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Background: The COVID-19 pandemic has had a major impact on liver transplantation (LT) and living donor programs globally., Purpose: In this study, we aimed to present the principles and strategies of our LT program during the pandemic period and describe its achievements., Basic Procedures: We retrospectively reviewed the outcomes of 1417 LTs performed at Asan Medical Center, Seoul, Korea, from 2020 to 2022. Of these, 216 recipients who received transplants from deceased donors were excluded, and 1201 recipients who received transplants from 1268 live donors were included in the study, including 38 children <18 years old., Main Findings: Among the 1201 living donor LT (LDLT) recipients, the most common indication for LT was unresectable hepatocellular carcinoma (315/1163, 27.1%) in adults and biliary atresia (29/38, 76.3%) in pediatric recipients. Emergency LDLT was performed in 40 patients (3.3%). The median model of end-stage liver disease and pediatric end-stage liver disease scores were 13.9 ± 7.2 and 13.8 ± 7.1, respectively. In-hospital mortality of recipients was higher than usual at 2.2%, but the cause of death was not related to COVID-19 infection. Of the 1268 live donors who underwent hepatectomy for liver donation, 660 (52.1%) underwent hepatectomy using a minimally invasive approach. Although 17 (1.3%) live donors experienced major complications, there were no serious life-threatening complications and no mortality., Conclusion: Even in a pandemic era, a team with well-established infection control protocols, patient-tailored surgical strategies, and thorough perioperative care can maintain LDLT at a similar quantitative and qualitative level as in a non-pandemic era., Competing Interests: Declaration of competing interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

The aim of this work was to assess the association between graft-to-recipient weight ratio (GRWR) in adult-to-adult living donor liver transplantation (LDLT) and hepatocellular carcinoma (HCC) recurrence. A search of the MEDLINE and EMBASE databases was performed until December 2022 for studies comparing different GRWRs in the prognosis of HCC recipients in LDLT. Data were pooled to evaluate 1- and 3-year survival rates. We identified three studies, including a total of 782 patients (168 GRWR < 0.8 vs. 614 GRWR ≥ 0.8%). The pooled overall survival was 85% and 77% at one year and 90% and 83% at three years for GRWR < 0.8 and GRWR ≥ 0.8, respectively. The largest series found that, in patients within Milan criteria, the GRWR was not associated with lower oncological outcomes. However, patients with HCC outside the Milan criteria with a GRWR < 0.8% had lower survival and higher tumor recurrence rates. The GRWR < 0.8% appears to be associated with lower survival rates in HCC recipients, particularly for candidates with tumors outside established HCC criteria. Although the data are scarce, the results of this study suggest that considering the individual GRWR not only as risk factor for small-for-size-syndrome but also as contributor to HCC recurrence in patients undergoing LDLT would be beneficial. Novel perfusion technologies and pharmacological interventions may contribute to improving outcomes.

