Publications by authors named "Woo-Hyoung Kang"

23 Publications

  • Page 1 of 1

Efficacy and Safety Evaluation After Conversion From Twice-Daily to Once-Daily Tacrolimus in Stable Liver Transplant Recipients: A Phase 4, Open-Label, Single-Center Study.

Transplant Proc 2021 Nov 11. Epub 2021 Nov 11.

Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background: Simplifying immunosuppressive therapy after liver transplant may improve patient compliance, thereby preventing acute rejection and graft loss. This phase 4, open-label, single-center study was conducted to evaluate the efficacy and safety of twice-daily to once-daily tacrolimus conversion in stable liver transplant recipients.

Methods: Between May 2017 and January 2019, twice-daily tacrolimus was converted to once-daily tacrolimus in 101 stable recipients at least 12 months post-liver transplant in Asan Medical Center. The doses of both drugs was converted to 1:1, and the target trough level was 5 to 10 ng/mL. We prospectively analyzed graft function, drug compliance, and adverse reactions after switching regimen for 24 weeks.

Results: There was no acute rejection confirmed histologically within 24 weeks, which was the primary endpoint, and there was no chronic rejection, fatal deterioration of liver function, or death in any patient during this period. After conversion, the trough level of tacrolimus decreased, and the mean ± standard deviation differences between the trough level and baseline level were 1.46 (±2.41) ng/mL, 0.43 (±2.08) ng/mL, and 0.07 (±2.73) ng/mL at 3, 12, and 24 weeks after conversion, respectively. Despite transient fluctuations of the trough level, there was no evidence of rejection or graft dysfunction. There were 37 adverse reactions after conversion; most of them were mild, and thrombocytopenia developed in 1 patient as an adverse drug response. Drug compliance improved after conversion according to questionnaire responses.

Conclusions: The conversion to once-daily tacrolimus in stable liver transplant recipients is an effective and safe therapeutic strategy improving drug compliance.
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http://dx.doi.org/10.1016/j.transproceed.2021.09.043DOI Listing
November 2021

Salvage living donor liver transplantation versus repeat liver resection for patients with recurrent hepatocellular carcinoma and Child-Pugh class A liver cirrhosis: A propensity score-matched comparison.

Am J Transplant 2021 Aug 12. Epub 2021 Aug 12.

Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.

Following curative liver resection (LR), resectable tumor recurrence in patients with preserved liver function leads to deciding between a repeat LR and a salvage liver transplantation (LT), if a donor's liver is available. This retrospective study compared survival outcomes and recurrence pattern following salvage living donor LT (LDLT) and repeat LR in patients with recurrent hepatocellular carcinoma (HCC). We reviewed the medical records of patients who underwent repeat LR (n = 163) or LDLT (n = 84) for recurrent HCC following curative resections, between January 2005 and December 2017 at a single institution. A 1:1 propensity score matching led to 42 patients per group. Disease-specific and recurrence-free survival were significantly better in the salvage LDLT group than in the repeat LR group (p = .042; HR = 2.40; 95% CI, 0.69-6.00 and p < .001; HR = 4.23; 95% CI, 2.05-8.71, respectively). Despite significant differences in recurrence patterns between the two groups (p = .019), the patient death rates, after recurrence, were similar for both groups (p = .760). This study indicates that salvage LDLT is superior to repeat LR for treating patients with transplantable, intrahepatic HCC recurrence, even in patients with Child-Pugh class A liver cirrhosis.
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http://dx.doi.org/10.1111/ajt.16790DOI Listing
August 2021

Should we be reluctant to perform pancreatectomy in patients with chronic liver disease? A single center 10-year experience.

Acta Chir Belg 2021 Aug 16:1-7. Epub 2021 Aug 16.

Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Korea University College of Medicine, Seoul, Korea.

Purpose: Many studies have shown extra-hepatic surgery in patients with chronic liver disease (CLD) with or without portal hypertension can result in complications. The aim of this study was to analyze the results of major pancreatectomy in patients with CLD including cirrhosis and to evaluate their efficacy and safety.

Methods: We retrospectively reviewed 319 patients undergoing open pancreatoduodenectomy (PD) or distal pancreatectomy (DP) in our center. Those who received PD and DP in patients without CLD were classified into groups A and D, and those with CLD into groups B and C, respectively. Group B and C were subdivided into groups 1 and 2 according to the presence of portal hypertension.

Results: Forty-three patients (13.5%) had CLD. Of the 221 patients who received PD, 25 had CLD. Of the 98 patients who received DP, 18 (Group C) had CLD. In the PD group, patients with portal hypertension (group B1) had longer operative time. However, the transfusion rate and complication rate were not significantly different from other groups. There was no mortality in patients with CLD without portal hypertension (group B2) and the complication and mortality rate was comparable to patients with normal liver function (group A). In the DP group, the transfusion rate, complication rate and mortality rate were significantly higher in patients with portal hypertension (group C1).

