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Background : Portal vein (PV) interposition can induce various PV-related complications, making more reliable techniques necessary. The present study describes the development of a modified patch venoplasty technique, combining the native PV wall and a vein homograft conduit, called modified patch-conduit venoplasty (MPCV). Methods : The surgical technique for MPCV was optimized by simulation and applied to seven pediatric patients undergoing liver transplantation (LT) for biliary atresia combined with PV hypoplasia. Results : The simulation study revealed that inserting the whole-length native PV wall as a longitudinal rectangular patch was more effective in preventing PV conduit stenosis than the conventional technique using triangular partial insertion. These findings were used to develop the MPCV technique, in which the native PV wall was converted into a long rectangular patch, acting as a backbone for PV reconstruction. A longitudinal incision on the vein conduit converted the cylindrical vein into a large vein patch. The wall of the native PV was fully preserved as the posterior wall of the PV conduit, thus preventing longitudinal redundancy and unwanted rotation of the reconstructed PV. This technique was applied to seven patients with biliary atresia undergoing living-donor and deceased-donor split LT. None of these patients has experienced PV complications for up to 12 months after transplantation. Conclusions: This newly devised MCPV technique can replace conventional PV interposition. MCPV may be a surgical option for reliable PV reconstruction using fresh or cryopreserved vein homografts during pediatric LT.

Fiber-reinforced composites (FRPs) are characterized by their lightweight nature and superior mechanical characteristics, rendering them extensively utilized across various sectors such as aerospace and automotive industries. Nevertheless, the precise mechanisms governing the interaction between the fibers present in FRPs and the polymer melt during industrial processing, particularly the manipulation of the flow–fiber coupling effect, remain incompletely elucidated. Hence, this study introduces a geometrically symmetrical 1 × 4 multi-cavity mold system, where each cavity conforms to the ASTM D638 Type V standard specimen. The research utilizes theoretical simulation analysis and experimental validation to investigate the influence of runner and overflow design on the flow–fiber coupling effect. The findings indicate that the polymer melt, directed by a geometrically symmetrical runner, results in consistent fiber orientation within each mold cavity. Furthermore, in the context of simulation analysis, the inclusion of the flow–fiber coupling effect within the system results in elevated sprue pressure levels and an expanded core layer region in comparison to systems lacking this coupling effect. This observation aligns well with the existing literature on the subject. Moreover, analysis of fiber orientation in different flow field areas reveals that the addition of an overflow area alters the flow field, leading to a significant delay in the flow–fiber coupling effect. To demonstrate the impact of overflow area design on the flow–fiber effect, the integration of fiber orientation distribution analysis highlights a transformation in fiber arrangement from the flow direction to cross-flow and thickness directions near the end-of-fill region in the injected part. Additionally, examination of the geometric dimensions of the injected part reveals asymmetrical geometric shrinkage between upstream and downstream areas in the end-of-fill region, consistent with microscopic fiber orientation changes influenced by the delayed flow–fiber coupling effect guided by the overflow area. In brief, the introduction of the overflow area extends the duration in which the polymer melt exerts control in the flow direction, consequently prolonging the period in which the fiber orientation governs in the flow direction (A11). This leads to the impact of fiber orientation on the flow of the polymer melt, with the flow reciprocally affecting the fibers. Subsequently, the interaction between these two elements persists until a state of equilibrium is achieved, known as the flow–fiber coupling effect, which is delayed.

Abstract Introduction Lenvatinib is approved for the treatment of patients with metastatic or recurrent hepatocellular carcinoma (HCC); however, clinical outcomes of lenvatinib therapy in patients with post‐liver transplantation (LT) HCC recurrence remain unclear. We investigated the efficacy and safety of lenvatinib in patients with post‐LT HCC recurrence. Methods This multinational, multicenter, retrospective study included 45 patients with recurrent HCC after LT who received lenvatinib at six institutions in three countries (Korea, Italy, and Hong Kong) from June 2017 to October 2021. Results At the time of lenvatinib initiation, 95.6% (n = 43) of patients had Child–Pugh A status, and 35 (77.8%) and 10 (22.2%) participants were classified as having albumin–bilirubin (ALBI) grades 1 and 2, respectively. The objective response rate was 20.0%. With a median follow‐up duration of 12.9 months (95% confidence interval [CI]: 11.2–14.7), the median progression‐free survival and overall survival (OS) were 7.6 (95% CI: 5.3–9.8) months, and 14.5 (95% CI: 0.8–28.2) months, respectively. Patients with ALBI grade 1 showed significantly better OS (52.3 months, [95% CI: not assessable]) than patients with ALBI grade 2 (11.1 months [95% CI: 0.0–30.4 months], p = 0.003). The most common adverse events were hypertension (n = 25, 55.6%), fatigue (n = 17, 37.8%), and anorexia (n = 14, 31.1%). Conclusion Lenvatinib showed consistent efficacy and toxicity profiles in patients with post‐LT HCC recurrence that were comparable to those reported from previous studies among non‐LT HCC patients. The baseline ALBI grade correlated with better OS in post‐LT lenvatinib‐treated patients.

Background : Infection is one of the most significant possible complications after liver transplantation (LT). This study identified patterns of infection and compared the characteristics of patients with and without infections during the first year after LT. Methods : This retrospective cohort study reviewed adult patients’ electronic medical records to identify infections occurring up to 1 year after LT. The criteria for identifying infections in the first year after LT were either a positive laboratory test or recorded clinical signs or symptoms meeting the accepted criteria for each infection. Results : The overall incidence of infection during the posttransplant year was 17.3%. The highest infection rate (8.2%) was identified in the first month after LT, with rates of 1.9% and 7.2% at 1–3 months and 3 months to 1 year after LT, respectively. Respiratory tract infections were the most common type of infection, and bacteria were the most common causal agents in the first month post-LT. Conclusions: It is difficult to compare the posttransplant incidence of infection in the present study with previous studies due to differences in study designs and definitions of infection. This study revealed that respiratory tract infections were the most common type of overall posttransplant infection, especially during the period from 3 months to 1 year after LT.

Background Intrahepatic cholangiocarcinoma (ICC) of the left liver often shows left-sided lymph node (LN) metastasis. If gastric lesser curvature is extensively dissected, it can induce an iatrogenic injury to the extragastric vagus nerve branches that control motility of the pyloric sphincter and lead to gastric stasis. To cope with such LN dissection-associated gastric stasis, we performed pyloroplasty preemptively. The objective of this study was to analyze our 20-year experience of preemptive pyloroplasty performed in 10 patients. Methods We investigated clinical sequences of 10 patients with ICC who underwent preemptive pyloroplasty following left hepatectomy and extended left-sided LN dissection. Incidence of gastric stasis and oncological survival outcomes were analyzed. Results All 10 patients were classified as stage IIIB due to T1-3N1M0 stage according to the 8th edition of American Joint Committee on Cancer staging system. The overall patient survival rate was 51.9% at 1 year, 25.9% at 2 years, and 0% at 3 years. Seven patients showed uneventful postoperative recovery after surgery. Two patients suffered from gastric stasis, which was successfully managed with supportive care. One patient suffered from overt gastric paresis, which was successfully managed with azithromycin administration for 1 month. Conclusion We believe that preemptive pyloroplasty is an effective surgical option to prevent gastric stasis in patients undergoing extensive left-sided LN dissection. Azithromycin appears to be a potent prokinetic agent in gastroparesis.

