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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.

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

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.

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.

Background In the management of operable hilar cholangiocarcinoma (HC) patients with hyperbilirubinemia, preoperative biliary drainage is a measure to bring down the bilirubin to a certain level so as to avoid adverse postoperative outcomes that would otherwise result from hyperbilirubinemia. A cutoff value of bilirubin level in this context is needed but has not been agreed upon without controversy. This retrospective study aimed to identify a cutoff of preoperative bilirubin level that would minimize postoperative morbidity and mortality. Methods Data of patients having hepatectomy with curative intent for HC were analyzed. Discriminative analysis was performed to identify the preoperative bilirubin level that would make a survival difference. The identified level was used as the cutoff to divide patients into two groups. The groups were compared. Results Ninety patients received hepatectomy with curative intent for HC. Their median preoperative bilirubin level was 23 μmol/L. A cutoff preoperative bilirubin level of 75 μmol/L was derived from Youden’s index (sensitivity 0.333; specificity 0.949) and confirmed to be optimal by logistic regression (relative risk 9.250; 95% confidence interval 1.932–44.291; p = 0.005), with mortality shown to be statistically different at 90 days (p = 0.008). Patients were divided into Group A (≤75 μmol/L; n = 82) and Group B (> 75 μmol/L; n = 8). Group B had a higher preoperative bilirubin level (p p = 0.008), transfusion (100% vs 42.0%; p = 0.011) and replacement (2.45 vs 0.0 L; p p = 0.036), more in-hospital deaths (50% vs 8.5%; p = 0.004), and more 90-day deaths (50% vs 9.8%; p = 0.008). Group A had a longer follow-up period (p = 0.008). The groups were otherwise comparable. Disease-free survival was similar between groups (p = 0.142) but overall survival was better in Group A (5-year, 25.2% vs 0%; p Conclusion A cutoff value of preoperative bilirubin level of 75 μmol/L is suggested, as the study showed that a preoperative bilirubin level ≤ 75 μmol/L resulted in significantly less blood replacement necessitated by blood loss during operation and significantly better patient survival after 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

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.

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.

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.

BackgroundHepatocellular carcinoma (HCC) is a rare hepatic malignancy in children. Hepatitis B virus (HBV) infection is a key predisposing factor in endemic regions but its impact on outcome has not been studied. We aim to evaluate the prognostic implication of HBV seropositivity and role of cancer surveillance in children with HCC from East Asian populations with national HBV vaccination.MethodsReview of population-based databases for patients (< 18 years old) diagnosed with HCC from 1993 to 2017 in two Southeast Asian regions with universal HBV vaccination (instituted since 1988 and 1987 in Hong Kong and Singapore, respectively).ResultsThirty-nine patients were identified (Hong Kong, 28; Singapore, 11). Thirty were male; median age at diagnosis was 10.8 years (range, 0.98–16.6). Abdominal pain was the commonest presentation while five patients were diagnosed through surveillance for underlying condition. Alpha-fetoprotein was raised in 36 patients (mean, 500,598 ng/ml). Nineteen had bilobar involvement, among the patients in whom pretreatment extent of disease (PRETEXT) staging could retrospectively be assigned, 3 had stage I, 13 had stage II, 4 had stage III, and 11 had stage IV disease. Seventeen had distant metastasis. HBsAg was positive in 19 of 38 patients. Two patients had fibrolamellar HCC. Upfront management involved tumor resection in 16 (liver transplantation, 2), systemic chemotherapy in 21, interventional procedures in 6 [transarterial chemoembolization (TACE), 5, radiofrequency ablation (RFA), 1], and radiotherapy in 4 (selective internal radiation, 3, external beam radiation, 1). Five-year event-free survival (EFS) and overall survival (OS) were 15.4 ± 6.0 and 26.1 ± 7.2%, respectively. Patient’s HBsAg positivity, metastatic disease and inability to undergo definitive resection represent poor prognostic factors in univariate and multivariable analyses. Patients diagnosed by surveillance had significantly better outcome.ConclusionPediatric HCC has poor outcome. HBV status remains relevant in the era of universal HBV vaccination. HBV carrier has inferior outcome and use of surveillance may mitigate disease course.

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.

