Left lobe living donor liver transplantation using the resection and partial liver segment 2-3 transplantation with delayed total hepatectomy (RAPID) procedure in cirrhotic patients: First case report in Korea.

In liver transplantation, the primary concern is to ensure an adequate future liver remnant (FLR) volume for the donor, while selecting a graft of sufficient size for the recipient. The living donor-resection and partial liver segment 2-3 transplantation with delayed total hepatectomy (LD-RAPID) procedure offers a potential solution to expand the donor pool for living donor liver transplantation (LDLT). We report the first case involving a cirrhotic patient with autoimmune hepatitis and hepatocellular carcinoma, who underwent left lobe LDLT using the LD-RAPID procedure. The living liver donor (LLD) underwent a laparoscopic left hepatectomy, including middle hepatic vein. The resection on the recipient side was an extended left hepatectomy, including the middle hepatic vein orifice and caudate lobe. At postoperative day 7, a computed tomography scan showed hypertrophy of the left graft from 320 g to 465 mL (i.e., a 45.3% increase in graft volume body weight ratio from 0.60% to 0.77%). After a 7-day interval, the diseased right lobe was removed in the second stage surgery. The LD-RAPID procedure using left lobe graft allows for the use of a small liver graft or small FLR volume in LLD in LDLT, which expands the donor pool to minimize the risk to LLD by enabling the donation of a smaller liver portion.

Light-Induced Self-Assembled Polydiacetylene/Carbon Dot Functional "Honeycomb".

The design of functional supramolecular assemblies from individual molecular building blocks is a fundamental challenge in chemistry and material science. We report on the fabrication of "honeycomb" films by light-induced coassembly of diacetylene derivatives and carbon dots. Specifically, modulating noncovalent interactions between the carbon dots, macrocyclic diacetylene, and anthraquinone diacetylene facilitates formation of thin films exhibiting a long-range, uniform pore structure. We show that light irradiation at distinct wavelengths plays a key role in the assembly process and generation of unique macro-porous morphology, by both initiating interactions between the carbon dots and the anthraquinone moieties and giving rise to the topotactic polymerization of the polydiacetylene network. We further demonstrate utilization of the macro-porous film as a photocatalytic platform for water pollutant degradation and as potential supercapacitor electrodes, both applications taking advantage of the high surface area, hydrophobicity, and pore structure of the film.

Biliary complications after adult-to-adult living-donor liver transplantation: An international multicenter study of 3633 cases.

In living-donor liver transplantation, biliary complications including bile leaks and biliary anastomotic strictures remain significant challenges, with incidences varying across different centers. This multicentric retrospective study (2016-2020) included 3633 adult patients from 18 centers and aimed to identify risk factors for these biliary complications and their impact on patient survival. Incidences of bile leaks and biliary strictures were 11.4% and 20.6%, respectively. Key risk factors for bile leaks included multiple bile duct anastomoses (odds ratio, [OR] 1.8), Roux-en-Y hepaticojejunostomy (OR, 1.4), and a history of major abdominal surgery (OR, 1.4). For biliary anastomotic strictures, risk factors were ABO incompatibility (OR, 1.4), blood loss >1 L (OR, 1.4), and previous abdominal surgery (OR, 1.7). Patients experiencing biliary complications had extended hospital stays, increased incidence of major complications, and higher comprehensive complication index scores. The impact on graft survival became evident after accounting for immortal time bias using time-dependent covariate survival analysis. Bile leaks and biliary anastomotic strictures were associated with adjusted hazard ratios of 1.7 and 1.8 for graft survival, respectively. The study underscores the importance of minimizing these risks through careful donor selection and preoperative planning, as biliary complications significantly affect graft survival, despite the availability of effective treatments.

Laparoscopic liver resection as a treatment option for intrahepatic cholangiocarcinoma.

