Bong-Wan Kim

Hepatic resection for hepatocellular carcinoma meeting Milan criteria in Child-Turcotte-Pugh class a patients with cirrhosis.

This study evaluated whether hepatic resection is a reasonable strategy as an initial treatment for hepatocellular carcinoma (HCC) meeting Milan criteria in patients with compensated cirrhosis. From the database of 435 consecutive patients with resection of HCC between July 1994 and May 2007, 213 patients were found to have Child-Turcotte-Pugh class A cirrhosis and HCC meeting Milan criteria, as shown by preoperative image studies. We examined long-term survivals and patterns of recurrence after hepatic resection among those patients. Overall survival rates at 1, 3, 5, and 10 years were 92%, 78%, 69%, and 52%, respectively, and 1-, 3-, 5-, and 10-year disease-free survival rates were 79%, 57%, 44%, and 19%, respectively. Pathological review indicated that 36/213 patients (16.9%) had another nodule and/or gross vascular invasion. Microvascular invasion, tumor size, and histological grade of cirrhosis were independent risk factors for recurrence. Sixty percent of recurrent cases met the Milan criteria. The six patients who underwent living donor salvage liver transplantation (OLT) for intrahepatic recurrence were alive without recurrence at a median of 24 (range = 8-31) months. These favorable data suggest that hepatic resection is a good option for small HCCs in patients with compensated cirrhosis; and salvage OLT may be reserved for patients with recurrences.

Salvage Liver Transplantation for Recurrent Hepatocellular Carcinoma After Liver Resection: Feasibility of the Milan Criteria and Operative Risk

INTRODUCTION Although the Milan criteria are widely accepted for liver transplantation (OLT) for hepatocellular carcinoma (HCC), they have not been fully evaluated as feasible for salvage liver transplantation (SLT) of recurrent HCC after hepatic resection. The operative difficulties of SLT increase the operative risk. The aim of this study was to evaluate the feasibility of the Milan criteria for SLT and its operative complications. PATIENTS AND METHODS From March 2005 to November 2007, 46 HCC patients received OLT including 15 SLTs after prior partial hepatectomy (SLT group) and 31 primary OLTs (PLT group). RESULTS There was no postsurgical hospital mortality among the SLT group but one case in the PLT group due to pneumonia followed by sepsis. There was no difference in the incidence of surgical complications between the two groups. Overall survival rates of SLT group patients were similar to those of the PLT group (P = .14), especially comparing both groups of patients within the Milan criteria (P = .89). There was no recurrence of HCC among the patients within the Milan criteria. CONCLUSIONS SLT is a feasible procedure for recurrent HCC meeting the Milan criteria; the operative risk of the SLT is also acceptable.

Decreased lactate dehydrogenase B expression enhances claudin 1-mediated hepatoma cell invasiveness via mitochondrial defects

Aerobic lactate production of which the final step is executed by lactate dehydrogenase (LDH) is one of the typical phenotypes in invasive tumor development. However, detailed mechanism of how LDH links to cancer cell invasiveness remains unclear. This study shows that suppressed LDHB expression plays a critical role in hepatoma cell invasiveness by inducing claudin-1 (Cln-1), a tight junction protein, via mitochondrial respiratory defects. First, we found that all the SNU human hepatoma cells with increased glycolytic lactate production have the defective mitochondrial respiratory activity and the Cln-1-mediated high invasive activity. Similar results were also obtained with human hepatocellular carcinoma tissues. Unexpectedly, the increased lactate production was due to LDH isozyme shifts to LDH5 by LDHB down-expression rather than LDHA induction, implying the importance of LDHB modulation. Second, LDHB knockdown did not only trigger Cln-1 induction at the transcriptional level, but also induced respiratory impairment. Interestingly, most respiratory inhibitors except KCN induced Cln-1 expression although complex I inhibition by rotenone was most effective on Cln-1 induction. Respiratory defect-mediated Cln-1 induction was further confirmed by knockdown of NDUFA9, one of complex I subunits. Finally, ectopic expression of LDHB attenuated the invasiveness of both SNU 354 and 449 cells whereas LDHB knockdown significantly augmented the invasiveness of Chang cells with Cln-1induction. The increased invasive activity by LDHB modulation was clearly reversed by knocking-down Cln-1. Taken together, our results suggest that LDHB suppression plays an important role in triggering or maintaining the mitochondrial defects and then contributes to cancer cell invasiveness by inducing Cln-1 protein.