Conclusions: Acceptable outcomes were obtainable following pancreatic surgery in cirrhotic, non-portal hypertensive patients with surgical outcomes equivalent to non-cirrhotic patients.
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http://dx.doi.org/10.1080/00015458.2021.1963911DOI Listing
August 2021

Fates of retained hepatic segment IV and its prognostic impact in adult split liver transplantation using an extended right liver graft.

Ann Surg Treat Res 2021 Jul 30;101(1):37-48. Epub 2021 Jun 30.

Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Purpose: When splitting a liver for adult and pediatric graft recipients, the retained left medial section (S4) will undergo ischemic necrosis and the right trisection graft becomes an extended right liver (ERL) graft. We investigated the fates of the retained S4 and its prognostic impact in adult split liver transplantation (SLT) using an ERL graft.

Methods: This was a retrospective analysis of 25 adult SLT recipients who received split ERL grafts.

Results: The mean model for end-stage liver disease (MELD) score was 27.3 ± 10.9 and graft-recipient weight ratio (GRWR) was 1.98 ± 0.44. The mean donor age was 26.5 ± 7.7 years. The split ERL graft weight was 1,181.5 ± 252.8 g, which resulted in a mean GRWR of 1.98 ± 0.44. Computed tomography of the retained S4 parenchyma revealed small ischemic necrosis in 16 patients (64.0%) and large ischemic necrosis in the remaining 9 patients (36.0%). No S4-associated biliary complications were developed. The mean GRWR was 1.87 ± 0.43 in the 9 patients with large ischemic necrosis and 2.10 ± 0.44 in the 15 cases with small ischemic necrosis (P = 0.283). The retained S4 parenchyma showed gradual atrophy on follow-up imaging studies. The amount of S4 ischemic necrosis was not associated with graft (P = 0.592) or patient (P = 0.243) survival. A MELD score of >30 and pretransplant ventilator support were associated with inferior outcomes.

Conclusion: The amount of S4 ischemic necrosis is not a prognostic factor in adult SLT recipients, probably due to a sufficiently large GRWR.
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http://dx.doi.org/10.4174/astr.2021.101.1.37DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255581PMC
July 2021

Third retransplantation using a whole liver graft for late graft failure from hepatic vein stent stenosis in a pediatric patient who underwent split liver retransplantation.

Ann Hepatobiliary Pancreat Surg 2021 May;25(2):299-306

Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

We present a case of third retransplantation using a whole liver graft in a 13-year-old girl who suffered graft failure and hepatopulmonary syndrome following split liver retransplantation with endovascular stenting of the hepatic and portal veins as an infant. She was diagnosed with biliary atresia-polysplenia syndrome, and thus underwent living donor liver transplantation from her mother at 9 months of age. The first liver graft failed due to stenosis of the portal vein. She underwent the second liver transplantation with a split left lateral section graft. Endovascular stenting was performed to the portal vein stenosis 2 months and hepatic vein stenosis 9 months after transplantation. During the next 9 years, 11 sessions of balloon angioplasty for hepatic vein stent stenosis were performed. Ten years after the second transplantation, she underwent third transplantation using a whole liver graft recovered from a 12-year-old-girl. The double inferior vena cava technique was used for outflow vein reconstruction. The graft portal vein was anastomosed with the stent-containing portal vein stump because it was not possible to remove the stent and the inner diameter of the portal vein stent was large enough. An aorto-hepatic jump graft was used for arterial reconstruction. The patient recovered slowly and is doing well for 6 months posttransplant. In conclusion, because stenting of the hepatic vein or portal vein can induce graft failure leading to late retransplantation, we emphasize secure vascular reconstruction to prevent endovascular stenting during LT in infants.
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http://dx.doi.org/10.14701/ahbps.2021.25.2.299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180402PMC
May 2021

Application of Proximal Splenic Vein Embolization to Interrupt Complicated Large Splenorenal Shunts in Adult Living Donor Liver Transplantation.

Ann Surg 2021 Mar 29. Epub 2021 Mar 29.

*Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea †Division of Intervention Radiology, Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Objective: The aim of present study is to evaluate efficacy and safety of proximal splenic vein embolization (PSVE) for liver transplant recipients having complicated large splenorenal shunts (SRS).

Background: In adult living donor liver transplantation (ALDLT) for a patient who has large splenorenal shunts (SRS), their interruption is utmost important to maintain adequate portal flow by avoidance of portal flow steal through the preexisting SRS. We effectively managed most of the recipients with surgical ligation and/or additional radiologic embolization using by intraoperative cine-portogram (IOP). However, when complete interruption is not achieved in a few recipients having complicated large SRS, it may leave a chance of lethal portal flow steal in the recipient afterwards.

Methods: PSVE was performed in 13 patients between April 2014 and November 2017. We performed a retrospective analysis of preoperative images, postoperative graft and recipient outcomes, and presence of isolated portal hypertension.