In 2010, the World Health Organization classified mucin-producing bile duct tumors of the liver into two distinct entities; mucinous cystic neoplasm of the liver (MCN-L) and intraductal papillary mucinous neoplasm of the bile duct. We present the case of a patient with MCN-L having a uniquely pedunculated shape. A 32‐year‐old woman was referred to our institution with a diagnosis of biliary cystic neoplasm. She had undergone left salpingo-oophorectomy for ovarian cancer 15 years ago. Imaging studies showed an 8 cm-sized well defined, multiloculated cystic lesion suggesting a mucinous cystic neoplasm. The cystic mass was pedunculated at the liver capsule and pathologically diagnosed as MCN-L. The mass was resected with partial hepatectomy. The patient recovered uneventfully. She was discharged 7 days postoperatively. The patient has been doing well for 6 months after the operation. The patient will be followed up annually because of the favorable postresection prognosis of MCN-L.

Biliary rhabdomyosarcoma is a rare tumor, but it is still the most common tumor of the biliary tract in children. We report a case of a 6-year-old boy with biliary embryonal rhabdomyosarcoma and liver metastasis, which were treated with neoadjuvant and adjuvant chemotherapy combined with living donor liver transplantation (LDLT). Initial imaging studies showed a low-attenuation intraductal mass from the left hepatic duct to the intrapancreatic common bile duct with diffuse upstream dilatation of the intrahepatic duct and liver metastasis. Endoscopic biopsy revealed embryonal rhabdomyosarcoma. After tumor size reduction through neoadjuvant chemotherapy, LDLT was planned to remove the tumor completely. A left lateral section graft weighing 330 g was harvested from his 38-year-old mother and the graft-to-recipient weight ratio was 1.94%. Routine pediatric LDLT operation was performed with deep excavation of intrapancreatic distal bile duct. The explant liver showed minimal residual embryonal rhabdomyosarcoma with no lymph node metastasis. The patient recovered uneventfully from LDLT operation. Scheduled adjuvant chemotherapy was performed for 6 months. The patient is doing well without any evidence of tumor recurrence for 26 months after LDLT. In conclusion, liver transplantation could be an effective treatment for unresectable biliary rhabdomyosarcoma in children according to the location of tumor.

Congenital web formations are extremely rare anomalies of the extrahepatic biliary tree. We herein report a case of common bile duct septum combined with multiple intrahepatic bile duct strictures in a 74‐year‐old female patient who was successfully treated with radiological intervention. The patient initially visited the hospital because of upper abdominal pain. Imaging studies revealed multifocal strictures with dilatation in both intra- and extrahepatic ducts; the final clinical diagnosis was congenital common bile duct web combined with multiple intrahepatic duct strictures. Surgical treatment was not indicated because multiple biliary strictures were untreatable, and the disease was clinically diagnosed as benign. The multiple strictures were extensively dilated twice through bilateral percutaneous transhepatic biliary drainage (PTBD) for 2 months. After 1 month of observation, PTBD catheters were successfully removed. The patient is doing well at 6 months after completion of the radiological intervention, with the maintenance of normal liver function. Congenital web of the bile duct is very rare, and its treatment may vary depending on the patterns of biliary stenosis. In cases where surgical intervention is not indicated for congenital web and its associated disease, radiological intervention with balloon dilatation can be a viable therapeutic option.

Progressive familial intrahepatic cholestasis (PFIC) is an autosomal recessive inherited disease requiring liver transplantation (LT). Hepatocellular carcinoma (HCC) is very rare in infants. We present a case of living donor LT using a left lateral section graft performed in a 7-month-old female infant diagnosed with PFIC type II and HCC. No mutation on ABCB11 gene was identified. Because of progressive deterioration of liver function, living donor LT with her mother’s left lateral section graft was performed. Pretransplant serum alpha-fetoprotein (AFP) level was increased to 2,740 ng/mL, but HCC was not taken into account because of its rarity. The explant liver showed micronodular liver cirrhosis, multiple infantile hemangiomas and two HCCs of 0.7 cm and 0.3 cm in size. The patient recovered uneventfully from the LT operation. This patient has been regularly followed up with abdomen ultrasonography and AFP measurement every 6 months. The patient has been continually doing well for 8 years after the LT. In conclusion, LT is currently the only effective treatment for PFIC-associated end-stage liver diseases. HCC can develop at the cirrhotic liver of any cause, thus elevation of HCC tumor markers in pediatric patients is an important clue to perform further investigation before LT.

Background : The outcomes of liver transplantation (LT) have improved, but actual 20-year survival data have rarely been presented. Methods : Longitudinal follow-up data of 20-year LT survivors were retrospectively analyzed. The LT database of our institution was searched to identify patients who underwent primary LT from January 2000 to December 2001. The study cohort of 251 patients was divided into three groups: 207 adults who underwent living donor LT (LDLT), 22 adults who underwent deceased donor LT (DDLT), and 22 pediatric patients who underwent LT. Results : Hepatitis B virus–associated liver cirrhosis and biliary atresia were the most common indications for adult and pediatric LT, respectively. Seven patients required retransplantation, including six who underwent DDLT and one who underwent LDLT. Twenty-two patients died within 3 months after LT and 69 died at later intervals. The overall survival rates at 1, 3, 5, 10, and 20 years were 86.4%, 79.6%, 77.7%, 72.8%, and 62.6%, respectively, in the adult LDLT group; 86.4%, 72.7%, 72.7%, 72.7%, and 68.2%, respectively, in the adult DDLT group; and 86.4%, 86.4%, 81.8%, 81.8%, and 77.3%, respectively, in the pediatric LT group (P=0.545). Common immunosuppressive regimens at 20 years included tacrolimus monotherapy, tacrolimus–mycophenolate dual therapy, cyclosporine monotherapy, and mycophenolate monotherapy. Conclusions: The present study is the first report of actual 20-year survival data from a Korean high-volume LT center. The graft and patient survival outcomes reflected the early experiences of LT in our institution, with long-term outcomes being similar regardless of graft type and patient age.

According to Murray Bowen’s family systems theory, the family is an emotional unit where members influence each other. Family strength, in that members care for, respect, and communicate with each other sincerely and freely and overcome difficulties together through joint efforts, is what every family yearns for and pursues. Maternal gatekeeping behavior not only affects the relationship between each family member but also has an impact on family strength. Father-perceived family strength and maternal gatekeeping were investigated in this study, along with the mediation effect of father involvement and mutual communication. In total, 320 fathers of children aged 3–5 were randomly recruited to complete self-report questionnaires. The correlation results indicated that maternal gate-opening behavior, father involvement, mutual communication, and family strength are positively correlated with each other, whereas maternal gate closing is negatively associated with father involvement, mutual communication, and family strength. Path analysis verified the partial (dual) mediation effect of father involvement and mutual communication between maternal gate opening and family strength, as well as a complete (dual) mediation effect upon maternal gate closing. The current study provides new insights into understanding the underlying mechanisms of father-perceived family strength influenced by maternal gatekeeping behavior. Meanwhile, the mediation effect of father involvement and mutual communication also highlights the importance of parenting preparation for fathers, such as psychological self-adjustment, especially under interception or restriction.

The respiratory rate (RR) is a significant indicator to evaluate a patient’s prognosis and status; however, it requires specific instrumentation or estimates from other monitored signals. A photoplethysmogram (PPG) is extensively used in clinical environments as well as in intensive care units (ICUs) to primarily monitor peripheral circulation while capturing indirect information about intrathoracic pressure changes. This study aims to apply and evaluate several deep learning models using a PPG for the continuous and accurate estimation of the RRs of patients. The dataset was collected twice for 2 min each in 100 patients aged 18 years and older from the surgical intensive care unit of a tertiary referral hospital. The BIDMC and CapnoBase public datasets were also analyzed. The collected dataset was preprocessed and split according to the 5-fold cross-validation. We used seven deep learning models, including our own Dilated Residual Neural Network, to check how accurately the RR estimates match the ground truth using the mean absolute error (MAE). As a result, when validated using the collected dataset, our model showed the best results with a 1.2628 ± 0.2697 MAE on BIDMC and RespNet and with a 3.1268 ± 0.6363 MAE on our dataset, respectively. In conclusion, RR estimation using PPG-derived models is still challenging and has many limitations. However, if there is an equal amount of data from various breathing groups to train, we expect that various models, including our Dilated ResNet model, which showed good results, can achieve better results than the current ones.

