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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).

Role of 18-FDG PET/CT had been well established in other more prevalent malignancies such as colorectal and lung cancer; however, this is not as well defined in cholangiocarcinoma. Literature focusing on the prognostic values of preoperative PET/CT for resectable cholangiocarcinoma is scarce. This is a retrospective cohort of 66 consecutive patients who had received curative resection for cholangiocarcinoma from 2010 to 2015. All patients had preoperative 18-FDG PET/CT performed. Accuracy of metastatic lymph node detection of PET/CT and the prognostic value of maximum standard uptake value (SUV-max) was explored. There were 38 male and 28 female recruited, and the median age was 66. Intrahepatic cholangiocarcinoma (ICC) constituted the majority (59.1%) of the cases, followed by hilar cholangiocarcinoma (22.8%), gallbladder cancer (13.6%) and common bile duct cancer (4.5%). The 3-year disease-free survival (DFS) and overall survival (OS) of the whole population were 27.1 and 39.2%, respectively. The median follow-up duration was 27 months. The accuracy of PET/CT in metastatic lymph node detection was 72.7% (P = 0.005, 95% CI 0.583–0.871) and 81.8% (P = 0.011, 95% CI 0.635–0.990) in whole population and ICC subgroup analysis, respectively. SUV-max was shown by multivariate analysis to be an independent factor for DFS (P = 0.007 OR 1.16, 95% CI 1.04–1.29) and OS (P = 0.012 OR 1.145, 95% CI 1.030–1.273) after resection. SUV-max of 8 was shown to be a discriminant cut-off for poor oncological outcomes in patients with early cholangiocarcinoma (TNM stage I or II) after curative resection (3-year DFS: 21.2 vs. 63.2%, P = 0.004, and 3-year OS: 29 vs. 74% P = 0.048, respectively). PET/CT is a reliable imaging modality for metastatic lymph node detection in cholangiocarcinoma. Tumour SUV-max is an independent factor for oncological outcomes in patients with resectable disease. For patients who have TNM stage I or II cholangiocarcinoma, tumour SUV-max over 8 is associated with significantly inferior disease-free and overall survival even after curative resection.

Objective. To study the correlations and discrepancies between Child-Pugh system and indocyanine green (ICG) clearance test in assessing liver function reserve and explore the possibility of combining two systems to gain an overall liver function assessment. Design. Retrospective analysis of 2832 hepatocellular carcinoma (HCC) patients graded as Child-Pugh A and Child-Pugh B with ICG clearance test being performed was conducted. Results. ICG retention rate at 15 minutes (ICG15) correlates with Child-Pugh score, however, with a large variance. Platelet count improves the correlation between Child-Pugh score and ICG15. ICG15 can be estimated using the following regression formula: estimated ICG15 (eICG15) = 45.1 + 0.435 × bilirubin − 0.917 × albumin + 0.491 × prothrombin time − 0.0283 × platelet (R2=0.455). Patients with eICG15 >20.0% who underwent major hepatectomy had a tendency towards more posthepatectomy liver failure (4.1% versus 8.0%, p=0.09) and higher in-hospital mortality (3.7% versus 8.0%, p=0.052). They also had shorter median overall survival (5.10±0.553 versus 3.01±0.878 years, p=0.015) and disease-free survival (1.37±0.215 versus 0.707±0.183 years, p=0.018). Conclusion. eICG15 can be predicted from Child-Pugh parameters and platelet count. eICG15 correlates with in-hospital mortality after major hepatectomy and predicts long-term survival.

