Outcomes of 6000 living donor liver transplantation procedures: a pioneering experience at ASAN Medical Center.

Living donor liver transplantation (LDLT) has emerged as a favorable alternative to deceased donor liver transplantation, significantly reducing waitlist mortality, particularly in Asian countries with very low deceased organ donation rates. Asan Medical Center (AMC) in South Korea has pioneered innovative LDLT surgical techniques and become established as an extremely high-volume center for LDLT. This retrospective study analyzed 6000 consecutive LDLT procedures, including 510 dual-graft procedures, performed at AMC between December 1994 and January 2021. Of these, 312 LDLT procedures were performed in children aged < 18 years. In adult recipients, liver cirrhosis (LC) related to viral hepatitis was the most common indication, occurring in 69.8% of cases. Biliary atresia (46.8%) was the most common indication for pediatric LDLT. This study demonstrated outstanding long-term outcomes, with patient survival rates at 1, 5, 10, and 20 years of 92.7%, 85.9%, 82.1%, and 70.9%, respectively, in LDLT group for adults aged 50 and under at the time of LDLT, and 92.9%, 89.0%, 88.1%, and 81.9%, respectively, in the pediatric group. The in-hospital mortality rate of adult recipients was 3.8% (n = 214/5688). This study demonstrates the importance of refined surgical techniques, selection of grafts tailored to the recipient, and comprehensive multidisciplinary perioperative patient care in expanding the scope of LDLT and improving recipient outcomes.

Association between body mass index and results of cryoballoon ablation in Korean patients with atrial fibrillation: an analysis from Korean Heart Rhythm Society Cryoablation registry.

BACKGROUND: Pulmonary vein isolation using cryoablation is effective and safe in patients with atrial fibrillation (AF). Although both obesity and underweight are associated with a higher risk for incident AF, there is limited data on the efficacy and safety following cryoablation according to body mass index (BMI) especially in Asians. METHODS: Using the Korean Heart Rhythm Society Cryoablation registry, a multicenter registry of 12 tertiary hospitals, we analyzed AF recurrence and procedure-related complications after cryoablation by BMI (kg/m2) groups (BMI<18.5, underweight, UW; 18.5-23, normal, NW; 23-25, overweight, OW; 25-30, obese Ⅰ, OⅠ; ≥30, obese Ⅱ, OⅡ). RESULTS: A total of 2,648 patients were included (median age 62.0 years; 76.7% men; 55.6% non-paroxysmal AF). Patients were categorized by BMI groups; 0.9% UW, 18.7% NW, 24.8% OW, 46.1% OI, and 9.4% OII. UW patients were the oldest, and had least percentage of non-paroxysmal AF (33.3%). During a median follow-up of 1.7 years, atrial arrhythmia recurred in 874 (33.0%) patients (incidence rate, 18.9 per 100 person-year). After multivariable adjustment, the risk of AF recurrence was higher in UW group compared to NW group (adjusted hazard ratio, 95% confidence interval; 2.55, 1.18-5.50, p=0.02). Procedure-related complications occurred in 123 (4.7%) patients and the risk was higher for UW patients (odds ratio, 95% confidence interval; 2.90, 0.94-8.99, p=0.07), mainly due to transient phrenic nerve palsy. CONCLUSION: UW patients showed a higher risk of AF recurrence after cryoablation compared to NW patients. Also, careful attention is needed on the occurrence of phrenic nerve palsy in UW patients.

Safety of right liver donation after improving steatosis through weight loss in living donors: a retrospective study.

BACKGROUND: Living donor liver transplantation using hepatic steatosis-improved grafts mitigates donor shortage. Herein, we aimed to evaluate the safety and feasibility of right-lobe adult-to-adult living donor liver transplantation using grafts improved through donor weight loss. METHODS: In this retrospective study conducted in a single institution in the Republic of Korea, we reviewed the medical records of living liver donors who lost ≥ 10% of their body weight to improve steatosis before right lobe donation between January 2015 and December 2020. Overall, 1040 right-lobe donors were included, with 150 and 890 donors in the weight loss and control (non-steatosis) groups, respectively. RESULTS: We performed 1:1 individual matching using the greedy matching method, by which 124 patients were included in each group. The median period from the date of the first visit to donation was 113 (interquartile range: 78-184) days in the weight loss group. As body weight changed from 82.8 ± 13.7 kg to 70.8 ± 11.8 kg (p < 0.0001), body mass index also improved from 27.8 ± 3.9 kg/m2 to 23.8 ± 3.1 kg/m2 (p < 0.0001). No significant between-group differences existed in the postoperative laboratory data for living donors and recipients. The incidence of postoperative complications in donors was comparable between the groups (control group, 9.7%; weight loss group, 13.7%; p = 0.3185). The graft and recipient survival rates were comparable between the groups (p = 1.000). CONCLUSION: Weight loss through diet and exercise significantly could improve hepatic steatosis in living donor candidates for liver transplantation, with the surgical outcomes in recipients and donors being equivalent to those in recipients and non-steatotic donors.

