Pure laparoscopic donor hepatectomy: Experience of 556 cases at Seoul National University Hospital.

Pure laparoscopic donor hepatectomy (PLDH) has become a routine procedure at Seoul National University Hospital, and the pure laparoscopic method is now being applied to liver recipients as well. This study aimed to review the procedure and outcomes of PLDH to identify any areas that required improvement. Data from 556 donors who underwent PLDH between November 2015 and December 2021 and their recipients were retrospectively reviewed. Among these, 541 patients underwent pure laparoscopic donor right hepatectomy (PLDRH). The mean hospital stay of the donor was 7.2 days, and the rate of grade I, II, IIIa, and IIIb complications was 2.2%, 2.7%, 1.3%, and 0.9%, respectively, without any irreversible disabilities or mortalities. The most common early and late major complications in the recipient were intraabdominal bleeding (n = 47, 8.5%) and biliary problems (n = 198, 35.6%), respectively. Analysis of the PLDRH procedure showed that operative time, liver removal time, warm ischemic time, Δhemoglobin%, Δtotal bilirubin%, and postoperative hospital stay decreased significantly as the number of cases accumulated. In conclusion, the operative outcomes of PLDRH improved as the number of cases increased. However, continuous caution is needed because major complications still occur in donors and recipients even after hundreds of cases.

Combined liver-kidney transplantation in pediatric patients.

Combined liver-kidney transplantation (CLKT) is a surgical procedure that involves transplanting both liver and kidney organs. There are two types of CLKT: simultaneous liver-kidney transplantation (smLKT) and sequential LKT (sqLKT). CLKT accounts for a small percentage of liver transplantations (LTs), particularly in pediatric cases. Nevertheless, the procedure has demonstrated excellent outcomes, with high survival rates and lower rejection rates. The main indications for CLKT in pediatric patients differ somewhat from that in adults, in which end-stage kidney disease after LT is the major indication. In children, congenital diseases are common reason for performing CLKT; the examples of such diseases include autosomal recessive polycystic kidney disease with congenital hepatic fibrosis which equally affects both organs, and primary hyperoxaluria type 1, a primary liver disease leading kidney failure. The decision between smLKT or sqLKT depends on the dominant organ failure, the specific pathophysiology, and available organ sources. However, there remain significant surgical and societal challenges surrounding CLKT. Innovations in pharmacology and genetic engineering have decreased the necessity for CLKT in early-diagnosed cases without portal hypertension or kidney replacement therapy. Nonetheless, these advancements are not universally accessible. Therefore, decision-making algorithms should be crafted, considering region-specific organ allocation systems and prevailing medical environments.

Initial outcome of external biliary drainage in living donor liver transplantation with pure laparoscopic donor hepatectomy.

Biliary complications after living donor liver transplantation (LDLT) are the most common and intractable complications due to both surgical and nonsurgical factors. External biliary drainage (EBD), a surgical option to prevent biliary complications, has recently been adopted in the era of pure laparoscopic donor right hepatectomy, which may result in increased bile duct problems in the recipients. This study retrospectively reviewed the patients who underwent LDLT with duct-to-duct anastomosis between July 2017 and October 2020 to analyze the initial outcomes of EBD and to compare the incidence of biliary complications in adult LDLT recipients who underwent duct-to-duct anastomosis with or without EBD. Only patients who underwent pure laparoscopic donor hepatectomy were included in this study. The patients were divided into 2 groups according to the application of EBD. The median follow-up period was 28.5 months. The overall incidence of Clavien-Dindo grade IIIa biliary complications was 35.0% (n=14) in the EBD group and 50.7% (n=76) in the non-EBD group ( p = 0.08). The incidence of biliary leakage was 0% in the EBD group and 15.3% in the non-EBD group ( p = 0.01). The EBD-related complication rate, that is, involving retraction, accidental removal, and dislocation, was 40.0%. EBD implementation is effective in preventing biliary leakage after LDLT with a graft procured using the pure laparoscopic donor right hepatectomy method with duct-to-duct biliary anastomosis. However, efforts should be made to prevent EBD-related complications. Further studies are needed to establish appropriate selection criteria for EBD.

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.

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.

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.

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.

Five Surfactin Isomers Produced during Cheonggukjang Fermentation by Bacillus pumilus HY1 and Their Properties.

