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Background/objective Complete resection is the most effective treatment of hilar cholangiocarcinoma (HC) but may result in high morbidity and mortality. Most HC patients have jaundice, and preoperative biliary drainage may reduce their risk of obstructive jaundice. ERCP and PTBD have been advocated for this purpose. This retrospective study investigated the influence of ERCP versus PTBD versus their combination on the short-term outcomes of curative HC resection. Methods Patients having curative HC resection with preoperative biliary drainage in a span of 26 years were reviewed and divided into groups according to drainage modality. Drainage-related and surgical complications and hospital mortality were compared between groups. Intention-to-treat analysis using a separate set of initial drainage data was performed. Results Eighty-six patients were divided into: Group A, ERCP only, n = 32 (32/86 = 37.2%); Group B, PTBD only, n = 10 (10/86 = 11.6%); Group C, ERCP + PTBD, n = 44 (44/86 = 51.2%). International normalized ratio was significantly higher in Group B (p = 0.008). The three groups were comparable in operative details, hospital stay, and mortality. Fifty-two patients had postoperative complications. Significantly more patients in Groups A and C had subphrenic abscess (A: 25%, B: 0%, C: 9.1%; p = 0.035) and subsequent radiological drainage. Group A had insignificantly more patients with wound infection (31.3% vs 10% vs 22.7%, p = 0.334), chest infection (28.1% vs 20% vs 11.4%, p = 0.178), and urinary tract infection (6.3% vs 0% vs 0%, p = 0.133). The three groups had similar rates of major complications (p = 0.501). They also had comparable survival outcomes (overall, p = 0.370; disease-free, p = 0.569). Fifteen and 71 patients received PTBD and ERCP respectively as first drainage mode. These two groups were comparable in liver function, preoperative comorbidity, intraoperative details, and postoperative outcomes. Conclusion In the preoperative management of HC, the use of ERCP, PTBD or their combination is acceptable and can optimize patients' condition for curative HC resection.

To test the hypothesis that ICG fluorescence cholangiography (ICG-FC) helps to identify critical structures during laparoscopic cholecystectomy (LC) and hence reduce biliary injuries and conversions. In LC, biliary injury and conversion often happen if the biliary anatomy is misidentified.This was a single-center randomized controlled trial from 2017 to 2019. Patients with acute cholecystitis requiring LC were assessed for eligibility for the trial. Patients in the trial were randomized to undergo either conventional LC (conventional arm) or LC with ICG-FC (ICG arm). Conversion rate and biliary injury incidence were outcome measures.Totally 92 patients participated (46 patients in each arm). The median age was 61 years in both arms (p = 0.472). The conventional arm had 22 men and 24 women; the ICG arm had 24 men and 22 women (p = 0.677). The two arms were comparable in all perioperative parameters. The time from ICG injection to surgery was 67 (16-1150) min. Both arms had an 8.7% conversion rate (p = 1.000). The median operative time was 140.5 min in the conventional arm and 149.5 min in the ICG arm (p = 0.086). The complication rate was 15.2% in the former and 10.9% in the latter (p = 0.536), and both had a 2.2% bile leakage rate. The median hospital stay was 3.5d in the former and 4.0d in the latter (p = 0.380).ICG-FC did not make any difference in conversion or complication rate. Its routine use in LC is questionable. However, it may be helpful in difficult cholecystectomies and may be used as an adjunct.The trial was registered with the Institutional Review Board of University of Hong Kong/Hospital Authority Hong Kong West Cluster ( http://www.med.hku.hk/en/research/ethics-and-integrity/human-ethics ).UW17-492.

This study verified whether radical treatment for hepatocellular carcinoma (HCC) oligo-recurrence after liver transplantation conveys survival benefits. A retrospective study of 144 patients with posttransplant HCC recurrence was performed. Propensity score matching was performed to adjust for baseline covariates between patients who received radical and palliative treatments. The primary endpoint was postrecurrence survival. A total of 50 patients (35%) received radical treatment for recurrence, and 76 (53%) and 18 (13%) patients received palliative and supportive treatments, respectively. Compared with the radical group, patients who received palliative treatment had more early recurrences (time from transplant 17 versus 11 months; P = 0.01) and more extensive disease in terms of tumor numbers (1 versus 4; P

Salvage liver transplantation (SLT) is the ideal treatment for patients with recurrent hepatocellular carcinoma (HCC) and liver cirrhosis. The optimal timing for offering SLT was controversial. This study aimed at investigating the impact of time to recurrence and other prognostic factors on survival outcome after SLT. Between May 2000 and April 2019, patients who had undergone hepatectomy or ablation for HCC and later received SLT in Queen Mary Hospital were included. Clinico-pathological data during primary treatment and SLT were retrospectively reviewed. Kaplan–Meier analysis and log-rank test were used to determine overall and disease-free survival after SLT. Prognostic factors affecting overall and disease-free survival were determined by multivariate analysis using Cox regression analysis. P-value of less than 0.05 was considered statistically significant. Fifty-three patients were identified within the specified period including 22 patients in early recurrence group (ER group, time to recurrence within 1 year) and 31 patients in late recurrence group (LR group, time to recurrence more than 1 year). The 1-, 5-, and 10-year overall survival after primary treatment was 100%, 76.6%, and 61.1% in the ER group and 100%, 90%, and 76.4% in the LR group (p = 0.59). There were no statistical differences in overall survival (p = 0.84) and disease-free survival (p = 0.85) after SLT between ER and LR group. Pre-transplant alpha-fetoprotein > = 400 ng/mL (p = 0.007) and macrovascular invasion in explant (p = 0.002) were independent risk factors for shorter overall survival after primary treatment. Time to recurrence after primary treatment of HCC did not affect survival outcome after SLT. With careful patient selection, SLT could be offered to patient with early or late tumor recurrence.

BACKGROUND AND AIMS There are no prospective data on stereotactic body radiation therapy (SBRT) as a bridge to liver transplantation for HCC. This study aimed to evaluate the efficacy and safety of SBRT as bridging therapy, with comparison with transarterial chemoembolization (TACE) and high-intensity focused ultrasound (HIFU). APPROACH AND RESULTS Patients were prospectively enrolled for SBRT under a standardized protocol from July 2015 and compared with a retrospective cohort of patients who underwent TACE or HIFU from 2010. The primary endpoint was tumor control rate at 1 year after bridging therapy. Secondary endpoints included cumulative incidence of dropout, toxicity, and posttransplant survival. During the study period, 150 patients were evaluated (SBRT, n = 40; TACE, n = 59; HIFU, n = 51). The tumor control rate at 1 year was significantly higher after SBRT compared with TACE and HIFU (92.3%, 43.5%, and 33.3%, respectively; P = 0.02). With competing risk analysis, the cumulative incidence of dropout at 1 and 3 years after listing was lower after SBRT (15.1% and 23.3%) compared with TACE (28.9% and 45.8%; P = 0.034) and HIFU (33.3% and 45.1%; P = 0.032). Time-to-progression at 1 and 3 years was also superior after SBRT (10.8%, 18.5% in SBRT, 45%, 54.9% in TACE, and 47.6%, 62.8% in HIFU; P

