High prevalence of de novo metabolic dysfunction-associated fatty liver disease after liver transplantation and the role of controlled attenuation parameter.

BACKGROUND & AIMS: Although non-alcoholic fatty liver disease (NAFLD) remains an uncommon indication for liver transplantation (LT) in the Chinese, the prevalence of NAFLD is increasing. We aimed to determine the prevalence of de novo steatosis and metabolic dysfunction-associated fatty liver disease (MAFLD) after LT. METHODS: Transient elastography assessment for liver stiffness and controlled attenuation parameter (CAP) were performed after LT in 549 patients at median time of 77 months from LT. CAP was compared with implant liver biopsy, and also validated in 42 patients with post-LT liver biopsy. Longitudinal history including diabetes mellitus (DM), dyslipidemia, hypertension, and immunosuppressive regimen were recorded. RESULTS: The optimal cut-off level of CAP for diagnosing at least mild (≥ S1) and moderate-to-severe steatosis (≥ S2/3) was 266 and 293 dB/m respectively, with AUROC of 0.740 and 0.954 respectively. Using this newly derived cut-off, 28.9% patients have de novo NAFLD, of which 95.6% fulfilled the criteria for MAFLD. After multivariate analysis, BMI (HR 1.34), DM (HR 2.01), hypertension (HR 2.03), HDL-cholesterol (HR 0.25), LDL-cholesterol (HR 1.5) and cryptogenic cirrhosis (HR 4.85) were associated with the development of S2/3 graft steatosis. de novo NAFLD was associated with higher incidence of new-onset hypertension (p < 0.001), graft dysfunction (defined as ALT > 40 U/L; p = 0.008), but not associated with graft fibrosis (defined as liver stiffness > 12 kPa; p = 0.761). CONCLUSION: Although NAFLD remains an uncommon primary liver disease indication for LT in Chinese patients, post-transplant de novo graft steatosis is common and the majority is classified as MAFLD. Development of graft steatosis is not associated with an increase in graft fibrosis but was associated with worse metabolic control and graft dysfunction. Routine CAP measurement to detect de novo graft steatosis should be considered after LT regardless of the primary indication of LT.

A machine learning model for colorectal liver metastasis post-hepatectomy prognostications.

Background: Currently, surgical resection is the mainstay for colorectal liver metastases (CRLM) management and the only potentially curative treatment modality. Prognostication tools can support patient selection for surgical resection to maximize therapeutic benefit. This study aimed to develop a survival prediction model using machine learning based on a multicenter patient sample in Hong Kong. Methods: Patients who underwent hepatectomy for CRLM between 1 January 2009 and 31 December 2018 in four hospitals in Hong Kong were included in the study. Survival analysis was performed using Cox proportional hazards (CPH). A stepwise selection on Cox multivariable models with Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to a multiply-imputed dataset to build a prediction model. The model was validated in the validation set, and its performance was compared with that of Fong Clinical Risk Score (CRS) using concordance index. Results: A total of 572 patients were included with a median follow-up of 3.6 years. The full models for overall survival (OS) and recurrence-free survival (RFS) consist of the same 8 established and novel variables, namely colorectal cancer nodal stage, CRLM neoadjuvant treatment, Charlson Comorbidity Score, pre-hepatectomy bilirubin and carcinoembryonic antigen (CEA) levels, CRLM largest tumor diameter, extrahepatic metastasis detected on positron emission-tomography (PET)-scan as well as KRAS status. Our CRLM Machine-learning Algorithm Prognostication model (CMAP) demonstrated better ability to predict OS (C-index =0.651), compared with the Fong CRS for 1-year (C-index =0.571) and 5-year OS (C-index =0.574). It also achieved a C-index of 0.651 for RFS. Conclusions: We present a promising machine learning algorithm to individualize prognostications for patients following resection of CRLM with good discriminative ability.

Impact of Three-Dimensional (3D) Visualization on Laparoscopic Hepatectomy for Hepatocellular Carcinoma.

