Eunkyoung Jwa

Adult Living Donor Liver Transplantation for Acute-on-Chronic Liver Failure in High–Model for End-Stage Liver Disease Score Patients

The large volume of adult living donor liver transplantations (ALDLTs) at our center affords a unique opportunity to examine the impact of acute‐on‐chronic liver failure (ACLF) among high–Model for End‐Stage Liver Disease MELD score patients. From February 1998 to March 2010, 1958 cirrhotic recipients were analyzed to study the relationship between MELD scores and ALDLT outcomes. A total of 327 high‐MELD score recipients were categorized into ACLF and non‐ACLF groups, and their outcomes were compared. The 5‐year graft and patient survival in the high‐MELD group were 75.2% and 76.4%, respectively, which were significantly worse than the low and intermediate MELD groups. The presence of ACLF associated with higher MELD scores appeared to be the dominant factor responsible for the inferior results of patients with MELD score of 30–34 points. The 5‐year graft survivals in the ACLF group was 70.5% and in the non‐ACLF group it was 81.0% (p = 0.035). Therefore, ALDLT should be performed as soon as possible in high‐MELD score patients prior to ACLF development. Moreover, ACLF patients should be separately categorized when analyzing the outcomes of ALDLT. ALDLT for ACLF patients should not be discouraged because favorable outcomes can be expected through timely ALDLT and comprehensive management.

Antitumor effect of sorafenib and mammalian target of rapamycin inhibitor in liver transplantation recipients with hepatocellular carcinoma recurrence

Both sorafenib and mammalian target of rapamycin inhibitor (mTORi) have antitumor effects. This study aimed to evaluate their antitumor effects in liver transplantation (LT) recipients with hepatocellular carcinoma (HCC) recurrence. We performed a laboratory study using sorafenib and mTORi and subsequently validated their survival benefit in a clinical LT setting. In the laboratory study, the HepG2.2.15 liver tumor cell line and 5 patient‐derived graft HCC cell lines were used for in vitro cytotoxic studies. After treatment with everolimus and sorafenib, cell viability and apoptosis assays revealed noticeable cytotoxic effects with individual agents and augmented effects by combination therapy. An in vivo mouse study also demonstrated similar cytotoxic outcomes. In the clinical study including 232 LT recipients with HCC recurrence, the 3‐month medication drop‐out rate was 35.6% for sorafenib administration and 23.5% for mTORi administration. Postrecurrence survival rates were not different according to sorafenib administration (P = 0.17) but were significantly improved following mTORi administration (P < 0.001). In mTORi subgroups with and without sorafenib, there was no difference in the overall postrecurrence patient survival period (P = 0.26), indicating an absence of synergistic or additional antitumor effect from sorafenib. The median progression‐free and overall survival period was 6.4 and 11.8 months, respectively, after sorafenib administration. Time of tumor recurrence and use of mTORi were independent risk factors. In conclusion, our laboratory study demonstrated synergistic antitumor effects of sorafenib and mTORi, but this was not reproduced in our clinical LT study. Our clinical result of mTORi administration showed improved postrecurrence survival, thus administering mTORi in LT recipients with HCC recurrence appears worthwhile. However, the antitumor effect of sorafenib on posttransplant recurrence was not determined in this retrospective study, thus requiring further studies with early start of sorafenib administration. Liver Transplantation 24 932–945 2018.

Dual-graft adult living donor liver transplantation with ABO-incompatible graft: short-term and long-term outcomes

ABO‐incompatible (ABOi) dual‐graft (DG) adult living donor liver transplantation (ALDLT) is not commonly performed due to its inherently intricate surgical technique and immunological complexity. Therefore, data are lacking on the short‐ and long‐term clinical outcomes of ABOi DG ALDLT. We performed a retrospective study by reviewing the medical records of patients who underwent ABOi DG ALDLT between 2008 and 2014. Additionally, computed tomography volumetric analysis was conducted to assess the graft regeneration rate. The mean age of a total of 28 recipients was 50.2 ± 8.5 years, and the mean model for end‐stage liver disease score was 12.2 ± 4.6. The 1‐, 3‐, and 5‐year patient survival rate was 96.4% during the mean follow‐up period of 57.0 ± 22.4 months. The 1‐, 3‐, and 5‐year graft survival rate was 96.4%, 94.2%, and 92.0%, respectively, and no significant differences were observed between ABO‐compatible (ABOc) and ABOi grafts (P = .145). The biliary complication rate showed no significant difference (P = .195) between ABOc and ABOi grafts. Regeneration rates of ABOi grafts were not significantly different from those of ABOc grafts. DG ALDLT with ABOi and ABOc graft combination seems to be a feasible option for expanding the donor pool without additional donor risks.