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

Background and Aim There is limited data on predictors of acute kidney injury in acute on chronic liver failure. We developed a PIRO model (Predisposition, Injury, Response, Organ failure) for predicting acute kidney injury in a multicentric cohort of acute on chronic liver failure patients. Patients and Methods Data of 2360 patients from APASL-ACLF Research Consortium (AARC) was analysed. Multivariate logistic regression model (PIRO score) was developed from a derivation cohort (n=1363) which was validated in another prospective multicentric cohort of acute on chronic liver failure patients (n=997). Results Factors significant for P component were serum creatinine[(≥2 mg/dL)OR 4.52, 95% CI (3.67-5.30)], bilirubin [(

Laparoscopic liver resection was slow to be adopted in the surgical arena at the beginning as there were major barriers including the fear of gas embolism, risk of excessive blood loss from the inability to control bleeding vessels effectively, suboptimal surgical instruments to perform major liver resection and the concerns about oncological safety of the procedure. However, it has come a long way since the early 1990s when the first successful laparoscopic liver resection was performed, spurring liver surgeons worldwide to start exploring the roles of laparoscopy in major liver resections. Till date, more than 9000 cases have been reported in the literature and the numbers continue to soar as the hepatobiliary surgical communities quickly learn and apply this technique in performing major liver resection. Large bodies of evidence are available in the literature showing that laparoscopic major liver resection can confer improved short-term outcomes in terms of lesser operative morbidities, lesser operative blood loss, lesser post-operative pain and faster recovery with shorter length of hospitalization. On the other hand, there is no compromise in the long-term and oncological outcomes in terms of comparable R0 resection rate and survival rates of this approach. Many innovations in laparoscopic major hepatectomies for complex operations have also been reported. In this article, we highlight the journey of laparoscopic major hepatectomies, summarize the technical advancement and lessons learnt as well as review the current standards of outcomes for this procedure.

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.

Objective To test the degree of agreement in selecting therapeutic options for patients suffering from colorectal liver metastasis (CRLM) among surgical experts around the globe. Summary/background Only few areas in medicine have seen so many novel therapeutic options over the past decades as for liver tumors. Significant variations may therefore exist regarding the choices of treatment, even among experts, which may confuse both the medical community and patients. Methods Ten cases of CRLM with different levels of complexity were presented to 43 expert liver surgeons from 23 countries and 4 continents. Experts were defined as experienced surgeons with academic contributions to the field of liver tumors. Experts provided information on their medical education and current practice in liver surgery and transplantation. Using an online platform, they chose their strategy in treating each case from defined multiple choices with added comments. Inter-rater agreement among experts and cases was calculated using free-marginal multirater kappa methodology. A similar, but adjusted survey was presented to 60 general surgeons from Asia, Europe, and North America to test their attitude in treating or referring complex patients to expert centers. Results Thirty-eight (88%) experts completed the evaluation. Most of them are in leading positions (92%) with a median clinical experience of 25 years. Agreement on therapeutic strategies among them was none to minimal in more than half of the cases with kappa varying from 0.00 to 0.39. Many general surgeons may not refer the complex cases to expert centers, including in Europe, where they also engage in complex liver surgeries. Conclusions Considerable inconsistencies of decision-making exist among expert surgeons when choosing a therapeutic strategy for CRLM. This might confuse both patients and referring physicians and indicate that an international high-level consensus statements and widely accepted guidelines are needed.

Background and aims Hepatitis B virus (HBV) integrations are common in hepatocellular carcinoma (HCC). In particular, alterations of the telomerase reverse transcriptase (TERT) gene by HBV integrations are frequent; however, the molecular mechanism and functional consequence underlying TERT HBV integration are unclear. Approach and results We adopted a targeted sequencing strategy to survey HBV integrations in human HBV-associated HCCs (n = 95). HBV integration at the TERT promoter was frequent (35.8%, n = 34/95) in HCC tumors and was associated with increased TERT mRNA expression and more aggressive tumor behavior. To investigate the functional importance of various integrated HBV components, we employed different luciferase reporter constructs and found that HBV enhancer I (EnhI) was the key viral component leading to TERT activation on integration at the TERT promoter. In addition, the orientation of the HBV integration at the TERT promoter further modulated the degree of TERT transcription activation in HCC cell lines and patients' HCCs. Furthermore, we performed array-based small interfering RNA library functional screening to interrogate the potential major transcription factors that physically interacted with HBV and investigated the cis-activation of host TERT gene transcription on viral integration. We identified a molecular mechanism of TERT activation through the E74 like ETS transcription factor 4 (ELF4), which normally could drive HBV gene transcription. ELF4 bound to the chimeric HBV EnhI at the TERT promoter, resulting in telomerase activation. Stable knockdown of ELF4 significantly reduced the TERT expression and sphere-forming ability in HCC cells. Conclusions Our results reveal a cis-activating mechanism harnessing host ELF4 and HBV integrated at the TERT promoter and uncover how TERT HBV-integrated HCCs may achieve TERT activation in hepatocarcinogenesis.