BACKGROUND: The impact of three-dimensional (3D) visualization on laparoscopic hepatectomy for hepatocellular carcinoma is largely unknown. METHODS: A retrospective review with propensity-score matched analysis of 3D and two-dimensional (2D) laparoscopic hepatectomy performed in a tertiary hepatobiliary surgery center. RESULTS: Since the availability of 3D laparoscopy, the proportion of laparoscopic major hepatectomies has significantly expanded (1.7% vs. 24.0%, p < 0.0001) and the percentage of difficult resections among patients who underwent laparoscopic hepatectomy has also increased (12.6% vs. 40.0%, p = 0.0001). A total of 305 patients (92 in the 3D group and 213 in the 2D group) underwent laparoscopic hepatectomy between 2002 and 2019. The 3D group had better liver function, larger tumors at more difficult locations, more major resections, and more difficult surgeries. After propensity score matching, 144 patients were analyzed (72 in both the 3D and 2D groups). Patients were comparable in terms of liver status, tumor status, and complexity of liver surgery. Operative time (218 vs. 218 mins, p = 0.50) and blood loss (0.2 vs. 0.2L, p = 0.49) were comparable between the two groups, however overall complications were higher in the 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 the feasibility of laparoscopic major hepatectomy and difficult laparoscopic liver resection. 3D resection was potentially associated with fewer operative morbidities and the 3D laparoscopic approach did not jeopardize the outcome of major hepatectomy.

Routine use of ICG to enhance operative safety in emergency laparoscopic cholecystectomy: a randomized controlled trial.

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

Alpha-Fetoprotein in Predicting Survival of Patients with Ruptured Hepatocellular Carcinoma after Resection.

Background/Aim: Alpha-fetoprotein (AFP) had been used as a prognostic factor in hepatocellular carcinoma but it was unknown what level of AFP could predict the survival of patients with ruptured hepatocellular carcinoma (rHCC) after resection. This retrospective study was to identify the best cutoff value of AFP for this prediction.Methods: Data of patients having hepatectomy for rHCC from 1989 to 2015 were reviewed. The receiver operating characteristic curve and Youden's index were used to identify the cutoff value of AFP affecting survival. The patients were then divided into two groups by the cutoff for comparison.Results: Totally 114 patients were included. An AFP level of 256 ng/ml was found to affect survival (area under curve 63.1%, 95% confidence interval 0.514-0.748, p = 0.027; sensitivity 0.6, specificity 0.706). The 114 patients were divided into Group A (AFP < 256 ng/ml, n = 56) and Group B (AFP ≥ 256 ng/ml, n = 58). The median AFP level was 13.0 ng/ml (range, 2-253 ng/ml) in Group A and 11206.5 ng/ml (range, 259-481,000 ng/ml) in Group B (p < 0.001). Group A had a larger proportion of patients receiving transarterial embolization at the time of rupture, and the time to hepatectomy was longer in this group. Patients in Group B had more blood loss, more complications, larger tumors, and more cases of macrovascular/microvascular invasion. Overall survival (p = 0.013) and disease-free survival (p = 0.024) were significantly better in Group A. On multivariate analysis, AFP ≥ 256 ng/ml was an independent risk factor for overall survival.Conclusion: AFP ≥ 256 ng/ml had an adverse impact on the survival of patients with rHCC after resection.

Adjuvant transarterial chemotherapy for margin-positive resection of hepatocellular carcinoma-a propensity score matched analysis.

BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Impact of Time to Recurrence on Survival Outcome of Salvage Liver Transplantation.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Impact of preoperative biliary drainage on postoperative outcomes in hilar cholangiocarcinoma.

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.

High-intensity focused ultrasound ablation of liver tumors in difficult locations.

High-intensity focused ultrasound (HIFU) has been shown to be a valuable tool in the management of small liver tumors such as hepatocellular carcinoma (HCC). It has been shown to be a safe and effective means to ablate small HCC even in the presence of advanced cirrhosis. This review examines the challenges faced during HIFU ablation when the target tumors are located in difficult locations such as the liver dome, close to the rib cage, near large blood vessels or the heart, or adjacent to hollow viscera; and the special maneuvers employed to tackle such lesions.

Critical appraisal of TNM versus HKU staging system for postoperative prognostic evaluation of hepatocellular carcinoma.

BACKGROUND: The 8th edition of the American Joint Committee on Cancer tumor-node-metastasis staging system (AJCC 8th) has been launched with modifications in T staging. The University of Hong Kong liver cancer staging system (HKUSS) has been proven to better categorize hepatocellular carcinoma (HCC) into different T stages. This study aimed to compare the two systems' predictive ability for HCC recurrence after primary surgical resection. METHODS: Patients who had primary, curative resection for HCC between 1989 and 2017 were reviewed. The Kaplan-Meier plot was used to estimate disease-free survival (DFS), and the log-rank test was used for survival comparison between subgroups. The two systems' prediction of recurrence was evaluated by the Cox regression model. RESULTS: Totally 1,815 patients were included. With AJCC 8th, the 5-year DFS was 58.9% for T1a, 52.3% for T1b, 30% for T2, 16.9% for T3, and 14.4% for T4. No survival difference was demonstrated between T1a and T1b (P=0.668) or between T3 and T4 (P=0.562). With HKUSS, the 5-year DFS was 57.7% for T1, 43.4% for T2, 28.9% for T3, and 15.7% for T4. The T staging in HKUSS showed significant survival differences (T1 vs. T2, T2 vs. T3, and T3 vs. T4; P<0.001). Using receiver operating characteristic curves to show the recurrence status in the two systems, HKUSS had the largest area under curve (AUC) (HKUSS: AUC =0.655, SE 0.014, P<0.001, 95% CI, 0.628-0.681; AJCC 8th: AUC =0.652, SE 0.013, P<0.001, 95% CI, 0.625-0.677). CONCLUSIONS: HKUSS showed better categorization of HCC. In the context of primary surgical resection, HKUSS may be more appropriate for stratification of patients with HCC with various T stages, and thus the choice of staging system when primary surgical resection is considered for patients of HCC.