Treatment of hepatocellular carcinoma (HCC) recurrences following liver transplant (LT) is challenging. Most clinical trials of systemic therapies for advanced HCC excluded patients with any history of organ transplant. We aimed to assess the outcomes in using various systemic therapies in patients with post-LT recurrence. Consecutive patients with HCC and recurrences following LT at a large tertiary centre from 2005 to 2018 were reviewed. Overall survival (OS), response rates and adverse events (AEs) were analysed. Forty-three consecutive patients with a recurrence of HCC following LT were identified from 2005 to 2018. Median OS from diagnosis of recurrence was 17 months (CI 11.3, 22.7). Early recurrence within 12 months of transplant was associated with a significantly worse median survival of 10 months (CI 8.5, 11.4) compared to 26 months (CI 18.8, 33.2) when recurrences occurred after 12 months from transplant (p

Background: We aimed to identify predictive factors for positron emission tomography (PET)-detected hepatocellular carcinoma (HCC) metastasis and a cost-effective approach to preoperative PET-computed tomography (CT) for detecting metastasis. Methods: Clinicopathological and survival data of HCC patients having PET-CT with 18F-fludeoxyglucose (FDG) and 11C-acetate (ACT) following contrast-enhanced CT/magnetic resonance imaging (MRI) for preoperative tumor staging were reviewed. Binary logistic regression was performed to identify predictive factors for PET-detected metastasis. A cost-benefit analysis model was built for the incurred costs and the impact of PET-CT findings on treatment strategy was studied. Results: Totally 152 patients were analyzed. Dual-tracer PET-CT detected metastasis in 17 patients (11%). By multivariate analysis, alpha-fetoprotein (AFP) ≥400 ng/mL [relative risk (RR): 4.30, 95% confidence interval (CI): 1.41–13.15, P=0.011] and bilobar disease (RR: 3.94, 95% CI: 1.24–12.52, P=0.014) were independent predictive factors for PET-detected metastasis. PET-CT findings altered the treatment strategy for 12 patients (7.9%); three partial hepatectomies, eight episodes of transarterial chemoembolization (TACE) and one episode of ablation were avoided, with an estimated cost-saving of US $91,000, $150,000 and $10,600 respectively. Had the PET-CT been performed only for patients with AFP ≥400 ng/mL or bilobar disease (n=74), metastasis would have been confirmed in 14 patients (18.9%), and the cost-saving per patient was estimated at US $1,070. Conclusions: Dual-tracer PET-CT is cost-effective and useful for preoperative HCC staging in patients with AFP ≥400 ng/mL or bilobar disease. Its routine use in preoperative workup for all HCC patients is not recommended. Unilobar disease with AFP

This retrospective, single-center study aimed to investigate the importance of chemotherapy and to come up with the optimal liver resection margin length for patients with resectable colorectal liver metastasis (CRLM). Patients who had undergone any form of liver resection for CRLM were reviewed and analyzed. The analyses were broken down into three parts: (1) overall effect of chemotherapy, (2) effect of chemotherapy with positive/negative resection margin, and (3) result of discriminative analysis with optimal margin length analysis. In total, 381 patients were studied. Among them, 279 received chemotherapy whereas 102 did not. Survival was significantly better in patients with chemotherapy (5-year, 43.6% vs. 25.8%) (p < 0.001). Patients who received chemotherapy (n = 93) with negative margins had better survival than patients (n = 8) with positive margins (5-year, 28.1% vs. 0%) (p = 0.019). On multivariate analysis, margin involvement was the poor prognostic factor for survival. Patients who had chemotherapy (n = 238) with negative margin showed a trend of better survival than patients (n = 41) with positive margins (5-year, 45.7% vs. 29.3%) (p = 0.085). Patients (n = 93) with negative margin and no chemotherapy and patients (n = 41) with positive margin and chemotherapy had comparable survival at 5 years (p = 0.422). On multivariate analysis, tumor number was the prognostic factor for survival. By the discriminant method, 1.09 cm (sensitivity 0.242, specificity 0.718) was determined as the cut-off for optimal margin length. Patients who had margin ≥ 1.09 cm (n = 81) enjoyed significantly better survival (5-year, 54.3% vs. 33.5%) (p = 0.041). On multivariate analysis, margin length ≥ 1.09 cm was the prognostic factor for favorable survival. The results demonstrated the important effect of perioperative chemotherapy and negative margin liver resection in management of patients suffered from CRLM.

Purpose In this systematic review, we aimed to clarify the useful anatomic structures and assess available surgical techniques and strategies required to safely perform minimally invasive anatomic liver resection (MIALR), with a particular focus on the hepatic veins (HVs). Methods A systematic review was conducted using MEDLINE/PubMed for English articles and Ichushi databases for Japanese articles through September 2020. The quality assessment of the articles was performed in accordance with the Scottish Intercollegiate Guidelines Network (SIGN). Results A total of 3,372 studies were obtained, and 59 were selected and reviewed. Due to the limited number of published comparative studies and case series, the degree of evidence from our review was low. Thirty-two articles examined the anatomic landmarks and crucial structures for approaching HVs. Regarding the direction of HV exposure, 32 articles focused on the techniques and advantages of exposing HVs from either the root or the periphery. Ten articles focused on the techniques to perform a segmentectomy 8 in particularly difficult cases of MIALR. In seven articles, bleeding control from HVs was also discussed. Conclusions This review may help experts reach a consensus regarding the best approach to the management of hepatic veins during MIALR.

Background /Aim: Laparoscopic hepatectomy has been gaining popularity but its evidence in major hepatectomy for cirrhotic liver is lacking. We studied the long-term outcomes of the pure laparoscopic approach versus the open approach in major hepatectomy without Pringle maneuver in patients with hepatocellular carcinoma (HCC) and cirrhosis using the propensity score analysis. Methods We reviewed patients diagnosed with HCC and cirrhosis who underwent major hepatectomy as primary treatment. The outcomes of patients who received the laparoscopic approach were compared with those of propensity-case-matched patients (ratio, 4:1) who received the open approach. The matching was made on the following factors: tumor size, tumor number, age, sex, hepatitis serology, HCC staging, comorbidity, and liver function. Results Twenty-four patients underwent pure laparoscopic major hepatectomy for HCC with cirrhosis. Ninety-six patients who underwent open major hepatectomy were matched by propensity scores. The laparoscopic group had less median blood loss (300 ml vs 645 ml, p = 0.001), shorter median hospital stay (6 days vs 10 days, p = 0.002), and lower rates of overall complication (12.5% vs 39.6%, p = 0.012), pulmonary complication (4.2% vs 25%, p = 0.049) and pleural effusion (p = 0.026). The 1-year, 3-year and 5-year overall survival rates in the laparoscopic group vs the open group were 95.2%, 89.6% and 89.6% vs 87.5%, 72.0% and 62.8% (p = 0.211). Correspondingly, the disease-free survival rates were 77.1%, 71.2% and 71.2% vs 75.8%, 52.7% and 45.5% (p = 0.422). Conclusions The two groups had similar long-term survival. The laparoscopic group had favorable short-term outcomes. Laparoscopic major hepatectomy without routine Pringle maneuver for HCC with cirrhosis is a safe treatment option at specialized centers.

In spite of early adoption of the brain death legislation, and all efforts at promoting deceased donation, various social, economic and cultural factors have acted as road blocks to the furthering of deceased donor liver transplantation (DDLT) in most Asian societies. On the other hand, Asian liver transplant centers have been the pioneers, innovators, and technical advancement catalysts for the world to follow, especially with regards to living donor liver transplantation (LDLT). With some high volume centers performing more than 200 LDLTs a year with good outcomes in the donor and recipient, techniques to expand the living donor pool have also been adopted like ABO-incompatible, paired exchange and dual lobe living donor liver transplants. Although large multicenter, and registry data as regards safety and outcomes of minimally invasive donor hepatectomy are awaited, expert centers have pioneered, and now regularly perform purely laparoscopic and robotic living donor hepatectomies, especially in Korea.