Insufficient future liver remnant (FLR) is an important factor that precludes patient from upfront major liver resection as it predisposes to post-hepatectomy liver failure and mortality. As such, augmentation of FLR by portal vein embolization (PVE) was the conventional approach to improve the safety profile of major hepatectomy.

Our study aimed to determine if a double-dose pre-S containing hepatitis B virus (HBV) vaccination (Sci-B-Vac) could elicit an adequate and sustainable immune response in HBV patients who developed spontaneous hepatitis B surface antibody (anti-HBs) response after liver transplant. Patients and Methods All patients who received transplants for HBV-related disease for >1 year with normal graft function and hepatitis B surface antigen seronegativity were evaluated. They received a 40-μg HBV vaccine if they were responders in our previous vaccine trial, if anti-HBs was positive for >1 year after liver transplant (LT), or if a peak anti-HBs at any time point after LT was >100 mIU/mL. Primary endpoint was the development of anti-HBs ≥ 10 mIU/mL from previous negative value or a 1-log increase from baseline. Results A total of 86 patients were recruited; 5 were responders from a previous trial; 45 patients had detectable anti-HBs >1 year after LT, and 36 patients had an anti-HBs >100 mIU/mL. All (5/5, 100%) previous responders responded to booster vaccination. For the remaining 81 patients, 10 of 81 (12.3%) responded. Conclusion All previous responders responded to booster vaccination, implying durability and memory of HBV immune response, which is an important prerequisite for definitive host immunity for HBV. In patients who had spontaneous anti-HBs production after LT, a single vaccination can induce response in 12.3% of patients.

Background Recurrent pyogenic cholangitis (RPC) is a known risk factor for intrahepatic cholangiocarcinoma (ICC), whether it represents a poor prognostic factor remains controversial. The aim of this study was to investigate the post-hepatectomy oncological outcomes of patients with ICC and coexisting RPC. Method A retrospective analysis with propensity score matching (PSM) was performed for comparison between ICC patient with and without RPC. Results There were 143 patients with ICC with a median follow-up of 21 months. RPC was diagnosed in 18% of patients. The time from RPC diagnosis to ICC diagnosis was 137(47–481) months. The 3-year disease-free (DFS) and overall survival for the whole population was 34% and 43% respectively. Preoperative child score, elevated carcinoembryonic antigen, presence of microvascular invasion, multiple tumours, presence of postoperative complications and RPC were independent factors for DFS and OS. After PSM, 60 ICC patients who did not have RPC were compared with 20 ICC patients with RPC. Patients with RPC had significantly worse median DFS (10 vs 23 months, P = 0.020) and OS (15 vs 45 months, P = 0.004) when compared to the patients without RPC. Conclusion RPC represents a poor prognostic factor affecting outcomes after hepatectomy for patients with ICC.

Salvage liver transplantation (sLT) and repeated resection (RR) are effective treatments for recurrent hepatocellular carcinoma (HCC), and comparisons of the oncological outcomes between these 2 modalities were scarce. Consecutive patients admitted for either sLT or RR for recurrent HCC were recruited. All patients in the present series received either prior hepatectomy, ablative therapy, or both before RR or sLT. Patient demographic, perioperative, and outcome data were analyzed. A survival analysis was performed after propensity score matching. There were 277 eligible patients recruited, and 67 and 210 of them underwent sLT and RR, respectively. Significant differences in preoperative hemoglobin, albumin, Model of End-Stage Liver Disease (MELD) score, and tumor number were found between the sLT and RR groups. After 1:3 propensity score matching, there were 36 sLT and 108 RR patients for comparison. The median age, MELD, alpha fetoprotein, and tumor size and number of the matched population were 57 years, 7.5, 16 ng/mL, 2.5 cm, and 1, respectively. There was no difference in the hospital mortality and complication rate (Clavien IIIa or above) between the groups. The recurrence rate after RR was significantly higher than for the patients who received sLT (72.2% versus 27.8%; P < 0.001). Following RR, 3 patients received liver transplantation for further recurrence, and 54.6% of the patients developed nontransplantable recurrence. The 5-year disease-free survival (DFS) and overall survival (OS) were both superior in the sLT group (DFS, 71.6% versus 32.8%, P < 0.001; OS, 72.8% versus 48.3%, P = 0.007). In conclusion, sLT is superior to RR for treatment of recurrent HCC in terms of DFS and OS. The high rate of nontransplantable recurrence after reresection underscores the importance of timely sLT.

