Anatomical classification and clinical outcomes of biliary strictures in living donor liver transplantation using right liver grafts.

This study aimed to classify the anatomical types of biliary strictures, including intrahepatic biliary stricture (IHBS), after living donor liver transplantations (LDLTs) using right liver grafts and evaluate their prognosis. Among 692 adult patients who underwent right liver LDLT, 198 recipients with biliary strictures (28.6%) were retrospectively reviewed. Based on data obtained during the first cholangiography, the patients' biliary strictures were classified into the following three types according to the levels and number of branches involved: Types 1 (anastomosis), 2 (second-order branch [a, one; b, two or more; c, extended to the third-order branch]), and 3 (whole graft [a, multifocal strictures; b, diffuse necrosis]). IHBS was defined as a nonanastomotic stricture. Among the 198 recipients with biliary strictures, the IHBS incidence rates were 38.4% ( n = 76). The most common type of IHBS was 2c ( n = 43, 56.6%), whereas Type 3 ( n = 10, 13.2%) was uncommon. The intervention frequency per year significantly differed among the types (Type 1, 2.3; Type 2a, 2.3; Type 2b, 2.8; Type 2c, 4.3; and Type 3, 7.2; p < 0.001). The intervention-free period for more than 1 year, which was as follows, also differed among the types: Type 1, 84.4%; Type 2a, 87.5%; Type 2b, 86.7%; Type 2c, 72.1%; and Type 3, 50.0% ( p = 0.048). The graft survival rates of Type 3 (80.0%) were significantly lower than those of the other types ( p = 0.001). IHBSs are relatively common in right liver LDLTs. Although Type 3 IHBSs are rare, they require more intensive care and are associated with poorer graft survival rates than anastomosis strictures and Type 2 IHBS.

Early experiences with developing techniques for pure laparoscopic explant hepatectomy in living donor liver transplantation.

In recent years, laparoscopic techniques for liver resection or living donor hepatectomy have become common surgical methods. However, reports on laparoscopic surgeries for recipients are lacking. Our center has launched the minimally invasive living donor liver transplantation (LDLT) program in March 2020, which is led by two surgeons who are experienced in laparoscopic surgeries. Recently, we reported our first successful pure laparoscopic recipient explant hepatectomy and the first laparoscopic explant hepatectomy and robotic-assisted graft implantation. In this article, we introduce a series of minimally invasive surgical cases that were conducted by a single experienced surgeon to share our early experiences leading to our recent successes. We included 10 cases performed from June 2020 to May 2021 in our initial attempt at laparoscopic explant hepatectomy, graft implantation using midline incision, and robotic-assisted graft implantation surgery. The first four cases required open conversion during the liver mobilization process because of bleeding. The next two cases required open conversion to facilitate portal vein and hepatic artery division. We successfully performed pure laparoscopic explant hepatectomy in the last four cases. For the last case, we attempted to perform graft implantation using a robotic system, but bleeding required open conversion. All patients recovered without any significant acute postoperative problems and were discharged within 2 weeks. All 10 patients were followed up at outpatient clinics, and only one of the 10 patients had a late complication of LDLT. This study has shown that the minimally invasive approach in LDLT may be conducted safely without significant complications if it is performed by highly experienced surgeons working in high-volume centers.

Redo hepatic artery reconstruction for thrombosis without retransplantation in 1355 adult living donor liver transplantations.

Hepatic artery thrombosis (HAT) after liver transplantation is associated with a marked increase in morbidity, leading to graft and patient loss. We evaluated the outcomes of adult living donor liver transplantation patients with HAT under an aggressive surgical intervention. A total of 1355 recipients underwent adult living donor liver transplantation at the Seoul National University Hospital. Surgical redo reconstruction for HAT was performed in all cases except in those with graft hepatic artery injury and late detection of HAT. Postoperative HAT developed in 33 cases (2.4%) at a median time of 3.5 days. Thirty patients (90.9%) underwent redo-arterial reconstruction. The survival rates in patients with HAT were similar to the rates in those without HAT (72.7% vs. 83.8%, p = 0.115). Although graft survival rates were lower in patients with HAT (84.8%) than in those without HAT (98.0%) ( p < 0.001), the graft survival rate was comparable (92.0% vs. 98.0%, p = 0.124) in the 25 patients with successful revascularization. Biliary complication rates were higher in patients with HAT (54.5%) than in those without HAT (32.0%) ( p = 0.008). In conclusion, the successful redo reconstruction under careful selection criteria saved the graft without retransplantation in 96.0% of the cases. Surgical revascularization should be preferentially considered for the management of HAT in adult living donor liver transplantation.

