B.-H. Jung

Long-Term Outcome of Liver Transplantation for Combined Hepatocellular Carcinoma and Cholangiocarcinoma

PURPOSEnCombined hepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CCC) is a rare pair of intrahepatic malignancies. Differential diagnosis among combined HCC-CCC, HCC, or CCC can be difficult; thus malignancies other than ordinary HCC are occasionally encountered unexpectedly in explanted liver specimens. The present study analyzed the long-term outcomes of liver transplantation (OLT) among patients with HCC-CCC.nnnMETHODSnBetween January 1999 and December 2009, we performed 2137 adult OLT atxa0our institution including 15 cases of pathologically confirmed HCC-CCC, who allxa0underwent OLT with a pretransplant diagnosis of HCC. We reviewed retrospectively the medical records of these 15 patients.nnnRESULTSnTheir mean age was 58.9 ± 7.2 years. The median preoperative alpha-fetoprotein level was 32.6 ng/mL. Fourteen patients underwent living donor and one deceased donor OLT. The Milan criteria were met in 12 cases. A single tumor was identified in 8 and multiple lesions in 7 patients. The maximal tumor diameter was 2.9 ± 1.7 cm. Seven patients experienced tumor recurrences: including 6 within the first 12 months. All of the patients who experienced recurrences died at a median 4 months after that diagnosis. The overall patient survival rates were 66.7% at 1 year and 60.0% at 3 and 5 years. Disease-free patient survival rates were 60.0% at 1 year and 53.3% atxa03 and 5 years.nnnCONCLUSIONSnPatients with combined HCC-CCC showed a high rate of early recurrences, particularly within the first year.

Role of Hand-Assisted Laparoscopic Surgery in Living-Donor Right Liver Harvest

OBJECTIVEnThe cosmetic aspects of abdominal skin incisions are a matter of concern for both live liver donors and surgeons. We performed a prospective comparative study on the use of minilaparotomy to perform right liver graft harvests with and without hand-assisted laparoscopic surgery (HALS).nnnMETHODSnYoung donors were indicated for surgery using minilaparotomy with or without HALS. In the non-HALS group (nxa0= 20), a 10-12-cm-long right subcostal incision was used for right liver graft harvest. In the HALS group (nxa0= 20), an 8-cm-sized right subcostal incision was used for hand assistance and 3 laparoscopic holes made for manipulation. The retrohepatic inferior vena cava (IVC) was initially laparoscopically dissected while using air inflation. The skin incision was extended to 10-12 cm, and then hilar dissection and hepatic transection were performed through the skin incision.nnnRESULTSnIn all 40 donors in the study cohort, safe uneventful harvesting of the right liver grafts was successfully achieved through the minilaparotomy incisions. The HALS group required an additional 30 minutes for laparoscopic preparation and dissection compared with the non-HALS group. HALS facilitated retrohepatic IVC dissection, and the remaining part of the surgery was the same as that for minimal-incision surgery. The minimal skin incision for the delivery of the liver from the abdomen was an average 10 cm for graftsxa0<500 g and 12 cm for grafts ≥700 g. Compared with the patient profiles, there were no differences regarding donor age, body mass index, graft weight, intraoperative blood loss, postoperative increase in peak liver enzymes, total hospital stay, and incidence of postoperative complications.nnnCONCLUSIONSnHALS facilitates the performance of donor hepatectomy with the use of a minimal incision, which probably allows for a wider selection of living donors.