Laparoscopic liver resection (LLR) remains controversial in the treatment of intrahepatic cholangiocarcinoma (ICC). The aim of the present study is to investigate the outcomes of LLR for ICC compared to open liver resection (OLR). We retrospectively reviewed patients who underwent surgery for ICC between January 2013 and February 2020. OLR and LLR were compared after propensity score matching (PSM). Overall survival (OS) and recurrence-free survival (RFS) were compared between the matched groups. During the study period, 219 patients met the inclusion criteria (OLR = 170 patients, 77.6%; LLR = 49 patients, 22.4%). Two groups of 43 patients each were analyzed after PSM. The 5-year RFS and OS were 44.6% and 47.9% in the OLR group and 50.9% and 39.8% in the LLR group, respectively. Hospital stay and intensive care unit care were significantly shorter and lower in the LLR group than in the OLR group, respectively. Total postoperative complications and complication rates for those Clavien-Dindo grade 3 or higher were similar between the OLR group and the LLR group. Multiple tumors and lymph node metastases were predisposing factors for tumor recurrence and death in multivariate analysis. The present study suggests that LLR should be considered in selective ICC because of short hospitalization and similar oncologic outcome and overall survival.

Comparison between laparoscopic liver resection and open liver resection in patients with hepatocellular carcinoma with portal vein tumor thrombosis.

BACKGROUND: Recently, the outcomes of surgical treatment for advanced hepatocellular carcinoma (HCC) have improved. However, despite the technical advancements in laparoscopic liver resection (LLR), it is still not recommended as the standard treatment for HCC with portal vein tumor thrombosis (PVTT) because of the poor oncological outcomes. This study aims to compare the clinical outcomes of open liver resection (OLR) and LLR in patients with HCC with PVTT. METHODS: A total of 86 patients with PVTT confirmed in the pathological report between January 2014 and December 2018, were enrolled. Short-term, postoperative, and long-term outcomes, including recurrence-free survival and overall survival rates, were evaluated. RESULTS: No difference between the two groups, except for age, was detected. The median age in the laparoscopic group was significantly higher than that in the open group. Regarding the pathological features, the maximal tumor size was significantly larger in the OLR; other pathological factors did not differ. There was no significant difference between overall survival (OS) and recurrence-free survival (RFS). Vp3 PVTT (hazards ratio [HR] 6.1, 95% confidence interval [CI] 1.9-18.5), Edmondson grade IV (HR 4.7, 95% CI 1.7-12.9, p = 0.003), and intrahepatic metastasis (HR 3.9, 95% CI 2.1-7.2, p < 0.001) remained the unique independent predictors of recurrence-free survival according to a multivariate Cox proportional hazard regression analysis. CONCLUSIONS: Laparoscopic liver resection for the management of HCC with PVTT provides the same short- and long-term results as those of the open approach.

Prevention of Cytomegalovirus Infection in Solid Organ Transplant Recipients: Guidelines by the Korean Society of Infectious Diseases and the Korean Society for Transplantation.

Cytomegalovirus (CMV) is the most important opportunistic viral pathogen in solid organ transplant (SOT) recipients. The Korean guideline for the prevention of CMV infection in SOT recipients was developed jointly by the Korean Society for Infectious Diseases and the Korean Society of Transplantation. CMV serostatus of both donors and recipients should be screened before transplantation to best assess the risk of CMV infection after SOT. Seronegative recipients receiving organs from seropositive donors face the highest risk, followed by seropositive recipients. Either antiviral prophylaxis or preemptive therapy can be used to prevent CMV infection. While both strategies have been demonstrated to prevent CMV infection post-transplant, each has its own advantages and disadvantages. CMV serostatus, transplant organ, other risk factors, and practical issues should be considered for the selection of preventive measures. There is no universal viral load threshold to guide treatment in preemptive therapy. Each institution should define and validate its own threshold. Valganciclovir is the favored agent for both prophylaxis and preemptive therapy. The evaluation of CMV-specific cell-mediated immunity and the monitoring of viral load kinetics are gaining interest, but there was insufficient evidence to issue recommendations. Specific considerations on pediatric transplant recipients are included.