Results: Ten patients underwent PSVE as an additional secondary method because of for portal steal syndrome through the remaining SRS after surgical interruption and/or embolization, and 3 patients underwent PSVE only as a primary method of SRS interruption. In all 13 patients, portal steal on the final IOP completely disappeared after PSVE All patients recovered with satisfactory regeneration of the partial liver graft without the reappearance of portosystemic collaterals, and there were no procedure-related complications.

Conclusions: PSVE is an effective and safe procedure to secure adequate portal flow without portal steal for patients with complicated large SRS arising from multiple sites of the splenic vein or escaping to multiple terminal ends.
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http://dx.doi.org/10.1097/SLA.0000000000004868DOI Listing
March 2021

National survey of Korean hepatobiliary-pancreatic surgeons on attitudes about the enhanced recovery after surgery protocol.

Ann Hepatobiliary Pancreat Surg 2020 Nov;24(4):477-483

Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Backgrounds/aims: The purpose of this study was to investigate attitudes regarding the Enhanced Recovery After Surgery (ERAS) protocol of hepato-biliary-pancreatic (HBP) surgeons in Korea and the extent to which they use the protocol for perioperative management.

Methods: An online survey was conducted among members of the Korean Association of Hepato-Biliary-Pancreatic Surgery (KAHBPS) for eight weeks beginning on August 2019. The questionnaire, which was written in Korean, was based on the latest ERAS guidelines. Total responses were collected from 127 surgeons.

Results: Of the 127 total respondents, the largest proportion (44.9%) were working in Seoul. In terms of established in-hospital clinical pathways (CP), 19.7% of the participating surgeons had and followed a CP in pancreaticoduodenectomy (PD) and 21.3% in hepatectomy. Regarding the ERAS protocol for each surgery, four items (18.2%) regarding PD and seven items (35.0%) related to hepatectomy were followed by more than 50% of respondents.

Conclusions: ERAS guidelines are one of the consensuses for better recovery in perioperative management of patients undergoing major surgeries and encompass the overall process of patient recovery including patient education, pain control, physiologic balance, and perioperative nutrition. A novel project is needed to successfully implement an evidence-based enhanced recovery strategy.
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http://dx.doi.org/10.14701/ahbps.2020.24.4.477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691206PMC
November 2020

Over 500 Liver Transplants Including More Than 400 Living-Donor Liver Transplants in 2019 at Asan Medical Center.

Transplant Proc 2021 Jan-Feb;53(1):83-91. Epub 2020 Oct 1.

Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background: More than 400 liver transplants were performed at Asan Medical Center (AMC) in 2011, and over 500 liver transplants including 420 living-donor liver transplants (LDLTs) were performed in 2019. Herein, we report the methodology of these procedures.

Methods: Since the first adult LDLTs at AMC using the left and right lobes were successfully performed, various innovative techniques and approaches have been developed: modified right lobe, dual graft, donor exchange for ABO incompatibility, expansion of indications and no-touch techniques for hepatocellular carcinoma, intraoperative cine-portogram and additional intervention for large collaterals, management of portal vein thrombosis (PVT) and stenosis, salvage LDLT after major hepatectomy, and timely LDLT for patients with acute-on-chronic liver failure.

Results: Four hundred twenty LDLTs in 403 adult and 17 pediatric patients and 85 deceased-donor liver transplants in 74 adult and 11 pediatric patients were performed. The number of deceased-donor liver transplants remained constant since 2011, but the number of LDLTs increased steadily. One hundred thirty patients (25.7%) required urgent liver transplantations and 24 patients with acute-on-chronic liver failure underwent LDLT. PVT including grade 1,2,3, and 4 was reported in 91 patients (18.0%), and Yerdel's grade 2, 3, and 4 PVT was reported in 47 patients (51.6%); all patients with PVT were successfully treated. Adult LDLTs for hepatocellular carcinoma and ABO incompatibility accounted for 52.6% and 24.3% of the cases, respectively. In-hospital mortality in 2019 was 2.97%.

Conclusion: Continual efforts to overcome challenging problems in LDLT with various innovations and dedication of the team members during the perioperative period to improve patient outcomes were crucial in increasing the number of liver transplantations at Asan Medical Center.
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http://dx.doi.org/10.1016/j.transproceed.2020.08.027DOI Listing
April 2021

Prognosis of Split Liver Transplantation Compared with Whole Liver Transplantation in Adult Patients: Single-center Results under the Korean MELD Score-based Allocation Policy.

J Korean Med Sci 2020 Sep 21;35(37):e304. Epub 2020 Sep 21.

Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background: Split liver transplantation (SLT) has been occasionally performed in Korea. This study compared the incidence and prognosis of SLT with whole liver transplantation (WLT) in adult patients.

Methods: Between June 2016 and November 2019, 242 adult patients underwent a total of 256 deceased donor liver transplantation operations. SLT was performed in 7 patients (2.9%).