Endoscopic versus Surgical Intervention for Painful Obstructive Chronic Pancreatitis: A Systematic Review and Meta-Analysis.

There is limited evidence on the standard care for painful obstructive chronic pancreatitis (CP), while comparisons of endoscopic and surgical modes for pain relief have yielded conflicting results from small sample sizes. We aimed to obtain a clear picture of the matter by a meta-analysis of these results. We searched the Pubmed, Embase, and Cochrane Library databases to identify studies comparing endoscopic and surgical treatments for painful obstructive CP. Pooled effects were calculated by the random effect model. Primary outcomes were overall pain relief (complete and partial), and secondary outcomes were complete and partial pain relief, complication rate, hospitalization duration, and endocrine insufficiency. Seven studies with 570 patients were included in the final analysis. Surgical drainage was associated with superior overall pain relief [OR 0.33, 95% CI 0.23-0.47, p < 0.001, I2 = 4%] and lesser incidence of endocrine insufficiency [OR 2.10, 95% CI 1.20-3.67, p = 0.01, I2 = 0%], but no significant difference in the subgroup of complete [OR 0.57, 95% CI 0.32-1.01, p = 0.054, I2 = 0%] or partial [OR 0.67, 95% CI 0.37-1.22, p = 0.19, I2 = 0%] pain relief, complication rates [OR 1.00, 95% CI 0.41-2.46, p = 0.99, I2 = 49%], and hospital stay [OR -0.54, 95% CI -1.23-0.15, p = 0.13, I2 = 87%] was found. Surgery is associated with significantly better overall pain relief and lesser endocrine insufficiency in patients with painful obstructive CP. However, considering the invasiveness of surgery, no significant differences in complete or partial pain relief, and heterogeneity of a few parameters between two groups, endoscopic drainage may be firstly performed and surgical drainage may be considered when endoscopic drainage fails.

Role of C11-FDG dual-tracer PET-CT scan in metastatic screening of hepatocellular carcinoma-a cost-effectiveness analysis.

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

Liver transplantation: would it be the best and last chance of cure for hepatocellular carcinoma with major venous invasion?

BACKGROUND: Hepatocellular carcinoma (HCC) with portal vein tumour thrombus (PVTT) signifies advanced disease, whether LT confers any survival superiority over resection remains uncertain. METHODS: A propensity score matched (PSM) analysis of liver transplantation (LT) and liver resection (LR) for HCC with PVTT was performed. RESULTS: A consecutive series of 88 patients who received either LT (10 DDLTs and 3 LDLTs) or LR (n=75) respectively were recruited. Before PSM, the LT group has a higher MELD score (17.3 vs. 7.8, P<0.001), lower serum AFP levels (96 vs. 2,164 ng/mL, P=0.017) and smaller tumour size (4 vs. 10 cm, P<0.001). The 5-year overall survival for LT and LR were 55.4% and 15.9% respectively (P=0.007). After matching for serum AFP levels and tumour size, 1-, 3- and 5-year overall survival for LT were 81 ng/mL, 3.9 cm, 80%, 70% and 70% and the corresponding rates for LR were 1,417 ng/mL, 5.3 cm, 51.8%, 19,6% and 9.8% (P value =0.12, 0.27 and 0.009 respectively). CONCLUSIONS: LT is associated with significantly better oncological outcomes in HCC patients with PVTT involving the lobar or segmental level. A modest expansion of selection criteria to include small HCC with segmental PVTT should be considered.

The Outcomes of Systemic Treatment in Recurrent Hepatocellular Carcinomas Following Liver Transplants.