Duct-to-Duct Biliary Reconstructions and Complications in 100 Living Donor Liver Transplantations

OBJECTIVE We evaluated the risk factors for biliary complications and surgical procedures for duct-to-duct reconstructions in adult living donor liver transplantation (LDLT). PATIENTS AND METHODS From February 2005 to March 2008, we performed 100 cases of adult LDLT with duct-to-duct biliary reconstruction, using 64 right lobe grafts, 33 left lobe grafts, and 3 right lateral grafts. We employed 4 types of duct-to-duct procedures: all interrupted 6-0 Prolene suture (group 1, n = 9); continuous posterior and interrupted anterior wall 6-0 Prolene suture (group 2, n = 49); all continuous 7-0 Prolene suture (group 3, n = 26); and all continuous 7-0 Prolene suture with external stent (group 4, n = 16). Biliary complications were defined as an anastomosis stricture or a leakage. RESULTS Thirty-four patients experienced biliary complications during the follow-up period (median, 27 months). The incidence of stricture was 27% and that of leakage, 8%. There were no perioperative, intraoperative, or anatomic risk factors for biliary complications, except the type of duct-to-duct procedure. Group 1 and 2 patients showed higher incidences of biliary strictures than groups 3 and 4 (43.1% vs 4.7%; P = .00). Group 3 patients experienced a higher incidence of bile leakage than the other groups (23.1% vs 2.7%; P = .004). CONCLUSIONS The type of biliary reconstruction is a factor affecting biliary complications following duct-to-duct anastomosis in LDLT. Duct-to-duct biliary anastomosis with 7-0 monofilament suture and a small external stent is a feasible procedure in LDLT that significantly reduces the incidence of biliary complications.

Endovascular treatment of acute arterial complications after living-donor liver transplantation.

AIM The aim of this study was to evaluate the efficacy of endovascular treatment for acute arterial complications following living-donor liver transplantation (LDLT). MATERIALS AND METHODS Of 79 LDLT patients, 17 (mean age 48+/-8 years, range 33-66 years) who had acute arterial complications and underwent endovascular treatment were evaluated. Transcatheter arterial embolization was performed to control peritoneal bleeding. Catheter-directed thrombolysis using urokinase was performed in hepatic artery thromboses. The locations of complications and materials used were evaluated. The technical and clinical success rates were calculated. RESULTS Twenty-three acute arterial complications, including four hepatic artery thromboses and 19 cases of peritoneal haemorrhages were identified in 22 angiographic sessions in 17 patients. The mean duration between LDLT and first angiography was 3.2+/-3.5 days (range 1-13 days). Hepatic artery recanalization with catheter-directed thrombolysis using urokinase was achieved in two patients. Transcatheter arterial embolization for peritoneal bleeding was successfully performed in 16 cases. The most common bleeding focus was the right inferior phrenic artery. Additional surgical management was needed in five patients to control bleeding or hepatic artery recanalization. Technical and clinical success rates of transcatheter arterial embolization were 84.2 and 63.1%, respectively. Overall technical success was achieved in 18 of 23 arterial complications (78.2%), and clinical success was achieved in 14 of 23 arterial complications (60.8%). CONCLUSION Endovascular treatment for the acute arterial complications of haemorrhage or thrombosis in LDLT patients is safe and effective. Therefore, it should be considered as the first line of treatment in selective cases.

Volumetry-based selection of right posterior sector grafts for adult living donor liver transplantation.

To determine the feasibility of volumetric criteria without anatomic exclusion for the selection of right posterior sector (RPS) grafts for adult‐to‐adult living donor liver transplantation (LDLT), we reviewed and compared our transplant data for RPS grafts and right lobe (RL) grafts. Between January 2008 and September 2010, adult‐to‐adult LDLT was performed 65 times at our institute; 13 of the procedures (20%) were performed with RPS grafts [the posterior sector (PS) group], and 39 (60%) were performed with RL grafts (the RL group). The volumetry of the 13 RPS donor livers showed that the RPS volume was 39.8% ± 7.6% of the total liver volume. Ten of the 13 donors had to donate RPS grafts because the left liver volume was inadequate. All donor procedures were performed successfully, and all donors recovered from hepatectomy. However, longer operative times were required for the procurement of RPS grafts versus RL grafts (418 ± 40 versus 345 ± 48 minutes, P < 0.001). The postoperative recovery of liver function was smoother for the donors of the PS group versus the donors of the RL group. The RPS grafts had significantly smaller hepatic artery and bile duct openings than the RL grafts. All recipients with RPS grafts survived LDLT. No recipients experienced vascular graft complications or small‐for‐size graft dysfunction. There were no significant differences in the incidence of posttransplant complications between the donors and recipients of the PS and RL groups. The 3‐year graft survival rates were favorable in both groups (100% in the PS group versus 91% in the RL group). In conclusion, the selection of RPS grafts by volume criteria is a feasible strategy for an adult‐to‐adult LDLT program. Liver Transpl 17:1046–1058, 2011.

Effects and problems of adult ABO-incompatible living donor liver transplantation using protocol of plasma exchange, intra-arterial infusion therapy, and anti-CD20 monoclonal antibody without splenectomy: case reports of initial experiences and results in Korea.