Concurrent spontaneous coronary dissection and reversible cerebral vasoconstriction syndrome during postnatal care.

BACKGROUND: Pregnancy-associated spontaneous coronary artery dissection (SCAD) and reversible cerebral vasoconstriction syndrome (RCVS) are rare conditions that may occur during pregnancy and the postpartum period. The coexistence of both diseases may pose a risk to patients, potentially resulting in a variety of complications and clinical manifestations. This is considered the first case of a patient who successfully recovered from a critical condition in the postpartum period, with contemporaneous SCAD and RCVS. CASE PRESENTATION: A 33-year-old female with no known medical history was referred to the emergency department after experiencing cardiac arrest, which occurred 1 week after giving birth to her third child. She complained of sudden anterior squeezing chest pain, accompanied by a headache, and eventually collapsed due to ventricular fibrillation with seizure. She was successfully resuscitated after receiving basic life support. She showed an alert mentality and did not experience any further seizure events or additional neurological symptoms. Although vital sign remained stable, the level of highly sensitive troponin I was significantly elevated. Electrocardiography revealed sinus rhythm with T-wave inversion at V1-4, while chest computed tomography (CT) demonstrated severe aspiration pneumonia. The patient was admitted to the intensive care unit due to a high requirement of O2 supply. A consultation with the neurologic department and a brain magnetic resonance angiography (MRA) were conducted for the thunderclap headache. The brain MRA demonstrated stenosis in the basilar artery, the right M2 segment, and bilateral A1 segments, along with sulcal hyperintensity on post-contrast fluid-attenuated inversion recovery (FLAIR) suggesting blood-brain barrier breakdown due to vasoconstriction. Formal echocardiography showed regional wall motion abnormality in the left anterior descending artery (LAD) territory. After the improvement of pneumonia, a coronary angiography was performed, revealing diffuse luminal narrowing from the mid to distal LAD due to a long segmental, extensive dissection. We decided to maintain the medical therapy. A follow-up coronary CT angiography performed 6 months later revealed complete remission of the dissected coronary vessel, and a brain MRA checked 3 months later showed resolved vasoconstriction of the relevant cerebral vessels. CONCLUSIONS: The physicians must be aware of pregnancy-associated complications in certain patients. Clear diagnoses and proper treatments are required in pregnant patients who may be exposed to multiple acute conditions, in order to reduce complications and achieve favorable outcomes.

Reconstruction of all hepatic arteries in right lobe grafts with 2 hepatic arteries and zero percent hepatic artery thrombosis.

Hepatic artery thrombosis (HAT) is a common cause of graft loss in living-donor liver transplantation, occurring in ~2.5%-8% of patients. Some right lobe grafts have 2 hepatic arteries (HAs), and the optimal reconstruction technique remains controversial. This study aimed to identify risk factors for HAT and to evaluate the efficacy of reconstructing 2 HAs in right lobe grafts. This retrospective, single-center study analyzed 1601 living-donor liver transplantation recipients with a right liver graft and divided them into 1 HA (n = 1524) and 2 HA (n = 77) groups. The reconstruction of all HAs was performed using a microscope with an interrupted suture. The primary outcome was any HAT event. Of the 1601 patients, 37.8% had a history of transcatheter arterial chemoembolization, and 130 underwent pretransplant hepatectomy. Extra-anatomical arterial reconstruction was performed in 38 cases (2.4%). HAT occurred in 1.2% of patients (20/1601) who underwent surgical revascularization. In the multivariate analysis, undergoing pretransplant hepatectomy ( p = 0.008), having a female donor ( p = 0.02), having a smaller graft-to-recipient weight ratio ( p = 0.002), and undergoing extra-anatomical reconstruction ( p = 0.001) were identified as risk factors for HAT. However, having 2 HA openings in right liver grafts was not a risk factor for HAT in our series. Kaplan-Meier survival analysis showed no significant difference in graft survival and patient survival rates between the 1 HA and 2 HA groups ( p = 0.09, p = 0.97). In our series, although the smaller HA in the 2 HA group should increase the risk of HAT, HAT did not occur in this group. Therefore, reconstructing both HAs when possible may be a reasonable approach in living-donor liver transplantation using a right liver graft with 2 HA openings.