Results: The mean age of SLT donors was 29.7 ± 7.4 years, and the mean age of recipients was 55.7 ± 10.6 years, with the latter having a mean model for end-stage liver disease score of 34.6 ± 3.1. Mean split right liver graft weight was 1,228.6 ± 149.7 g and mean graft-recipient weight ratio was 1.97 ± 0.39. Of the seven SLT recipients, Korean Network for Organ Sharing (KONOS) status was one in status 1, one in status 2 and five in status 3. The graft ( = 0.72) and patient ( = 0.84) survival rates were comparable in the SLT and WLT groups. Following propensity score matching, graft ( = 0.61) and patient ( = 0.91) survival rates remained comparable in the two groups. Univariate analysis showed that pretransplant ventilator support and renal replacement therapy were significantly associated with patient survival, whereas KONOS status category and primary liver diseases were not. Multivariate analysis showed that pretransplant ventilator support was an independent risk factor for patient survival.

Conclusion: Survival outcomes were similar in adult SLT and WLT recipients, probably due to selection of high-quality grafts and low-risk recipients. Prudent selection of donors and adult recipients for SLT may expand the liver graft pool for pediatric patients without affecting outcomes in adults undergoing SLT.
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http://dx.doi.org/10.3346/jkms.2020.35.e304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505731PMC
September 2020

Feasibility and safety of bisegmentectomy 7-8 while preserving hepatic venous outflow of the right liver - A retrospective cohort study.

Int J Surg 2020 Jul 6;79:273-279. Epub 2020 Jun 6.

Division of HBP Surgery and Liver Transplantation, Department of Surgery, Korea University College of Medicine, Seoul, South Korea. Electronic address:

Background: When a hepatic tumor is deeply located in segments 7 and 8 around the right hepatic vein (RHV), right hemihepatectomy (RH) could be excessive owing to the resection of large tumor-free segments. This study aimed to evaluate the feasibility and safety of bisegmentectomy 7-8 (S7-8) and to compare its surgical outcomes with those of RH.

Materials And Methods: Consecutive patients who underwent S7-8 and RH were enrolled in this study. In the S7-8 group, 14 patients with an obvious inferior right hepatic vein (IRHV) (median: 6 mm; range: 3.6-8.8 mm) underwent S7-8 without hepatic vein reconstruction. RHV reconstruction was performed in six patients without an IRHV, involving direct anastomosis of the RHV in five patients and reconstruction using a cryo-preserved iliac vein in one patient.

Results: A total of 61 patients were included (20 in S7-8 group; 41 in RH group). No significant differences were observed other than higher a model of end-stage liver disease score in the RH group than in the S7-8 group (7 [6-20] vs. 6 [6-9], P = 0.003). Post-hepatectomy liver failure including severe grades was more frequent in the RH group (43.9% vs. 10%, P = 0.008). In the S7-8 group, two patients with direct RHV reconstruction had RHV anastomosis obstruction, and eventually required insertion of a metallic stent. However, computed tomography performed 4 weeks after the operation showed intact venous outflow of the right liver in the S7-8 group.

Conclusion: S7-8 can be performed safely in selected patients with a thick IRHV. For patients with no obvious IRHV, RHV reconstruction could be a good surgical strategy to retain venous outflow of the right liver with feasible outcomes.
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http://dx.doi.org/10.1016/j.ijsu.2020.05.075DOI Listing
July 2020

Right-side versus left-side hepatectomy for the treatment of hilar cholangiocarcinoma: a comparative study.

World J Surg Oncol 2020 Jan 4;18(1). Epub 2020 Jan 4.

Division of HBP Surgery and Liver Transplantation, Department of Surgery, Korea University College of Medicine, 73, Goryedae-ro, Seongbuk-gu, Seoul, 02841, Korea.

Background: Radical resection is the only curative treatment for patients with hilar cholangiocarcinoma. While left-side hepatectomy (LH) may have an oncological disadvantage over right-side hepatectomy (RH) owing to the contiguous anatomical relationship between right hepatic inflow and biliary confluence, a small future liver remnant after RH could cause worse surgical morbidity and mortality. We retrospectively compared surgical morbidity and long-term outcome between RH and LH to determine the optimal surgical strategy for the treatment of hilar cholangiocarcinoma.

Methods: This study considered 83 patients who underwent surgical resection for hilar cholangiocarcinoma between 2010 and 2017. Among them, 57 patients undergoing curative-intent surgery including liver resection were enrolled for analysis-33 in the RH group and 27 in the LH group. Prospectively collected clinicopathologic characteristics, perioperative outcomes, and long-term survival were evaluated.

Results: Portal vein embolization was more frequently performed in the RH group than in the LH group (18.2% vs. 0%, P = 0.034). The proportion of R0 resection was comparable in both groups (75.8% vs. 75.0%, P = 0.948). The 5-year overall and recurrence-free survival rates did not differ between the groups (37.7% vs. 41.9%, P = 0.500, and 26.3% vs. 33.9%, P = 0.580, respectively). The side of liver resection did not affect long-term survival. In multivariate analysis, transfusion (odds ratio, 3.12 [1.42-6.87], P = 0.005) and post-hepatectomy liver failure (≥ grade B, 4.62 [1.86-11.49], P = 0.001) were independent risk factors for overall survival.