INTRODUCTION Adult ABO-incompatible liver transplantation is associated with a high risk of graft failure due to antibody-mediated humoral rejection (AMR). We evaluated the effects of a protocol using preoperative removal of isohemagglutinin, rituximab prophylaxis, and intrahepatic arterial infusion (HAI) therapy for ABO-incompatible adult living donor liver transplantation (LDLT). PATIENTS AND METHODS Between March 2005 and September 2007, we performed 94 adult LDLTs, including 3 ABO-incompatible cases. All ABO-incompatible LDLT patients underwent administration of 375 mg/m(2) rituximab on preoperative days 15 and 8 without splenectomy, as well as preoperative removal of isohemagglutinin using plasma exchange, and HAI therapy for postoperative 21 days. RESULTS Postoperative anti-donor blood-type antibody titer and B-cell level were effectively suppressed by early rituximab prophylaxis in all patients. HAI therapy was effective to prevent AMR and even resolved mild AMR. However, all patients suffered bacterial infections, and 1 died of septicemia with good graft function. Another subject died of late-onset AMR that occurred after discontinuation of HAI therapy. CONCLUSION An ABO-incompatible LDLT protocol using plasma exchange, rituximab prophylaxis, and intra-HAI therapy effectively suppressed anti-A/B antibody and prevented AMR. But this protocol should be further improved to reduce infectious complications and late onset of AMR.

Does hepatorenal syndrome affect the result of liver transplantation? Clinical observations.

Hepatorenal syndrome (HRS) is a reversible, functional renal failure that occurs in patients with advanced hepatic failure. However, the reported rates of complete recovery of renal function and patient survivals after orthotopic liver transplantation (OLT) are variable. The aim of this study was to compare the outcomes after OLT between patients with HRS and those without HRS (no-HRS). We established exclusion criteria to select study patients who underwent OLT in a single center between January 2005 and October 2008. The exclusion criteria included the following: (1) malignancy, (2) <18 years of age, (3) other than primary OLT, (4) ABO mismatch or hemophilia, (5) no liver cirrhosis, and (6) survival >1 month after OLT. We selected 71 subjects, including 8 HRS and 63 no-HRS patients. No significant differences were observed in the estimated glomerular filtration rate (eGFR) between the 2 groups except for a lower eGFR on the day of and 1 month after OLT in the HRS group: 108.3 ± 40.5 versus 31.4 ± 14.1 mL/min and 85.4 ± 15.0 versus 57.3 ± 12.1 mL/min (P = .000 and P = .014, respectively). The renal function of 6/7 HRS patients who survived >1 year improved. The 1-year patient survival rate after OLT in HRS patients was similar to that without HRS: 95% versus 86% (P = .37). We concluded that HRS had minimal effects on patient survival and return of acceptable renal function.

Auxiliary Partial Orthotopic Living Donor Liver Transplantation in a Patient With Wilson's Disease: A Case Report

A patient with end-stage liver cirrhosis and neurological disorder due to Wilsons disease (WD) underwent auxiliary partial orthotopic liver transplantation (APOLT) using a living donor. He first visited our institute complaining of hand tremor, which was diagnosed as WD. Despite medical therapy, hepatic impairment progressed toward portal hypertensive complications. He was considered a suitable candidate for living donor-related liver transplantation. However, because of the impossibility of mobilization of the lateral section due to severe splenomegaly at the time of the recipient operation, we performed an APOLT using a right lobe graft. After transplantation, he suffered hepatic vein stenosis and biliary stenosis, receiving interventional therapy. The remnant native liver volume decreased, and the volume of the graft increased serially after transplantation. At the time of reporting, the patient had a normal working life with normal serum ceruloplasmin level and without neurologic problems at 26 months posttransplantation. APOLT may be a therapeutic option for patients with WD.

Blood Neutrophil-to-Lymphocyte Ratio Predicts Tumor Recurrence in Patients with Hepatocellular Carcinoma within Milan Criteria after Hepatectomy

Purpose The systemic inflammation biomarker, Neutrophil-to-Lymphocyte Ratio (NLR), has been reported as one of the adverse prognostic factors for hepatocellular carcinoma (HCC) patient. The purpose of this study was to evaluate whether NLR could predict the risk of recurrence and death for the HCC patient, according to Milan criteria after hepatectomy. Materials and Methods Retrospective analysis was performed on a database of HCC patients who underwent hepatectomy between March 2001 and December 2011. The cutoff value of NLR was decided by receiver operating characteristic (ROC) curve analysis. Univariate and multivariate regression analyses were performed to identify predictive factors of recurrence and death. Results A total of 213 patients were included in the present study. The median follow-up period was 48 months. One hundred and seven patients were experienced tumor recurrence; forty of them recurred within 12 months (early recurrence). NLR ≥1.505, albumin ≤3.75 g/dL, microvascular invasion and high grade of cirrhosis were found to be independent factors for adverse recurrence-free survival in multivariate regression analysis. And NLR ≥1.945 was also found as a prognosis factor for early recurrence by univariate regression analysis. Conclusion Elevated preoperative NLR can be easily obtained and reliable biomarker for assessing the tumor recurrence and early recurrence of Milan criteria HCC after the initial hepatectomy.