Background: With the recent rapid increase in the prevalence of obesity, the number of obese patients requiring liver resection, including laparoscopy, has increased. Accordingly, evaluating the outcome of laparoscopic liver resection in obese patients is increasingly important. This study aimed to compare the safety and feasibility of laparoscopic major liver resection (LMR) and open major liver resection (OMR) in patients with a high body mass index (BMI > 25.0 kg/m 2 )., Methods: We reviewed 521 patients with high BMI (> 25.0 kg/m 2 ) who underwent major liver resection for various indications between January 2009 and November 2018 at Asan Medical Center. We performed 1:1 propensity score matching of the LMR and OMR groups, with 120 patients subsequently included in each group., Results: LMR was associated with lower blood loss and shorter postoperative hospital stays (p < 0.001). Although there was no significant difference in overall complications (p = 0.080), non-liver-specific complications were observed less frequently after LMR (p = 0.025). American Society of Anesthesiologists class > II, BMI > 30 kg/m 2 , and malignancy were independent predictors of morbidity. In a subgroup analysis of patients with hepatocellular carcinoma, there was no significant difference between the two groups in overall survival (hazard ratio 0.225; 95% confidence interval 0.049-1.047; p = 0.057) and recurrence-free survival (hazard ratio 0.761; 95% confidence interval 0.394-1.417; p = 0.417)., Conclusions: Obesity should not be considered a contraindication for major liver resection using a laparoscopic approach; however, when applying this approach for resecting malignancies in patients with a BMI > 30 kg/m 2 and comorbid diseases, special attention should be paid to the possibility of complications., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Hepatocellular carcinoma (HCC) recurrence and development of de novo malignancy (DNM) after liver transplantation (LT) are the major causes of late recipient death., Methods: We analyzed the incidence of extrahepatic DNM following living donor LT according to the status of pretransplant hepatic malignancy. We selected 2,076 adult patients who underwent primary LDLT during 7 years from January 2010 to December 2016., Results: The pretransplant hepatic malignancy group (n = 1,012) showed 45 cases (4.4%) of the following extrahepatic DNMs: posttransplant lymphoproliferative disease (PTLD) in 10; lung cancer in 10; stomach cancer in 6; colorectal cancer in 5; urinary bladder cancer in 3; and other cancers in 11. The pretransplant no hepatic malignancy group (n = 1,064) showed 25 cases (2.3%) of the following extrahepatic DNMs: colorectal cancer in 3; stomach cancer in 3; leukemia in 3; lung cancer in 3; PTLD in 2; prostate cancer in 2; and other cancers in 9. Incidences of extrahepatic DNM in the pretransplant hepatic malignancy and no hepatic malignancy groups were as follows: 1.1% and 0.5% at 1 year, 3.2% and 2.0% at 3 years, 4.6% and 2.5% at 5 years, and 5.4% and 2.8% at 8 years, respectively ( P = 0.006). Their overall patient survival rates were as follows: 97.3% and 97.2% at 1 year, 91.6% and 95.9% at 3 years, 89.8% and 95.4% at 5 years, and 89.2% and 95.4% at 8 years, respectively ( P < 0.001). Pretransplant hepatic malignancy was the only significant risk factor for posttransplant extrahepatic DNM., Conclusion: Our results suggest that patients who had pretransplant hepatic malignancy be followed up more strictly because they have a potential risk of primary hepatic malignancy recurrence as well as a higher risk of extrahepatic DNM than patients without pretransplant hepatic malignancy., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2020 The Korean Academy of Medical Sciences.)

Background: Laparoscopic treatment for hepatocellular carcinoma (HCC) has increased. We retrospectively compared the perioperative and long-term oncological outcomes of laparoscopic liver resection (LLR) with those of open liver resection (OLR) for hepatocellular carcinoma (HCC) in well-matched patient groups using propensity score matching (PSM)., Methods: We reviewed medical records of patients with HCC who underwent liver resection between July 2007 and April 2016 at our center. In total, 2335 patients were included in this study and divided into LLR (n = 264) and OLR (n = 2071) groups. For group comparisons, 1:2 PSM was used with covariates of baseline characteristics, including tumor characteristics and surgical liver resection procedures., Results: After PSM, there were 217 and 434 patients in the LLR and OLR groups, respectively. The LLR group had shorter hospital stays (8.9 vs. 14.8 days; P < 0.001) and lower postoperative morbidity (6.5% vs. 12.0%; P = 0.022). The 1-, 3-, and 5-year overall survival rates were 98.1%, 87.0%, and 78.6%, respectively, for the LLR group, and 98.3%, 90.8%, and 84.3%, respectively, for the OLR group (P = 0.570). The 1-, 3-, and 5-year disease-free survival rates were 81.0%, 62.0%, and 49.1%, respectively, for the LLR group, and 85.3%, 64.7%, and 56.2%, respectively, for the OLR group (P = 0.563)., Conclusions: Long-term oncological outcomes were comparable between LLR and OLR for selected patients. LLR was associated with multiple benefits, even for selected patients with cirrhosis who underwent major hepatectomy. LLR for HCC performed by an experienced surgeon could be considered a safe and feasible alternative to OLR for selected patients.