Liver Transplantation in Korea: Past, Present, and Future

PURPOSEnThis study reviewed the past and present status of liver transplantation (LT) and outlooks for the future of LT in Korea.nnnMETHODnThe first LT in Korea was successfully performed using a deceased donor graft in 1988. Pediatric and adult living donor liver transplantations (LDLTs) were initiated in 1994 and 1997, respectively. From 1988 to 2013, 10,581 LTs were performed at 40 centers, whereas LDLT accounted for 76.5% of all LTs.nnnRESULTSnIn the early 1990s, the deceased organ donation rate was less than 1.5 per million population (PMP) per year, but it increased to 5 PMP beginning in 2008. Despite the increasing number of deceased donor liver transplantations (DDLTs), high prevalence of hepatitis B virus (HBV)-induced cirrhosis and hepatocellular carcinoma (HCC) has provoked persistent performance of adult LDLT with technical advancement including middle hepatic vein (MHV) reconstruction of right lobe graft and dual graft LDLT with 1 nationwide donor mortality.nnnCONCLUSIONnThe number of LTs in Korea in 2010 was 23.2 PMP (1042 LTs/45 million population), lower than 23.5 PMP of Spain, but higher than 20 PMP of the United States. However, future LT numbers may decrease because of lowering the HBV carrier rate (neonatal HBV universal vaccination began in 1992), new potent anti-HBV agents, and lowest birth rate (1.22 children per family) with a decrease of potential live donors.

Long-Term Outcome of Living Donor Liver Transplantation for Patients With Alcoholic Liver Disease

BACKGROUNDnBecause most liver transplantation (LT) studies for alcoholic liver disease (ALD) were performed on deceased donor LT, little was still known following living donor LT (LDLT).nnnMETHODSnThe clinical outcomes of 126 ALD patients who underwent LDLT for 11 years in a high-volume LT center were assessed retrospectively.nnnRESULTSnALD cases were 5.7% of adult LDLT indication (nxa0= 2196). ALD was 1.9% (4xa0of 207) during 2000 to 2001, whereas the proportion gradually increased up to 11.3% (34xa0of 301) in 2010. The model for end-stage liver disease score was 22.1 ± 9.9, and 6-month abstinence was observed in 105 (83.3%). There were 123 (97.6%) related donors. Single-graft and dual-graft were implanted into 111 and 15 patients, respectively. Main graft type was single right liver graft (nxa0= 108; 85.7%). Graft-to-recipient weight ratio was 1.02 ± 0.16. Perioperative mortality within 3 months occurred in 5 (4.0%). Overall 1-, 3-, 5-, and 10-year patient survival rates were 92.1%, 88.0%, 85.8%, and 83.7%, respectively. Three patients died of alcohol abuse. De novo hepatitis B virus infection occurred in 2 of 26 patients after implantation of core antibody-positive graft and no further cases happened after strict application of prophylaxis.nnnCONCLUSIONSnThe results of this study revealed that the survival outcome of LDLT in ALD patients is comparable with that of deceased donor LT. To achieve favorable long-term survival, a multidisciplinary approach can be an effective strategy, including the interaction between the patient, the physician, and the family members.

Complications Analysis of Polytetrafluoroethylene Grafts Used for Middle Hepatic Vein Reconstruction in Living-Donor Liver Transplantation

BACKGROUNDnWe previously showed that ringed polytetrafluoroethylene (PTFE) grafts combined with small allograft patches showed high patency rates similar to those of iliac vein grafts and therefore that they can be used for middle hepatic vein (MHV) reconstruction. Although such use of PTFE graft showed high patency rates, its long-term safety regarding infection and other types of complications were not presented. In this study, wexa0investigated the actual risk of complications directly associated with PTFE graft interposition for MHV reconstruction.nnnMETHODSnDuring the study period of 30 months, we performed 215 cases of adult living-donor liver transplantation with modified right lobe graft and PTFE grafts. We classified the potential complications directly associated with PTFE graft interposition as infectious and surgical complications. The medical records of study patients were retrospectively reviewed.nnnRESULTSnMHV graft patency rate was 76.3% at 6 months and 36.7% at 12 months. Their 1-year graft and patient survival rates were 92.6% and 93.5%, respectively. The 1-year actual incidences of infectious complication and surgical complication were near zero and 1 case (0.5%), respectively. In 1 recipient, the PTFE graft penetrated into the stomach wall 6 months after transplantation, but the patient did not complain of any specific symptoms. The PTFE graft was removed with the use of laparotomy, and the patient recovered uneventfully.nnnCONCLUSIONSnAlthough the incidence of PTFE graft-associated complication rate is very low, we suggest that it is necessary to closely monitor the PTFE graft, because unexpected complications can happen during long-term follow-up.

Long-term survival analysis of liver transplantation for hepatocellular carcinoma with bile duct tumor thrombus.