Background : The severity of the coronavirus disease 2019 (COVID-19) pandemic has discouraged organ donation. However, the prevalence of COVID-19 in Korea was much lower in comparison to Western countries. With this, the authors decided to determine the real-world impact of COVID-19 on organ donation and transplantation in Korea. Methods : The number of kidney transplantations (KTs) and liver transplantations (LTs) performed in 2020 were compared with those in 2019 using the Korean Network for Organ Sharing database and Asan Medical Center (AMC) database. Results : The annual number of deceased donors (DDs) was 450 in 2019 compared to 478 in 2020. Monthly DD number was 37.5±5.9 in 2019 and 39.8±4.4 in 2020 (P=0.284). Annual number of DD kidney transplant (DDKT) was 794 in 2019 and 848 in 2020, and monthly number was 66.1±10.4 in 2019 and 70.7±9.8 in 2020 (P=0.285). The annual number of DDLT was 391 in 2019 and 395 in 2020, and the monthly number was 32.6±5.7, 2019 and 32.9±4.7 in 2020 (P=0.877). The annual number of living donor (LD) KT was 2,293 in 2019 and 1,432 in 2020, and the monthly number was 191.1±19.5 in 2019 and 119.3±11.7 in 2020 (P

Hepatic artery thrombosis (HAT) following living donor liver transplantation (LDLT) is a lethal complication. We present the case of a patient who underwent salvage redo hepatic artery reconstruction using an aorto-hepatic jump graft because of HAT following LDLT. A 64-year-old female patient diagnosed with hepatitis C virus-associated liver cirrhosis and hepatocellular carcinoma underwent salvage LDLT using a modified right liver graft. Partial graft infarct was identified at posttransplant day 4, and by day 9, it had spread. Celiac arteriography showed complete occlusion of the graft hepatic artery. We performed redo hepatic artery reconstruction using a fresh iliofemoral artery homograft 10 days after the LDLT operation because such a vessel homograft was available at our institutional tissue bank. The infrarenal aorta was dissected and an iliofemoral artery graft was anastomosed. Soon after hepatic artery revascularization, liver function progressively improved, and the infarct area at the liver graft was reduced. The patient has been doing well for 10 years without any vascular complications. In conclusion, our experience with this case suggests that salvage redo hepatic artery reconstruction using an aorto-hepatic jump graft is a feasible option to treat HAT following LDLT, as in deceased donor liver transplantation.

Background: Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CCA) has wide histologic diversity. This study investigated the prognostic impacts of cHCC-CCA histology according to the 2019 World Health Organization (WHO) classification. Methods: This retrospective observational study included 153 patients who underwent surgical resection for cHCC-CCA at Asan Medical Center between August 2012 and July 2019. Results: During the study period, 153 patients, 112 (73.2%) men and 41 (26.8%) women with a mean age of 56.4 ± 10.8 years, underwent R0 resection for cHCC-CCA. Mean tumor diameter was 4.2 ± 2.6 cm, and 147 (96.1%) patients had solitary tumors. According to 2019 WHO classification, 111 (72.5%) patients had cHCC-CCA alone, and 29 of them (26.1%) showed stem cell features. cHCC-CCA-intermediate cell carcinoma and cHCC-CCA-cholangiolocellular carcinoma were identified in 27 (17.6%) and 15 (9.8%), respectively. The 1-, 3-, and 5-year tumor recurrence and patient survival rates were 31.8% and 92.1%, 49.8% and 70.9%, and 59.0% and 61.7%, respectively. Univariate analyses revealed that significant prognostic factors were tumor size >5 cm, microscopic and macroscopic vascular invasion, lymph node metastasis, 8th American Joint Committee on Cancer (AJCC) tumor stage, and status of stem cell features. Multivariate analysis revealed 8th AJCC tumor stage and status of stem cell features as independent prognostic factors. 2019 WHO classification was not associated with post-resection prognosis. Conclusions: 2019 WHO classification was not associated with post-resection prognosis, thus was considered as simplified histologic classification requiring prognostic validation. We suggest that stem cell features should be included as an essential component of the pathology report for cHCC-CCA.

The anatomy of middle hepatic vein (MHV) varies widely, and some individuals have aberrant MHV anatomy, thus there is risk of iatrogenic damage to graft MHV during liver splitting. We present the clinical sequences of an adult recipient who received a split right liver graft with erroneous deprivation of the MHV trunk. This is the case was a 58-year-old male patient with hepatitis B virus-associated liver cirrhosis who suffered from hepatic encephalopathy. The split right liver graft had a graft-to-recipient weight ratio of 2.1%. Soon after graft reperfusion, large-sized hepatic venous congestion (HVC) appeared at the graft liver surface, indicating lack of MHV drainage. The amount of HVC was approximately 20% of the right liver graft mass at day 1, which had gradually reduced on follow-up computed tomography (CT) scans. Although liver function recovered progressively, the patient remained bed-ridden because of pre-existing hypoxic brain damage. The patient passed away 4 years after transplantation because of pneumonia and multi-organ failure. The present case implies that there is some possibility of unrecognized damage to the graft MHV during liver splitting, suggesting the necessity of preoperative donor abdomen CT scan and preparation of intraoperative ultrasonography for easy evaluation of graft liver MHV anatomy.

We have preferentially used the right gastroepiploic artery (RGEA) as an alternative for the recipient hepatic artery (HA) inflow during living donor liver transplantation (LDLT), but it was not always available. We herein present a case of adult LDLT with HA reconstruction using a greater saphenous vein (GSV) conduit because of the absence of the RGEA due to prior subtotal gastrectomy. A 55-year-old male patient diagnosed with hepatitis B virus-associated liver cirrhosis and secondary biliary cirrhosis underwent LDLT using a modified right liver graft. The upper abdominal cavity was heavily adhered due to prior abdominal surgeries, thus we had to sacrifice the common bile duct and the right HA completely. A 6-cm-long GSV segment was harvested from the left ankle and interposed between the recipient gastroduodenal artery and the graft HA. The patient recovered from LDLT and HA complications did not occur. However, 8 years after LDLT, chronic rejection occurred, thus repeated deceased donor liver transplantation was performed. This patient has been doing well for 2 years after retransplantation. In conclusion, we suggest that interposition of an autologous GSV conduit can be an alternative for establishing HA inflow in LDLT when other inflow source is not available.

Background : Some young adults have a long survival period with native liver after Kasai portoenterostomy (KPE) for biliary atresia (BA). However, a considerable proportion of these patients require liver transplantation (LT). This study aimed to analyze the indications and outcomes of LT in young adults after a long survival period with native liver after KPE. Methods : We selected seven patients who were 18 years or older at the time of LT out of 116 BA patients who underwent primary LT from 2008 to 2019 at Asan Medical Center. Results : The mean ages at KPE and LT were 2.1±0.9 months and 22.0±5.1 years, respectively. Mean serum total bilirubin level and model for end-stage liver disease score at LT were 7.91±7.22 mg/dL and 15.3±6.0, respectively. The main reasons for LT were liver cirrhosis with portal hypertension-associated complications in five patients and intractable cholangitis in two patients. There were five cases of living donor LT and two cases of deceased donor LT. All the seven patients are currently alive during the mean follow-up period of 74.7±40.9 months. One patient suffered from outflow graft vein obstruction requiring endovascular stenting. Another patient showed core antibody-positivity-induced de novo hepatitis B virus infection, which was well managed with antiviral therapy. Conclusions: Young adult patients with BA are a unique group of patients requiring specialist care regarding transition from pediatric to adult services. The outcomes of LT in young adult BA patients were excellent. Therefore, LT should be considered in patients showing serious BA-associated complications.