Background: Mulberry silkworm larvae (Bombyx mori) are known as the oldest resource of food and traditional medicine. Although silkworm larvae have been reported to treat various chronic diseases, the effect of fermentation by microorganisms improving the biological activities of silkworm larvae was not reported. In the present study, fermented silkworm larvae was developed via solid-state fermentation with Aspergillus kawachii and investigated its anti-cancer activity in human hepatocellular carcinoma cells., Methods: We investigated the anti-cancer effects of unfermented (SEE) and fermented silkworm larva ethanol extract (FSEE) on HepG2 human hepatocellular carcinoma cells as well as compared changes in free amino acid, fatty acid, and mineral contents. Anti-cancer activities were evaluated by SRB staining, cell cycle analysis, Annexin V staining, Hoechst staining, DNA fragmentation analysis and western blot analysis. Fatty acid, free amino acid and mineral contents of SEE and FSEE were determined by gas chromatography, amino acid analyzer and flame atomic absorption spectrophotometer, respectively., Results: Compared with SEE, treatment with FSEE resulted in apoptotic cell death in HepG2 cells characterized by G0/G1 phase cell cycle arrest, DNA fragmentation, and formation of apoptotic bodies. Furthermore, FSEE significantly up-regulated pro-apoptotic as well as down-regulated anti-apoptotic proteins in HepG2 cells. However, an equivalent concentration of SEE did not induce cell cycle arrest or apoptosis in HepG2 cells. Moreover, fermentation process by Aspergillus kawachii resulted in enhancement of fatty acid contents in silkworm larvae, whereas amino acid and mineral contents were decreased., Conclusion: Collectively, this study demonstrates that silkworm larvae solid state-fermented by Aspergillus kawachii strongly potentiates caspase-dependent and -independent apoptosis pathways in human hepatocellular carcinoma cells by regulating secondary metabolites.

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.

BACKGROUND This study aimed to assess patterns of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) and to establish long-term surveillance protocols for late HCC recurrence. MATERIAL AND METHODS The 232 LT recipients experiencing subsequent HCC recurrence were categorized as Group 1, early recurrence (within 1 year of LT; n=117); Group 2, late recurrence (occurring in years 2-5; n=93); and Group 3, very late recurrence (after year 5; n=22). RESULTS Recurrence was detected by only elevated tumor marker levels in 11.1%, 30.1%, and 45.5% of patients in Groups 1, 2, and 3, respectively (p<0.001). The proportion of intrahepatic and extrahepatic metastases was similar in all 3 groups. Common sites of extrahepatic metastasis were the lung and bone; these were also similar across the 3 groups. Overall post-recurrence patient survival rates were 60.2% at 1 year, 28.2% at 3 years, 20.5% at 5 years, and 7.0% at 10 years. Median post-recurrence survival periods were 10.2, 23.8, and 37.0 months in Groups 1, 2, and 3, respectively. CONCLUSIONS While the pattern of HCC recurrence was similar regardless of time of recurrence, post-recurrence survival was significantly longer in patients with later recurrence. Long-term surveillance for HCC recurrence beyond 5 years after LT is recommended.

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 2 /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., (Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

We report here two cases of foreign body granulomas that arose from the pelvic wall and liver, respectively, and simulated recurrent colorectal carcinomas in patients with a history of surgery. On contrast-enhanced CT and MR images, a pelvic wall mass appeared as a well-enhancing mass that had invaded the distal ureter, resulting in the development of hydronephrosis. In addition, a liver mass had a hypointense rim that corresponded to the fibrous wall on a T2-weighted MR image, and showed persistent peripheral enhancement that corresponded to the granulation tissues and fibrous wall on dynamic MR images. These lesions also displayed very intense homogeneous FDG uptake on PET/CT.