BACKGROUNDnLong-term prognosis of liver transplantation (LT) for hepatocellular carcinoma (HCC) with macroscopic bile duct tumor thrombus (BDTT) has not been well assessed. This study intended to analyze the post-transplantation outcomes in patients who had HCC with macroscopic BDTT.nnnMETHODSnA retrospective study was performed with 14 patients who underwent LT for HCC with BDTT (0.7%) after selection from an institutional database of 2052 adult LT cases.nnnRESULTSnTypes of LT were living donor LT in 13 and deceased donor LT in 1. The extents of BDTT were Ueda type 1 in 4, type 2 in 3, and type 3 in 7. Milan criteria were met in 8 (57.1%). Concurrent bile duct resection was performed in 7 (50%). Mean model for end-stage liver disease score was 18.7 ± 4.9. Mean graft-recipient weight ratio was 1.2 ± 0.3. There was one case of perioperative mortality and one case of HCC-unrelated late mortality. Cumulative HCC recurrence rates were 15.4% at 1 year, 46.2% at 3 years, and 46.2% at 5 years. Overall patient survival rates were 92.9% at 1 year, 57.1% at 3 years, and 50% at 5 years. Univariate risk factor analyses revealed that only macrovascular invasion was a significant risk factor for HCC recurrence (Pxa0= .019).nnnCONCLUSIONSnThe results of this study revealed that LT for HCC with macroscopic BDTT has a high risk of post-transplantation HCC recurrence; therefore, further large-volume studies are necessary to elucidate the risk factors.

External Biliary Drainage in Living Donor Liver Transplantation Using Duct-to-Duct Anastomosis

PURPOSEnThis study compared the incidence of biliary complication (BC) in adult living donor liver transplant recipients who underwent right-lobe duct-to-duct anastomosis (DDA) with or without external biliary drainage (EBD) and intended to optimize EBD tube clamping.nnnMETHODSnThis study consisted of a retrospective assessment of EBD effect and a prospective trial for EBD tube-clamping optimization. The retrospective study included the EBD group (nxa0= 208) and the non-EBD group (nxa0= 145). The prospective study included 60 patients with EBD.nnnRESULTSnIn the retrospective study, single DDA was performed in 83.7% of the EBD group and 80.7% of the non-EBD group (Pxa0= .47). One-year overall incidence of BC was 14.4% in the EBD group and 16.8% in the non-EBD group (Pxa0= .48). The incidence of early anastomotic bile leakage was 1.0% in the EBD group and 4.8% in the non-EBD group (Pxa0= .036). In the prospective study, there was no difference in tube-clamping success rates between low- and high-output EBD groups. There was also no statistical difference between the success and failure groups in terms of graft duct size, liver function tests, and post-transplant days at tube clamping.nnnCONCLUSIONSnThe size of our EBD tube was too small for the graft duct size, therefore itsxa0main role appeared to be early biliary decompression, which helped prevent bile leakage and also simplified the route of cholangiogram in detecting early BC. Hence, EBD is worthy of performing in selected patients with a high risk of anastomotic bile leak.

A Pilot Study on the Safety and Efficacy of Generic Mycophenolate Agent as Conversion Maintenance Therapy in Stable Liver Transplant Recipients

PURPOSEnThe patent covering mycophenolate mofetil (MMF) in Korea has expired and, thus, several generic MMF agents are now commercially available. The supply of Cellcept (Roche Korea) was interrupted at the end of 2011, so it was inevitable that a generic MMF would be used instead. During this period, we performed a prospective pilot study to examine the safety and efficacy of a generic mycophenolate agent (Myconol: Hanmi Pharmaceutical, Seoul Korea) for use as conversion maintenance therapy in stable liver transplantation (OLT) recipients.nnnMETHODSnOLT recipients, who were treated with MMF on an outpatient basis from January 2012 to March 2012, attended follow-up interviews conducted. The patients had undergone OLTxa0≥ 2 years before the study, had tolerated Cellcept, and showed stable liver function. Fifty-three patients were followed up for more than 3 months after conversion to the same dose of Myconol.nnnRESULTSnAfter conversion to Myconol, 6 patients (11.3%) experienced new side effects, which disappeared when they reverted to Cellcept (nxa0= 5) or stopped taking Myconol medication (nxa0= 1). The side effects associated with Myconol included gastrointestinal symptoms (indigestion and diarrhea; nxa0= 3), skin eruptions (nxa0= 1), pruritus (nxa0= 1), and insomnia (nxa0= 1). The mean mycophenolic acid levels were 1.71 ± 0.88 μg/mL for Cellcept and 1.83 ± 0.91 μg/mL for Myconol, which showed a strong correlation (r(2)xa0= 0.92, Pxa0< .001).nnnCONCLUSIONSnMyconol showed similar pharmacokinetics to those of Celcept, but a small proportion of patients experienced agent-specific side effects; therefore, patients should be closely monitored when taking Myconol. Also, further studies, with a greater number of patients, are required to identify the full spectrum of drug-associated side effects.