Pure laparoscopic donor right hepatectomy in patients over 50 years old: Why age should not be a barrier.

INTRODUCTION: Given the global aging population, the average age of liver donors is increasing. This study aimed to evaluate the surgical outcomes of grafts from pure laparoscopic donor right hepatectomy (PLDRH) in liver donors aged > 50 years. METHODS: The medical records of liver donors were retrospectively reviewed. The donors underwent conventional donor right hepatectomy (CDRH) from January 2011 to May 2019 or PLDRH from March 2016 to May 2019. We divided the donors into three groups: PLDRH donors aged ≥50 (n = 26; Group 1) and aged < 50 (n = 257; Group 2), and CDRH donors aged ≥50 years (n = 66; Group 3). RESULTS: Operation time (p < .01) and hospital stay (p < .01) were significantly lower in Group 1 than in Group 3. Other postoperative outcomes of donors including graft anatomical variation, graft weight, graft-to-recipient weight ratio, and hepatic steatosis were similar among the three groups. Although no postoperative complications occurred in Groups 1 and 3, they were detected in 17 cases (6.6%) in Group 2. No postoperative complications were detected among the recipients. CONCLUSIONS: PLDRH was feasible and safe in donors aged over 50 years, with outcomes similar to those for donors aged <50 years. PLDRH should not be avoided solely based on the donor's age ≥50 years.

Posttransplant renal replacement therapy is an alarm signal for survival outcomes in pediatric liver transplantation.

BACKGROUND: The impact of renal replacement therapy (RRT) on the long-term survival outcomes of pediatric liver recipients remains controversial. METHODS: A total of 224 patients aged <18 years, who underwent liver transplantation (LT), were divided into two groups: patients who underwent renal replacement therapy (RRT) (group R, n = 25, 11.2%) and those who did not (group N, n = 199, 88.8%). The posttransplant patient survival outcomes according to RRT use constituted the primary end-point. RRT was initiated preoperatively in 12 patients (48.0%) and postoperatively in 13 [early: <6 months after LT (n = 5, 20.0%) and late: ≥6 months after LT (n = 8, 32.0%)]. The indications for RRT included liver disease involving the kidney (44.0%) and hepatorenal syndrome (56.0%). RESULTS: The age at the time of LT (71.6 vs. 19.1 months) was higher, the pediatric end-stage liver disease score was lower (9.9 vs. 21.2), and the duration of hospitalization posttransplantation (41.0 vs. 27.0 days) was longer, while the rates of hepatic artery thrombosis (8.0% vs. 3.5%) were higher in group R (p < .05). The number of patients (60.0% vs. 93.0%; p < .001) and graft survival rates (68.0% vs. 93.0%; p < .001) were significantly lower in group R. Multivariate analysis revealed that posttransplant RRT and hepatic artery complications were risk factors for patient survival outcomes. Renal function was recovered in 7 patients (28.0%) in group R, and 9 (36.0%) eventually underwent kidney transplantation. CONCLUSION: The survival outcomes of children requiring posttransplant RRT were significantly worse than those of children, who did not undergo RRT. Physicians should pay meticulous attention to patients requiring post-LT RRT.

Laparoscopic donor and recipient hepatectomy followed by robot-assisted liver graft implantation in living donor liver transplantation.

Minimally invasive surgery has been introduced for liver transplantations. Although laparoscopic or robot-assisted living donor hepatectomy is being used, minimally invasive surgery is rarely performed in recipients during liver transplantation. A 63-year-old patient (body mass index: 21.9 kg/m2 ) with primary biliary cirrhosis underwent total laparoscopic explant hepatectomy, followed by robot-assisted liver engraftment using advanced technological innovations. The total operation time for the recipient was 12 h 20 min, including laparoscopic explant hepatectomy (140 min) and robot-assisted engraftment (220 min). Achieving hepatic and portal vein anastomoses consumed 35 and 28 min, respectively. The hepatic artery anastomosis and bile duct reconstruction took 83 and 66 min, respectively. The estimated blood loss was 3600 ml. The warm and cold ischemic times were 87 and 220 min, respectively. The patient received 10 units each of red blood cells and fresh frozen plasma during the surgery and recovered from early allograft dysfunction after liver transplantation. This case study suggests that laparoscopic explant hepatectomy followed by robot-assisted engraftment is feasible in selected recipients only. We obtained informed consent for this innovative procedure from the patient and from her living donor.