Conclusions: We recommend deciding the side of liver resection according to the possibility of achieving radical resection considering the anatomical differences between RH and LH.
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http://dx.doi.org/10.1186/s12957-019-1779-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942359PMC
January 2020

A Multicenter, Randomized, Open-Label Study to Compare Micafungin with Fluconazole in the Prophylaxis of Invasive Fungal Infections in Living-Donor Liver Transplant Recipients.

J Gastrointest Surg 2020 04 7;24(4):832-840. Epub 2019 May 7.

Department of Surgery, College of Medicine, Yonsei University, Seoul, South Korea.

Background: Although invasive fungal infections (IFIs) contribute to substantial morbidity and mortality in liver transplant recipients, only a few randomized studies analyzed the results of antifungal prophylaxis with echinocandins. The aim of this open-label, non-inferiority study was to evaluate the efficacy and safety of micafungin in the prophylaxis of IFIs in living-donor liver transplantation recipients (LDLTRs), with fluconazole as the comparator.

Methods: LDLTRs (N = 172) from five centers were randomized 1:1 to receive intravenous micafungin 100 mg/day or fluconazole 100~200 mg/day (intravenous or oral). A non-inferiority of micafungin was tested against fluconazole.

Results: The per-protocol set included 144 patients without major clinical trial protocol violations: 69 from the micafungin group and 75 from the fluconazole group. Mean age of the study patients was 54.2 years and mean model for end-stage liver disease (MELD) score amounted to 16.5. Clinical success rates in the micafungin and fluconazole groups were 95.65% and 96.10%, respectively (difference: - 0.45%; 90% confidence interval [CI]: - 6.93%, 5.59%), which demonstrated micafungin's non-inferiority (the lower bound for the 90% CI exceeded - 10%). The study groups did not differ significantly in terms of the secondary efficacy endpoints: absence of IFIs at the end of the prophylaxis and the end of the study, time to proven IFI, fungal-free survival, and adverse reactions. A total of 17 drug-related adverse events were observed in both groups; none of them was serious and all resolved.

Conclusion: Micafungin can be used as an alternative to fluconazole in the prevention of IFIs in LDLTRs.

Clinical Trials Registration: NCT01974375.
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http://dx.doi.org/10.1007/s11605-019-04241-wDOI Listing
April 2020

Once-daily, prolonged-release tacrolimus vs twice-daily, immediate-release tacrolimus in de novo living-donor liver transplantation: A Phase 4, randomized, open-label, comparative, single-center study.

Clin Transplant 2018 09 26;32(9):e13376. Epub 2018 Aug 26.

Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Randomized, open-label, comparative, single-center, Phase 4, 24-week study comparing pharmacokinetics (PK), safety, and efficacy of once-daily, prolonged-release tacrolimus (PR-T) with twice-daily, immediate-release tacrolimus (IR-T) in adult de novo living-donor liver transplant (LDLT) recipients in Korea. All patients received intravenous tacrolimus from Day 0 (transplantation) for 4 days and were randomized (1:1) to receive oral PR-T or IR-T from Day 5. PK profiles were taken on Days 6 and 21. Primary endpoint: area under the concentration-time curve over 24 hour (AUC ). Predefined similarity interval for confidence intervals of ratios: 80%-125%. Secondary endpoints included: tacrolimus concentration at 24 hour (C ), patient/graft survival, biopsy-confirmed acute rejection (BCAR), treatment-emergent adverse events (TEAEs). One-hundred patients were included (PR-T, n = 50; IR-T, n = 50). Compared with IR-T, 40% and 66% higher mean PR-T daily doses resulted in similar AUC between formulations on Day 6 (PR-T:IR-T ratio of means 96.8%), and numerically higher AUC with PR-T on Day 21 (128.8%), respectively. Linear relationship was similar between AUC and C , and formulations. No graft loss/deaths, incidence of BCAR and TEAEs similar between formulations. Higher PR-T vs IR-T doses were required to achieve comparable systemic exposure in Korean de novo LDLT recipients. PR-T was efficacious; no new safety signals were detected.
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http://dx.doi.org/10.1111/ctr.13376DOI Listing
September 2018

Long-term results of laparoscopic liver resection for the primary treatment of hepatocellular carcinoma: role of the surgeon in anatomical resection.

Surg Endosc 2018 11 24;32(11):4481-4490. Epub 2018 Apr 24.

Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

Background: Liver resection is a potentially curative therapy for hepatocellular carcinoma (HCC). LLR is a newly developed and safe technique associated with shorter hospital stay, less pain, better cosmetic outcomes, and similar complication rates as open surgery; however, data on its long-term outcomes remain scarce.

