Fungal infection was defined as proposed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group. Preemptive treatment (intravenous fluconazole and trimethoprim-sulfamethoxazole) was started when the BDG level was greater than 40 pg/ml.Results:Twenty-four patients (13%) were diagnosed with invasive fungal infection. The responsible pathogens included Candida spp. in 14 cases, Aspergillus fumigatus in 5, Cryptococcus neoformans in 3, and Pneumocystis jiroveci in 2. Preemptive treatment was performed in 22% of patients (n = 40). Renal impairment and mild gastrointestinal intolerance due to the drugs were observed in 28% (11/40) of patients during treatment. Among them 14 patients were diagnosed with fungal infection including seven candidiasis, five aspergillosis, and two Pneumocystis jiroveci pneumonia. The sensitivity and specificity of BDG for overall fungal infection was 58% and 83%, respectively, with a positive predictive value of 35% and a negative predictive value of 93%, and a positive likelihood ratio of 3.41 and a negative likelihood ratio of 1.98. The overall mortality for fungal infection in our series was 0.6%.Conclusion:Although the sensitivity and positive predictive value were low, the low mortality rate after fungal infection and the mild side effects of the preemptive treatment might justify our therapeutic strategy. Based on the effectiveness, this strategy warrants further investigation.

Splenectomy and preemptive interferon therapy for hepatitis C patients after living-donor liver transplantation

Abstract:  Recurrent hepatitis C after liver transplantation is a major cause of graft failure. We routinely perform preemptive interferon and ribavirin therapy in patients after living‐donor liver transplantation indicated for hepatitis C‐related cirrhosis. One of the obstacles for the therapy includes blood cytopenia. To overcome this problem, we recently performed splenectomy concurrently with liver transplantation. Thirty‐five patients underwent liver transplantation and received preemptive therapy for hepatitis C. They were divided into two groups: those with splenectomy (group A, n = 21) and those without (group B, n = 14). There was no significant difference in the frequency of morbidity between the groups. Platelet counts were well maintained in group A patients during the therapy, and cytopenia led to the discontinuation of the therapy in one group B patient. The results of the preliminary study warrant a randomized control trial to examine the feasibility of splenectomy and preemptive viral therapy during liver transplantation for hepatitis C.

Prediction of hepatic artery thrombosis by protocol Doppler ultrasonography in pediatric living donor liver transplantation.

Abstract Hepatic arterial thrombosis (HAT) after liver transplantation is a life-threatening event. Previous reports have suggested that the resistive index (RI) of the hepatic artery predicts HAT. Doppler ultrasonography (US) to measure RI, however, is not routinely performed. The subjects were 70 pediatric patients who underwent living donor liver transplantation (LDLT). Protocol Doppler US was performed once or twice a day for 2 weeks postoperatively and 692 records were examined. Changes in RI values were examined separately in patients with and without HAT complications. The incidence of HAT was 10% (seven of 70). HAT was diagnosed an average of 6.2 days after LDLT. In patients without HAT complications (n = 63), average RI levels at 14 days after LDLT were 0.71 ± 0.1 (records, n = 625). In patients with HAT complications, RI decreased gradually within 2 days before the onset of HAT. RI values of less than 0.6 predicted HAT within 2 days before onset, with 83% sensitivity and 85% specificity. RI during the first 2 weeks after LDLT is a sensitive predictor for HAT. Thrombectomy and reanastomosis should be considered when RI values are less than 0.6 in Doppler US.

Living Donor Liver Transplantation for Patients with Hepatocellular Carcinoma

Background: Liver transplantation has become an established treatment for cirrhotic patients with hepatocellular carcinoma (HCC), and the Milan criteria are now widely accepted and applied as an indication for deceased donor liver transplantation (DDLT) in Western countries. In contrast, however, due to the severe organ shortage, living donor liver transplantation (LDLT) is mainstream in Japan and in other Asian countries. Summary: Unlike DDLT, LDLT is not limited by the restrictions imposed by the nationwide allocation system, and the indication for LDLT in patients with HCC often depends on institutional or case-by-case considerations, balancing the burden on the donor, the operative risk, and the overall survival benefit for the recipient. Accumulating data from a nationwide survey as well as individual center experience indicate that extending the Milan criteria is warranted. Key Messages: While the promotion of DDLT should be intensified in Japan and other Asian countries, LDLT will continue to be a mainstay for the treatment of HCC in cirrhotic patients.

Surgical strategy for bile duct cancer: Advances and current limitations

The aim of this review is to describe recent advances and topics in the surgical management of bile duct cancer. Radical resection with a microscopically negative margin (R0) is the only way to cure cholangiocarcinoma and is associated with marked survival advantages compared to margin-positive resections. Complete resection of the tumor is the surgeons ultimate aim, and several advances in the surgical treatment for bile duct cancer have been made within the last two decades. Multidetector row computed tomography has emerged as an indispensable diagnostic modality for the precise preoperative evaluation of bile duct cancer, in terms of both longitudinal and vertical tumor invasion. Many meticulous operative procedures have been established, especially extended hepatectomy for hilar cholangiocarcinoma, to achieve a negative resection margin, which is the only prognostic factor under the control of the surgeon. A complete caudate lobectomy and resection of the inferior part of Couinauds segment IV coupled with right or left hemihepatectomy has become the standard surgical procedure for hilar cholangiocarcinoma, and pylorus-preserving pancreaticoduodenectomy is the first choice for distal bile duct cancer. Limited resection for middle bile duct cancer is indicated for only strictly selected cases. Preoperative treatments including biliary drainage and portal vein embolization are also indicated for only selected patients, especially jaundiced patients anticipating major hepatectomy. Liver transplantation seems ideal for complete resection of bile duct cancer, but the high recurrence rate and decreased patient survival after liver transplant preclude it from being considered standard treatment. Adjuvant chemotherapy and radiotherapy have a potentially crucial role in prolonging survival and controlling local recurrence, but no definite regimen has been established to date. Further evidence is needed to fully define the role of liver transplantation and adjuvant chemo-radiotherapy.

Hepatic arterial anatomy for right liver procurement from living donors.

Living donor liver transplantation (LDLT) using right liver grafts is now widely performed. Anatomic classifications of the hepatic artery for right liver procurement, however, are limited. In this study, celiac and mesenteric angiograms of 223 consecutive living donors in a single institution were evaluated. Details of the arterial anastomosis and results were reviewed in 72 patients who underwent primary LDLT using right liver grafts. There was a 6% incidence of hepatic arterial bifurcations that might provide multiple orifices in a right liver graft. Only one right liver graft (1%) had multiple arterial orifices. Single arterial anastomosis without interposition was possible in all patients with right liver grafts and none of them were complicated with hepatic arterial thrombosis. Single arterial anastomosis, therefore, has a high probability of success in right liver graft implantation. (Liver Transpl 2004;10:129–133.)