Background : Living liver donation by minors is regarded as justifiable only if minors possess the capacity to consent to donation and the procedure is in their best interests. This study analyzed the incidence of and reasons for living donor liver transplantation (LDLT) by minor donors in Korea, and discussed ethical issues regarding liver donation by minors. Methods : The databases of the Korean Network for Organ Sharing (KONOS) and Asan Medical Center (AMC) from 2010 to 2019 were retrospectively reviewed to determine the incidence of LDLT by minor donors. Results : From 2010 to 2019, 590 (4.1%) of 14,243 liver donors in the KONOS database and 276 (7.5%) of 3,401 liver donors in the AMC database were minors. The proportions of minor donors in the KONOS and AMC databases were highest in 2012, at 4.1% and 12.6%, respectively, and lowest in 2019, at 1.1% and 3.0%, respectively. Because most LDLT recipients had relatively low model for end-stage liver disease scores and hepatocellular carcinoma, they were unlikely candidates for deceased-donor liver transplantation and were highly likely to drop out of LDLT if they waited for 1–2 years. The donor-recipient relationship of minor donors in the AMC database was first-degree in 256 (92.8%) and second- or third-degree in 20 (7.2%). Conclusions: Liver donation by minors is limitedly acceptable only when the minor proves informed, well‐considered, and autonomous consent to the procedure and the procedure is in the minor's best interests. We suggest that minors be allowed to donate only to first-degree family members.

Background/Aims To analyze the incidence and risk factors of outcomes after liver transplantation (LT) in the Korean population. Methods This study analyzed data from the liver cohort of Korean Organ Transplantation Registry (KOTRY) who had LT between May 2014 and December 2017. Study measures included the incidence of post-LT outcomes in recipients of living donor LT (LDLT) and deceased donor LT (DDLT). Cox multivariate proportional hazards model was used to determine the potential risk factors predicting the outcomes. Results A total of 2,563 adult recipients with LT (LDLT, n=1,956; DDLT, n=607) were included, with mean±standard deviation age of 53.9±8.9 years, and 72.2% were male. The post-LT outcomes observed in each LDLT and DDLT recipients were death (4.0% and 14.7%), graft loss (5.0% and 16.1%), rejection (7.0% and 12.0%), renal failure (2.7% and 13.8%), new onset of diabetes (12.5% and 15.4%), and hepatocellular carcinoma (HCC) recurrence (both 6.7%). In both LDLT and DDLT recipients, the most common post-LT complications were renal dysfunction (33.6% and 51.4%), infection (26.7% and 48.4%), and surgical complication (22.5% and 23.9%). Incidence of these outcomes were generally higher among recipients of DDLT than LDLT. Multivariate analysis indicated recipient age and DDLT as significant risk factors associated with death and graft loss. DDLT and ABO incompatible transplant were prognostic factors for rejection, and HCC beyond Milan criteria at pre-transplant was a strong predictor of HCC recurrence. Conclusions This study is a good indicator of the post-LT prognosis in the Korean population and suggests a significant burden of post-LT complications.

Salvage liver transplantation (LT) is a definite treatment for recurrent hepatocellular carcinoma (HCC) after hepatectomy. Combined hepatocellular carcinoma-cholangio-carcinoma (cHCC-CC) is not eligibly indicated for LT because of high post-transplant recurrence. We present a case of salvage living donor liver transplantation (LDLT) in a patient with tumor recurrence after surgical resection of cHCC-CC. A 61-year-old male patient diagnosed with chronic hepatitis B underwent right posterior sectionectomy for HCC. The pathological diagnosis revealed presence of a 3.2-cm-sized cHCC-CC with stem cell features and intermediate cell-subtype. Intrahepatic tumor recurrence occurred 9 months later and transarterial chemoembolization was performed. Due to the progress of recurrent tumors, ABO-incompatible LDLT was performed. The explant liver pathology revealed four small masses of cHCC-CC with stem cell features. Pulmonary metastasectomy and chest wall resection were performed for metastatic lesions at 10 months after LT. Multiple tumor recurrence was detected at 21 months after LT with progression despite sorafenib administration. Currently, the patient is alive for past 26 months after LT. In conclusion, the clinical sequences of this case suggest that the role of salvage LT for cHCC-CC is much more limited than that for HCC because the tumor biology of cHCC-CC is more aggressive compared with HCC.

Background : Liver transplantation (LT) for foreign patients is a sensitive issue because of possibility of transplant tourism and difficulty in posttransplant follow-up. This study describes the institutional standard framework and experience of living donor LT (LDLT) for overseas non-Korean patients in a Korean high-volume LDLT center. Methods : The framework and experience of LDLT for 105 non-Korean patients from 2010 to 2019 were retrospectively investigated. Results : Only 3.1% of patients who underwent LDLT were overseas non-Koreans; of these, 83.8% were from the United Arab Emirates and Mongolia. Selection criteria for recipients and donors were the same as for Korean citizens. Of the 105 recipients, 95 (90.5%) were adults. The most common reasons for transplantation were hepatitis B or C virus-associated liver cirrhosis. Of the 95 adults, 78 (82.1%) received right liver grafts, and 16 (16.8%) received dual grafts. The most frequent donors for adult recipients were sons and daughters, whereas the most frequent donors for pediatric recipients were parents. Of the 10 pediatric patients, eight were from the United Arab Emirates; their common primary diseases were biliary atresia, acute liver failure, hepatoblastoma, and genetic metabolic diseases. The 1-, 3-, and 5-year posttransplant overall patient survival rates in all patients were 96.2%, 92.4%, and 92.4%, respectively. The 5-year overall patient survival rates were 91.8% in adult recipients and 100% in pediatric recipients (P=0.47). Conclusions: LDLT at Korean high-volume LT centers including our institution is safe and effective for non-Korean patients with end-stage liver disease seeking alternatives not available in their own countries.

We present a case of recipient hepatectomy under total hepatic vascular exclusion (THVE) and venovenous bypass for living donor liver transplantation (LDLT) in a patient with multiple hepatocellular carcinomas (HCCs) closely located to the retrohepatic inferior vena cava (IVC). A 19-year-old male patient diagnosed with multiple HCCs underwent left lateral sectionectomy 14 months before and received four sessions of transarterial chemoembolization due to post-hepatectomy tumor recurrence. These pretransplant sequences implicated high risk of posttransplant HCC recurrence. However, LDLT was performed with expectation of prolonged survival. During recipient operation, the portal vein was transected and active venovenous bypass was performed. Supra- and infra-hepatic portions of the retrohepatic IVC were then clamped. Under THVE and portal vein bypass, recipient hepatectomy was meticulously performed. A modified right liver graft recovered from his brother was implanted according to standard procedures of LDLT. The patient recovered uneventfully from LDLT operation. However, multiple pulmonary metastasis occurred. The patient has been doing well for 12 months after LDLT, with administration of chemotherapeutic agents. Although early pulmonary metastasis occurred in this patient, we suggest that recipient hepatectomy under THVE and venovenous bypass can be a feasible technical option to cope with risk of iatrogenic tumor cell spread during LDLT operation.

Recipient hepatectomy for an enlarged stony-hard liver is a demanding procedure, thus it is often accompanied by massive blood loss. Recipient liver splitting under prolonged hepatic inflow occlusion would facilitate the piggyback recipient hepatectomy. We herein present a case of recipient liver splitting, which was used for living donor liver transplantation (LDLT). A 48-year-old male patient diagnosed with acute-on-chronic liver failure underwent LDLT. During the recipient operation, the native liver was stony-hard and heavily adherent to the retrohepatic inferior vena cava (IVC). During liver mobilization, diffuse oozing occurred due to disseminated intravascular coagulation. As a change in the concept, we decided to perform in situ liver splitting of the recipient liver to facilitate dissection of the retrohepatic IVC. Under hepatic inflow occlusion, right-left liver splitting was performed along the usual plane of extended left hepatectomy. The procedures time for recipient liver splitting and removal was 60 minutes. A modified right liver graft recovered from his daughter was implanted according to the standard procedures of LDLT. We think that recipient liver splitting is a feasible technical option for coping with difficult recipient hepatectomy, especially in patients with an enlarged stony-hard liver and heavy adhesion around the IVC.