Methods: We retrospectively examined the clinical and follow-up data of 234 patients who underwent LLR (performed by a single surgeon in all cases) for the primary treatment of HCC between July 2007 and December 2015 at Asan Medical Center.

Results: The mean patient age was 55.63 (range 31-76) years; 167 were men. The median follow-up duration was 38 (range 6-116) months. A total of 227 patients (97.0%) had Child-Turcotte-Pugh grade A disease. Of them, 167 (71.4%) underwent anatomical resections and 63 (28.6%) underwent non-anatomical partial hepatectomies. Overall survival rates were 98.3, 91.7, and 87.1%, and recurrence-free survival rates were 82.1, 67.5, and 55.3% at 1, 3, and 5 years, respectively. In Cox regression analysis, anatomical resection was a risk factor for recurrence (univariate analysis: hazard ratio [HR] 0.49; 95% confidence interval [CI] 0.31-0.75; p = 0.001; multivariate analysis: HR 0.59; 95% CI 0.38-0.94; p = 0.025).

Conclusions: LLR is an acceptable primary treatment for patients with HCC with good hepatic function and with an appropriate anatomical structure, and is associated with improved prognosis. LLR can achieve lower recurrence rates through anatomical resection.
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http://dx.doi.org/10.1007/s00464-018-6194-0DOI Listing
November 2018

Metformin-associated Chemopreventive Effects on Recurrence After Hepatic Resection of Hepatocellular Carcinoma: From to a Clinical Study.

Anticancer Res 2018 04;38(4):2399-2407

Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Background/aim: We investigated metformin-induced cytotoxic effects in vitro and assessed the chemopreventive effects of metformin in patients undergoing hepatic resection (HR) for hepatocellular carcinoma (HCC).

Materials And Methods: This study consisted of laboratory and clinical studies.

Results: In vitro study using HCC cell lines revealed noticeable cytotoxic effects of metformin, that were largely weaker than those of sorafenib. In the clinical study, no statistical differences were found in tumor recurrence or overall survival between metformin and control groups. In contrast, there was a non-significant difference in tumor recurrence between metformin and propensity score-matched control groups, but there was a significant difference in overall patient survival. Metformin administration was an independent risk factor for patient survival.

Conclusion: In conclusion, our in vitro laboratory study demonstrated the presence of cytotoxic effects of metformin. Metformin administration was associated with reduced tumor recurrence and helped induce significant improvements in overall patient survival in patients who underwent HR for HCC.
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http://dx.doi.org/10.21873/anticanres.12490DOI Listing
April 2018

Outcome of ABO-incompatible adult living-donor liver transplantation for patients with hepatocellular carcinoma.

J Hepatol 2018 06 13;68(6):1153-1162. Epub 2018 Feb 13.

Division of Transplantation, Department of Surgery and Asan-Minnesota Institute for Innovating Transplantation, University of Minnesota, Minneapolis, MN, USA.

Background & Aims: Living-donor liver transplantation (LDLT) can simultaneously cure hepatocellular carcinoma (HCC) and underlying liver cirrhosis, improving long-term results in patients with HCC. ABO-incompatible LDLT could expand the living-donor pool, reduce waiting times for deceased-donor liver transplantation, and improve long-term survival for some patients with HCC.

Methods: We retrospectively reviewed the medical records of patients undergoing LDLT for HCC from November 2008 to December 2015 at a single institution in Korea. In total, 165 patients underwent ABO-incompatible and 753 patients underwent ABO-compatible LDLT for HCC. ABO-incompatible recipients underwent desensitization to overcome the ABO blood group barrier, including pretransplant plasma exchange and rituximab administration (300-375 mg/m /body surface area).

Results: We performed 1:1 propensity score matching and included 165 patients in each group. 82.4% of ABO-incompatible and 83.0% of -compatible LDLT groups had HCC within conventional Milan criteria, respectively, and 92.1% and 92.7% of patients in each group had a Child-Pugh score of A or B. ABO-incompatible and -compatible LDLT groups were followed up for 48.0 and 48.7 months, respectively, with both groups showing comparable recurrence-free survival rates (hazard ratio [HR] 1.14; 95% CI 0.68-1.90; p = 0.630) and overall patient-survival outcomes (HR 1.10; 95% CI 0.60-2.00; p = 0.763).

Conclusions: These findings suggested that ABO-incompatible liver transplantation is a feasible option for patients with HCC, especially for those with compensated cirrhosis with HCC within conventional Milan criteria.

Lay Summary: Despite hypothetical immunological concerns that the desensitization protocol for breaking through the ABO blood group barrier might have a negative impact on the recurrence of hepatocellular carcinoma, our experience demonstrated no significant differences in the long-term overall survival and recurrence-free survival rates between patients receiving ABO-compatible or ABO-incompatible liver transplantation. In conclusion, results from our institution indicated that ABO-incompatible living-donor liver transplantation constitutes a potentially feasible option for patients with hepatocellular carcinoma, especially those with compensated cirrhosis with hepatocellular carcinoma within conventional Milan criteria.
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http://dx.doi.org/10.1016/j.jhep.2018.02.002DOI Listing
June 2018

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.