Safety and efficacy of early corticosteroid withdrawal in liver transplant recipients: A randomized controlled trial.

Backgrounds/Aims: Prolonged use of steroids after liver transplantation (LT) significantly increases the risk of diabetes or cardiovascular disease, which can adversely affect patient outcomes. Our study evaluated the effectiveness and safety of early steroid withdrawal within the first year following LT. Methods: This study was conducted as an open-label, multicenter, randomized controlled trial. Liver transplant recipients were randomly assigned to one of the following two groups: Group 1, in which steroids were withdrawn two weeks posttransplantation, and Group 2, in which steroids were withdrawn three months posttransplantation. This study included participants aged 20 to 70 years who were scheduled to undergo a single-organ liver transplant from a living or deceased donor at one of the four participating centers. Results: Between November 2012 and August 2020, 115 patients were selected and randomized into two groups, with 60 in Group 1 and 55 in Group 2. The incidence of new-onset diabetes after transplantation (NODAT) was notably higher in Group 1 (32.4%) than in Group 2 (10.0%) in the per-protocol set. Although biopsy-proven acute rejection, graft failure, and mortality did not occur, the median tacrolimus trough level/dose/weight in Group 1 exceeded that in Group 2. No significant differences in safety parameters, such as infection and recurrence of hepatocellular carcinoma, were observed between the two groups. Conclusions: The present study did not find a significant reduction in the incidence of NODAT in the early steroid withdrawal group. Our study suggests that steroid withdrawal three months posttransplantation is a standard and safe immunosuppressive strategy for LT patients.

Liver resection in selective hepatocellular carcinoma with Vp3 or Vp4 portal vein tumor thrombosis improves prognosis.

BACKGROUND/AIM: Hepatocellular carcinoma (HCC) tumor thrombi located in the first branch of the portal vein (Vp3) or in the main portal trunk (Vp4) are associated with poor prognosis. This study aimed to investigate the clinicopathological characteristics and risk factors for HCC recurrence and mortality following liver resection (LR) in patients with Vp3 or Vp4 HCC. METHODS: The study included 64 patients who underwent LR for HCC with Vp3 or Vp4 portal vein tumor thrombosis (PVTT). RESULTS: Fifty-eight patients (90.6%) had Vp3 PVTT, whereas the remaining six patients exhibited Vp4 PVTT. The median tumor size measured 8 cm, with approximately 36% of patients presented with multiple tumors. Fifty-four patients (84.4%) underwent open LR, whereas 10 patients underwent laparoscopic LR. In the Vp4 cases, combined LR and tumor thrombectomy were performed. The 3-year cumulative disease-free survival rate was 42.8% for the Vp3 group and 22.2% for the Vp4 group. The overall survival (OS) rate at 3 years was 47.9% for the Vp3 group and 60.0% for the Vp4 group. Intrahepatic metastasis has been identified as an important contributor to HCC recurrence. High hemoglobin levels are associated with high mortality. CONCLUSION: LR is a safe and effective treatment modality for selected patients with Vp3 or Vp4 HCC PVTT. This suggests that LR is a viable option for these patients, with favorable outcomes in terms of OS.

Asian Pacific Association for the Study of the Liver clinical practice guidelines on liver transplantation.

Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines.

Macrocyclic Diacetylene / Sulfonate Fluorophore Hierarchical Multifunctional Nanotoroids.

Functional supramolecular materials exhibit important features including structural versatility and versatile applications. Here, this study reports the construction of unique hierarchically organized nanotoroids exhibiting fluorescence, photocatalytic, and sensing properties. The nanotoroids comprise of macrocyclic diacetylenes (MCDA) and 8-anilino-1-naphthalene sulfonate (ANS), a negatively charged aromatic fluorescent dye. This study shows that the hierarchical structure of the nanotoroids consist of MCDA nanofibers formed by stacked diacetylene monomers as the basic units, which are further bent and aligned into toroidal organization by electrostatic and hydrophobic interactions with the ANS molecules. The amine moieties on the nanotoroids surface are employed for deposition of gold nanostructures - Au nanoparticles or Au nanosheets - which constitute effective platforms for photocatalysis and surface enhanced Raman scattering (SERS)-based sensing.