Post-Transplant Assessment of Consciousness in Acute-on-Chronic Liver Failure Patients Undergoing Liver Transplantation Using Bispectral Index Monitoring

PURPOSEnDeterioration of consciousness is a critical situation for liver transplantation (OLT) recipients. The bispectral (BIS) index based on electroencephalographic parameters, is primarily used to monitor the depth of unconsciousness. The present study sought to assess the usefulness of posttransplant BIS index to monitor acute-on-chronic liver failure patients.nnnMETHODSnThis 1-year retrospective study of 28 adult patients with acute-on-chronic liver failure was performed from July 2011 to June 2012, using post-transplant BIS monitoring.nnnRESULTSnThe mean patient age was 51 ± 8 years. Their mean pretransplant Child-Turcotte-Pugh score was 12.3 ± 1.4, and the mean Model for End-stage Liver Disease score, 36.4 ± 5.9. After OLT, the mean initial Glasgow Coma Scale (GCS) score and BIS index were 3.4 ± 1.7 and 43.5 ± 9.1, respectively. After 6 hours the mean GCS and BIS values rose to 8.6 ± 4.0 and 52.4 ± 10.3 and after 12 hours to 9.7 ± 3.4 and 61.3 ± 15.7 respectively. Eye opening in response to a voice occurred at a mean of 8.9 ± 6.7 hours after arrival in the intensive care unit regardless of graft function. The mean GCS and BIS values were 10.6 ± 2.8 and 69.1 ± 13.5, respectively. The endotracheal tube was removed after a median of 140 hours; 9 patients required a tracheostomy. Among them 2 died within the first 3 months after OLT.nnnCONCLUSIONSnBIS monitoring is a noninvasive, simple, easy-to-interpret method to measure consciousness among patients intubated with an endotracheal tube.

Long-term survival outcomes for living donor liver transplant recipients with pathologically nonviable hepatocellular carcinoma.

PURPOSEnComplete necrosis of hepatocellular carcinoma (HCC) lesions has occasionally been found by explant pathology after pretransplant neoadjuvant treatment. This study sought to investigate the long-term prognostic effect of loss of tumor viability after HCC treatment in living donor liver transplant (LDLT) recipients.nnnMETHODSnWe reviewed retrospectively the 5-year records of 37 patients who demonstrated nonviable HCC on explant pathology.nnnRESULTSnThe most common primary disease was hepatitis-B-virus-associated liver cirrhosis (nxa0= 34). Single explant tumors were found in 29 patients; the mean maximal tumor size was 2.1 ± 0.9 cm (range: 0.8-4.0). No patients showed microvascular invasion. The median level of alpha-fetoprotein was 12 ng/mL (range: 1-1160). The 1 patient who showed a recurrence at 20 months remains alive more than 6 years after adrenalectomy and repeated pulmonary metastasectomy. The 5-year HCC recurrence rate was thus 2.1%. There were 2 late mortalities, each due to graft failure and recurrent gastric cancer. The overall patient survival rate was 97.3% at 5 and 92.7% at 10 years.nnnCONCLUSIONSnThe results of this study revealed that the loss of tumor viability induced by pretransplant neoadjuvant treatment definitely decreased the risk of post-transplant HCC recurrence. Therefore, patients with nonviable HCC can be regarded as members of a superselect group with minimal risk for HCC recurrence, and may be exempted from routine HCC screening.