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

Introduction To assess the impact of three-dimensional (3D) visualization on laparoscopic hepatectomy for hepatocellular carcinoma. Methods A retrospective review with propensity-score matched analysis of 3D and two-dimensional (2D) laparoscopic hepatectomy performed in a tertiary hepatobiliary surgery centre. Results Since 3D laparoscopy was available, the proportion of laparoscopic major hepatectomy has significantly expanded (1.7% vs. 24.0%, p < 0.0001). The percentage of difficult resection among laparoscopic hepatectomy also increased (12.6% vs. 40.0%, p = 0.0001). A total of 305 patients (3D group: 92 patients; 2D group: 213 patients) underwent laparoscopic hepatectomy between 2002 and 2019. The 3D group had better liver function, larger tumours at more difficult locations, more major resections, and more difficult surgeries. After propensity score matching 144 patients were analysed (3D group: 72 patients; 2D group: 72 patients). They were comparable in terms of liver status, tumour status and complexity of liver surgery. The operative time (218 vs. 218 min, p = 0.50) and blood loss (0.2 vs. 0.2 L, p = 0.49) were comparable between two groups. Overall complications were higher in 2D group (1.4 vs. 11.1%, p = 0.03). Patients who underwent 3D laparoscopic major hepatectomy had a shorter hospital stay than their comparable counterparts operated through an open approach (7 vs. 6 days, p = 0.003). Conclusions 3D visualization enhanced feasibility to laparoscopic major hepatectomy and difficult laparoscopic liver resection. 3D resection was potentially associated with fewer operative morbidities. 3D laparoscopic approach did not jeopardize the outcome of major hepatectomy.

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.

To evaluate if living donor liver transplantation (LDLT) should be offered to patients with Model for End-stage Liver Disease (MELD) scores ≥35.No data was available to support LDLT of such patients.Data of 672 consecutive adult liver transplant recipients from 2005 to 2014 at our center were reviewed. Patients with MELD scores ≥35 were divided into the deceased donor liver transplantation (DDLT) group and the LDLT group and were compared. Univariate analysis was performed to identify risk factors affecting survival.The LDLT group (n = 54) had younger (33 yrs vs 50 yrs, P0.001) and lighter (56 Kg vs 65 Kg, P = 0.004) donors, lighter grafts (627.5 g vs 1252.5 g, P0.001), lower graft-weight-to-recipient-standard-liver-volume rates (51.28% vs 99.76%, P0.001), shorter cold ischemic time (106.5 min vs 389 min, P0.001), and longer operation time (681.5 min vs 534 min, P0.001). The groups were comparable in postoperative complication, hospital mortality, and graft survival and patient survival at one year (88.9% vs 92.5%; 88.9% vs 94.7%), three years (87.0% vs 86.9%; 87.0% vs 88.8%), and five years (84.8% vs 81.8%; 84.8% vs 83.3%). Univariate analysis did not show inferior survival in LDLT recipients.At centers with experience, the outcomes of LDLT can be comparable with those of DDLT even in patients with MELD scores ≥35. When donor risks and recipient benefits are fully considered and balanced, an MELD score ≥35 should not be a contraindication to LDLT. In Hong Kong, where most waitlisted patients have acute-on-chronic liver failure from hepatitis B, LDLT is a wise alternative to DDLT.