Effects of 4-week downhill treadmill walking on the vertebral angle and postural muscle activity in participants with thoracic kyphosis and forward head posture: A comparative longitudinal study.

BACKGROUND: Maintaining correct posture and optimal spine function has become an important issue due to the increased use of computers and smartphones. OBJECTIVE: To investigate the effect of a 4-week downhill treadmill exercise (DTWE) program on participants with thoracic kyphosis and forward head posture (FHP). METHODS: Twenty-eight male participants were randomly assigned to the DTWE (n= 14) or standard treadmill walking exercise (STWE) (n= 14) group. They performed 30-minute exercise three times a week for 4 weeks. The vertebral angle was measured using a three-dimensional (3D) motion analysis system. Surface electromyography (EMG) was performed to record muscle activity in the thoracic erector spinae (TES), sternocleidomastoid muscle (SCM), and cervical erector spinae (CES). RESULTS: The DTWE group showed significant increases in the craniovertebral angle (CVA) and TES EMG activity and significant decreases in the thoracic kyphosis angle and SCM and CES EMG activity compared with those shown by the STWE group following the intervention (p< 0.05). However, lumbar lordosis or pelvic tilt angles did not differ significantly between the groups after the intervention (p> 0.05). CONCLUSIONS: DTWE can be effective in reducing thoracic kyphosis and FHP without causing compensatory movements of the lumbar spine and pelvis.

Benefit of living donor liver transplantation in graft survival for extremely high model for end-stage liver disease score ≥35.

BACKGROUND AND AIMS: Living liver donation with high model for end-stage liver disease (MELD) score was discouraged despite organ shortage. This study aimed to compare graft survival between living donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT) recipients with extremely high-MELD (score of ≥35). METHODS: Between 2008 and 2018, 359 patients who underwent liver transplantation with a MELD score ≥35 were enrolled. We compared graft survival between LDLT and DDLT after propensity score matching (PSM) and performed subgroup analysis according to donor type. RESULTS: After PSM, there was no statistical difference in graft survival between the LDLT and DDLT groups (p = .466). Old age, acute on chronic liver failure, re-transplantation, preoperative intensive care unit stay and red blood cell (RBC) transfusion during the operation were risk factors for graft failure (p = .046, .005, .032, .015 and .001, respectively). Biliary complications were more common in the LDLT group (p = .021), while viral infection, postoperative uncontrolled ascites, and postoperative hemodialysis were more common in the DDLT group (p = .002, .018, and .027, respectively). In the LDLT group, acute chronic liver failure, intraoperative RBC transfusion, and early postoperative complications were risk factors for graft failure (p = .007, <.001, and .001, respectively). CONCLUSION: Our study showed that LDLT is not inferior to DDLT in graft survival if appropriate risk evaluation is performed in cases of extremely high-MELD scores. This result will help overcome organ shortages in high-MELD liver transplantation.

Long-Term Outcomes of Liver Transplantation in Hepatocellular Carcinoma with Bile Duct Tumor Thrombus: A Comparison with Portal Vein Tumor Thrombus.

Liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) remains controversial. This study analyzed the recurrence and overall survival rates through long-term results after LT in HCC patients with BDTT and compared the results after LT in HCC patients with portal vein tumor thrombus (PVTT). We performed a retrospective study of 45 patients with PVTT, 16 patients with BDTT, and 11 patients with coexisting PVTT and BDTT among HCC patients who underwent LT at a single center from 1999 to 2020. The HCC recurrence rates were 40.4% at 1 year, 30.3.3% at 2 years, and 27.6% at 3 years in the PVTT group; 66.7%, 53.3%, and 46.7% in the BDTT group; and 22.2%, 22.2%, and 0% in the coexisting group (p = 0.183). Overall patient survival rates were 68.4% at 1 year, 54.3% at 2 years, and 41.7% at 3 years in the PVTT group; 81.3%, 62.5%, and 48.2% in the BDTT group; and 63.6%, 27.3%, and 0% in the coexisting group (p = 0.157). In the multivariate analysis, the pre-transplantation model for tumor recurrence after liver transplantation (MoRAL) score and model for end-stage liver disease (MELD) score were found to be independent risk factors for recurrence and survival in all groups. HCC patients with BDTT showed no difference in recurrence and survival compared with HCC patients with PVTT at the long-term follow-up after LT.