Extended pancreatic transection for secure pancreatic reconstruction during pancreaticoduodenectomy

Backgrounds/Aims Pancreaticoduodenectomy (PD) is associated with various surgical complications including healing failure of the pancreaticojejunostomy (PJ). This study intended to ensure blood supply to the pancreatic stump through extended pancreatic transection (EPT). Methods This study assessed whether EPT reduces PJ-associated complications and whether EPT is harmful on the remnant pancreatic function. The EPT group included 19 patients undergoing PD, pylorus-preserving PD (PPPD) or hepatopancreaticoduodenectomy. The propensity score matched control group included 45 patients who had undergone PPPD. Pancreatic transection was performed at the level of the celiac axis in the EPT group, by which the pancreatic body was additionally removed by 3 cm in length comparing with the conventional pancreatic transection. Results A small invagination fissure suspected as the embryonic fusion site was identified at the ventro-caudal edge of the pancreatic body in all patients undergoing EPT. A sizable fissure permitting easy separation of the pancreatic parenchyma was identified in 15 of 19 patients (78.9%). The incidence of significant postoperative pancreatic fistula was significantly lower in the EPT group than in the control group (p=0.047). There was no significant increase in the postoperative de novo diabetes mellitus in EPT group (p=0.60). Conclusions The EPT technique contributes to the prevention of major pancreatic fistula without impairing remnant pancreatic function. EPT is feasible for routine clinical application or at least in patients with any known risk of PJ leak.

Successful introduction of Model for End-stage Liver Disease scoring in deceased donor liver transplantation in Korea: analysis of first 1 year experience at a high-volume transplantation center

Backgrounds/Aims Model for End-stage Liver Disease (MELD) score was adopted in June 2016 in Korea. Methods We analyzed changes in volumes and outcomes of deceased donor liver transplantation (DDLT) for 1 year before and after introduction of MELD scoring at Asan Medical Center. Results There were 64 cases of DDLT in 1 year before MELD introduction and 106 in 1 year after MELD introduction, an increase of 65%. The volume of DDLTs abruptly increased during first 3 months, but then returned to its usual level before MELD introduction, which indicated 3-month depletion of accumulated recipient pool with high MELD scores. The number of pediatric DDLT cases increased from 3 before MELD introduction to 11 after it, making up 21.4% and 47.8% of all cases of pediatric liver transplantation, respectively. The number of cases of retransplanted DDLTs increased from 4 to 27, representing 6.3% and 25.5% of all DDLT cases, respectively. The number of status 1 DDLT cases increased from 5 to 12, being 7.8% and 11.3% of all cases. Patient survival outcomes were similar before and after MELD introduction. Conclusions The number of DDLTs temporarily increased after adoption of MELD scoring due to accumulated recipient pool with high MELD scores. The numbers of retransplanted and pediatric DDLT cases significantly increased. Patient survival in adult and pediatric DDLT was comparable before and after adoption of MELD scoring. These results imply that Korean MELD score-based allocation system was successfully established within its first year.

Clinicopathological features and post-resection outcomes of biliary cystadenoma and cystadenocarcinoma of the liver

Backgrounds/Aims Biliary cystadenoma (BCA) and biliary cystadenocarcinoma (BCAC) account for 5%-10% of liver cystic diseases. In this study, we analysed the clinical presentation and surgical management of patients with BCA and BCAC. Methods We retrospectively analysed the medical records of 23 BCA and 7 BCAC cases diagnosed between January 2007 and December 2013. Results There was a statistically significant difference in age (p=0.044) and sex (p=0.048) between BCA and BCAC groups. In the BCA group, 17 patients showed no symptoms (74%), 5 had abdominal pain (22%) and 1 showed abdominal distension (4%). In the BCAC group, two patients were without any symptoms (29%), three had abdominal pain (43%), one showed abdominal distension (14%) and one had fever and chills (14%). The cystic lesion size was widely variable; thus, there was no statistical difference (p=0.84). Complete resection was performed in all patients with BCA and BCAC. No tumour recurrence developed in patients with BCA. In patients with BCAC, 1-, 3- and 5-year disease-free survival rates were 100%, 85.7% and 57.1%, respectively, and 1-, 3- and 5-year overall patient survival rates were 100%, 100% and 75.0%, respectively. Conclusions It is difficult to distinguish between BCA and BCAC via clinical manifestations and diagnostic imaging findings. Surgical resection is the treatment of choice for BCA and BCAC, and patient prognosis after complete resection was very favourable.

In vitro immune cell monitoring as a guide for long-term immunosuppression in adult liver transplant recipients

Backgrounds/Aims We evaluated the clinical usability of immune cell monitoring in adult liver transplantation (LT) recipients. Methods This study was composed of two parts as using calcineurin phosphatase (CNP) activity assay and ImmuKnow assay independently as in vitro monitoring tools of immune cell function in adult LT recipients. Results There was a rough correlation between CNP activity and tacrolimus concentration in 33 patients. This association was evident in patients who were only administered tacrolimus, but disappeared after the co-administration of mycophenolate. In 118 healthy individuals, the mean proportion of helper T-cells was 37.4±8.1%. According to ImmuKnow assay, their immune responses were strong in 12 patients (10.2%), moderate in 92 patients (78.0%), and low in 14 patients (11.9%). In 85 patients waiting for LT, there was a rough correlation between the ImmuKnow ATP level and age. Their immune responses were strong in 0 patients (0%), moderate in 8 patients (9.4%), and low in 77 patients (90.6%). There was a difference in the ImmuKnow ATP levels between healthy individuals and patients with liver disease. In 137 LT recipients, there was no correlation between the ImmuKnow ATP levels and tacrolimus concentration. This trend did not change after grouping the patients according to co-administration with mycophenolate. Eight recipients experienced acute rejection, but none showed strong immune response. Conclusions We think that both CNP activity assay and ImmuKnow assay are too limited to objectively determine the level of immunosuppression. Further studies should be performed to identify other methods for immune function monitoring.