BACKGROUND: Treatment of hepatocellular carcinoma (HCC) recurrences following liver transplant (LT) is challenging. Most clinical trials of systemic therapies for advanced HCC excluded patients with any history of organ transplant. We aimed to assess the outcomes in using various systemic therapies in patients with post-LT recurrence. METHODS: Consecutive patients with HCC and recurrences following LT at a large tertiary centre from 2005 to 2018 were reviewed. Overall survival (OS), response rates and adverse events (AEs) were analysed. RESULTS: Forty-three consecutive patients with a recurrence of HCC following LT were identified from 2005 to 2018. Median OS from diagnosis of recurrence was 17 months (CI 11.3, 22.7). Early recurrence within 12 months of transplant was associated with a significantly worse median survival of 10 months (CI 8.5, 11.4) compared to 26 months (CI 18.8, 33.2) when recurrences occurred after 12 months from transplant (p < 0.001) with a hazard ratio of 0.104 (log-rank test, p < 0.001). A total of 41 patients had received systemic therapies and 79.1% of them were on sorafenib as the first-line treatment. Among these patients treated with sorafenib, median OS from recurrence was 14 months (CI 7.3, 20.7). Hand-foot syndrome (34.7%) was most common among AEs followed by diarrhoea (26.7%). Overall, AEs led to dose interruptions in 8.8% of patients. Notably, 47.1% of patients received subsequent lines of systemic therapies after sorafenib. CONCLUSIONS: Early recurrence within 1 year from transplant was the most significant risk factor. Treatment efficacy and adverse events and tolerability of sorafenib were comparable with those in the setting of advanced HCC without transplant.

Relevance of chemotherapy and margin status in colorectal liver metastasis.

PURPOSE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: The results demonstrated the important effect of perioperative chemotherapy and negative margin liver resection in management of patients suffered from CRLM.

A review on radiofrequency, microwave and high-intensity focused ultrasound ablations for hepatocellular carcinoma with cirrhosis.

IMPORTANCE: Hepatocellular carcinoma (HCC) is usually accompanied by liver cirrhosis, which makes treatment of this disease challenging. Liver transplantation theoretically provides an ultimate solution to the disease, but the maximal surgical stress and the scarcity of liver graft make this treatment option impossible for some patients. In an ideal situation, a treatment that is safe and effective should provide a better outcome for patients with the dilemma. OBJECTIVE: This article aims to give a comprehensive review of various types of loco-ablative treatment for HCC. EVIDENCE REVIEW: Loco-ablative treatment bridges the gap between surgical resection and transarterial chemotherapy. Various types of ablative therapy have their unique ability, and evidence-based outcome analysis is the most important key to assisting clinicians to choose the most suitable treatment modality for their patients. FINDINGS: Radiofrequency ablation (RFA) has a relatively longer history and more evidence to support its effectiveness. Microwave ablation (MWA) is gaining momentum because of its shorter ablation time and consistent ablation zone. High-intensity focused ultrasound (HIFU) ablation is a relatively new technology that provides non-invasive treatment for patients with HCC. It has been carried out at centers of excellence and it is a safe and effective treatment option for selected patients with HCC and liver cirrhosis. CONCLUSION AND RELEVANCE: Selective use of different loco-ablative therapies will enhance clinicians' treatment options for treatment of HCC.

The Use of Cabozantinib in Advanced Hepatocellular Carcinoma in Hong Kong-A Territory-Wide Cohort Study.

(1) Background: Cabozantinib is approved in sorafenib-exposed advanced hepatocellular carcinoma (aHCC). We evaluated the real-life pattern of use, efficacy, and tolerability of cabozantinib in aHCC. (2) Methods: This territory-wide study included consecutive aHCC patients who received cabozantinib between February 2018 and September 2020 in Hong Kong. The objective response rate (ORR), disease control rate (DCR), overall survival (OS), and adverse events (AE) were assessed. (3) Results: Overall, 42 patients were included. Approximately 83.3% had Child-Pugh A cirrhosis. About 64.3% received cabozantinib as a single agent, and the remaining 35.7% received cabozantinib as an add-on to immune checkpoint inhibitors (ICIs). For single-agent patients, the median follow-up was 6.7 months. The ORR was 3.7%, DCR was 44.4%, and the median OS was 8.28 months. About 74.1% of patients experienced any AEs with 7.4% having grade ≥3 AEs. Among patients who received prior ICIs (n = 16), the ORR was 6.3%, and the median OS was 8.28 months. An exploratory analysis of patients who received cabozantinib as an add-on to ICIs showed an ORR of 6.7% and a median OS of 15.1 months, with 73.3% having any AE and 13.3% having grade ≥3 AEs. (4) Conclusions: Cabozantinib had good anti-tumor activity, survival benefits, and acceptable tolerability in real-life aHCC patients.