Regorafenib plus nivolumab in unresectable hepatocellular carcinoma: the phase 2 RENOBATE trial.

Regorafenib has anti-tumor activity in patients with unresectable hepatocellular carcinoma (uHCC) with potential immunomodulatory effects, suggesting that its combination with immune checkpoint inhibitor may have clinically meaningful benefits in patients with uHCC. The multicenter, single-arm, phase 2 RENOBATE trial tested regorafenib-nivolumab as front-line treatment for uHCC. Forty-two patients received nivolumab 480 mg every 4 weeks and regorafenib 80 mg daily (3-weeks-on/1-week-off schedule). The primary endpoint was the investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The secondary endpoints included safety, progression-free survival (PFS) and overall survival (OS). ORR per RECIST version 1.1 was 31.0%, meeting the primary endpoint. The most common adverse events were palmar-plantar erythrodysesthesia syndrome (38.1%), alopecia (26.2%) and skin rash (23.8%). Median PFS was 7.38 months. The 1-year OS rate was 80.5%, and the median OS was not reached. Exploratory single-cell RNA sequencing analyses of peripheral blood mononuclear cells showed that long-term responders exhibited T cell receptor repertoire diversification, enrichment of genes representing immunotherapy responsiveness in MKI67+ proliferating CD8+ T cells and a higher probability of M1-directed monocyte polarization. Our data support further clinical development of the regorafenib-nivolumab combination as front-line treatment for uHCC and provide preliminary insights on immune biomarkers of response. ClinicalTrials.gov identifier: NCT04310709 .

Achieving 400 Living Donor Liver Transplantations Annually During the COVID-19 Pandemic: A Single-Center Experience.

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.

Clinical outcomes after transplantation of domino grafts or standard deceased donor livers: a systematic review and meta-analysis.

BACKGROUND AND AIM: Domino liver transplantation (DLT) utilizes otherwise discarded livers as donor grafts for another recipients. It is unclear whether DLT has less favorable outcomes compared to deceased donor liver transplantation (DDLT). We aimed to assess the outcomes of DLT compared to DDLT. METHODS: MEDLINE, Embase, and Web of Science database were searched to identify studies comparing outcomes after DLT with DDLT. Data were pooled using random-effects modeling, evaluating odds ratios (OR) or mean difference (MD) for outcomes including waiting list time, severe hemorrhage, intensive care unit (ICU), length hospital stay (LOS), rejection, renal, vascular, and biliary events, and recipient survival at 1, 3, 5, and 10 years. RESULTS: Five studies were identified including 945 patients (DLT = 409, DDLT = 536). The DLT recipients were older compared to the DDLT group (P = 0.04), and both cohorts were comparable regarding lab MELD, hepatocellular carcinoma, and waitlist time. There were no differences in vascular (OR: 1.60, P = 0.39), renal (OR: 0.62, P = 0.24), biliary (OR: 1.51, P = 0.21), severe hemorrhage (OR: 1.09, P = 0.86), rejection (OR: 0.78, P = 0.51), ICU stay (MD: 0.50, P = 0.21), or LOS (MD: 1.68, P = 0.46) between DLT and DDLT. DLT and DDLT were associated with comparable 1-year (78.9% vs 80.4%; OR: 1.03, P = 0.89), 3-year (56.2% vs 54.1%; OR: 1.35, P = 0.07), and 10-year survival (6.5% vs 8.5%; OR: 0.8, P = 0.67) rates. DLT was associated with higher 5-year survival (41.6% vs 36.4%; OR: 1.70; P = 0.003) compared to DDLT, which was not confirmed at sensitivity analysis. CONCLUSION: This meta-analysis of the best available evidence (Level 2a) demonstrated that DLT and DDLT have comparable outcomes. As indications for liver transplantation expand, future high-quality research is encouraged to increase the DLT numbers in clinical practice, serving the growing waiting list candidates, with the caveat of uncertain de novo disease transmission risks.