Ann Hepatobiliary Pancreat Surg 2017 Nov 30;21(4):199-204. Epub 2017 Nov 30.

Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

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.
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http://dx.doi.org/10.14701/ahbps.2017.21.4.199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5736739PMC
November 2017

In Situ Split Liver Transplantation for 2 Adult Recipients: A Single-Center Experience.

Ann Transplant 2017 Apr 21;22:230-240. Epub 2017 Apr 21.

Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Background Material and Methods Results Conclusions.
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http://dx.doi.org/10.12659/AOT.902567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6248301PMC
April 2017

Prognostic effect of transarterial chemoembolization-induced complete pathological response in patients undergoing liver resection and transplantation for hepatocellular carcinoma.

Liver Transpl 2017 06;23(6):781-790

Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Transarterial chemoembolization (TACE)-induced complete pathological response (CPR) is known to improve postresection outcomes of hepatocellular carcinoma (HCC). We aimed to assess the prognostic effects of CPR after preoperative TACE for HCC in patients who underwent hepatic resection (HR) or liver transplantation (LT). The clinical outcomes of patients showing CPR after HR (n = 110) or LT (n = 233) were analyzed. The control groups comprised patients with minimal recurrence risk as naïve single HCC ≤ 2 cm for HR (n = 476), and 1 or 2 HCCs ≤ 2 cm for LT (n = 184). Among HR study patients, 1-, 3-, and 5-year tumor recurrence rates were 18.5%, 50.6%, and 58.7% respectively, which were higher than those of controls (P < 0.001). The 1-, 3-, and 5-year patient survival rates were 97.8%, 82.0%, and 69.1%, respectively, which were lower than those of controls (P < 0.001). Among LT study patients, 1-, 3-, and 5-year tumor recurrence rates were 4.1%, 7.9%, and 7.9%, respectively, which were higher than those of controls (P = 0.019). The 1-, 3-, and 5-year patient survival rates were 92.7%, 89.2%, and 86.9%, respectively, which were not different than those of controls (P = 0.11). LT recipients had lower recurrence and higher survival rates compared with HR patients (P < 0.001). The tumor recurrence site was mainly intrahepatic in HR patients. There was no difference between the incidences of extrahepatic recurrence in the HR study group and all-site recurrence in the LT study group (P = 0.61). We concluded that the prognostic effect of TACE-induced CPR for HCC patients appears to be limited to downstaging. LT recipients benefited more from CPR than HR patients. Liver Transplantation 23 781-790 2017 AASLD.
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http://dx.doi.org/10.1002/lt.24752DOI Listing
June 2017

Preoperative prognostic values of α-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) in patients with hepatocellular carcinoma for living donor liver transplantation.

Hepatobiliary Surg Nutr 2016 Dec;5(6):461-469

Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background: Adult living donor liver transplantation (LDLT) is one of the best treatments for hepatocellular carcinoma (HCC). However, when recurrence of HCC after LDLT occurs, the prognosis is poor because of rapid progression. Preoperative level of α-fetoprotein (AFP) and protein induced by vitamin K antagonist-II (PIVKA-II) reportedly correlate with recurrence of HCC after LDLT.

Methods: We examined AFP and PIVKA-II preoperatively as predictors of HCC recurrence in 461 patients who underwent LDLT using right liver graft for HCC from May 2007 to December 2013.

Results: Among these, 77 patients (16.7%) who experienced recurrence were retrospectively reviewed. Multivariate analysis revealed tumor size >5 cm, AFP >150 nag/mol and PIVKA-II >100 maul/mol as significant independent risk factors for recurrence. The median time to recurrence was 10 months. The median survival time after recurrence was 26 months, and the 1-, 3- and 5-year survival rates after recurrence were 80.5%, 58%, and 28.3% respectively.

Conclusions: Preoperatively, not only morphology of the tumor but also AFP and PIVKA-II levels can offers important information for the recurrence after LDLT for HCC. Thus, combination of tumor markers might be used for expansion of pre-existing strict selection criteria of liver transplantation for HCC.
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http://dx.doi.org/10.21037/hbsn.2016.11.05DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5218910PMC
December 2016

Clinicopathological Features and Prognosis of Intrahepatic Cholangiocarcinoma After Liver Transplantation and Resection.

Ann Transplant 2017 Jan 26;22:42-52. Epub 2017 Jan 26.

Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

BACKGROUND Intrahepatic cholangiocarcinoma (ICC) can be incidentally diagnosed after liver transplantation (LT). We investigated the clinicopathological features of LT recipients with ICC and compared prognosis with that of the control group. MATERIAL AND METHODS We identified 16 recipients with ICC in our institutional database. The propensity score-matched control group comprised 100 ICC patients who underwent hepatic resection (HR). RESULTS ICC incidence was 0.5% in all adult LT patients and 1.2% in adult recipients with primary liver cancer. Mean age was 58.0±4.8 years and 15 were male. All ICCs were diagnosed incidentally in the explanted livers. Mean ICC tumor diameter was 2.5±1.1 cm and 14 recipients had a single tumor. Tumor stages were I in 9, II in 5, and IV in 2. Concurrent second primary liver cancer was detected as hepatocellular carcinoma in 7 and combined hepatocellular carcinoma-cholangiocarcinoma in 1. Tumor recurrence and patient survival rates were 56.2% and 81.3% at 1 year and 78.1% and 52.4% at 5 years, respectively. Presence of second cancer did not affect tumor recurrence (p=0.959) or patient survival (p=0.737). All 3 patients with very early ICC did not show ICC recurrence. Compared with the control group, the tumor recurrence rate was higher after LT (p=0.024), but this difference disappeared after analysis was confined to recipients with ICC alone (p=0.121). Post-recurrence survival was not different after HR and LT (p=0.082). CONCLUSIONS ICC is rarely diagnosed after LT and half of such patients have second liver cancer. Post-transplant prognosis of ICC is poor except for very early ICC; thus, strict surveillance is mandatory.
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http://dx.doi.org/10.12659/aot.901504DOI Listing
January 2017

Longterm prognosis of combined hepatocellular carcinoma-cholangiocarcinoma following liver transplantation and resection.

Liver Transpl 2017 03;23(3):330-341

Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Ulsan College of Medicine, Seoul, South Korea.

Combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CC) is a rare disease. We investigated the clinicopathological features of cHCC-CC and compared the longterm outcomes following liver transplantation (LT) and hepatic resection (HR). We identified 32 LT patients with cHCC-CC through an institutional database search. The HR control group (n = 100) was selected through propensity score-matching. The incidence of cHCC-CC among all adult LT patients was 1.0%. Mean patient age was 53.4 ± 6.7 years, and 26 patients were male. Thirty patients had hepatitis B virus infection. All patients of cHCC-CC were diagnosed incidentally in the explanted livers. Mean tumor diameter was 2.5 ± 1.3 cm, and 28 patients had single tumors. Tumor stage was stage I in 23 and II in 9. Concurrent hepatocellular carcinoma (HCC) was detected in 12 patients with stage I in 5 and II in 7. Mean tumor diameter was 1.9 ± 1.2 cm, and 5 had single tumors. Tumor recurrence and survival rates were 15.6% and 84.4% at 1 year and 32.2% and 65.8% at 5 years, respectively. Patients with very early stage cHCC-CC (1 or 2 tumors ≤ 2.0 cm) showed 13.3% tumor recurrence and 93.3% patient survival rates at 5 years, which were significantly improved than those with advanced tumors (P = 0.002). Tumor recurrence and survival rates did not differ significantly between the LT and HR control groups (P = 0.22 and P = 0.91, respectively); however, postrecurrence patient survival did (P = 0.016). In conclusion, cHCC-CC is rarely diagnosed following LT, and one-third of such patients have concurrent HCC. The longterm posttransplant prognosis was similar following LT and HR. Very early cHCC-CC resulted in favorable posttransplant prognosis, thus this selection condition can be prudently considered for LT indication. Liver Transplantation 23 330-341 2017 AASLD.
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http://dx.doi.org/10.1002/lt.24711DOI Listing
March 2017

Portal vein stenting as a significant risk factor for biliary stricture in adult living donor liver transplantation.

Hepatobiliary Pancreat Dis Int 2016 Oct;15(5):480-486

Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43 gil, Songpa-gu, Seoul 05505, Korea.

Background: Although perioperative portal vein (PV) stent implantation is an effective treatment for steno-occlusive disease in adult living donor liver transplantation (LDLT) recipients, we experienced high incidence of biliary anastomotic strictures (BAS) after PV stenting. In this study, we sought to clarify the relation between BAS and PV stenting and to suggest the possible mechanism of BAS and measures to reduce its incidence.

Methods: We retrospectively analyzed 44 LDLT recipients who underwent PV stent implantation across the line of PV anastomosis regardless of the location of steno-occlusion (stent group) and their matched controls (non-stented LDLT recipients, n=131).

Results: The incidence of BAS was higher in patients in the stent group than that in the control group (43.2% vs 17.6%, P=0.001). Cumulative 6-month and 1-, 2- and 5-year BAS rates were 31.8%, 34.1%, 41.4% and 43.2%, respectively, in the stent group and 13.0%, 13.8%, 16.1% and 17.8%, respectively, in the control group (P=0.001). Multivariate analysis revealed that PV stenting was an independent risk factor for BAS.

Conclusions: Although PV stent implantation is a reliable treatment modality for steno-occlusive PV in adult LDLT recipients, innovative methods to prevent the PV stent from crossing the line of PV anastomosis may be necessary to reduce the incidence of postoperative BAS.
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http://dx.doi.org/10.1016/s1499-3872(16)60126-1DOI Listing
October 2016
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