Gallbladder cancer (GBCA) is a rare and fatal disease and the majority of patients presents with advanced stage. Surgical resection associated with lymphadenectomy is the only chance for cure. For patients in stages III and IV, extended resection is the only treatment to achieve R0 margins. For GBCA invading the hepatoduodenal ligament and pancreatoduodenal region, the resection of extrahepatic bile duct and pancreas is necessary. Hepatopancreatoduodenectomy (HPD) represents the most complex and challenging procedure in the hepatopancreatobiliary region. Kuno at the Cancer Institute Hospital Tokyo performed the first HPD in Japan in 1974 and in 1980 Takasaki presented five cases and the 30-day mortality was 60%. After that, other countries started to perform the procedure including United States and Brazil. The main complications are liver failure and pancreatic fistula. Advancements in perioperative care, surgical technique, medical instruments and postoperative at intensive care unit have resulted in reduction in morbidity and mortality. The use of portal vein embolization is indicated to increase the liver volume in patients with insufficient remnant. Preoperative biliary drainage can prevent cholangitis and improve hepatic function. This procedure should be recommended before extended HPD in jaundiced patients. Operative results with mortality rates below 5% at high volume centers suggest that HPD should be performed at centers with expertise in hepatopancreatobiliary surgery.

OBJECTIVE To study the impact of LT experience on the outcome of CLR for locally advanced hepatobiliary malignancy SUMMARY OF BACKGROUND DATA:: Despite evolution in LT knowledge and surgical techniques in the past decades, there is yet data to evaluate the significance of LT experience in performing CLR. METHODS Postoperative outcome after CLR between 1995 and 2019 were reviewed and correlated with LT experience in a single center with both LT and CLR service. CLR was defined as hepatectomy with vasculobiliary reconstruction, or multivisceral resection, central bisectionectomy (S4/5/8), or associating liver partition and portal vein ligation for staged hepatectomy. Spearman rank correlation and receiver operating characteristic analysis were used to define the association between CLR-related outcomes and LT experience. RESULTS With cumulative single-center experience of 1452 LT, 222 CLR were performed during the study period [hepatectomy with biliary (27.0%), or vascular (21.2%) reconstruction, with multivisceral resections (9.9%), with associating liver partition and portal vein ligation for staged hepatectomy (18.5%)] mainly for hepatocellular carcinoma (53.2%), and hilar cholangiocarcinoma (14%). Median tumor size was 7.0 cm. Other features include macrovascular invasion (23.4%), and juxta-visceral invasion (14%). Major postoperative complication rate was 25.2% and mortality rate was 6.3%. CLR-complication rate was inversely associated with LT experience (R = -0.88, P < 0.005). Receiver operator characteristic analysis revealed the cutoff for LT experience to have the greatest influence on CLR was 95 with a sensitivity of 100% and Youden index of 1. Multivariable analysis showed that blood transfusion, prolonged operating time, LT experience

BACKGROUND: Graft hepatocellular carcinoma (HCC) recurrence after liver transplant is more frequently encountered. Graft hepatectomy is technically challenging and is associated with high morbidity. Stereotactic body radiation therapy (SBRT) has been shown to be safe and effective for the treatment of primary HCC. However, its role in HCC recurrence in a liver graft remains unclear. AIM: To evaluate the safety and efficacy of SBRT for the treatment of graft HCC recurrence after liver transplantation. METHODS: A retrospective study was conducted. From 2012 to 2018, 6 patients with intrahepatic HCC recurrence after liver transplant were treated with SBRT at Queen Mary Hospital, the University of Hong Kong. The primary outcome was time to overall disease progression and secondary outcomes were time to local progression and best local response, as assessed with the Modified response Evaluation Criteria for Solid Tumours criteria. Patients were monitored for treatment related toxicities and graft dysfunction. RESULTS: A total of 9 treatment courses were given for 13 tumours. The median tumour size was 2.3 cm (range 0.7-3.6 cm). Two (22%) patients had inferior vena cava tumour thrombus. The best local treatment response was: 5 (55%) complete response, 1 (11%) partial response and 3 (33%) stable disease. After a median follow up duration of 15.5 mo, no local progression or mortality was yet observed. The median time to overall disease progression was 6.5 mo. There were 6 regional progression in the liver graft (67%) and 2 distant progression in the lung (22%). There was no grade 3 or above toxicity and there was no graft dysfunction after SBRT. CONCLUSION: SBRT appears to be safe in this context. Regional progression is the mode of failure.

BACKGROUND The aggressive approach of vascular resection plus reconstruction in curative resection of hilar cholangiocarcinoma (HC) remains controversial. This retrospective study investigated its short- and long-term outcomes. METHODS Data of HC patients from 1989 to 2016 were reviewed. Operated patients were divided into two groups (with and without vascular resection) and compared in terms of perioperative results. Patients who had unresectable HC were also compared with patients who had been operated. RESULTS Ninety patients underwent curative HC resection. They were divided into group A (without aggressive approach, n = 68) and group B (with aggressive approach, n = 22). The groups were comparable in all parameters including rates of overall and major complication and in-hospital, 30-day and 90-day mortality except that group B had more patients with more advanced disease (P = 0.008), more patients with tumour invasion of the vasculature (40.9% versus 7.4%, P = 0.001), and fewer patients with blood transfusion (27.3% versus 52.9%, P = 0.036). The groups had similar disease-free survival (group A: median, 17.9 months, 5 years, 27.4%; group B: median, 11.7 months, 5 years, 14.3%; P = 0.427) and overall survival (group A: median, 22.0 months, 5 years, 26.5%; group B: median, 26.5 months, 5 years, 14.7%; P = 0.90). Two hundred patients with unresectable HC were compared with patients who had received operation and found to have worse survival outcomes (P

Liver resection is the best treatment option for patients with resectable colorectal liver metastasis (CRLM). A 10-year follow-up can reflect the true curative potential of resection. This retrospective study investigated factors for long-term survival of CRLM patients.Data of patients who underwent liver resection for CRLM without extrahepatic disease from 1990 to 2012 at our hospital were reviewed. Patients who survived for 10 years were compared with those who survived for 10 years.Totally, 315 patients were included in the study. They were divided into 2 groups: 10-year group and 10-year group. Patients in the 10-year group had more tumor nodules (P = 0.016), more bilobar involvement (P = 0.004), narrower resection margin (P 0.001), and worse disease-free and overall survival (P 0.001). On multivariate analysis, low preoperative hemoglobin level, large number of tumor nodules, and bilobar involvement were poor prognostic factors for overall survival, while adjuvant chemotherapy was a favorable factor. Further analysis of patients with bilobar disease showed that perioperative blood transfusion was a poor prognostic factor for overall survival while adjuvant chemotherapy was a favorable one. In patients with multiple bilobar tumor nodules, adjuvant chemotherapy had a positive impact on disease-free survival and overall survival.Patients who survived for 10 years after liver resection for CRLM tended to have normal preoperative hemoglobin level, unilobar disease, fewer tumor nodules, and have received adjuvant chemotherapy. Adjuvant chemotherapy favorably affected long-term survival of CRLM patients.