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

Background/objective: One thousand liver transplantations have been performed at the only liver transplant center in Hong Kong over a period of 22 years, which covered the formative period of living donor liver transplantation. These 1000 transplantations, which marked the journey of liver transplantation from development to maturation at the center, should be educational. This research was to study the experience and to reflect on the importance of technical innovations and case selection. Methods: The first 1000 liver transplantations were studied. Key technical innovations and surgical therapeutics were described. Recipient survival including hospital mortality was analyzed. Recipient survival comparison was made for deceased donor liver transplantation and living donor liver transplantation indicated by hepatocellular carcinoma and other diseases. Results: Among the 1000 transplantations, 418 used deceased donor grafts and 582 used living donor grafts. With the accumulation of experience, hospital mortality improved to < 2% in the past 2 years. In the treatment of diseases other than hepatocellular carcinoma, living donor liver transplantation was superior to deceased donor liver transplantation, with a 10-year recipient survival around 90%. Conclusion: Transplant outcomes have been improving consistently over the series, with a very low hospital mortality and a predictably high long-term survival.

Summary Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterized by high morbidity and mortality and its treatment remains challenging. Dendritic cells (DCs) have been shown to participate in the initiation and perpetuation of lupus pathogenesis and the DCs that can induce tolerogenicity appear as potential cell-based therapy in this condition. In this study, we examined the in vitro tolerogenic properties of bone-marrow derived DCs (BMDCs) in the murine lupus setting. We used lentiviral transduction of RelB-silencing short hairpin RNA to modify the expression of RelB, a key transcription factor regulating DC maturation, in BMDCs from MRL/MpJ mice. Tolerogenic properties of RelB-modified DCs were compared with scrambled control (SC) -modified DCs. RelB expression was found to be significantly reduced in RelB-modified DCs derived from MRL/MpJ mice, wild-type of the same genetic background as MRL/lpr lupus-prone mice. These MRL/MpJ RelB-modified DCs displayed semi-mature phenotype with expression of lower levels of co-stimulatory molecules compared with SC-modified DCs. RelB-modified DCs were found to be low producers of interleukin-12p70 (IL-12p70) and could induce hyporesponsiveness of splenic T cells from MRL/MpJ and MRL/lpr mice. Furthermore, they down-regulated interferon-γ expression and induced IL-10-producing T cells in MRL/MpJ splenocytes, and attenuated interferon-γ and IL-17 expression in MRL/lpr splenic CD4+ lymphocytes. Splenocytes primed by RelB-modified DCs demonstrated antigen-specific suppressive effects on allogeneic splenocytes. In conclusion, RelB-silencing in DCs generates DCs of tolerogenic properties with immunomodulatory function and appears as potential option of cell-targeted therapy.

Purpose of review This article provides an update on the latest development on deploying oral nucleosides in an immunoglobulin-free regime against hepatitis B virus (HBV) recurrence after liver transplantation. Recent findings Entecavir and tenofovir are the two newer oral nucleosides that are associated with a low virological rebound rate at less than 2% at 5 years. As a result, they have been applied as standalone treatment against HBV recurrence after liver transplantation without immunoglobulin. Recent evidence has shown that a hepatitis B surface antigen seroclearance rate of 86% and 91% after 1 and 2 years was achievable with entecavir monotherapy. Moreover, none of the patients had histological graft damage because of HBV recurrence and an overall survival over 80% at 7 years has been reported. Summary With newer and more potent oral nucleos(t)ide (NA) available, a hepatitis B immune globulin-free regimen after liver transplantation has become safe and feasible for suppression of HBV recurrence after liver transplantation, and for avoidance of HBV-related graft complications.