Background : Favorable outcomes achieved after deceased donor liver transplantation (DDLT) suggest that use of elderly donors may be an effective way to expand donor pool. Methods : This was a retrospective analysis of adult DDLT using elderly donors. It was a double-arm study that compared posttransplant outcomes to ascertain whether use of elderly donors (aged ≥76 years) has adverse effects on outcome of DDLT. Elderly donor study group included 14 donors aged ≥76 years and elderly donor control group comprised 39 donors aged 66–75 years. Results : Mean donor age of the study and control groups was 78.2±3.1 years and 68.9±2.7 years, respectively (P

Congenital factor X (FX) deficiency is a rare autosomal-recessive disease that induces bleeding disorder. Herein, we present the 10-year posttransplant course of a pediatric patient who underwent liver transplantation (LT) with portal vein (PV) stenting for correction of severe congenital FX deficiency, with focus on long-term maintenance of coagulation function and patency of PV stenting. A 17-month-old infant with recurrent hemorrhagic episodes due to FX deficiency underwent split LT using a left lateral section graft. The graft-recipient weight ratio was 2.2%. The graft implantation procedures were performed by following the standard pediatric split LT procedure. Nevertheless, a wall stent was inserted due to PV anastomotic stenosis on posttransplant day 1. Graft function recovered slowly because of partial parenchyma infarct, and the patient was discharged at 46 days after LT operation. The FX activity started to increase soon after LT and gradually normalized; the coagulation profiles have been maintained well for the past 10 years. The patient has been doing well for the past 10 years after LT without any episodes of abnormal bleeding. Due to the risk of vascular complications owed to PV stenting, life-long follow-up is mandatory with special attention until attainment of complete physical growth to adolescent and adulthood.

Background : Epithelioid hemangioendothelioma (EHE) is a rare borderline vascular tumor. Due to its rarity and protean behavior, the optimal treatment of hepatic EHE has not yet been standardized. This single-center study describes outcomes in patients with hepatic EHE who underwent living donor liver transplantation (LDLT). Methods : The medical records of patients who underwent LDLT for hepatic EHE from 2007 to 2016 were reviewed. Results : During 10-year period, four patients, one man and three women, of mean age 41.3±11.1 years, underwent LDLT for hepatic EHE. Based on imaging modalities, these patients were preoperatively diagnosed with EHE or hepatocellular carcinoma, with percutaneous liver biopsy confirming that all four had hepatic EHE. The tumors were multiple and scattered over entire liver, precluding liver resection. Blood tumor markers were not elevated, except that CA19-9 and des-γ-carboxy prothrombin was slightly elevated in one patient. Mean model for end-stage liver disease score was 10.8±5.7. All patients underwent LDLT using modified right liver grafts, with graft-recipient weight ratio of 1.11±0.19, and all recovered uneventfully after LDLT. One patient died due to tumor recurrence at 9 months, whereas the other three have done well without tumor recurrence, resulting in 5-year disease-free and overall patient survival rates of 75% each. The patient with tumor recurrence was classified as a high-risk patient based on the original and modified hepatic EHE-LT scoring systems. Conclusions: LDLT can be an effective treatment for patients with unresectable hepatic EHEs that are confined within the liver and absence of macrovascular invasion and lymph node metastasis.

Congenital absence of the portal vein (CAPV) is a rare venous malformation in which mesenteric venous blood drains directly into systemic circulation. Herein, we report a case of pediatric deceased donor liver transplantation (DDLT) for symptomatic CAPV with whole liver graft from a hepatitis B surface antigen (HBsAg)-positive donor. A 4-year-old boy suffered from CAPV and secondary portal hypertension. He was also diagnosed with DiGeorge syndrome and heart anomalies. After waiting for 4 months, a 5-year-old donor weighing 19 kg with positive HBsAg was allocated to this 4-year-old patient weighing 15 kg. Recipient operation was performed according to the standard procedures of pediatric DDLT. Portal vein reconstruction was performed using interposition of a vascular homograft conduit to the superior mesenteric vein-splenic vein confluence. The patient recovered uneventfully from DDLT. He has been administered with lamivudine to prevent hepatitis B virus infection. This patient has been doing well for 5 years after DDLT without growth retardation. In conclusion, CAPV patients can have various vascular anomalies, thus combined vascular anomalies should be thoroughly assessed before and during liver transplantation operation. The most effective reconstruction techniques should be used to achieve satisfactory results following liver transplantation.

Introduction: This study examined associations between the graft-to-recipient weight ratio (GRWR) for adult-to-adult living donor liver transplantation (LDLT) and hepatocellular carcinoma (HCC) outcomes. Materials and Methods: Data from patients in the Korean Organ Transplantation Registry who underwent LDLT for HCC from 2014 to 2021 were retrospectively reviewed. Patients were categorized using the cutoff GRWR for HCC recurrence determined by an adjusted cubic spline (GRWR <0.7% vs. GRWR =0.7%). Recurrence-free survival (RFS) and HCC recurrence were analyzed in the entire and a 1:5 propensity-matched cohort. Results: The eligible cohort consisted of 2005 LDLT recipients [GRWR <0.7 (n =59) vs. GRWR =0.7 (n= 1946)]. In the entire cohort, 5-year RFS was significantly lower in the GRWR <0.7 than in the GRWR =0.7 group (66.7% vs. 76.7%, P=0.019), although HCC recurrence was not different between groups (77.1% vs. 80.7%, P= 0.234). This trend was similar in the matched cohort (P =0.014 for RFS and P= 0.096 for HCC recurrence). In multivariable analyses, GRWR <0.7 was an independent risk factor for RFS [adjusted hazard ratio (aHR) 1.89, P =0.012], but the result was marginal for HCC recurrence (aHR 1.61, P= 0.066). In the pretransplant tumor burden subgroup analysis, GRWR <0.7 was a significant risk factor for both RFS and HCC recurrence only for tumors exceeding the Milan criteria (aHR 3.10, P< 0.001 for RFS; aHR 2.92, P=0.003 for HCC recurrence) or with MoRAL scores in the fourth quartile (aHR 3.33, P<0.001 for RFS; aHR 2.61, P= 0.019 for HCC recurrence). Conclusions: A GRWR <0.7 potentially leads to lower RFS and higher HCC recurrence after LDLT when the pretransplant tumor burden is high. [ABSTRACT FROM AUTHOR]

Background : We investigated the incidence and outcomes of pediatric deceased donor liver transplantation (DDLT) using whole liver grafts in a high-volume liver transplantation (LT) center. Methods : The study was a retrospective single-center analysis of whole LT in pediatric recipients. The study period was set as 20 years between January 2000 and December 2019. We defined pediatric recipients and donors to be aged ≤18 years. Results : During the study period, there were 98 cases of pediatric DDLT, and 34 patients (34.7%) received whole liver grafts. The age range of the deceased donors was 3 months to 56 years and that of pediatric recipients was 7 months to 17 years. Common primary diseases for LT were biliary atresia in 13, acute liver failure in four, Wilson disease in four, congenital portal vein agenesis in three, and genetic metabolic diseases in three. Pediatric-to-pediatric and adult-to-pediatric whole LTs were 22 (64.7%) and 12 (35.3%), respectively. A good correlation was noted between the donor and the recipient’s body weight, and the recipient’s body weight and allograft’s weight. Graft and overall patient survival rates were 91.2% and 91.2% at 1 year, 88.0% and 88.0% at 3 years, and 88.0% and 88.0% at 5 years, respectively. Conclusions: The results of this study revealed that Korean Network for Organ Sharing (KONOS) regulations with donor-recipient body weight matching exhibited good performance. Considering the reciprocal trades of liver organs among pediatric and adult donors and recipients, it is necessary to establish a policy for pediatric donor liver grafts to pediatric recipients on a priority basis.