The Brisbane 2000 Terminology for Liver Anatomy and Resections, based on Couinaud's segments, did not address how to identify segmental borders and anatomic territories of less than one segment. Smaller anatomic resections including segmentectomies and subsegmentectomies, have not been well defined. The advent of minimally invasive liver resection has enhanced the possibilities of more precise resection due to a magnified view and reduced bleeding, and minimally invasive anatomic liver resection (MIALR) is becoming popular gradually. Therefore, there is a need for updating the Brisbane 2000 system, including anatomic segmentectomy or less. An online "Expert Consensus Meeting: Precision Anatomy for Minimally Invasive HBP Surgery (PAM-HBP Surgery Consensus)" was hosted on February 23, 2021.The Steering Committee invited 34 international experts from around the world. The Expert Committee (EC) selected 12 questions and two future research topics in the terminology session. The EC created seven tentative definitions and five recommendations based on the experts' opinions and the literature review performed by the Research Committee. Two Delphi Rounds finalized those definitions and recommendations.This paper presents seven definitions and five recommendations regarding anatomic segmentectomy or less. In addition, two future research topics are discussed.The PAM-HBP Surgery Consensus has presented the Tokyo 2020 Terminology for Liver Anatomy and Resections. The terminology has added definitions of liver anatomy and resections that were not defined in the Brisbane 2000 system.

Background The concept of Minimally invasive anatomic liver resection (MIALR) is gaining popularity. However, specific technical skills need to be acquired to safely perform MIALR. The "Expert Consensus Meeting: Precision Anatomy for Minimally Invasive HBP Surgery (PAM-HBP Surgery Consensus)" was developed as a special program during the 32nd meeting of the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS). Methods Thirty-four international experts gathered online for the consensus. A Research Committee performed a comprehensive literature review, classifying studies according to the Scottish Intercollegiate Guidelines Network (SIGN) method. Based on the literature review and experts' opinions, tentative recommendations were drafted and circulated among experts using online Delphi Rounds. Finally, formulated recommendations were presented online in the Expert Consensus Meeting of the JSHBPS on February 23rd, 2021. The final recommendations were validated and finalized by the 2nd Delphi Round in May 2021. Results Seven Clinical Questions (CQs) were selected, and 22 recommendations were formulated. All recommendations reached more than 85% consensus among experts at the final Delphi Round. Conclusions The Expert Consensus Meeting for safely performing MIALR has presented a set of clinical guidelines based on available literature and experts' opinions. We expect these guidelines to have a favorable effect on the safe implementation and development of MIALR.

The 25th Annual Congress of the International Liver Transplantation Society was held in Toronto, Canada, from May 15 to 18, 2019. Surgeons, hepatologists, anesthesiologists, critical care intensivists, radiologists, pathologists, and research scientists from all over the world came together with the common aim of improving care and outcomes for liver transplant recipients and living donors. Some of the featured topics at this year's conference included multidisciplinary perioperative care in liver transplantation, worldwide approaches to organ allocation, donor steatosis, and updates in pediatrics, immunology, and radiology. This report presents excerpts and highlights from invited lectures and select abstracts, reviewed and compiled by the Vanguard Committee of International Liver Transplantation Society. This will hopefully contribute to further advances in clinical practice and research in liver transplantation.

Since its introduction in 2012, associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) has significantly expanded the pool of candidates for liver resection. It offers patients with insufficient liver function a chance of a cure. ALPPS is most controversial when its high morbidity and mortality is concerned. Operative mortality is usually a result of post-hepatectomy liver failure and can be minimized with careful patient selection. Elderly patients have limited reserve for tolerating the demanding operation. Patients with colorectal liver metastasis have normal liver and are ideal candidates. ALPPS for cholangiocarcinoma is technically challenging and associated with fair outcomes. Patients with hepatocellular carcinoma have chronic liver disease and limited parenchymal hypertrophy. However, in selected patients with limited hepatic fibrosis satisfactory outcomes have been produced. During the inter-stage period, serum bilirubin and creatinine level and presence of surgical complication predict mortality after stage II. Kinetic growth rate and hepatobiliary scintigraphy also guide the decision whether to postpone or omit stage II surgery. The outcomes of ALPPS have been improved by a combination of technical modifications. In patients with challenging anatomy, partial ALPPS potentially reduces morbidity, but remnant hypertrophy may compare unfavorably to a complete split. When compared to conventional two-stage hepatectomy with portal vein embolization or portal vein ligation, ALPPS offers a higher resection rate for colorectal liver metastasis without increased morbidity or mortality. While ALPPS has obvious theoretical oncological advantages over two-stage hepatectomy, the long-term outcomes are yet to be determined.

Purpose of review Application of living donor liver transplantation (LDLT) in model for end-stage liver disease (MELD) 35+ patients has been regarded with skepticism. There is concern that a partial graft may not achieve favourable outcomes, and that a healthy donor is risked for a transplant which might turn out to be futile. Recent findings In practice, LDLT improves access to liver graft and allows timely transplantation. Long-term results from high-volume centres revealed that outcomes of LDLT in these patients have not been jeopardized by limited graft volumes. With unimpeded vascular outflow, a partial graft could provide sufficient function to overcome the stress of transplant operation. However, LDLT is a complex operation with immense technical demand. A steep learning curve is encountered before optimal outcomes could be produced. Meanwhile, donor safety remains the paramount concern. Donor should not be evaluated for futile candidates. MELD 35+ patients with refractory sepsis or cardiac event are unlikely to benefit from liver transplantation. Borderline donors, in terms of donor safety or graft quality, should not be accepted. As in recipient operation, accumulation of experience is crucial to reduce donor mortality and morbidity. Summary LDLT is justified for MELD 35+ in high-volume centres with vast experience. Satisfactory recipient outcomes can be produced with minimal donor morbidity.

BACKGROUND Small-for-size grafts (SFSGs) in living donor liver transplantation (LDLT) could optimize donor postoperative outcomes and also expand the potential donor pool. Evidence on whether SFSGs would affect medium-term and long-term recipient graft survival is lacking. AIM To evaluate the impact of small-for-size liver grafts on medium-term and long-term graft survival in adult to adult LDLT. METHODS A systematic review and meta-analysis were performed by searching eligible studies published before January 24, 2019 on PubMed, EMBASE, and Web of Science databases. The primary outcomes were 3-year and 5-year graft survival. Incidence of small-for-size syndrome and short term mortality were also extracted. RESULTS This meta-analysis is reported according to the guidelines of the PRISMA 2009 Statement. Seven retrospective observational studies with a total of 1821 LDLT recipients were included in the meta-analysis. SFSG is associated with significantly poorer medium-term graft survival. The pooled odds ratio for 3-year graft survival was 1.58 [95% confidence interval 1.10-2.29, P = 0.014]. On the other hand, pooled results of the studies showed that SFSG had no significant discriminatory effect on 5-year graft survival with an odds ratio of 1.31 (95% confidence interval 0.87-1.97, P = 0.199). Furthermore, incidence of small-for-size syndrome detected in recipients of SFSG ranged from 0-11.4% in the included studies. CONCLUSION SFSG is associated with inferior medium-term but not long-term graft survival. Comparable long-term graft survival based on liver graft size shows that smaller grafts could be accepted for LDLT with appropriate flow modulatory measures. Close follow-up for graft function is warranted within 3 years after liver transplantation.