Pure laparoscopic living donor liver transplantation: Dreams come true.

Minimally invasive approaches are increasingly being applied in surgeries and have recently been used in living donor hepatectomy. We have developed a safe and reproducible method for minimally invasive living donor liver transplantation, which consists of pure laparoscopic explant hepatectomy and pure laparoscopic implantation of the graft, which was inserted through a suprapubic incision. Pure laparoscopic explant hepatectomy without liver fragmentation was performed in a 60-year-old man with alcoholic liver cirrhosis and hepatocellular carcinoma. The explanted liver was retrieved through a suprapubic incision. A modified right liver graft, procured from his 24-year-old son using the pure laparoscopic method, was inserted through a suprapubic incision, and implantation was performed intracorporeally throughout the procedure. The time required to remove the liver was 369 min, and the total operative time was 960 min. No complications occurred during or after the surgery. The patient recovered well, and his hospital stay was of 11 days. Pure laparoscopic living donor liver transplantation from explant hepatectomy to implantation was performed successfully. It is a feasible procedure when performed by a highly experienced surgeon and transplantation team. Further studies with larger sample sizes are needed to confirm its safety and feasibility.

Different Risk Factors for Early and Late Recurrence After Curative Resection of Hepatocellular Carcinoma.

BACKGROUND: Factors of early and late recurrence after curative resection of hepatocellular carcinoma (HCC) may be different. The aim of this study was to identify clinical factors, including liver stiffness measurement (LSM), which are associated with HCC recurrence after curative resection. METHODS: Patients who underwent preoperative LSM and primary curative resection for HCC between October 2015 and May 2018 were retrospectively reviewed, with 1 year as the cut-off between early and late recurrence. RESULTS: Recurrence was observed in 42/149 (28.2%) patients over a median follow-up of 38.3 months (early recurrence: 10 [6.7%] patients; late recurrence: 32 [21.5%] patients). Multivariate analysis identified LSM (P = 0.026) and tumor size (P = 0.010) as the only factors that were significantly associated with recurrence-free survival. Compared with patients without recurrence, those with early recurrence had larger tumor size (P = 0.035) and those with late recurrence had higher LSM (P = 0.024). Receiver-operating characteristic analysis indicated that the optimal LSM cut-off value for predicting HCC recurrence was 7.4 kPa. CONCLUSION: Tumor size was associated with early HCC recurrence after curative resection and LSM was associated with late recurrence. LSM cut-off of 7.4 kPa is recommended in predicting recurrence.

Short-term therapy with anti-ICAM-1 monoclonal antibody induced long-term liver allograft survival in nonhuman primates.

Tolerance induction remains challenging following liver transplantation and the long-term use of immunosuppressants, especially calcineurin inhibitors, leads to serious complications. We aimed to test an alternative immunosuppressant, a chimeric anti-ICAM-1 monoclonal antibody, MD-3, for improving the outcomes of liver transplantation. We used a rhesus macaque liver transplantation model and monkeys were divided into three groups: no immunosuppression (n = 2), conventional immunosuppression (n = 4), and MD-3 (n = 5). Without immunosuppression, liver allografts failed within a week by acute rejection. Sixteen-week-long conventional immunosuppression that consisted of prednisolone, tacrolimus, and an mTOR inhibitor prolonged liver allograft survival; however, recipients died of acute T cell-mediated rejection (day 52), chronic rejection (days 62 and 66), or adverse effects of mTOR inhibitor (day 32). In contrast, 12-week-long MD-3 therapy with transient conventional immunosuppression in the MD-3 group significantly prolonged the survival of liver allograft recipients (5, 96, 216, 412, 730 days; p = .0483). MD-3 effectively suppressed intragraft inflammatory cell infiltration, anti-donor T cell responses, and donor-specific antibody with intact anti-cytomegalovirus antibody responses. However, this regimen ended in chronic rejection. In conclusion, short-term therapy with MD-3 markedly improved liver allograft survival to 2 years without maintenance of immunosuppressant. MD-3 is therefore a promising immune-modulating agent for liver transplantation.