Ventilator support in the pretransplant period predisposes early graft failure after deceased donor liver transplantation.

Purpose: Deceased donor liver transplantation (DDLT) recipients in Korea are generally sicker due to an increasing organ shortage. In the present study, the risk factors for early 30-day liver graft failure after DDLT were identified. Methods: From August 2017 to February 2021, 265 adult DDLTs were performed. The characteristics of patients with and without 30-day graft failure were compared. Results: Liver graft failure occurred in 11 patients (17.7%) after DDLT. Baseline and perioperative characteristics of donors and recipients were not statistically significantly different between the 2 groups. The cumulative graft and overall survival rates at 6 months were 83.9% and 88.7%, respectively. Multivariate analysis showed ventilator support in the pretransplant period was a predisposing factor for 30-day graft failure after DDLT. Conclusion: Present study indicates that cautious decision is required when allocating DDLT in critically ill patients on mechanical ventilatory support.

Cancer Incidence in Living Liver Donors After Donor Hepatectomy.

Living liver donors (LLDs) are screened for transmissible diseases including cancer. We investigated the actual cancer incidence of LLDs compared with a matched healthy control group from the general Korean population using data from the Korean National Health Insurance Services (NHIS). A total of 12,372 LLDs who donated a liver graft between 2002 and 2018 were registered in the Korean Network for Organ Sharing. They were compared to a matched healthy control group selected from the Korean NHIS. Cancer diagnosis was identified in 175 LLDs (1.4%) and 1,014 controls (0.8%). Compared to the healthy control group, the incidence rate ratio of liver and thyroid cancer in the LLD group were significantly higher at 18.30 and 1.39, respectively. The incidences of 11 other specified cancers were not different between the two groups. The present study suggests that LLD after donor hepatectomy may require medical surveillance, especially for liver cancer.

Cyclized proteins with tags as permeable and stable cargos for delivery into cells and liposomes.

Despite the therapeutic potential of recombinant proteins, their cell permeabilities and stabilities remain significant challenges. Here we demonstrate that cyclized recombinant proteins can be used as universal cargos for permeable and stable delivery into cells and polydiacetylene liposomes. Utilizing a split intein-mediated process, cyclized model fluorescent proteins containing short tetraarginine (R4) and hexahistidine (H6) tags were generated without compromising their native protein functions. Strikingly, as compared to linear R4/H6-tagged proteins, the cyclized counterparts have substantially increased permeabilities in both cancer cells and synthetic liposomes, as well as higher resistances to enzymatic degradation in cancer cells. These properties are likely a consequence of structural constraints imposed on the proteins in the presence of short functional peptides. Additionally, photodynamic therapy by cyclized photoprotein-loaded liposomes in cancer cells was significantly improved in comparison to that by their non-cyclized counterparts. These findings suggest that our strategy will be universally applicable to intercellular delivery of proteins and therapeutics.

Liver transplantation for combined hepatocellular carcinoma and cholangiocarcinoma: A multicenter study.