Therapeutic maintenance effect of finasteride 1 mg every other month regimen in androgenetic alopecia and study on the difference in response to finasteride treatment: A prospective cohort study.

Finasteride is commonly used for androgenetic alopecia (AGA) treatment. The aim of this study was to assess the therapeutic maintenance effect of a finasteride every other month (EOM) regimen and analyze clinical and laboratory differences in patients with AGA according to their treatment response. One hundred males with AGA who received finasteride 1 mg daily treatment for a year were enrolled in the study. At 1 year follow-up, treatment responses of patients who completed the visit schedule were assessed using five scales. The patients were assigned to good or bad response groups according to their assessment. Further, they were randomly divided into two groups (daily vs. EOM) and treated with finasteride (1 mg) for 1 more year. At 2 years follow-up, treatment efficacy was assessed. At 1-year follow-up, 36 patients completed the schedule, including eight and three patients in the good and bad response groups, respectively. At the 2-year follow-up, 23 patients completed the schedule, with nine in the daily group and 14 in the EOM group. Changes in global photographic assessment in the second year were 1.33 and 1.29 for the daily and EOM groups, respectively. The daily group showed an elevated hair density and lower concentration of dihydrotestosterone (DHT) and the DHT to testosterone ratio (DHT/T). However, the EOM group showed decreased hair density and elevated DHT and DHT/T. Following treatment response assessment after 1 year of treatment, the good response group showed early onset which was associated with maternal AGA. Analysis of serum androgen hormone magnitude of DHT reduction was much greater (54.4% vs. 44.4%). DHT/T was higher in the bad response group (1.98 vs. 2.33). We concluded that the finasteride EOM regimen showed similar maintenance effects to the daily regimen.

Engineering Escherichia coli for constitutive production of monophosphoryl lipid A vaccine adjuvant.

During the COVID-19 pandemic, expedient vaccine production has been slowed by the shortage of safe and effective raw materials, such as adjuvants, essential components to enhance the efficacy of vaccines. Monophosphoryl lipid A (MPLA) is a potent and safe adjuvant used in human vaccines, including the Shingles vaccine, Shingrix. 3-O-desacyl-4'-monophosphoryl lipid A (MPL), a representative MPLA adjuvant commercialized by GSK, was prepared via chemical conversion of precursors isolated from Salmonella typhimurium R595. However, the high price of these materials limits their use in premium vaccines. To combat the scarcity and high cost of safe raw materials for vaccines, we need to develop a feasible MPLA production method that is easily scaled up to meet industrial requirements. In this study, we engineered peptidoglycan and outer membrane biosynthetic pathways in Escherichia coli and developed a Escherichia coli strain, KHSC0055, that constitutively produces EcML (E. coli-produced monophosphoryl lipid A) without additives such as antibiotics or overexpression inducers. EcML production was optimized on an industrial scale via high-density fed-batch fermentation, and obtained 2.7 g of EcML (about 135,000 doses of vaccine) from a 30-L-scale fermentation. Using KHSC0055, we simplified the production process and decreased the production costs of MPLA. Then, we applied EcML purified from KHSC0055 as an adjuvant for a COVID-19 vaccine candidate (EuCorVac-19) currently in clinical trial stage III in the Philippines. By probing the efficacy and safety of EcML in humans, we established KHSC0055 as an efficient cell factory for MPLA adjuvant production.

The impact of early cryoballoon ablation on clinical outcome in patients with atrial fibrillation: From the Korean cryoballoon ablation registry.

INTRODUCTION: Influence of early atrial fibrillation (AF) ablation, particularly cryoballoon ablation (CBA), on clinical outcome during long-term follow-up has not been clarified. The objective was to determine whether an early CBA (diagnosis-to-ablation of ≤6 months) strategy could affect freedom from AF recurrence after index CBA. METHODS: The study included 2605 patients from Korean CBA registry data with follow-up >12 months after de novo CBA. The primary outcome was recurrence of atrial tachyarrhythmias (ATs) of ≥30-s after a 3-month blanking period. RESULTS: Compared to patients in early CBA group, patients in late CBA group had higher prevalence of diabetes, congestive heart failure, and chronic kidney disease, and higher mean CHA2 DS2 -VAS score. During mean follow-up of >21 months, ATs recurrence was detected in 839 (32.2%) patients. The early CBA group showed a significantly lower 2-year recurrence rate of ATs than the late CBA group (26.1% vs. 31.7%, p = 0.043). In subgroup analysis, the early CBA group showed significantly higher 1-year and 2-year freedom from ATs recurrence than the late CBA group only in paroxysmal atrial fibrillation (PAF) patients in overall and propensity score matched cohorts. Multivariate analysis showed that early CBA was an independent factor for preventing ATs recurrence in PAF (hazard ratio: 0.637; 95% confidence intervals: 0.412-0.984). CONCLUSION: Early CBA strategy, resulting in significantly lower ATs recurrence during 2-year follow-up after index CBA, might be considered as an initial rhythm control therapy in patients with paroxysmal AF.