e14057 Background: This study aimed to investigate the prognostic value of transcriptome and clinical data of Hepatocellular carcinoma (HCC) patients for overall survival (OS) by deep learning method. Methods: A total of 371 HCC patients with 20530 level three RNA-sequencing data were from The Cancer Genome Atlas (TCGA). Cox-nnet model, a deep learning model through an artificial neural network extension of the Cox regression model, was used for OS prediction. The patients were randomly split into train-set and test-set (7:3). In train-set, the significant genes associated with OS under univariate Cox regression were considered for modeling. Clinical parameters, including age, gender, pathologic stage, child pugh classification, creatinine level etc. were also considered. The Cox-nnet model was developed by cross-validation. Its discrimination was determined by the concordance index (CI) in the independent test-set and compared with multivariable Cox regression. The clustering method Uniform Manifold Approximation and Projection (UMAP) was used for revealing biological information from the hidden layer in the model. Results: In the train-set (n = 259), 1505 genes and two clinical variables (child pugh score and creatinine level) were significantly associated with OS (adjusted P-value < 0.05). To avoid overfitting, only 40 most significant genes were included in the Cox-nnet model. In the test-set (n = 112), the CI of Cox-nnet (0.76, se = 0.04) is better than the CI of multivariable Cox regression (0.71, se = 0.05). The difference between good or poor survival subgroups classified by Cox-nnet was remarkably significant ( P-value = 1e-4, median OS: 80.7 vs. 25.1 months). In the Cox-nnet model with all significant variables, the weights in the hidden layer were clustered by UMAP into 3 positive clusters and 2 negative clusters, which are enriched in GO/KEGG. The “cell cycle” and “complement and coagulation cascades” are the most important signal pathways in positive and negative clusters, respectively. Conclusions: Combining transcriptomic and clinical data, and with deep learning algorithm, we built and validated a robust model for survival prediction in HCC patients. Our study would be useful to explore the clinical implications in survival prediction and corresponding genetic mechanisms. Clinical trial information: 5U24CA143799, 5U24CA143835, 5U24CA143840, 5U24CA143843, 5U24CA143845, 5U24CA143848, 5U24CA1438.

We sought to develop a nomogram for the prediction of tumor recurrence after resection of hepatocellular carcinoma (HCC) within the Milan criteria. Consecutive HCC patients admitted for hepatectomy between 1994 and 2014 were enrolled in this study. Patients were excluded if they had recurrent HCC or tumors beyond the Milan criteria. Patients were randomized and assigned to the derivation and validation sets in a 1:1 ratio. Independent factors for disease-free survival were identified using the Cox regression model. A nomogram was derived and validated with the receiver-operating characteristic (ROC) and calibration curves. There were 617 eligible patients included in the analysis. The median age was 59 years, 481 were male, and 87.8% of the patients were hepatitis B virus carriers. The median follow-up was 68.7 months. The 5-year overall survival rate was 73.3% and HCC recurrence was detected in 55% of the patients. In the derivation set, a nomogram was constructed based on the seven independent factors for disease-free survival: age, alpha-fetoprotein, preoperative prothrombin time, magnitude of hepatectomy, postoperative complication, number of tumor nodules, and presence of microvascular invasion. A satisfactory discrimination ability was observed in both the derivation and validation sets (c-stat 0.672 and 0.665, respectively). The calibration plot yielded agreement between the predicted and observed outcomes, using the derived nomogram. A validated nomogram quantifies the risk of recurrence after hepatectomy for HCC within the Milan criteria, and assists with the planning of individual postoperative surveillance protocols.