BACKGROUND: Patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) are not traditionally considered eligible for liver transplantation (LT) due to poor outcomes. AIM: To compare outcomes between living donor LT (LDLT) patients with hepatocellular carcinoma (HCC) and LT patients with cHCC-CC and to identify risk factors for tumor recurrence and death after LT in cHCC-CC patients. METHODS: Data for pathologically diagnosed cHCC-CC patients (n = 111) who underwent LT from 2000 to 2018 were collected for a nine-center retrospective review. Patients (n = 141) who received LDLT for HCC at Samsung Medical Center from January 2013 to March 2017 were selected as the control group. Seventy patients in two groups, respectively, were selected by 1:1 matching. RESULTS: Cumulative disease-free survival (DFS) and overall survival (OS) in the cHCC-CC group were significantly worse than in the HCC group both before and after matching. Extrahepatic recurrence incidence in the cHCC-CC group was higher than that in the HCC group (75.5% vs 33.3%, P < 0.001). Multivariate analysis demonstrated that the cHCC-CC group had significantly higher rates of tumor recurrence and death compared to the HCC group. In cHCC-CC subgroup analysis, frequency of locoregional therapies > 3, tumor size > 3 cm, and lymph node metastasis were predisposing factors for tumor recurrence in multivariate analysis. Only a maximum tumor size > 3 cm was a predisposing factor for death. CONCLUSION: The poor prognosis of patients diagnosed with cHCC-CC after LT can be predicted based on the explanted liver. Frequent regular surveillance for cHCC-CC patients should be required for early detection of tumor recurrence.

Retro Diels-Alder-triggered self-assembly of a polymerizable macrocyclic diacetylene.

A new triggered self-assembly method, which utilizes retro Diels-Alder (rDA)-promoted self-assembly of a macrocyclic diacetylene, was developed. The steric bulk present in a Diels-Alder (DA) adduct was released by a thermally promoted rDA reaction, resulting in the generation of a linear diacetylene that readily self-assembles to form a supramolecular polymer. The maleimide-containing blue-colored polydiacetylene, which was generated by UV irradiation, was utilized as a thiol specific colorimetric sensor.

Novel Benchmark for Adult-to-Adult Living-donor Liver Transplantation: Integrating Eastern and Western Experiences.

OBJECTIVE: To define benchmark values for adult-to-adult living-donor liver transplantation (LDLT). BACKGROUND: LDLT utilizes living-donor hemiliver grafts to expand the donor pool and reduce waitlist mortality. Although references have been established for donor hepatectomy, no such information exists for recipients to enable conclusive quality and comparative assessments. METHODS: Patients undergoing LDLT were analyzed in 15 high-volume centers (≥10 cases/year) from 3 continents over 5 years (2016-2020), with a minimum follow-up of 1 year. Benchmark criteria included a Model for End-stage Liver Disease ≤20, no portal vein thrombosis, no previous major abdominal surgery, no renal replacement therapy, no acute liver failure, and no intensive care unit admission. Benchmark cutoffs were derived from the 75th percentile of all centers' medians. RESULTS: Of 3636 patients, 1864 (51%) qualified as benchmark cases. Benchmark cutoffs, including posttransplant dialysis (≤4%), primary nonfunction (≤0.9%), nonanastomotic strictures (≤0.2%), graft loss (≤7.7%), and redo-liver transplantation (LT) (≤3.6%), at 1-year were below the deceased donor LT benchmarks. Bile leak (≤12.4%), hepatic artery thrombosis (≤5.1%), and Comprehensive Complication Index (CCI ® ) (≤56) were above the deceased donor LT benchmarks, whereas mortality (≤9.1%) was comparable. The right hemiliver graft, compared with the left, was associated with a lower CCI ® score (34 vs 21, P < 0.001). Preservation of the middle hepatic vein with the right hemiliver graft had no impact neither on the recipient nor on the donor outcome. Asian centers outperformed other centers with CCI ® score (21 vs 47, P < 0.001), graft loss (3.0% vs 6.5%, P = 0.002), and redo-LT rates (1.0% vs 2.5%, P = 0.029). In contrast, non-benchmark low-volume centers displayed inferior outcomes, such as bile leak (15.2%), hepatic artery thrombosis (15.2%), or redo-LT (6.5%). CONCLUSIONS: Benchmark LDLT offers a valuable alternative to reduce waitlist mortality. Exchange of expertise, public awareness, and centralization policy are, however, mandatory to achieve benchmark outcomes worldwide.