Optimal Coverage of Full Frequency Reuse in FFR Networks in Relation to Power Scaling of a Base Station.

As a strategy to coordinate inter-cell interference in cellular networks, a fractional frequency reuse (FFR) system is proposed, in which the frequency bandwidth is split into two orthogonal bands; users staying near the center of a FFR cell use the band with a frequency reuse (FR) factor of one (i.e., full FR), and users located close to the cell edge utilize the band with a FR factor greater than one (i.e., partial FR). Full FR coverage, which identifies full FR and partial FR regions (that is, near-center and near-edge regions) within a FFR cell, has a crucial effect on system performance. Some of the authors of this paper recently investigated the optimization of full FR coverage to maximize system throughput. They analytically showed that under the constraint of satisfying a specified target outage probability, the optimal full FR coverage is a non-increasing function of base station power when all base station powers in the cellular network are scaled at an equal rate. Interestingly, in this paper, it is proven that as the power of a single base station is scaled, the optimal full FR coverage in that cell is a non-decreasing function of base station power. Our results provide useful insight into the design of full FR coverage in relation to the transmit power of a base station. It gives a deeper understanding of the intricate relationship between important FFR system parameters of base station power and full FR coverage.

Robotic and laparoscopic right lobe living donation compared to the open approach: A multicenter study on 1194 donor hepatectomies.

Due to the success of minimally invasive liver surgery, laparoscopic and robotic minimally invasive donor hepatectomies (MIDH) are increasingly performed worldwide. We conducted a retrospective, multicentre, propensity score-matched analysis on right lobe MIDH by comparing the robotic, laparoscopic, and open approaches to assess the feasibility, safety, and early outcomes of MIDHs. From January 2016 until December 2020, 1194 donors underwent a right donor hepatectomy performed with a robotic (n = 92), laparoscopic (n = 306), and open approach (n = 796) at 6 high-volume centers. Donor and recipients were matched for different variables using propensity score matching (1:1:2). Donor outcomes were recorded, and postoperative pain was measured through a visual analog scale. Recipients' outcomes were also analyzed. Ninety-two donors undergoing robotic surgery were matched and compared to 92 and 184 donors undergoing laparoscopic and open surgery, respectively. Conversions to open surgery occurred during 1 (1.1%) robotic and 2 (2.2%) laparoscopic procedures. Robotic procedures had a longer operative time (493 ± 96 min) compared to laparoscopic and open procedures (347 ± 120 and 358 ± 95 min; p < 0.001) but were associated with reduced donor blood losses ( p < 0.001). No differences were observed in overall and major complications (≥ IIIa). Robotic hepatectomy donors had significantly less pain compared to the 2 other groups ( p < 0.001). Fifty recipients of robotic-procured grafts were matched to 50 and 100 recipients of laparoscopic and open surgery procured grafts, respectively. No differences were observed in terms of postoperative complications, and recipients' survival was similar ( p =0.455). In very few high-volume centers, robotic right lobe procurement has shown to be a safe procedure. Despite an increased operative and the first warm ischemia times, this approach is associated with reduced intraoperative blood losses and pain compared to the laparoscopic and open approaches. Further data are needed to confirm it as a valuable option for the laparoscopic approach in MIDH.

How Much Is Enough? A Surgical Perspective on Imaging Modalities to Estimate Function and Volume of the Future Liver Remnant before Hepatic Resection.