Surveillance Endoscopy Guidelines for Postgastrectomy Patients Based on Risk of Developing Remnant Gastric Cancer.

BACKGROUND: Remnant gastric cancer (RGC) has a major impact on the long-term survival of postgastrectomy patients. In this study, we established surveillance endoscopy guidelines for postgastrectomy patients based on the risk of RGC. PATIENTS AND METHODS: A total of 6365 patients who underwent gastrectomy at Seoul St. Mary's Hospital from September 2005 to June 2018 were retrospectively reviewed; 85 patients were identified as having RGC. We divided the RGC patients into subgroups according to the interval between primary and secondary gastrectomy. RESULTS: The curative resection rate was significantly lower in patients with an interval of ≤ 5 years versus > 5 years (p = 0.017). RGC developed more frequently after Billroth II reconstruction, and at the anastomotic site, in patients with a > 10- versus ≤ 10-year interval (p = 0.006 and p = 0.014, respectively). Similar results were observed based on the 15-year interval cutoff (p = 0.001 and 0.018, respectively). The 5-year overall survival rate of patients with a ≤ 5-year interval was significantly lower than that of patients with a > 5-year interval (60.0% versus 85.7%, p = 0.015), while overall survival did not differ between the ≤ 10- and > 10-year, or ≤ 15- and 15-year interval groups. RGC incidence showed a decrease after around 20 years postoperatively. CONCLUSIONS: Thorough endoscopic examination should be conducted for up to 5 years postgastrectomy. Routine annual endoscopic follow-up should be performed for up to 20 years after the primary operation for gastric cancer, to allow for early detection of RGC.

Proposal of a Network System to Solve the Problem of Small Volume in Liver Transplantation; Catholic Medical Center Network.

INTRODUCTION: Liver transplantation (LT) is a complex and demanding procedure associated with significant perioperative challenges and risks. Concerns have arisen regarding LT outcomes in low-volume centers. We implemented an integrated training and surgical team network to address these concerns within the Catholic Medical Center (CMC) network. This study presents a comprehensive review of our 9-year LT experience within the CMC medical network. METHOD: A retrospective study of LT procedures conducted between January 2013 and August 2021 in 6 CMC-affiliated hospitals was performed. One center was categorized as a high-volume center, conducting over 60 cases annually, and the remaining 5 were considered small-volume centers. The primary endpoints assessed were 1-year and 5-year survival rates. RESULTS: A total of 793 LTs were performed during the study period. The high-volume center performed 411 living donor LT (LDLT) cases and 127 deceased donor LT (DDLT) cases. Also, 146 LDLT cases and 109 DDLT cases were performed in 5 small-volume centers. One-year and 5-year patient survival for LDLT recipients was 88.3% and 78.8% in the high-volume center and 85.6% and 80.6% in the low-volume center. Five-year survival was not significantly different in small-volume centers (P = .903). For DDLT recipients, 1-year and 5-year patient survival was 80.3% and 70.6% in the high-volume center and 76.1% and 67.6% in the low-volume center. In DDLT cases, 5-year survival was not significantly different in small-volume centers (P = .445). CONCLUSION: In conclusion, comparable outcomes for liver transplantation can be obtained in a small-volume center with a high level of integrated training systems and networks.

Total robot-assisted recipient's surgery in living donor liver transplantation: First step towards the future.

Lee and colleagues describe a groundbreaking total robot-assisted explant hepatectomy followed by robotic engraftment for a patient requiring a living donor liver transplant. This report represents a crucial step towards implementing robot-assisted liver transplantation, a cutting-edge surgical technique that could change the surgical trend in recipient surgery for liver transplantation.

Long-term outcomes of liver transplantation using grafts from donors with active hepatitis B virus replication: a multicenter cohort study.