Biliary atresia (BA)-polysplenia syndrome (PS) is diagnosed in a small proportion of BA patients. We present a case of split liver transplantation (LT) successfully performed in a pediatric recipient with BA-PS. The recipient was 29-month-old boy who underwent Kasai procedure. The coexisting malformations included agenesis of the inferior vena cava with azygos vein continuation, polysplenia, intestinal malrotation, truncated pancreas, and preduodenal portal vein and annular pancreas. With pediatric end-stage liver disease score of 33, the patient was allocated for split LT. Under this condition, the left lateral section graft was equivalent to a graft-recipient weight ratio of 2.6%. The recipient surgery was performed according to the standard procedures of pediatric LT. The graft hepatic vein was directly anastomosed with the suprahepatic confluence of the recipient hepatic veins. An external iliac vein homograft was interposed for portal vein reconstruction. Portal collateral veins were embolized intraoperatively to secure portal vein inflow. No surgical complications were developed. Currently, the patient has been doing well for 4 years after transplantation. Our pediatric patient with BA-PS had various anatomical malformations. Thorough preoperative and intraoperative assessment of these anomalies, adoption of customized reconstruction techniques of LT, and careful posttransplant monitoring are necessary for successful LT.

Laparoscopically harvested left liver (LL) grafts have drawbacks with respect to the size and shape of graft hepatic vein orifices. We present two cases of pediatric living donor liver transplantation (LDLT) using laparoscopically harvested LL grafts and describe refined surgical techniques for graft hepatic vein venoplasty. The first case was a boy aged 4 years and 5 months, with hepatoblastoma. The donor was his 35-year-old mother, and LL graft weighed 315 g. Two separate openings of the graft at the left hepatic vein (LHV) and middle hepatic vein (MHV) were unified through septotomy and septoplasty, and cryopreserved vein homograft patch was attached. Standard procedures of LDLT were performed. This patient recovered uneventfully and has been doing well for 4 years without tumor recurrence. The second case was a 6-year-old girl with ornithine transcarbamylase deficiency. The donor was her 35-year-old mother, and the LL graft weighed 310 g. Two separate openings of graft MHV, with segment III and segment II veins, were unified through septoplasty, and vein patch was attached. Standard procedures of LDLT were performed. This patient has been doing well for 4 years. In conclusion, separate graft hepatic vein openings are a drawback of laparoscopically harvested LL grafts, which thus require unification venoplasty of customized design individually tailored for LL graft and pediatric recipient.

Interest in utilizing organs from non–heart-beating donors (NHBDs) has increased because of the organ shortage. However, liver transplantation (LT) from NHBDs has been scarcely performed in Korea because only Maastricht category IV is legally permitted. We present one case of LT from an NHBD with extracorporeal membrane oxygenation (ECMO) support. The case was a 42-year-old male patient with alcoholic liver cirrhosis. The model for end-stage liver disease score was 28. The donor was a 47-year-old female who was diagnosed with brain death due to cerebral infarct, but cardiac arrest occurred before brain death was finally confirmed. Thus, venous-arterial type ECMO was initiated for circulatory support. In the operating room, asystole developed just after ECMO was stopped. After waiting for 5 minutes, cardiac death was declared. It took 6 minutes from skin incision to aorta perfusion. The recipient hepatectomy and graft implantation were performed according to the standard procedures of adult whole LT. The patient recovered from LT uneventfully and has been doing well for 9 years after LT. The use of NHBDs is a method to increase the potential pool of organ donors, thus changes toward enhanced public awareness and acceptance of donating organs, and legal support at the government level are necessary.

Introduction: There is no consensus regarding selection criteria on liver transplantation (LT) for hepatocellular carcinoma (HCC), especially for living donor liver transplantation, although emerging evidence has been found for the effectiveness of bridging or downstaging. Objective: We evaluated the long-term outcomes of patients who underwent LT with or without bridging or downstaging for HCC. Methods: This retrospective study included 896 LT recipients with HCC between June 2005 and May 2015. Recurrence-free survival (RFS), overall survival (OS), and their associated factors were evaluated. Results: The 5-year RFS in the full cohort of 896 patients was 82.4%, and the OS was 85.3%. In patients with initial Organ Procurement and Transplantation Network (OPTN) T1 and T2, the 5-year RFS and OS did not significantly differ between LT groups with and without bridging (all p ≥ 0.05). The 5-year RFS and OS of OPTN T3 patients with successful downstaging were not significantly different from those of patients with OPTN T2 with primary LT (p = 0.070 and p = 0.185), but were significantly higher than in patients with OPTN T3 with downstaging failure and initial OPTN T1 or T2 with progression (all p < 0.001). In the multivariate analysis, last alpha-fetoprotein before LT ≥70 ng/mL (hazard ratio [HR]: 1.77, p = 0.001; HR: 1.72, p = 0.004), pretransplant HCC status exceeding the Milan criteria (HR: 5.12, p < 0.001; HR: 3.31, p < 0.001), and positron emission tomography positivity (HR: 2.57, p < 0.001; HR: 2.57, p < 0.001) were independent predictors for worse RFS and OS. Conclusions: The impact of bridging therapy on survival outcomes is limited in patients with early-stage HCC, whereas OPTN T1 or T2 with progression provides worse prognosis. OPTN T3 should undergo LT after successful downstaging, and OPTN T3 with successful downstaging allows for acceptable long-term posttransplant outcomes.

We present a case of successful split liver transplantation (LT) using a hyperreduced left lateral segment (LLS) graft in a 106-day-old female infant patient weighing 4 kg. The patient was diagnosed with progressive familial intrahepatic cholestasis. Her general condition and liver function deteriorated progressively and she was finally allocated for a split LT under status 1. The deceased donor was a 20-year-old female weighing 63.7 kg. We performed in situ liver splitting and in situ size reduction sequentially. The weight of the hyperreduced LLS graft was 225 g, with a graft-recipient weight ratio of 5.5%. We performed recipient hepatectomy and graft implantation according to the standard procedures for pediatric living-donor LT. Since the graft was too large for primary abdomen closure, the abdominal wall was closed in three stages to make a prosthetic silo, temporary closure with a xenograft sheet, and final primary repair over 2 weeks. The patient has been doing well for more than 6 years after transplantation. In conclusion, split LT using a hyperreduced LLS graft can be a useful option for treating small infants. However, large-for-size graft-related problems, particularly in terms of graft thickness, still remain to be solved.

Background : The present study intended to investigate the allocation status of pediatric deceased donor liver allografts. We analyzed the incidence of pediatric deceased donors in the Korean Network for Organ Sharing (KONOS) database and single-institutional status of liver transplantation (LT) using pediatric donors. Methods : We assessed the nationwide incidence of pediatric donors aged ≤15 years and conducted single-center analysis of LT using pediatric donors. Results : Between 2010 and 2019, pediatric donors aged ≤15 years accounted for 171 out of 4,395 donors (3.9%) in the KONOS database and 31 out of 640 liver donors (4.8%) in Asan Medical Center (AMC) database. In AMC, 11 (35.5%) and 20 (64.5%) grafts were allocated to pediatric recipients aged ≤15 years and adult recipients aged ≥19 years, respectively. All nine livers from donors aged ≤5 years were implanted in pediatric recipients aged ≤5 years. From 21 donors aged ≥9 years, 16 whole liver grafts and four split extended right liver grafts were implanted in 20 adult recipients and two split left lateral section grafts were implanted in two pediatric recipients. Four split liver grafts were implanted in other institutions. The overall patient survival rates at 1, 3, and 5 years were 90.9%, 80.8%, and 80.8%, respectively in pediatric-to-pediatric LT group and 69.6%, 58.4%, and 58.4%, respectively in pediatric-to-adult LT group (P=0.21). Conclusions: More than half of the pediatric donor livers were allocated to adult patients. Recipient criteria for allocation of liver allografts from pediatric donors need revision for children on pediatric LT waitlist.