Liver resection is the first curative option for most hepatic primary and secondary malignancies. However, post-hepatectomy liver failure (PHLF) still represents a non-negligible postoperative complication, embodying the most frequent cause of hepatic-related mortality. In the absence of a specific treatment, the most effective way to deal with PHLF is its prevention through a careful preoperative assessment of future liver remnant (FLR) volume and function. Apart from the clinical score and classical criteria to define the safe limit of resectability, new imaging modalities have shown their ability to assist surgeons in planning the best operative strategy with a precise estimation of the FLR amount. New technologies leading to liver and tumor 3D reconstruction may guide the surgeon along the best resection planes combining the least liver parenchymal sacrifice with oncological appropriateness. Integration with imaging modalities, such as hepatobiliary scintigraphy, capable of estimating total and regional liver function, may bring about a decrease in postoperative complications. Magnetic resonance imaging with hepatobiliary contrast seems to be predominant since it simultaneously integrates hepatic function and volume information along with a precise characterization of the target malignancy.

Donor safety of remnant liver volumes of less than 30% in living donor liver transplantation: A systematic review and meta-analysis.

PURPOSE: This meta-analysis aimed to investigate the acceptability of donor remnant liver volume (RLV) to total liver volume (TLV) ratio (RLV/TLV) being <30% as safe in living donor liver transplantations (LDLTs). METHODS: Online databases were searched from January 2000 to June 2022. Pooled odds ratios (ORs) and standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using fixed- or random-effects model. RESULTS: One prospective and seven retrospective studies comprising 1935 patients (164 RLV/TLV <30% vs. 1771 RLV/TLV ≥30%) were included. Overall (OR = 1.82; 95% CI [1.24, 2.67]; p = .002) and minor (OR = 1.88; 95% CI [1.23, 2.88]; p = .004) morbidities were significantly lower in the RLV/TLV ≥30% group than in the RLV/TLV <30% group (OR = 1.82; 95% CI [1.24, 2.67]; p = .002). No significant differences were noted in the major morbidity, biliary complications, and hepatic dysfunction. Peak levels of bilirubin (SMD = .50; 95% CI [.07, .93]; p = .02) and international normalized ratio (SMD = .68; 95% CI [.04, 1.32]; p = .04) were significantly lower in the RLV/TLV ≥ 30% group than in the RLV/TLV <30% group. No significant differences were noted in the peak alanine transferase and aspartate transaminase levels and hospital stay. CONCLUSIONS: Considering the safety of the donor as the top priority, the eligibility of a potential liver donor in LDLT whose RLV/TLV is expected to be <30% should not be accepted.

Structure-based drug discovery of a corticotropin-releasing hormone receptor 1 antagonist using an X-ray free-electron laser.

Thus far, attempts to develop drugs that target corticotropin-releasing hormone receptor 1 (CRF1R), a drug target in stress-related therapy, have been unsuccessful. Studies have focused on using high-resolution G protein-coupled receptor (GPCR) structures to develop drugs. X-ray free-electron lasers (XFELs), which prevent radiation damage and provide access to high-resolution compositions, have helped accelerate GPCR structural studies. We elucidated the crystal structure of CRF1R complexed with a BMK-I-152 antagonist at 2.75 Å using fixed-target serial femtosecond crystallography. The results revealed that two unique hydrogen bonds are present in the hydrogen bond network, the stalk region forms an alpha helix and the hydrophobic network contains an antagonist binding site. We then developed two antagonists-BMK-C203 and BMK-C205-and determined the CRF1R/BMK-C203 and CRF1R/BMK-C205 complex structures at 2.6 and 2.2 Å, respectively. BMK-C205 exerted significant antidepressant effects in mice and, thus, may be utilized to effectively identify structure-based drugs against CRF1R.

Donor Safety and Risk Factors of Pure Laparoscopic Living Donor Right Hepatectomy: A Korean Multicenter Study.