Background & Aims The impact of hepatitis B core antibody (anti-HBc) positive liver grafts on survival and the risk of de novo hepatitis B virus (HBV) infection after liver transplantation (LT) remain controversial. Therefore, we aimed to analyze this risk and the associated outcomes in a large cohort of patients. Methods This was a retrospective study that included all adults who underwent LT at Queen Mary Hospital, Hong Kong, between 2000 and 2015. Data were retrieved from a prospectively collected database. Antiviral monotherapy prophylaxis was given for patients receiving grafts from anti-HBc positive donors. Results A total of 964 LTs were performed during the study period, with 416 (43.2%) anti-HBc positive and 548 (56.8%) anti-HBc negative donors. The median follow-up time was 7.8 years. Perioperative outcomes (hospital mortality, complications, primary nonfunction and delayed graft function) were similar between the 2 groups. The 1-, 5- and 10-year graft survival rates were comparable in anti-HBc positive (93.3%, 85.3% and 76.8%) and anti-HBc negative groups (92.5%, 82.9% and 78.4%, p = 0.944). The 1-, 5- and 10-year patient survival rates in anti-HBc positive group were 94.2%, 87% and 79% and were similar to the anti-HBc negative group (93.5%, 84% and 79.7%, p = 0.712). One-hundred and eight HBsAg negative recipients received anti-HBc positive grafts, of whom 64 received lamivudine and 44 entecavir monotherapy prophylaxis. The risk of de novo HBV was 3/108 (2.8%) and all occurred in the lamivudine era. There were 659 HBsAg-positive patients and 308 (46.7%) received anti-HBc positive grafts. The risk of HBV recurrence was similar between the 2 groups. Donor anti-HBc status did not impact on long-term patient and graft survival, or the risk of hepatocellular carcinoma recurrence after LT. Conclusions De novo HBV was exceedingly rare especially with entecavir prophylaxis. Anti-HBc positive grafts did not impact on perioperative and long-term outcomes after transplant. Lay summary The risk of de novo hepatitis B infection after liver transplantation was rare when using hepatitis B core positive liver grafts with entecavir monotherapy prophylaxis. Hepatitis B core antibody status did not impact on perioperative and long-term outcomes after liver transplantation. This provides support for the clinical use of hepatitis B core positive liver grafts when required.

BACKGROUND Liver transplantation (LT) is regarded as the best treatment for both primary and recurrent hepatocellular carcinoma (HCC). Post-transplant HCC recurrence rate is relatively low but significant, ranging from 10%-30% according to different series. When recurrence happens, it is usually extrahepatic and associated with poor prognosis. A predictive model that allows patient stratification according to recurrence risk can help to individualize post-transplant surveillance protocol and guidance of the use of anti-tumor immunosuppressive agents. AIM To develop a scoring system to predict HCC recurrence after LT in an Asian population. METHODS Consecutive patients having LT for HCC from 1995 to 2016 at our hospital were recruited. They were randomized into the training set and the validation set in a 60:40 ratio. Multivariable Cox regression model was used to identity factors associated with HCC recurrence. A risk score was assigned to each factor according to the odds ratio. Accuracy of the score was assessed by the area under the receiver operating characteristic curve. RESULTS In total, 330 patients were eligible for analysis (183 in training and 147 in validation). Recurrent HCC developed in 14.2% of them. The median follow-up duration was 65.6 mo. The 5-year disease-free and overall survival rates were 78% and 80%, respectively. On multivariate analysis, alpha-fetoprotein > 400 ng/mL [P = 0.012, hazard ratio (HR) 2.92], sum of maximum tumor size and number (P = 0.013, HR 1.15), and salvage LT (P = 0.033, HR 2.08) were found to be independent factors for disease-free survival. A risk score was calculated for each patient with good discriminatory power (c-stat 0.748 and 0.85, respectively, in the training and validation sets). With the derived scores, patients were classified into low- (0–9), moderate- (> 9–14), and high-risk groups (> 14), and the risk of HCC recurrence in the training and validation sets was 10%, 20%, 54% (c-stat 0.67) and 4%, 22%, 62% (c-stat 0.811), accordingly. The risk stratification model was validated with chi-squared goodness-of-fit test (P = 0.425). CONCLUSION A validated predictive model featuring alpha-fetoprotein, salvage LT, and the sum of largest tumor diameter and total number of tumor nodule provides simple and reliable guidance for individualizing postoperative surveillance strategy.

Most management guidelines and much of the available clinical trial evidence for immunosuppressants in liver transplantation (LT) pertain to Western practice. While evidence from Western studies may not translate to Asian settings, there is a paucity of Asian randomized controlled trials of immunosuppression in liver recipients. Nonetheless, there are notable differences in the indications and procedures for LT between Western and Asian settings. The Asian Liver Transplant Network held its inaugural meeting in Singapore in November 2016 and aimed to provide an Asian perspective on aspects of immunosuppression following LT. Because of their importance to outcome following LT, the meeting focused on (1) reducing the impact of renal toxicity, (2) hepatocellular carcinoma recurrence, and (3) nonadherence with immunosuppressant therapy.

Background and aims Acute-on-chronic liver failure (ACLF) is considered a main prognostic event in patients with chronic liver disease (CLD). We analyzed the 28-day and 90-day mortality in ACLF patients with or without underlying cirrhosis enrolled in the ACLF Research Consortium (AARC) database. Methods A total of 1,621 patients were prospectively enrolled and 637 (39.3%) of these patients had cirrhosis. Baseline characteristics, complications and mortality were compared between patients with and without cirrhosis. Results Alcohol consumption was more common in cirrhosis than non-cirrhosis (66.4% vs. 44.2%, p p p p p p p Conclusions The 28-day and 90-day mortality rates of ACLF patients without cirrhosis were significantly higher than those with cirrhosis in alcoholic CLD. The presence of cirrhosis and its stage should be evaluated at baseline to guide for management. Thai Clinical Trials Registry, TCTR20191226002.

Background. Precise staging is essential in the management of patients with recurrent hepatocellular carcinoma (HCC) after liver transplantation. There is no current consensus on the optimal staging strategy. We conducted this study to evaluate the performance of dual-tracer positron emission tomography-computed tomography (PET-CT) for this purpose and to investigate whether the results of dual-tracer PET-CT affected patient management. Methods. A retrospective study was conducted. Patients who underwent dual-tracer PET-CT for suspected or confirmed HCC recurrence after liver transplant were included. The lesion-based sensitivity and positive predictive value of dual-tracer PET-CT were determined. Results. Fifty-six patients and 189 recurrent tumors were included. The lesion-based sensitivity and positive predictive value of dual-tracer PET-CT were 94.7% and 90.4%, respectively. The sensitivity of dual-tracer PET-CT was better than the standard imaging in the surveillance protocol (82.5% versus 94.7%, P < 0.001), especially for detecting liver recurrence (71.0% versus 96.8%, P < 0.001). Half of the dual-tracer PET-CT detected additional recurrence (n = 26, 46.4%) and one-third led to a change in management (n = 19, 33.9%). Ten patients (17.9%) with inconclusive standard imaging had metabolic recurrence confirmed on PET-CT and treatment was commenced early. Four patients (7.1%) had revised locoregional treatment, and 5 (8.9%) had to withdraw from locoregional treatment after the detection of additional metastatic disease. Conclusions. Dual-tracer PET-CT is effective for staging posttransplant HCC recurrence. It often provides valuable information to guide clinical management.