The aim of this study was to examine the merits of the anterior approach, if any, in colorectal liver metastasis (CRLM) resection. Data of patients who underwent partial hepatectomy for CRLM were reviewed. Patients treated by the anterior approach were compared with patients treated by the conventional approach. Ninety-eight patients had right hepatectomy, extended right hepatectomy, or right trisectionectomy. Among them, 71 patients underwent the conventional approach (CA group) and 27 underwent the anterior approach (AA group). The two groups were comparable in demographic, pathological, and perioperative characteristics except that the AA group had higher levels of aspartate transaminase (median, 41 vs. 31 U/L; p = 0.006) and alanine transaminase (median, 27 vs. 22 U/L; p = 0.009), larger tumors (median, 7 vs. 4 cm; p = 0.000), and more extensive resections (p

INTRODUCTION Laparoscopic hepatectomy is considered an acceptable treatment of choice in selected patients with primary hepatocellular carcinoma (HCC). Whether indocyanine green (ICG) immunofluorescence, a new technology, may improve surgery outcomes has yet to be tested. The aim of the present study was to investigate and compare the effect of ICG fluorescence imaging on the outcomes of pure laparoscopic hepatectomy and open hepatectomy for primary HCC with background cirrhosis. METHODS From January 2015 to June 2016, 20 patients with HCC and liver cirrhosis underwent laparoscopic hepatectomy with ICG immunofluorescence. The outcomes of pure laparoscopic hepatectomy with ICG immunofluorescence were compared with those of open hepatectomy. To avoid selection bias, patients were propensity score matched in a ratio of 1 : 6, with 20 patients in the laparoscopic group and 120 in the open group. RESULTS The laparoscopic group had 20 patients, and the open group had 120 patients. The laparoscopic group had less blood loss (125 vs 450 mL, P

Uncommon primary hepatic malignancies such as intrahepatic cholangiocarcinoma (ICC) and hepatocholangiocarcinoma (HCC-CC) were generally considered contraindications for liver transplantation(LT), and studies comparing the efficacy of LT and resection (LR) for ICC/HCC-CC were scarce. To compare the survival outcomes of ICC/HCC-CC patients treated by LT and LR in a propensity score-matched population. This is a retrospective study from 1995 to 2015. Consecutive patients with the pathological diagnosis of ICC or HCC-CC in the surgical specimens were included. All patients had either hepatectomy or LT with curative intent. Factors associated with survival were identified with multivariate analysis using cox-regression model. Propensity score-matched analysis was performed. There were 181 patients diagnosed to have ICC/HCC_CC. Nine patients received LT (all with incidental ICC/HCC-CC) and 172 received hepatectomy. The median follow-up period was 27.5 months. The median age was 60 years (range 3–86); Hepatitis B and C carrier status was found in 48.1 and 2.3% of the patients, respectively. The median tumor size was 6 cm and 71.3% of them had solitary tumor. Microvascular invasion was present in 47% of the patients. After propensity score matching, there were 54 (9 in LT and 45 in LR group) patients for analysis. Cox-regression analysis showed that early AJCC (7th) staging and LT were the independent factors associated with overall survival. Patients in the LT group had significantly better overall survival (5-year OS 77.8 vs 36.6%, log-rank p = 0.013). ICC/HCC-CC are uncommon tumors with poor long-term oncological outcomes despite curative hepatectomy. Liver transplantation might be a better treatment option for patients with early ICC/HCC-CC.

Liver metastasis is common among patients who suffer from neuroendocrine tumors (NETs). Radical surgery is the standard treatment whenever possible but there is still controversies concerning the treatment strategies such as resection of the primary, role of debulking surgery, liver transplantation (LT) and neoadjuvant or adjuvant therapies. This article aims to review the current evidence available, together with some latest updates, focusing on the surgical management.