The cyclic lipopeptide produced from Bacillus pumilus strain HY1 was isolated from Korean soybean sauce cheonggukjang. The chemical structures of the surfactin isomers were analyzed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and electrospray ionization tandem mass spectrometry (ESI-MS/MS). The five potential surfactin isoforms were detected with protonated masses of m/z 994.7, 1008.7, 1022.7, 1036.7, and 1050.7 and different structures in combination with Na+, K+, and Ca2+ ions. ESI-MS/MS analysis revealed that the isolated surfactin possessed the precise amino acid sequence LLVDLL and hydroxyl fatty acids with 12 to 16 carbons. The surfactin content during cheonggukjang fermentation increased from 0.3 to 51.2 mg/kg over 60 h of fermentation. The mixture of five surfactin isoforms of cheonggukjang inhibited the growth of two cancer cell lines. The growth of both MCF-7 and Caco-2 cells was strongly inhibited with 100 µg/µL of surfactin. This study is the first-time report of five surfactin isomers of Bacillus pumilus strain HY1 during Korean soybean sauce cheonggukjang fermentation, which has cytotoxic properties.

Network analysis of the metabolome and transcriptome reveals novel regulation of potato pigmentation.

To gain insights into the regulatory networks related to anthocyanin biosynthesis and identify key regulatory genes, we performed an integrated analysis of the transcriptome and metabolome in sprouts germinated from three colored potato cultivars: light-red Hongyoung, dark-purple Jayoung, and white Atlantic. We investigated transcriptional and metabolic changes using statistical analyses and gene-metabolite correlation networks. Transcript and metabolite profiles were generated through high-throughput RNA-sequencing data analysis and ultraperformance liquid chromatography quadrupole time-of-flight tandem mass spectrometry, respectively. The identification and quantification of changes in anthocyanin were performed using molecular formula-based mass accuracy and specific features of their MS(2) spectra. Correlation tests of anthocyanin contents and transcriptional changes showed 823 strong correlations (correlation coefficient, R (2)>0.9) between 22 compounds and 119 transcripts categorized into flavonoid metabolism, hormones, transcriptional regulation, and signaling. The connection network of anthocyanins and genes showed a regulatory system involved in the pigmentation of light-red Hongyoung and dark-purple Jayoung potatoes, suggesting that this systemic approach is powerful for investigations into novel genes that are potential targets for the breeding of new valuable potato cultivars.

Complete chloroplast genome sequences of Solanum commersonii and its application to chloroplast genotype in somatic hybrids with Solanum tuberosum.

KEY MESSAGE: Chloroplast genome of Solanum commersonii and S olanum tuberosum were completely sequenced, and Indel markers were successfully applied to distinguish chlorotypes demonstrating the chloroplast genome was randomly distributed during protoplast fusion. Somatic hybridization has been widely employed for the introgression of resistance to several diseases from wild Solanum species to overcome sexual barriers in potato breeding. Solanum commersonii is a major resource used as a parent line in somatic hybridization to improve bacterial wilt resistance in interspecies transfer to cultivated potato (S. tuberosum). Here, we sequenced the complete chloroplast genomes of Lz3.2 (S. commersonii) and S. tuberosum (PT56), which were used to develop fusion products, then compared them with those of five members of the Solanaceae family, S. tuberosum, Capsicum annum, S. lycopersicum, S. bulbocastanum and S. nigrum and Coffea arabica as an out-group. We then developed Indel markers for application in chloroplast genotyping. The complete chloroplast genome of Lz3.2 is composed of 155,525 bp, which is larger than the PT56 genome with 155,296 bp. Gene content, order and orientation of the S. commersonii chloroplast genome were highly conserved with those of other Solanaceae species, and the phylogenetic tree revealed that S. commersonii is located within the same node of S. tuberosum. However, sequence alignment revealed nine Indels between S. commersonii and S. tuberosum in their chloroplast genomes, allowing two Indel markers to be developed. The markers could distinguish the two species and were successfully applied to chloroplast genotyping (chlorotype) in somatic hybrids and their progenies. The results obtained in this study confirmed the random distribution of the chloroplast genome during protoplast fusion and its maternal inheritance and can be applied to select proper plastid genotypes in potato breeding program.

Criteria for selecting living liver donors to optimize recipient outcomes in pure laparoscopic donor right hepatectomy: a cohort study.