Colorectal cancer is a prevalent disease worldwide, with more than 50% of patients developing metastases to the liver. Despite advances in improving resectability, most patients present with non-resectable colorectal liver metastases requiring palliative systemic therapy and locoregional disease control strategies. There is a growing interest in the use of liver transplantation to treat non-resectable colorectal liver metastases in well selected patients, leading to a surge in the number of studies and prospective trials worldwide, thereby fuelling the emerging field of transplant oncology. The interdisciplinary nature of this field requires domain-specific evidence and expertise to be drawn from multiple clinical specialities and the basic sciences. Importantly, the wider societal implication of liver transplantation for non-resectable colorectal liver metastases, such as the effect on the allocation of resources and national transplant waitlists, should be considered. To address the urgent need for a consensus approach, the International Hepato-Pancreato-Biliary Association commissioned the Liver Transplantation for Colorectal liver Metastases 2021 working group, consisting of international leaders in the areas of hepatobiliary surgery, colorectal oncology, liver transplantation, hepatology, and bioethics. The aim of this study was to standardise nomenclature and define management principles in five key domains: patient selection, evaluation of biological behaviour, graft selection, recipient considerations, and outcomes. An extensive literature review was done within the five domains identified. Between November, 2020, and January, 2021, a three-step modified Delphi consensus process was undertaken by the workgroup, who were further subgrouped into the Scientific Committee, Expert Panel, and Transplant Centre Representatives. A final consensus of 44 statements, standardised nomenclature, and a practical management algorithm is presented. Specific criteria for clinico-patho-radiological assessments with molecular profiling is crucial in this setting. After this, the careful evaluation of biological behaviour with bridging therapy to transplantation with an appropriate assessment of the response is required. The sequencing of treatment in synchronous metastatic disease requires special consideration and is highlighted here. Some ethical dilemmas within organ allocation for malignant indications are discussed and the role for extended criteria grafts, living donor transplantation, and machine perfusion technologies for non-resectable colorectal liver metastases are reviewed. Appropriate immunosuppressive regimens and strategies for the follow-up and treatment of recurrent disease are proposed. This consensus guideline provides a framework by which liver transplantation for non-resectable colorectal liver metastases might be safely instituted and is a meaningful step towards future evidenced-based practice for better patient selection and organ allocation to improve the survival for patients with this disease.

We present a 37 years’ experience in the management of biliary atresia (BA) and discuss long-term complications after Kasai portoenterostomy (KPE). A retrospective territory-wide study from 1980 to 2017 on 231 patients with open KPE from three tertiary paediatric surgical centres was performed. Outcome parameters were clearance of jaundice (COJ), native liver survival (NLS) and long-term complications. Factors affecting the operative outcomes were analyzed. The median duration of follow up was 17.5 (IQR: 13.5–22) years. Over 66% of patients became jaundice-freed at 1 year after KPE. Seventy patients (30.3%) received liver transplant (LT) at a median age of 6.2 (IQR: 4.3–8.4) years. The NLS rates at 10 and 20 years were 70.7% and 61.5% respectively with no significant change over the study period. The median age at KPE was 59 (IQR: 49–67) days. KPE performed before 70 days was associated with higher odd ratios for successful drainage but the age of KPE did not have an impact on the long-term NLS. Among all native liver survivors (n = 153), the median bilirubin level was 24 (IQR: 16–36) µmol/L. Portal hypertension (PHT) and recurrent cholangitis were found in 51.6% and 27.5% of them respectively. With a vigilant follow up program, more than 60% of BA patients could remain stable with the disease and achieve long-term survival without LT. Although cholestasis, portal hypertension and recurrent cholangitis are common in long-term NLS, with a comprehensive follow management strategy, they do not always necessitate LT. Our study serves as an example for countries where deceased donor organs are scarce due to very low donation rate.

PURPOSE/OBJECTIVE(S) We reported the first study of combined stereotactic body radiotherapy and immunotherapy (SBRT-IO) in unresectable hepatocellular carcinoma (uHCC) and found this combination was synergistic and safe. Based on these results, we conducted a propensity score matching analysis to compare the clinical outcome of this combination versus TACE alone. MATERIALS/METHODS This was a retrospective study conducted in a tertiary center of Hong Kong. Eligible patients were HCC patients, who were unsuitable or refractory to curative surgical interventions. Patients with extra-hepatic vascular invasion or metastasis were excluded. 16 and 202 patients received SBRT-IO and TACE alone respectively. Propensity score matching was used to adjust for the differences in patients' demographics and tumor characteristics. The primary outcome was progression-free survival (PFS); the secondary outcomes included overall survival (OS), objective response rate (ORR) per modified response evaluation criteria in solid tumors (mRECIST version 1.1) and toxicities. RESULTS After matching, 16 patients were in the SBRT-IO group and 48 patients in the TACE group with similar baseline characteristics. Median 2 sessions of TACE (range: 1-16) were given in TACE group; for SBRT-IO arm, median dose of 35Gy in 5 fractions (range: 27.5-37.5Gy) was prescribed and median 10 cycles of nivolumab (range: 1-20 doses) were given. The median size of tumor was 10cm (range: 3.4-19.6cm) and 20.3% had portal vein invasion. The 12-month and 24-month PFS were better in SBRT-IO group (93.3% vs. 41.7% and 77.8% vs. 2.1%, P < 0.001); the 12-month and 24-month OS were also better in combination arm (93.8% vs. 54.2% and 80.4% vs. 8.3%, P < 0.001). The ORR was 87.5% (CR: 50%, PR: 37.5%) in patients receiving SBRT-IO compared to 11.9% (CR: 2.4%, PR: 9.5%) in those receiving TACE alone (P < 0.001). There were fewer ≥ grade 3 adverse events (AE) and treatment discontinuation due to AE in SBRT-IO arm (60.4% vs. 18.8%, P = 0.004; 25% vs. 12.5%, P = 0.295). No classical RILD and treatment-related death was reported in SBRT-IO arm. In multivariate analysis, SBRT-IO was an independent good prognostic factor for OS and PFS (HR of OS = 0.14 [0.30-0.96], P = 0.036; HR of PFS = 0.1 [range 0.03-0.33], P < 0.001) CONCLUSION: SBRT-IO resulted in better survival than TACE alone in unresectable HCC. Our results provided strong rationale for studying this combination in prospective trial.

Hepatectomy is a well-established curative treatment for hepatocellular carcinoma. However, the role of adjuvant therapy is controversial. This study examines the efficacy of adjuvant transarterial chemotherapy for hepatocellular carcinoma. The data of hepatocellular carcinoma patients undergoing curative hepatectomy was reviewed. Those with adjuvant transarterial chemotherapy were matched with those without using propensity score analysis, by tumour size and number, indocyanine green retention rate, disease staging and Child–Pugh grading. The groups were compared. Eighty-seven patients with hepatocellular carcinoma who underwent hepatectomy received adjuvant transarterial chemotherapy (TAC group), and were matched with 870 patients who did not (no-TAC group). The groups were largely comparable in patient and disease characteristics, but the TAC group experienced more blood loss, higher transfusion rates, narrower margins and more positive margins. The two groups were found to be comparable in disease-free and overall survival rates. In margin-positive patients, those given TAC survived longer than those without, and margin-positive patients in the TAC group had overall survival rates similar to margin-negative patients in the no-TAC group. Margin involvement is an adverse factor for survival in HCC. Adjuvant transarterial chemotherapy may offer survival benefits to hepatocellular carcinoma patients with positive surgical margins.

ObjectiveWe present a 37 years’ experience in the management of biliary atresia (BA) and discuss long-term complications after Kasai portoenterostomy (KPE).MethodsA retrospective territory-wide study from 1980 to 2017 on 231 patients with open KPE from three tertiary paediatric surgical centres was performed. The jaundice clearance (JC) rate, native liver survival (NLS) rate and complications were analyzed.ResultsThe mean follow up period was 15.4 +/- 6.2 years. Over 60% of patients remained JC within 2 years after KPE. Seventy patients (30.3%) received liver transplant (LT) at a median age of 6.2 years (range: 0.5 to 25 years). The NLS rates at 10, 20 and 30 years were 70.7%, 61.5% and 53.0% respectively with no significant change over the study period. The median bilirubin level among all native liver survivors (n=153) was 24 µmol/L (2 to 162 µmol/L). Portal hypertension (PHT) and recurrent cholangitis were found in 51.6% and 27.5% of them respectively.ConclusionWith a vigilant follow up program, more than 60% of BA patients could remain stable with the disease and achieve long term survival without LT. Although portal hypertension and recurrent cholangitis are common, they do not need to be the indications for LT if managed properly.