Pancreatic neuroendocrine tumor (PNET) is slow-growing, and account only for 2% of all pancreatic primary tumors. Surgical resection is still the only curative treatment for PNET patients. Unfortunately, most of PNETs was found with unresectable multiple liver metastases and extrahepatic metastasis as their characteristics of non-functional and asymptomatic. With advances in liver surgery in these years, especially combined associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), provide a new curative surgical treatment for PNET with liver metastases patient. Here we report a PNET with multiple liver metastases case underwent ALPPS (followed by left trisectionectomy) and Whipple operation within one-stage.

To derive and validate a scoring system for major complication after hepatectomy.Complications after hepatectomy significantly compromise survival outcomes, method to predict such risk is lacking. A reliable scoring system is therefore awaited.Consecutive adult patients receiving hepatectomy for primary or secondary liver malignancy from 1995 to 2014 were recruited. After randomization, patients were allocated to derivation and validation group respectively. A scoring system predicting occurrence of major complication was developed.There were 2613 patients eligible for the study. The overall complication rate for the series was 10%. Impaired performance status (p = 0.014), presence of pre-existing medical illness (p = 0.008), elevated ALP (p = 0.005), urea (p 0.001), and hypoalbuminemia (p = 0.008), and major hepatectomy (p 0.001) were found to be independently associated major complications. A score was assigned to each of these factors according to their respective odd ratio. A total score of 0-17 was calculated for all patients. This score was shown to discriminate well with complication rate in both derivation and validation group (c-statistic: 0.71, p 0.001 and 0.74, p 0.001 respectively). The complication rate for low (score 0-5), moderate (score 6-10) and high (score 10 or above) risk group were respectively 5%, 16% and 28%. This risk stratification model was tested and confirmed in the validation group using Chi-square goodness-of-fit test (p = 0.864).A validated risk stratification model provides an accurate and easy-to-use reference tool for patients and clinicians during the informed consent process.

Background Hepatic resection and radiofrequency ablation (RFA) are treatment options for early-stage hepatocellular carcinoma (HCC). Whether tumour recurrence and long-term survival favour either treatment has not been established. This randomized trial aimed to test the hypothesis that RFA is superior to hepatic resection in terms of lower tumour recurrence rate and better long-term survival. Methods Patients with early-stage HCC (solitary tumour no larger than 5 cm; or no more than 3 tumours, each 3 cm or smaller) were randomized into hepatic resection and RFA groups. Demographic and clinical characteristics, and short- and long-term outcome measures were compared between groups. Primary and secondary outcome measures were overall tumour recurrence and survival respectively. Results Clinicopathological data were similar in the two groups, which each contained 109 patients. The RFA group had a shorter treatment duration, less blood loss and shorter hospital stay than the resection group. Mortality and morbidity rates were similar in the two groups. The overall tumour recurrence rate was similar in the resection and RFA groups (71·3 versus 81·7 per cent respectively). The 1-, 3-, 5- and 10-year overall survival rates were 94·5, 80·6, 66·5 and 47·6 per cent respectively in the resection group, compared with 95·4, 82·3, 66·4 and 41·8 per cent in the RFA group (P = 0·531). Corresponding disease-free survival rates were 74·1, 50·9, 41·5 and 31·9 per cent in the resection group, and 70·6, 46·6, 33·6 and 18·6 per cent in the RFA group (P = 0·072). Conclusion RFA for early-stage HCC is not superior to hepatic resection, in terms of tumour recurrence, overall survival and disease-free survival. Registration number: HKUCTR-10 (http://www.hkuctr.com).

The objective of this article is to derive a more accurate and easy-to-use formula for finding estimated standard liver volume (ESLV) using novel computed tomography (CT) measurement parameters. New formulas for ESLV have been emerging that aim to improve the accuracy of estimation. However, many of these formulas contain body surface area measurements and logarithms in the equations that lead to a more complicated calculation. In addition, substantial errors in ESLV using these old formulas have been shown. An improved version of the formula for ESLV is needed. This is a retrospective cohort of consecutive living donor liver transplantations from 2005 to 2016. Donors were randomly assigned to either the formula derivation or validation groups. Total liver volume (TLV) measured by CT was used as the reference for a linear regression analysis against various patient factors. The derived formula was compared with the existing formulas. There were 722 patients (197 from the derivation group, 164 from the validation group, and 361 from the recipient group) involved in the study. The donor's body weight (odds ratio [OR], 10.42; 95% confidence interval [CI], 7.25-13.60; P