Purpose: Liver grafts from donors with HBV infection contributed to expanding the donor pool under the hepatitis B immunoglobulin and antiviral agents (nucleos(t)ide analogues) in the HBV-endemic area. We report long-term outcomes of liver transplantations (LTs) using grafts from donors with active or chronic HBV infection. Methods: Overall, 2,260 LTs performed in 3 major hospitals in Seoul from January 2000 to April 2019 were assessed for inclusion. Twenty-six grafts (1.2%) were obtained from HBsAg (+), HBeAb (+), or HBcAb (+) donors, and recipient outcomes were retrospectively reviewed. Donor and recipient demographics and transplantation outcomes were analyzed. Results: Sixteen deceased donor LTs were performed using active HBsAg (+) grafts. Ten other LTs were sourced from 10 living donors. There was no significant difference in survival in patients who received deceased donor LTs compared with that in those who underwent LT with non-hepatitis virus-infected grafts. Fourteen patients who were followed up for >5 years were stable, and no difference in hepatocellular carcinoma recurrence rate was observed 5 years after transplantation between transplants from donors with and those without HBV. Conclusion: Considering long-term outcomes, liver grafts from donors with active HBV replication can be safely used for LT.

Swine Partial Liver Transplantation Model for Practicing Living Donor Liver Transplantation Based on a New Liver Segmentation Method.

BACKGROUND: Living donor liver transplantation (LDLT) is one of the most technically demanding and complicated procedures. However, unlike deceased donor liver transplantation, there is no suitable animal model for practicing LDLT. Herein, we propose a new liver segmentation method and a feasible pig LDLT model for practicing for LDLT in humans. METHODS: Four Landrace pigs weighing 25, 25, 27, and 28 kg were used as donors and recipients to establish a partial liver transplantation model. Partial liver transplantation was performed using a right liver and a left liver, respectively, based on a new segmentation system compatible with that of humans. RESULTS: We established a new segmentation system for porcine liver transplantation and a partial liver transplantation model. For right liver transplantation, 91 and 142 min were required to operate on the donor and recipient, respectively; for left liver transplantation, 57 and 104 min were required to operate on the donor and recipient, respectively. All pigs that underwent partial liver transplantation remained alive until the operation was completed. CONCLUSIONS: It is expected that this new pig model based on the new segmentation system will be suitable as an educational tool for LDLT training and will replace the existing animal models for partial liver transplantation.

Modified Charlson comorbidity index as a survival prediction tool for older patients after liver transplantation.

Purpose: An increasing number of older patients now undergo liver transplantation (LT). Although the overall outcomes in older patients are not different from those of younger patients, there is no tool to predict LT prognosis in older patients. We hypothesized that a modified Charlson comorbidity index (mCCI) and 5-factor modified frailty index (mFI-5) can predict outcomes in older patients after LT. Methods: This retrospective study included 155 patients (aged >65 years) who underwent LT at Seoul National University Hospital. The recipients were subcategorized into 2 groups based on the mCCI score and mFI-5: the low (0-1) and high (2-5) mCCI groups, and low (≤0.4) and high (>0.4) mFI-5 groups. The independent effect of each variable on post-LT survival was determined using the mCCI subgroup, age at transplantation, sex, Child-Turcotte-Pugh score, model for end-stage liver disease (MELD) score, and mFI-5 subgroup. Results: The high-mCCI group (41 patients) showed significantly lower 1- and 3-month and 1-, 3-, and 5-year survival than the low-mCCI group. Using the Cox regression model, the mCCI, sex, and MELD score remained significant. The mFI-5 was not a significant factor to predict patients' survival. Conclusion: The mCCI and MELD scores could be used to predict post-LT survival in older patients.

Impact of tumor size on hepatectomy outcomes in hepatocellular carcinoma: a nationwide propensity score matching analysis.

Purpose: The aim of this study was to compare surgical outcomes after liver resection for hepatocellular carcinoma (HCC) according to tumor size using a large, nationwide cancer registry-based cohort and propensity score matching. Methods: From 2008 to 2015, a total of 12,139 patients were diagnosed with liver cancer and registered in the Korean Primary Liver Cancer Registry. Patients without distant metastasis who underwent hepatectomy as a primary treatment were selected. We performed 1:1 propensity score matching between the small (<5 cm), large (≥5 cm and <10 cm), and huge (≥10 cm) groups. Results: Overall, 265 patients in the small and large groups were compared, and 64 patients each in the large and huge groups were compared. The overall and progression-free survival rates were significantly lower in the large group than in the small group (P < 0.001 and P < 0.001, respectively). Overall survival tended to be poorer in the huge group than in the large group (P = 0.051). The progression-free survival rate was significantly lower in the huge group than in the large group (P = 0.002). Conclusion: Although primary liver resection can be considered even in patients with huge HCC, greater caution with careful screening for recurrence is needed.