Background: Liver transplantation (LT) activities during the COVID-19 pandemic have been curtailed in many countries which has led to increased percentage of waitlist deaths. The impact of various policies restricting LT on outcomes of patients on the LT waitlist is unclear. This study aims to model effects of various scenarios and duration of LT disruption on outcomes. Methods: Using nationwide data from Hong Kong and Singapore of 571 patients between January 2016 and May 2020, we utilized a continuous time Markov chains model approach to evaluate the three following outcomes: (a) overall survival, (b) proportion of waitlist dropout in HCC patients, and (c) proportion of patients that developed acuteon-chronic liver failure (ACLF) while on the LT waitlist under the five scenarios. The five scenarios were: (1) no limitation to LT (both deceased donor liver transplant [DDLT] and living donor liver transplant [LDLT]), (2) no limitation to DDLT, only urgent (acute liver failure [ALF] or ACLF) LDLT allowed, (3) only urgent LT (DDLT and LDLT) allowed, (4) only DDLT, no LDLT allowed and (5) complete cessation of LT. For each scenario, varying periods of 1-, 3-, 6- and 12-month duration of disruption were simulated. Results: With complete cessation of LT, the projected 1-year overall survival (OS) decreased by 3.6%, 10.51% and 19.21% for a 1-, 3- and 6-month disruption respectively when compared to no limitation to LT, while 5-year OS decreased by 5.3%, 15.81%, and 31.11% respectively. When only urgent LT was allowed, the projected 1-year OS decreased by a similar proportion: 3.1%, 8.41% and 15.20% respectively. When only DDLT was allowed to take place, the 1-year projected OS decreased by a smaller proportion - 1.9%, 6.30% and 10.79% for a 1-, 3-, 6-month disruption respectively. When DDLT and only urgent LDLT were allowed, 1-year projected OS was similar to when only DDLT was allowed, at 1.2%, 5.1% and 8.85% for a 1-, 3- and 6-month disruption respectively (Figure 1A). Complete cessation of LT activities resulted in an increased projected incidence of ACLF at 1-year by 17.6%, 49.1% and 95.5%, as well as an increase in hepatocellular carcinoma (HCC) dropout resulting in delisting at 1-year by 31.8%, 107.96% and 176.06% for a 1-, 3- and 6- month disruption respectively (Figure 1B). When only urgent LT was allowed, HCC dropout and ACLF incidence were comparable to the rates seen in the scenario of complete LT cessation. Conclusion: A short and wide-ranging disruption to LT results in better outcomes compared with a longer duration of partial restrictions. Findings from our study provide useful guidance for LT units worldwide in navigating the peaks and troughs of COVID-19 surges and highlight the impact of LT disruption on waitlisted patients during this prolonged pandemic. Once the peak of the COVID-19 wave has passed, DDLT at minimum should be resumed as soon as possible.

BACKGROUND: The 8(th) edition of the American Joint Committee on Cancer tumor-node-metastasis staging system (AJCC 8(th)) has been launched with modifications in T staging. The University of Hong Kong liver cancer staging system (HKUSS) has been proven to better categorize hepatocellular carcinoma (HCC) into different T stages. This study aimed to compare the two systems’ predictive ability for HCC recurrence after primary surgical resection. METHODS: Patients who had primary, curative resection for HCC between 1989 and 2017 were reviewed. The Kaplan-Meier plot was used to estimate disease-free survival (DFS), and the log-rank test was used for survival comparison between subgroups. The two systems’ prediction of recurrence was evaluated by the Cox regression model. RESULTS: Totally 1,815 patients were included. With AJCC 8(th), the 5-year DFS was 58.9% for T1a, 52.3% for T1b, 30% for T2, 16.9% for T3, and 14.4% for T4. No survival difference was demonstrated between T1a and T1b (P=0.668) or between T3 and T4 (P=0.562). With HKUSS, the 5-year DFS was 57.7% for T1, 43.4% for T2, 28.9% for T3, and 15.7% for T4. The T staging in HKUSS showed significant survival differences (T1 vs. T2, T2 vs. T3, and T3 vs. T4; P

Background Liver stiffness (LS) assessed by transient elastography is associated with adverse events in patients with heart failure. However, the predictive value of LS for adverse outcome is uncertain in patients undergoing tricuspid annuloplasty (TA). This study sought to evaluate the prognostic value and reversibility of LS in patients undergoing TA during left-sided valve surgery. Methods and results A total of 158 patients who underwent TA were prospectively evaluated. Patients were divided into three groups according to tertile of LS. Adverse outcome was defined as heart failure that required hospital admission or all-cause mortality following TA. The median LS was 13.9 (inter-quartile range 8.1–22.3) kPa and independently correlated positively with tricuspid regurgitation (TR) severity, inferior vena cava diameter and negatively with tricuspid annular plane systolic excursion. During a median follow-up of 31 months, 49 adverse events occurred. Multivariable Cox regression analysis revealed that LS was an independent predictor of adverse events. Significant improvement in LS at 1-year post-TA (13.1–7.8 kPa, P Conclusions This study demonstrated that LS is predictive of adverse outcome and is reversible in patients undergoing TA without TR recurrence at 1 year. These findings suggest that assessing LS, an integrative correlate of right heart condition, may aid the pre-operative risk assessment of candidate for heart surgery including TA.

OBJECTIVE The aim of this study was to determine the outcomes of living donor liver transplantation (LDLT) according to various graft-to-recipient weight ratio (GRWR). BACKGROUND The standard GRWR in LDLT is >0.8%. Our center accepted predicted GRWR ≥0.6% in selected patients. METHODS Data from patients who underwent LDLT from 2001 to 2017 were included. Patients were stratified according to actual GRWR (Group 1:GRWR ≤0.6%; Group 2: 0.6% 0.8%). RESULTS There were 545 LDLT (group 1 = 39; group 2 = 159; group 3 = 347) performed. Pretransplant predicted GRWR showed good correlation to actual GRWR (R2 = 0.834) and these figures differed within a ± 10%margin (P = 0.034) using an equivalence test. There were more left lobe grafts in group 1 (33.3%) than group 2 (10.7%) and 3 (2.9%). Median donor age was 10% was rare.There was no difference in postoperative complication, vascular and biliary complication rate between groups. Over one-fifth (20.5%) of group 1 patients required portal flow modulation (PFM) and was higher than group 2 (3.1%) and group 3 (4%) (P = 0.001). Twenty-six patients developed small-for-size syndrome (SFSS): 5 of 39 (12.8%) in group 1 and 21 of 159 (13.2%) in group 2 and none in group 3 (P < 0.001). There were 2 hospital mortalities; otherwise, the remaining patients [24/26 (92.3%)] survive with a functional liver graft. The 5-year graft survival rates were 85.4% versus 87.8% versus 84.7% for group 1, 2, and 3, respectively (P = 0.718). GRWR did not predict worse survivals in multivariable analysis. CONCLUSIONS Graft size in LDLT can be lowered to 0.6% after careful recipient selection, with low incidence of SFSS and excellent outcomes. Accurate graft weight prediction, donor-recipient matching, meticulous surgical techniques, appropriate use of PFM, and vigilant perioperative care is important to the success of such approach.