Liver resection remains one of the most technically challenging surgical procedure in abdominal surgery due to the complex anatomical arrangement in the liver and its rich blood supply that constitutes about 20% of the cardiac output per cycle. The challenge for resection in cirrhotic livers is even higher because of the impact of surgical stress and trauma imposed on borderline liver function and the impaired ability for liver regeneration in cirrhotic livers. Nonetheless, evolution and advancement in surgical techniques as well as knowledge in perioperative management of liver resection has led to a substantial improvement in surgical outcome in recent decade. The objective of this article was to provide updated information on the recent developments in liver surgery, from preoperative evaluation, to technicality of resection, future liver remnant augmentation and finally, postoperative management of complications.

Background: Current treatments of unresectable hepatocellular carcinoma (HCC) are trans-arterial chemo-embolization (TACE), stereotactic body radiotherapy (SBRT), and targeted therapy. However, these treatments are limited in efficacy and safety for patients with large tumor sizes. Here, we report a case series of combined SBRT and anti-PD-1 therapy in patients with unresectable HCC of large tumors. Methods: This is a retrospective case series of five patients with unresectable hepatocellular carcinoma who were treated with SBRT followed by anti-PD1 antibodies. Four patients (80%) received a single dose of TACE prior to SBRT. All patients had advanced HCC ineligible of curative intervention. In this study, we report their treatment responses according to modified RECIST (response evaluation criteria in solid tumor) criteria, 1-year local control (LC), progression-free survival (PFS), 1-year overall survival (OS) rate, and toxicities. Results: Among the five evaluated patients, three patients had underlying diseases of hepatitis B and four patients had Barcelona clinic liver cancer stage C. The median size of their tumors was 9.8 cm (range: 9–16.1 cm). In addition, two patients had tumor vascular thrombosis and one had extra-hepatic disease. Five out of five patients (100%) responded to treatment, with two complete responses (CR) and three partial responses (PR). Among the partial responders, one had a down-staged tumor that became amenable for radiofrequency ablation for tumor clearance. No patient developed tumor progression at the time of analysis during the median follow-up of 14.9 months (range 8.6–19 months). The median PFS was 14.9 months (range: 8.6–19 months); 1-year LC and OS rate were both 100%. One patient had grade ≥ 3 toxicities (pneumonitis and skin reaction). There was no classical radiation-induced liver disease. Conclusions: The results obtained from these 5 cases demonstrate impressive tumor control from the combination of SBRT and checkpoint inhibitors in patients with large tumors of advanced HCC. Further prospective trials are warranted.

BACKGROUND AND AIMS The prognosis in severe acute flares of chronic hepatitis B (AFOCHB) is often unclear. The current study aimed to establish the predictive value using the Model for End-Stage Liver Disease (MELD) score for short-term mortality for severe AFOCHB. APPROACH AND RESULTS Patients with severe AFOCHB with bilirubin > 50 µmol/L, alanine aminotransferase > 10× upper limit of normal, and international normalized ratio > 1.5 were included. All patients were commenced on entecavir and/or tenofovir. Laboratory results and MELD scores were pooled to calculate mortality at four time points (days 7, 14, 21, and 28). A total of 240 patients were included. Median hepatitis B virus DNA was 7.77 log IU/mL (range, 4.11-10.06), and 49 (20.4%) were hepatitis B e antigen-positive. The 7, 14, 21, and 28-day survival was 96.7%, 88.5%, 79.5%, and 72.8%, respectively. Using pooled results derived from 4,201 blood samples, the area under the receiver operating curve for the MELD score to predict day 7, 14, 21, and 28 mortality was 0.909, 0.892, 0.883, and 0.871, respectively. For MELD ≤ 28, mortality at day 28 was low ( 50% mortality for MELD ≥ 32. For MELD = 28-32, higher day-28 mortality was observed for four criteria: age ≥52 years, alanine aminotransferase > 217 U/L, platelets < 127, and abnormal baseline imaging (all P