Spontaneous tumor rupture (STR) is a life-threatening complication of hepatocellular carcinoma (HCC). Yet, interval partial hepatectomy (PH) is feasible in selected patients after hemostasis for the rupture event. Little is known, however, about the extent of negative prognostic impact STR had on these patients after resection. Our aim was to determine the impact of STR on the oncologic outcome of interval PH for ruptured HCC, and the prognostic value of STR on the current tumor node metastasis (TNM) classification.From 1989 to 2010, 84 of 364 patients (23%) with STR received staged PH. Clinicopathologic variables associated with STR were identified by logistic regression analysis and ruptured tumor size with prognostic impact was determined by receiver operating characteristic analysis. Comparison of survival curves was performed after stratification by the American Joint Committee on Cancer/TNM, 7th edition.Ruptured HCC had substantially worse survival than nonruptured tumor (5-year overall survival: 22.3% vs 53.4% P .001). Anti-HCV status (hazard ratio [HR]: 3.225 confidence interval [95% CI]: 1.175-8.847, P = .023), platelet count (HR: 1.003, CI 1.0001-1.006, P = .042), tumor size (HR: 1.089, CI 1.025-1.156, P = .006) and microvascular invasion (HR 2.377, CI 1.255-4.502, P = .008) were independently associated with STR. When stratified by the TNM system after excluding STR as a component of T-staging, ruptured HCC had worse survival outcomes than nonruptured HCC in T1-T2 disease and tumors ≤10 cm only. A receiver operating characteristic analysis confirmed that STR had no additional adverse prognostic impact over other tumor features when size10 cm (area under curve 0.65, P .001).STR affects the outcome of PH for T1-T2 disease or tumor ≤10 cm only. Assigning all resectable ruptured tumors to T4 may overestimate the severity of disease.

Background and aim Bile leakage is a major complication after right lobe living donor liver transplantation (RLDLT). It can result in significant morbidities and, occasionally, mortalities. Endo-radiology is a non-surgical means that has been used to manage this complication. This study reviews the outcomes of the endo-radiological approach to the management of bile leakage after RLDLT with duct-to-duct anastomosis (DDA) at a high-volume center. Method A retrospective study was conducted on all adult patients who received RLDLT at our center between January 2001 and December 2013. There were 496 RLDLTs performed during the study period. Only patients who had DDA as the only bile duct reconstruction method were included in the study. Results Twelve (3.7%) out of the 328 study subjects developed bile leakage after RLDLT. Six out of these 12 patients were successfully treated with the endo-radiological approach without the need for laparotomy. They had endoscopic retrograde cholangiography with stenting followed by percutaneous drainage of biloma. One of the 12 patients died from recurrence of hepatocellular carcinoma 37 months after transplantation. The remaining 11 patients are all alive. Conclusion The endo-radiological approach should be the first-line management for bile leakage for selected patients with DDA as the bile duct reconstruction method.

This study was presented at the 11th World IHPBA Congress, 22–27 March 2014, Seoul., BACKGROUND: Hepatocellular carcinoma (HCC) with bile duct tumour thrombus (BDTT) is rare. The aim of the present study was to determine the prognosis of HCC with BDTT after a hepatectomy. METHODS: A retrospective analysis was performed on all HCC patients with BDTT having a hepatectomy from 1989 to 2012. The outcomes in these patients were compared with those in the control patients matched on a 1:6 ratio. RESULTS: Thirty-seven HCC patients with BDTT having a hepatectomy (the BDTT group) were compared with 222 control patients. Patients in the BDTT group had poorer liver function (43.2% had Child-Pugh B disease). More patients in this group had a major hepatectomy (91.9% versus 27.5%, P = 0.001), portal vein resection (10.8% versus 1.4%, P = 0.006), en-bloc resection with adjacent structures (16.2% versus 5.4%, P = 0.041), hepaticojejunostomy (75.7% versus 1.6%, P < 0.001) and complications (51.4% versus 31.1%, P = 0.016). The two groups had similar hospital mortality (2.7% versus 5.0%, P = 0.856), 5-year overall survival (38.5% versus 34.6%, P = 0.59) and 5-year disease-free survival (21.1% versus 20.8%, P = 0.81). Multivariate analysis showed that lymphovascular permeation, tumour size and post-operative complication were significant predictors for worse survival whereas BDTT was not. DISCUSSION: A major hepatectomy, extrahepatic biliary resection and hepaticojejunostomy should be the standard for HCC with BDTT, and long-term survival is possible after radical surgery. © 2014 International Hepato-Pancreato-Biliary Association., link_to_OA_fulltext