Changes in Indices of Steatosis and Fibrosis in Liver Grafts of Living Donors After Weight Reduction.

Background: A short-term weight reduction program for potential living donors was introduced to reduce the extent of hepatic steatosis prior to liver transplantation. We aimed to investigate changes in non-invasive hepatic steatosis and fibrosis indices among those who completed the program. Methods: Among 1,950 potential living liver donors between January 2011 and May 2019, 160 living donors joined the weight reduction program. The prospectively collected clinical data of these potential liver donors were analyzed retrospectively. Hepatic steatosis and fibrosis scores were determined using the fatty liver index (FLI), hepatic steatosis index (HSI), and NAFLD fibrosis score (NFS) and compared to MR spectroscopy (MRS) fat fraction results before and after weight reduction. Results: Thirty-nine potential living donors who had undergone MRS both before and after weight reduction were included in the analysis. Their body weight decreased from 78.02 ± 10.89 kg to 72.36 ± 10.38 kg over a mean of 71.74 ± 58.11 days. FLI, HSI, and MRS values decreased significantly from 41.52 ± 19.05 to 24.53 ± 15.93, 39.64 ± 3.74 to 35.06 ± 3.82, and 12.20 ± 4.05 to 6.24 ± 3.36, respectively. No significant decreases in NFS were observed. There was a significant correlation between the extent of HSI change and the extent of MRS change (R2 value = 0.69, P < 0.001), although there was no correlation between MRS and FLI. Conclusion: The weight reduction program significantly improved non-invasive indices of hepatic steatosis over a short period. HSI may allow for prediction of simple decreases in hepatic steatosis.

Hepatitis B immunoglobulin prophylaxis for de novo hepatitis B infection in liver transplantation: a 30-year experience.

Background: Donors positive for hepatitis B core antibody (HBcAb) are an important source of organs in hepatitis B virus (HBV) endemic areas despite the risk of occult infection. We analyzed the long-term outcomes of hepatitis B immunoglobulin in de novo HBV prevention following liver transplantation (LT) using HBcAb-positive grafts. Methods: The prospectively collected data from 2,201 recipients at Seoul National University Hospital (SNUH) and Seoul National University Boramae Medical Center between 1988 and 2018 were retrospectively reviewed. A total of 1,458 patients were enrolled. Of the 1,458, 478 (32.8%) grafts were core-positive, 152 (10.4%) of which belonged to HBV surface antigen-negative recipients. During the anhepatic phase, hepatitis B immunoglobulin 4,000 IU was administered intravenously and daily until postoperative day 3. Results: The 152 patients with hepatitis B surface antigen-negative received HBcAb-positive graft. De novo HBV developed in 21 (13.8%) of these recipients. De novo HBV occurred in 1, 11, 0, and 9 of the 4 HBcAb- and hepatitis b surface antibody (anti-HB)-negative, 49 HBcAb-negative and anti-HB-positive, 1 HBcAb-positive and anti-HB-negative, and 98 HBcAb- and anti-HB-positive recipients, respectively. Patients with higher Model for End-stage Liver Disease (MELD) score (23.8±8.7 vs. 19.5±9.2) or HBcAb-negative recipients (22.6% vs. 9.1%) had a higher risk of de novo infection. The median follow-up and serum HBV surface antigen-positivity detection time was 69 and 18 months, respectively. The median HBV surface antibody titer was 65.0 IU/L at de novo infection. Nineteen patients of 21 were treated with nucleoside analogs (NAs), and seven of 19 achieved seroconversion. No patient died of de novo HBV infection. Conclusions: With close monitoring of viral serum markers and appropriate initiation of NAs, de novo HBV infection can be prevented and treated appropriately with the hepatitis B immunoglobulin monoprophylaxis protocol.