Laparoscopically harvested left lateral section (LLS) grafts have drawbacks regarding the size of the graft left hepatic vein (LHV) orifice although they have the merit of cosmetics concerning the donor’s wound. We present a case of pediatric living donor liver transplantation (LDLT) using a laparoscopically harvested LLS graft and describe the refined surgical techniques for graft LHV venoplasty with a circumferential vein patch. The patient was a 46-month-old boy with marked growth retardation who was diagnosed with progressive familial intrahepatic cholestasis type 2. The donor was his 25-year-old mother. The LLS graft weighed 285 g. A circumferential patch of external iliac vein homograft was attached to the graft LHV orifice after incisions were made at the medial wall of the LHV trunk and superficial LHV branch, which made the graft LHV orifice much larger. The recipient’s hepatic vein orifice was also enlarged by unifying the three hepatic vein orifices. Other surgical procedures followed the standard LDLT operation. This patient recovered uneventfully and has been doing well for 1 year. In conclusion, our incision-and-patch venoplasty to enlarge the graft outflow vein orifice was beneficial for reducing the risk of hepatic vein outflow obstruction in LDLT using a laparoscopically harvested LLS graft.

Background : Living donor liver transplantation (LDLT) causes bleeding in recipients during the careful preservation of most perihilar structures during this surgery. This case-control study aimed to analyze the effect of prolonged hepatic inflow occlusion (PHIO) when applied during recipient hepatectomy in LDLT. Methods : The study group comprised patients who underwent PHIO with Model for End-Stage Liver Disease (MELD) scores ranging from 26 to 35 (n=20). The following two control groups were selected according to their MELD scores: the low-MELD score group (MELD scores of 15-20, n=40) and the high-MELD score group (MELD scores of 26-35, n=40). Total dissection time for hepatic mobilization and dissection and blood loss during these procedures were compared between the two groups. Results : In the PHIO study group, mean total dissection time and mean PHIO duration were 226.3±59.4 and 68.2±19.1 minutes, respectively. Twelve patients underwent PHIO twice, and the other eight patients underwent PHIO once. The low-MELD score control group and the PHIO study group showed similar dissection duration (216.0±43.9 vs. 226.3±59.4 minutes, P=0.82) and similar blood loss volume during dissection (2,112.5±1,614.9 vs. 2,350.0±951.9 mL, P=0.17). The high-MELD score control group and the PHIO study group showed similar dissection duration (241.0±41.9 vs. 226.3±59.4 minutes, P=0.71), but the PHIO group showed a significantly lower blood loss during dissection than the high-MELD score group (2,350.0±951.9 vs. 2,815.0±1,813.9 mL, P=0.002). During and after PHIO, no adverse complication was observed, except for transient splanchnic congestion. Conclusions: Our findings suggest that PHIO is a simple effective method to reduce intraoperative bleeding during hepatic mobilization and dissection during LDLT operation requiring difficult dissection.

Background : Homologous vein allografts are adequate for reconstruction of the middle hepatic vein (MHV) in living-donor liver transplantation (LDLT). However, supply is a matter of concern. To replace homologous vein allografts, polytetrafluoroethylene (PTFE) grafts were used. This study aimed to assess the long-term patency rates and complications of PTFE grafts used for MHV reconstruction of LDLT in a high-volume liver transplantation center. Methods : We analyzed the patency rates of PTFE-interposed MHV in 100 LDLT recipients and reviewed complications including PTFE graft migration. Results : The mean age was 53.5±5.4 years and male to female ratio was 73:27. Primary diagnoses were hepatitis B virus infection (n=71) and other (n=28). Mean model for endstage liver disease score was 16.2±8.3. V5 reconstruction was performed as either single anastomosis (n=85) or double anastomoses (n=14). No V5 reconstruction was required in one patient. V8 reconstruction was performed as single anastomosis, double anastomoses, and no reconstruction in 75, 0, and 25 patients, respectively. During a mean follow-up of 6 years, three recipients required early MHV stenting within 2 weeks. After 3 months, there were no episodes of congestion-associated infarct, regardless of MHV patency. Patency rates of PTFE-interposed MHV were 54.0%, 37.0%, and 37.0% at 1, 3, and 5 years, respectively. Unwanted PTFE graft migration occurred in two recipients, and the actual incidence was 2% at 5 years. Conclusions: PTFE grafts combined with small-artery patches demonstrated acceptably high short- and long-term patency rates. Since the risk of unwanted migration of PTFE graft is not negligibly low, lifelong surveillance is necessary to detect unexpected rare complications.

Background : To understand the changing demands and recent trends in the indications for living donor liver transplantation (LDLT), the present study aimed to analyze the indications for LDLT performed in a high-volume transplantation center over 10 years. Methods : The liver transplantation database at our institution was searched to identify patients who underwent LDLT during a 10-year period from January 2008 to December 2017. The study subjects (n=3,145) were divided into two groups: adult patients (n=3,019, 92.7%) and pediatric patients (n=126, 3.9%). Results : In the adult recipients, the primary diagnoses were hepatitis B virus (HBV)- associated liver cirrhosis (n=1,898, 62.9%), alcoholic liver disease (n=482, 16.0%), hepatitis C virus-associated cirrhosis (n=203, 6.7%), acute liver failure (n=127, n=4.2%), and other diseases (n=157, 5.2%). The mean Model for End-Stage Liver Disease score was 15.6±8.8 (range, 6-40). The proportion of patients with HBV-associated liver disease gradually decreased, but the proportion of those with alcoholic liver disease increased. Hepatocellular carcinoma (HCC) was diagnosed in 1,467 patients (48.6%). The mean proportion of patients with HCC was 63.1% among those with HBVassociated liver disease. In pediatric recipients, the primary diagnoses were biliary atresia (n=51, 40.5%), liver failure of various causes (n=37, 29.4%), metabolic disease (n=22, 17.5%), hepatoblastoma (n=12, 9.5%), and infectious diseases (n=4, 3.2%). Conclusions: Our results showed that there were some significant changes in the indications of LDLT. We believe that our results may reflect the real changes in the indications of LDLT and they will be useful for predicting further changes in the future.