BACKGROUND: Although the adoption of pure laparoscopic donor hepatectomy has expanded driven by considerations of donor cosmesis and function, the criteria for selecting candidates for pure laparoscopic donor right hepatectomy (PLDRH) continue to be debated. This study aimed to delineate the distinctive characteristics of donors and recipients who underwent conventional open-donor right hepatectomy (CDRH) during the era of PLDRH. MATERIALS AND METHODS: The authors conducted a retrospective review of a prospectively collected single-centre database encompassing all right hepatectomies at Seoul National University Hospital from April 2016 to December 2021, a period during which there were no absolute contraindications for PLDRH. RESULTS: During the exclusive PLDRH period, there were still 63 cases of CDRH alongside 362 cases of PLDRH. The CDRH donors were older, had a lower estimated remnant liver volume, and a higher incidence of expected multiple openings in the portal vein and bile duct based on preoperative imaging compared with PLDRH donors. In the subgroup analysis, including only donors meeting two or more criteria (age ≥40 years, estimated remnant liver volume ≥35%, or multiple anticipated vessel openings), recipients in the PLDRH group exhibited significantly more early major complications ( P =0.029) compared with those in the CDRH group. CONCLUSION: As PLDRH gains traction in practice, it is essential to acknowledge that specific donor conditions, such as advanced age, limited remnant liver volume, and anticipation of multiple portal or bile duct openings, may merit contemplating CDRH as a means of optimizing recipient outcomes.

Machine-learning model to predict the tacrolimus concentration and suggest optimal dose in liver transplantation recipients: a multicenter retrospective cohort study.

Titrating tacrolimus concentration in liver transplantation recipients remains a challenge in the early post-transplant period. This multicenter retrospective cohort study aimed to develop and validate a machine-learning algorithm to predict tacrolimus concentration. Data from 443 patients undergoing liver transplantation between 2017 and 2020 at an academic hospital in South Korea were collected to train machine-learning models. Long short-term memory (LSTM) and gradient-boosted regression tree (GBRT) models were developed using time-series doses and concentrations of tacrolimus with covariates of age, sex, weight, height, liver enzymes, total bilirubin, international normalized ratio, albumin, serum creatinine, and hematocrit. We conducted performance comparisons with linear regression and populational pharmacokinetic models, followed by external validation using the eICU Collaborative Research Database collected in the United States between 2014 and 2015. In the external validation, the LSTM outperformed the GBRT, linear regression, and populational pharmacokinetic models with median performance error (8.8%, 25.3%, 13.9%, and - 11.4%, respectively; P < 0.001) and median absolute performance error (22.3%, 33.1%, 26.8%, and 23.4%, respectively; P < 0.001). Dosing based on the LSTM model's suggestions achieved therapeutic concentrations more frequently on the chi-square test (P < 0.001). Patients who received doses outside the suggested range were associated with longer ICU stays by an average of 2.5 days (P = 0.042). In conclusion, machine learning models showed excellent performance in predicting tacrolimus concentration in liver transplantation recipients and can be useful for concentration titration in these patients.

Donor body mass index over 30 is no barrier for pure laparoscopic donor right hepatectomy.

Backgrounds/Aims: Challenges arise when translating pure laparoscopic donor right hepatectomy (PLDRH) results from Asian to Western donors, due to differences in body mass index (BMI). This study compares the outcomes of PLDRH and conventional open donor right hepatectomy (CDRH) in donors with BMI over 30. Methods: Medical records of live liver donors (BMI > 30) undergoing right hepatectomy (2010-2021) were compared: 25 PLDRH cases vs. 19 CDRH cases. Donor and recipient demographics, operative details, and outcomes were analyzed. Results: PLDRH and CDRH had similar donor and recipient characteristics. PLDRH had longer liver removal and warm ischemic times, but a shorter post-liver removal duration than CDRH. Donor complication rates were comparable, with the highest complication being grade IIIa in PLDRH, necessitating needle aspiration for biloma on postoperative day 11. Fortunately, this donor fully recovered without additional treatment. No complications exceeding Clavien-Dindo grade IIIa occurred in either group. Recipient outcomes between the groups were similar. Conclusions: This study supports PLDRH as a viable option for donors with BMI over 30, challenging the notion that high BMI should deter considering PLDRH. The findings provide valuable insights into the safety and feasibility of PLDRH, encouraging further exploration of this technique in diverse donor populations.