Background Recent evidence suggested that associating liver partition and portal vein ligation for staged hepatectomy with a partial split could effectively induce the same degree of future liver remnant hypertrophy as a complete split in non-cirrhotic and non-cholestatic livers with better postoperative safety profiles. Our aim was to evaluate if the same phenomenon could be applied to hepatitis-related chronic liver diseases. Methods In the study, 25 patients who underwent associating liver partition and portal vein ligation for staged hepatectomy from October 2013 to January 2016 for hepatocellular carcinoma were analyzed. Partial-associating liver partition and portal vein ligation for staged hepatectomy ( n = 12) was defined as 50–80% of the transection surface split and complete-associating liver partition and portal vein ligation for staged hepatectomy ( n = 13) was split down to inferior vena cava. Perioperative outcomes stratified by split completeness were evaluated. Results There was no significant difference in operating times and blood loss for stage I and II operations between complete-associating liver partition and portal vein ligation for staged hepatectomy and partial-associating liver partition and portal vein ligation for staged hepatectomy. All patients underwent stage II operation without any inter-stage complications. Complete split induced greater future liver remnant hypertrophy than partial split (hypertrophy rate: 31.2 vs 17.5 mL/day, P = .022) with more pronounced effect in chronic hepatitis ( P = .007) than cirrhosis ( P = .283). Complete-associating liver partition and portal vein ligation for staged hepatectomy was more likely to attain a future liver remnant/estimated standard liver volume ratio >35% within 10 days (76.9% vs 33.3%, P = .024) and proceed to stage II within 14 days after stage I (100% vs 58.4%, P = .009). The overall postoperative morbidity (≥grade 3a) after stage II was 16% (complete versus partial split: 7.7% vs 25%, P = .238) and hospital mortality after stage II was 8% (complete versus partial split: 0% vs 16.7%, P = .125). Conclusion Complete-associating liver partition and portal vein ligation for staged hepatectomy induced more rapid future liver remnant hypertrophy than partial-associating liver partition and portal vein ligation for staged hepatectomy without increased perioperative risk in chronic liver diseases.

There is presently no evidence-based recommendation for surveillance of recurrent hepatocellular carcinoma after liver transplantation (LT). We aim to evaluate and develop evidence-based alternate surveillance imaging schedules for post-LT hepatocellular carcinoma patients.Imaging and pathologic reports for consecutive post-LT patients followed up by regular surveillance imaging from a single institution's prospective database were evaluated with institutional review board approval. Outcome variable was time to diagnosis of first recurrence post-LT by surveillance imaging. Recurrence-free survival times from alternative surveillance schedules were compared with the existing schedule (every 3 months) using a parametric frailty model. Expected delay (EpD) in diagnosis compared to the existing schedule was also computed for the alternate surveillance schedules. A P value less than 0.05 was considered to indicate a significant difference.One hundred twenty-five patients (108 men; 59.4 ± 16.6 years) underwent 1953 computed tomography and 255 magnetic resonance imaging scans. Recurrence-free survival time was not significantly different in the first 5 years after LT when the imaging interval was extended from current every 3 months to every 6 months (P = 0.786, EpD = 55 days). This alternative schedule incurred 10 (50.0%) fewer surveillance scans than the 20 in the original schedule, and a corresponding reduction in radiation dose (if involved) and cost during the 5-year follow-up period.In conclusion, modeled alternative surveillance schedules have the potential to reduce the frequency of scans without compromising surveillance benefits.

OBJECTIVE To investigate the impact of intraoperative blood transfusion on the long-term outcomes of liver transplantation for hepatocellular carcinoma. METHOD Adult patients who had non-salvage liver transplantation at our centre between January 2005 and December 2012 for hepatocellular carcinomas that were within the University of California, San Francisco criteria and could not be resected or ablated were divided into groups with and without intraoperative blood transfusion. Comparisons were made between groups. RESULTS Ninety-nine patients were included in the study. Sixty-two (62.6%) patients received intraoperative blood transfusion. Patients without transfusion were younger (54 versus 56 years; P = 0.04) and had a lower Model for End-stage Liver Disease score (11 versus 14; P

Objective:To investigate the long-term outcomes of pure laparoscopic hepatectomy versus open hepatectomy for hepatocellular carcinoma (HCC) with background cirrhosis.Background:Laparoscopic hepatectomy has been gaining popularity, but has not been widely accepted, because published data were gathere