Background : The mammalian target of the rapamycin inhibitor has dual inhibitory effects on cell growth and angiogenesis. This study aimed to analyze the usage of everolimus on actual immunosuppression (IS) regimens through a cross-sectional study in a high-volume liver transplantation (LT) center. Methods : Our institutional LT database was searched for adult patients who underwent primary LT surgery between January 2010 and December 2016. We identified 2,093 LT recipients with observation periods of 1 to 8 years.Results : We divided the 2,093 recipients into three groups according to the posttransplant follow-up period as follows: group A (12-36 months; n=680), group B (37-60 months; n=560), and group C (>60 months; n=853). The individual IS agents were tacrolimus in 1,807 patients (86.3%), cyclosporine in 169 patients (8.1%), mycophenolate mofetil (MMF) in 1,310 patients (62.6%), and everolimus in 115 patients (5.5%). The most common IS regimens were tacrolimus-MMF combination and tacrolimus monotherapy, regardless of the posttransplant period. Patients with pretransplant malignancies were administered everolimus more frequently than those without pretransplant malignancies (P

Background : The Korean model for end-stage liver disease (MELD) score-based liver allocation system was started in June 2016 in Korea.Methods : This study analyzed the detailed allocation results of deceased donor liver transplantation (DDLT) during the first 2 years after the MELD score-based liver allocation system implementation at a high-volume liver transplantation (LT) center in Korea.Results : This study included 174 patients with age above 12 years. The patient ABO blood groups were A (n=65, 37.4%), B (n=51, 29.3%), O (n=28, 16.1%), and AB (n=30, 17.2%). The LT types were primary LT in 141 patients (81.0%) and retransplantation in 33 (19.0%). The Korean Network for Organ Sharing status categories at LT were as follows: status 1 (n=11, 6.3%), status 2 (n=82, 47.1%), status 3 (n=63, 36.2%), and status 4 (n=18, 10.3%). The mean MELD score at LT and waiting period were 36.6±4.6 and 62.1±98.2 days in blood group A; 37.6±3.6 and 25.7±38.1 days in blood group B; 38.8±2.7 and 26.0±30.5 days in blood group O; and 34.8±5.5 and 68.4±110.5 days in blood group AB (P

Background : Autologous portal vein Y-graft (PYG) interposition has been the standard procedure for reconstruction of double portal vein (PV) orifices of right liver grafts during living donor liver transplantations. However, it has the disadvantage of being vulnerable to anastomotic stenosis. A refined technique of conjoined unification venoplasty (CUV) was developed to secure PV reconstruction. Methods : We reviewed the surgical outcomes in PV reconstructions using CUVs in 21 cases which were followed up for >3 years. Results : The mean age of recipients was 51.7±4.9 years. The model for end-stage liver disease score was 15.3±6.4. The graft-recipient weight ratio was 1.12±0.21. Recipient PYGs were harvested in all cases. All living donors were blood relatives or relatives through marriage with type III PV anomalies. The number of right liver graft PV orifices was two in 19 cases and three in two cases. For the central intervening vein patch, a PV segment was used in six cases, and an autologous greater saphenous vein patch was used in the remaining 15 cases. The 21 patient cohort displayed a 100% 4-year patient survival rate. None of them underwent any PV interventions including interventional stenting. Serial follow-up computed tomography scans revealed that the reconstructed PV showed early reshaping with a stable streamlined configuration for over 3 years.Conclusion : s: PV reconstruction using the CUV technique appears to be significantly more effective in preventing PV complications. We believe that CUV is a useful technique to reconstruct right liver grafts with multiple PV orifices.

BackgroundGallbladder cancer (GBC) has a poor prognosis. Although complete surgical resection is the only successful approach for improving survival, additional therapeutic modalities are required for recurrent or surgically unresectable GBCs.Materials and MethodsTo determine the expression status of HER2 and the mismatch repair (MMR) proteins MLH1, MSH2, MSH6, and PMS2, immunohistochemical staining of MMR proteins and HER2 was carried out in 216 surgically resected GBCs. HER2 labeling was scored by adopting a scoring system for gastric carcinomas. Tissues scoring 0 to 2+ were defined as HER2 negative, whereas those scoring 3+ were regarded as HER2-positive. In addition, silver in situ hybridization and microsatellite instability (MSI) analysis were conducted to confirm HER2 amplification and MSI, respectively.ResultsThree of 216 GBCs (1.3%) showed MMR protein deficiency. All three observed MSI cases exhibited dual loss of MSH2 and MSH6 protein expression. However, no cases showed loss of either MLH1 or PMS2 expression. No association was observed between MMR protein deficiency and other clinicopathological factors. HER2 amplification was noted in 30 (13.9%) GBCs and associated with Crohn-like lymphoid reaction (P = 0.023). No survival difference was observed based on HER2 overexpression or HER2 amplification status.ConclusionMMR protein deficiency and HER2 overexpression were observed in a small subset (1.3% and 13.9%, respectively) of GBCs without simultaneous occurrence of deficient MMR protein expression and HER2 overexpression. The presence of Crohn-like lymphoid reaction may help identify cases with HER2 amplification, by using hematoxylin-stained slides. Although the proportion of MMR protein-deficient- and HER2-overexpressing GBCs was small, applying immunotherapy to MMR protein-deficient GBCs and herceptin to HER2-overexpressing GBCs may provide alternative treatment options for patients with GBC.

Background Stimulation of 4-1BB with agonistic antibodies is a promising strategy for improving the therapeutic efficacy of immune checkpoint inhibitors (ICIs) or for overcoming resistance to ICIs. However, dose-dependent hepatotoxicity was observed in clinical trials with monoclonal anti-4-1BB agonistic antibodies due to the activation of 4-1BB signaling in liver resident Kupffer cells.Methods To avoid this on-target liver toxicity, we developed a novel bispecific antibody (4-1BB×PD-L1 bispecific antibody, termed “ABL503”) uniquely designed to activate 4-1BB signaling only in the context of PD-L1, while also blocking PD-1/PD-L1 signaling.Results Functional evaluation using effector cells expressing both 4-1BB and PD-1 revealed superior biological activity of ABL503 compared with the combination of each monoclonal antibody. ABL503 also augmented T-cell activation in in vitro assays and further enhanced the anti-PD-L1-mediated reinvigoration of tumor-infiltrating CD8+ T cells from patients with cancer. Furthermore, in humanized PD-L1/4-1BB transgenic mice challenged with huPD-L1-expressing tumor cells, ABL503 induced superior anti-tumor activity and maintained an anti-tumor response against tumor rechallenge. ABL503 was well tolerated, with normal liver function in monkeys.Conclusion The novel anti-4-1BB×PD-L1 bispecific antibody may exert a strong anti-tumor therapeutic efficacy with a low risk of liver toxicity through the restriction of 4-1BB stimulation in tumors.

Background Multiple types of immune cells producing IL-17 are found in the tumor microenvironment. However, their roles in tumor progression and exhaustion of CD8+ tumor-infiltrating lymphocytes (TILs) remain unclear.Methods To determine the role of type 17 immunity in tumor, we investigated the growth of B16F10 melanoma and the exhaustion of CD8+ TILs in Il17a−/− mice, Il17aCreR26DTA mice, RORγt inhibitor-treated mice, or their respective control mice. Adoptive transfer of tumor-specific IL-17-producing T cells was performed in B16F10-bearing congenic mice. Anti-CD4 or anti-Ly6G antibodies were used to deplete CD4+ T cells or CD11b+Gr-1hi myeloid cells in vivo, respectively. Correlation between type 17 immunity and T cell exhaustion in human cancer was evaluated by interrogating TCGA dataset.Results Depletion of CD4+ T cells promotes the exhaustion of CD8+ T cells with a concomitant increase in IL-17-producing CD8+ T (Tc17) cells in the tumor. Unlike IFN-γ-producing CD8+ T (Tc1) cells, tumor-infiltrating Tc17 cells exhibit CD103+KLRG1−IL-7Rαhi tissue resident memory-like phenotypes and are poorly cytolytic. Adoptive transfer of IL-17-producing tumor-specific T cells increases, while depletion of IL-17-producing cells decreases, the frequency of PD-1hiTim3+TOX+ terminally exhausted CD8+ T cells in the tumor. Blockade of IL-17 or RORγt pathway inhibits exhaustion of CD8+ T cells and also delays tumor growth in vivo. Consistent with these results, human TCGA analyses reveal a strong positive correlation between type 17 and CD8+ T cell exhaustion signature gene sets in multiple cancers.Conclusion IL-17-producing cells promote terminal exhaustion of CD8+ T cells and tumor progression in vivo, which can be reversed by blockade of IL-17 or RORγt pathway. These findings unveil a novel role for IL-17-producing cells as tumor-promoting cells facilitating CD8+ T cell exhaustion, and propose type 17 immunity as a promising target for cancer immunotherapy.