Background and Aims Previous recommendations suggested living donor liver transplantation (LDLT) should not be considered for patients with Model for End‐Stage Liver Disease (MELD) > 25 and hepatorenal syndrome (HRS). Approach and Results Patients who were listed with MELD > 25 from 2008 to 2017 were analyzed with intention‐to‐treat (ITT) basis retrospectively. Patients who had a potential live donor were analyzed as ITT‐LDLT, whereas those who had none belonged to ITT‐deceased donor liver transplantation (DDLT) group. ITT‐overall survival (OS) was analyzed from the time of listing. Three hundred twenty‐five patients were listed (ITT‐LDLT n = 212, ITT‐DDLT n = 113). The risk of delist/death was lower in the ITT‐LDLT group (43.4% vs. 19.8%, P 25 and patients with both MELD > 25 and HRS (56% vs. 33.8%, P 25 (88% vs. 85.4%, P = 0.279) and patients with both MELD > 25 and HRS (77% vs. 76.4%, P = 0.701) after LDLT and DDLT, respectively. The LDLT group has a higher rate of renal recovery by 1 month (77.4% vs. 59.1%, P = 0.003) and 3 months (86.1% vs, 74.5%, P = 0.029), whereas the long‐term estimated glomerular filtration rate (eGFR) was similar between the 2 groups. ITT‐LDLT reduced the hazard of mortality (hazard ratio = 0.387‐0.552) across all MELD strata. Conclusions The ITT‐LDLT reduced waitlist mortality and allowed an earlier access to transplant. LDLT in patients with high MELD/HRS was feasible, and they had similar perioperative outcomes and better renal recovery, whereas the long‐term survival and eGFR were comparable with DDLT. LDLT should be considered for patients with high MELD/HRS, and the application of LDLT should not be restricted with a MELD cutoff.

Objective: Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) has been tested in various indications and clinical scenarios, leading to steady improvements in safety. This report presents the current status of ALPPS. Summary Background Data: ALPPS offers improved resectability, but drawbacks are regularly pointed out regarding safety and oncologic benefits. Methods: During the 12th biennial congress of the European African-Hepato-Pancreato-Biliary Association (Mainz, Germany, May 23-26, 2017) an expert meeting "10th anniversary of ALPP" was held to discuss indications, management, mechanisms of regeneration, as well as pitfalls of this novel technique. The aim of the meeting was to make an inventory of what has been achieved and what remains unclear in ALPPS. Results: Precise knowledge of liver anatomy and its variations is paramount for success in ALPPS. Technical modifications, mainly less invasive approaches like partial, mini- or laparoscopic ALPPS, mostly aiming at minimizing the extensiveness of the first-stage procedure, are associated with improved safety. In fibrotic/cirrhotic livers the degree of future liver remnant hypertrophy after ALPPS appears some less than that in noncirrhotic. Recent data from the only prospective randomized controlled trial confirmed significant higher resection rates in ALPPS with similar peri-operative morbidity and mortality rates compared with conventional 2-stage hepatectomy including portal vein embolization. ALPPS is effective reliably even after failure of portal vein embolization. Conclusions: Although ALPPS is now an established 2-stage hepatectomy additional data are warranted to further refine indication and technical aspects. Long-term oncological outcome results are needed to establish the place of ALPPS in patients with initially nonresectable liver tumors.

Background The outbreak of Covid-19 has vastly increased the operational burden on healthcare systems worldwide. For patients with end-stage liver failure, liver transplantation is the only option. However, the strain on intensive care facilities caused by the pandemic is a major concern. There is an urgent need for ethical frameworks to balance the need for liver transplantation against the availability of national resources. Methods We performed an international multi-center study of transplant centers to understand the evolution of policies for transplant prioritization in response to the pandemic in March 2020. To describe the ethical tension arising in this setting, we propose a novel ethical framework, the Quadripartite Equipoise (QE) score, that is applicable to liver transplantation in the context of limited national resources. Results Seventeen large- and medium- sized liver transplant centers from twelve countries across four continents participated. Ten centers opted to limit transplant activity in response to the pandemic, favoring a “sickest-first” approach. Conversely, some larger centers opted to continue routine transplant activity in order to balance waiting list mortality. To model these and other ethical tensions, we computed a QE score using 4 factors - Recipient Outcome, Donor/Graft Safety, Waiting List Mortality and Healthcare Resources for seven countries. The fluctuation of the QE score over time accurately reflects the dynamic changes in the ethical tensions surrounding transplant activity in a pandemic. Conclusions This four-dimensional model of Quadripartite Equipoise addresses the ethical tensions in the current pandemic. It serves as a universally applicable framework to guide regulation of transplant activity in response to the increasing burden on healthcare systems to allow greater global solidarity and transparency in these austere times., Graphical abstract, HIGHLIGHTS • Increased operational burden on healthcare systems worldwide from Covid-19 outbreak • Frameworks to balance need for liver transplant against limited resources needed • International multi-center study of policies for transplant prioritization conducted • Novel four-dimensional model of Quadripartite Equipoise to balance ethical tensions • Fluctuation of model over time guides need to pursue or limit transplant activity, There is an urgent need for ethical frameworks to balance the need for liver transplantation against the availability of national resources in the Covid-19 pandemic. We describe a four-dimensional model of Quadripartite Equipoise that models these ethical tensions and can guide the regulation of transplant activity in response to the increasing burden on healthcare systems.

Background & Aims Mutational profiling of patient tumors has suggested that hepatocellular carcinoma (HCC) development is mainly driven by loss-of-function mutations in tumor suppressor genes. p90 ribosomal S6 kinase 2 (RSK2) functions as a direct downstream kinase of ERK1/2 and elevated RSK2 expression has been reported to support oncogenic functions in some cancers. We investigated if RSK2 was also dysregulated by inactivating mutations in cancers including HCC. Methods We performed exome sequencing and targeted DNA sequencing on HBV-associated HCCs to examine recurrent RSK2 mutations. The functional significance and mechanistic consequences of RSK2 mutations were examined in natural RSK2-null HCC cells, and RSK2-knockout HCC cells. The potential downstream pathways underlying RSK2 mutations were investigated by RNA sequencing, qRT-PCR and mass spectrometry. Results We detected recurrent somatic RSK2 mutations at a rate of 6.3% in our HCC cohorts and revealed that, among many cancer types, HCC was the cancer most commonly harboring RSK2 mutations. The RSK2 mutations were inactivating and associated with a more aggressive tumor phenotype. We found that, functionally, restoring RSK2 expression in natural RSK2-null HBV-positive Hep3B cells suppressed proliferation and migration in vitro and tumorigenicity in vivo. Mechanistically, RSK2-inactivating mutations attenuated a SOS1/2-dependent negative feedback loop, leading to the activation of MAPK signaling. Of note, this RSK2 mutation-mediated MAPK upregulation rendered HCC cells more sensitive to sorafenib, a first-line multi-kinase inhibitor for advanced HCC. Furthermore, such activation of MAPK signaling enhanced cholesterol biosynthesis-related gene expression in HCC cells. Conclusions Our findings reveal the mechanistic and functional significance of RSK2-inactivating mutations in HCC. These inactivating mutations may serve as an alternative route to activate MAPK signaling and cholesterol metabolism in HCC. Lay summary In this study, we identified and functionally characterized RSK2-inactivating mutations in human hepatocellular carcinoma and demonstrated their association with aggressive tumor behavior. Mutations in RSK2 drive signaling pathways with known oncogenic potential, leading to enhanced cholesterol biosynthesis and potentially sensitizing tumors to sorafenib treatment.