Ipilimumab and nivolumab/pembrolizumab in advanced hepatocellular carcinoma refractory to prior immune checkpoint inhibitors.

BACKGROUND: Programmed cell death protein 1 (PD-1) pathway blockade with immune checkpoint inhibitors (ICIs) is a standard therapy in advanced hepatocellular carcinoma (HCC) nowadays. No strategies to overcome ICI resistance have been described. We aimed to evaluate the use of ipilimumab and anti-PD-1 ICIs (nivolumab or pembrolizumab) combinations in patients with advanced HCC with progression on prior ICIs. METHODS: Patients with advanced HCC with documented tumor progression on prior ICIs and subsequently received ipilimumab with nivolumab/pembrolizumab were analyzed. Objective response rate (ORR), median duration of response (DOR), time-to-progression (TTP), overall survival (OS), and treatment-related adverse events (TRAEs) were assessed. RESULTS: Twenty-five patients were included. The median age was 62 (range: 51-83). About 68% were of Child-Pugh (CP) Grade A and 48% had primary resistance to prior ICI. At median follow-up of 37.7 months, the ORR was 16% with a median DOR of 11.5 months (range: 2.76-30.3). Three patients achieved complete response. The median TTP was 2.96 months (95% CI: 1.61 to 4.31). Median OS was 10.9 months (95% CI: 3.99 to 17.8) and the 1 year, 2 year and 3 year survival rates were 42.4%, 32.3% and 21.6%, respectively. The ORR was 16.7% in primary resistance group and 15.4% in acquired resistance group (p=1.00). All responders were of CP A and Albumin-Bilirubin (ALBI) Grade 1 or 2. CP and ALBI Grades were significantly associated with OS (p=0.006 and p<0.001, respectively). Overall, 52% of patients experienced TRAEs and 12% experienced Grade 3 or above TRAEs. CONCLUSIONS: Ipilimumab and nivolumab/pembrolizumab can achieve durable antitumor activity and encouraging survival outcomes with acceptable toxicity in patients with advanced HCC who had prior treatment with ICIs.

Analysis of Survival Benefits of Living Versus Deceased Donor Liver Transplant in High Model for End-Stage Liver Disease and Hepatorenal Syndrome.

BACKGROUND AND AIMS: Previous recommendations suggested living donor liver transplantation (LDLT) should not be considered for patients with Model for End-Stage Liver Disease (MELD) > 25 and hepatorenal syndrome (HRS). APPROACH AND RESULTS: Patients who were listed with MELD > 25 from 2008 to 2017 were analyzed with intention-to-treat (ITT) basis retrospectively. Patients who had a potential live donor were analyzed as ITT-LDLT, whereas those who had none belonged to ITT-deceased donor liver transplantation (DDLT) group. ITT-overall survival (OS) was analyzed from the time of listing. Three hundred twenty-five patients were listed (ITT-LDLT n = 212, ITT-DDLT n = 113). The risk of delist/death was lower in the ITT-LDLT group (43.4% vs. 19.8%, P < 0.001), whereas the transplant rate was higher in the ITT-LDLT group (78.3% vs. 52.2%, P < 0.001). The 5-year ITT-OS was superior in the ITT-LDLT group (72.6% vs. 49.5%, P < 0.001) for patients with MELD > 25 and patients with both MELD > 25 and HRS (56% vs. 33.8%, P < 0.001). Waitlist mortality was the highest early after listing, and the distinct alteration of slope at survival curve showed that the benefits of ITT-LDLT occurred within the first month after listing. Perioperative outcomes and 5-year patient survival were comparable for patients with MELD > 25 (88% vs. 85.4%, P = 0.279) and patients with both MELD > 25 and HRS (77% vs. 76.4%, P = 0.701) after LDLT and DDLT, respectively. The LDLT group has a higher rate of renal recovery by 1 month (77.4% vs. 59.1%, P = 0.003) and 3 months (86.1% vs, 74.5%, P = 0.029), whereas the long-term estimated glomerular filtration rate (eGFR) was similar between the 2 groups. ITT-LDLT reduced the hazard of mortality (hazard ratio = 0.387-0.552) across all MELD strata. CONCLUSIONS: The ITT-LDLT reduced waitlist mortality and allowed an earlier access to transplant. LDLT in patients with high MELD/HRS was feasible, and they had similar perioperative outcomes and better renal recovery, whereas the long-term survival and eGFR were comparable with DDLT. LDLT should be considered for patients with high MELD/HRS, and the application of LDLT should not be restricted with a MELD cutoff.