OBJECTIVE: The aim of this study was to identify safety and risk factors of living donor after pure laparoscopic donor right hepatectomy in a Korean multicenter cohort study. BACKGROUND: Pure laparoscopic donor right hepatectomy is not yet a standardized surgical procedure due to lack of data. METHODS: This retrospective study included 543 patients undergoing PLRDH between 2010 and 2018 in 5 Korean transplantation centers. Complication rates were assessed and multivariate logistic regression analyses were performed to identify risk factors of open conversion, overall complications, major complications, and biliary complications. RESULTS: Regarding open conversion, the incidence was 1.7% and the risk factor was body mass index >30 kg/m 2 [ P =0.001, odds ratio (OR)=22.72, 95% CI=3.56-146.39]. Rates of overall, major (Clavien-Dindo classification III-IV), and biliary complications were 9.2%, 4.4%, and 3.5%, respectively. For overall complications, risk factors were graft weight >700 g ( P =0.007, OR=2.66, 95% CI=1.31-5.41), estimated blood loss ( P <0.001, OR=4.84, 95% CI=2.50-9.38), and operation time >400 minutes ( P =0.01, OR=2.46, 95% CI=1.25-4.88). For major complications, risk factors were graft weight >700 g ( P =0.002, OR=4.01, 95% CI=1.67-9.62) and operation time >400 minutes ( P =0.003, OR=3.84, 95% CI=1.60-9.21). For biliary complications, risk factors were graft weight >700 g ( P =0.01, OR=4.34, 95% CI=1.40-13.45) and operation time >400 minutes ( P =0.01, OR=4.16, 95% CI=1.34-12.88). CONCLUSION: Careful donor selection for PLRDH considering body mass index, graft weight, estimated blood loss, and operation time combined with skilled procedure can improve donor safety.

Evolution of the technique of renoportal anastomosis for patients with complete portal venous occlusion in living donor liver transplantation: a retrospective cohort study.

BACKGROUND: This study aimed to present our surgical technique and the long-term outcomes of living donor liver transplantations with renoportal anastomosis for patients with complete portal venous occlusion. Renoportal anastomosis (RPA) is a promising technique for portal flow reconstruction during liver transplantation in patients with complete occlusion of the portal vein and extensive splanchnic vein thrombosis. However, reports demonstrating living donor liver transplantations (LDLT) with renoportal anastomosis are rarer than those demonstrating deceased donor liver transplantation. MATERIALS AND METHODS: In this single-centre retrospective cohort study, the authors analyzed the medical records of patients who underwent portal flow reconstruction via RPA with end-to-end anastomosis between the interposition graft and LRV-connected inferior vena cava (VC) cuff. The outcomes included postoperative RPA-related morbidity and patient and allograft survival for patients who underwent LDLT with RPA. RESULTS: Fifteen patients underwent LDLT with portal flow reconstruction via RPA from January 2005 to December 2019. The median follow-up period was 80.7 months (range: 27 days-195.2 months). RPA evolved from end-to-end anastomosis in 1 (6.7%) patient to end-to-side anastomoses in the next 6 (40%) patients and finally, to end-to-end anastomoses between the inferior VC cuff connected to the left renal vein and interposing vascular grafts in 8 (53.3%) patients. After standardization of the RPA technique from the eighth case in 2011, the incidence rate of RPA-related complications significantly decreased from 42.9% (3/7) to 12.5% (1/8). At the last follow-up, all 11 surviving patients had normal liver function, and 10 patients had patent anastomoses on imaging examination. CONCLUSIONS: This standardized RPA technique using an inferior VC cuff connected to the left renal vein creates a safe end-to-end RPA.

Favorable Prognostic Factors for Survival Outcomes of Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis After Hepatectomy.

BACKGROUND: This study aimed to investigate prognostic factors of recurrence and survival associated with hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). PATIENTS AND METHODS: This retrospective study included 161 patients with HCC with PVTT who underwent hepatectomy between January 2003 and January 2014 at the Asan Medical Center. Regression analyses were conducted to identify favorable predictive factors for overall survival (OS) and recurrence-free survival (RFS). RESULTS: The median follow-up was 15.9 months, while 1-, 3-, and 5-year OS was 65.0%, 38.4%, and 36.0%, respectively, and 1-year RFS was 25.5%. There were no significant differences in OS and RFS between the patients with portal vein invasion (Vp) 1-2 and Vp3-4 PVTT. Patients with intrahepatic recurrence had significantly better overall survival than patients with extrahepatic recurrence. Transcatheter arterial chemoembolization and radiofrequency ablation were the most effective treatments for intrahepatic metastasis, and surgery was the most effective treatment for extrahepatic metastasis. On multivariate analysis, absence of esophageal varices, maximal tumor size < 5 cm, tumor location in single lobe, and anatomical resection were favorable prognostic factors for OS and R0 resection, and absence of microvascular invasion was a favorable prognostic factor for RFS. CONCLUSION: The long-term outcome of patients with HCC with PVTT can be improved under consideration of favorable prognostic factors including absence of esophageal varices, maximal tumor size < 5 cm, tumor location in single lobe, and anatomical resection, R0 resection, and absence of microvascular invasion. In addition, recurrent HCC required aggressive management to prolong overall survival.