Stereotactic Body Radiotherapy and Liver Transplant for Liver Cancer: A Nonrandomized Controlled Trial.

Importance: Whether stereotactic body radiotherapy (SBRT) as a bridge to liver transplant for hepatocellular carcinoma (HCC) is effective and safe is still unknown. Objective: To investigate the feasibility of SBRT before deceased donor liver transplant (DDLT) for previously untreated unresectable HCC. Design, Setting, and Participants: In this phase 2 nonrandomized controlled trial conducted between June 1, 2015, and October 18, 2019, 32 eligible patients within UCSF (University of California, San Francisco) criteria underwent dual-tracer (18F-fluorodeoxyglucose and 11C-acetate [ACC]) positron emission tomography with computed tomography (PET-CT) and magnetic resonance imaging (MRI) with gadoxetate followed by SBRT of 35 to 50 Gy in 5 fractions, and the same imaging afterward while awaiting DDLT. Statistical analysis was performed on an intention-to-treat basis between October 1 and 31, 2023. Intervention: Patients received SBRT followed by DDLT when matched deceased donor grafts were available. Main Outcomes and Measures: Coprimary end points were progression-free survival (PFS) and objective response rates (ORRs) by the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), modified RECIST (mRECIST), and PET Response Criteria in Solid Tumors (PERCIST). Secondary end points were local control rate, overall survival (OS), and safety. Results: A total of 32 patients (median age, 59 years [IQR, 54-63 years]; 22 men [68.8%]) with 56 lesions received SBRT. After a median follow-up of 74.6 months (IQR, 40.1-102.9 months), the median PFS was 17.6 months (95% CI, 6.6-28.6 months), and the median OS was 60.5 months (95% CI, 29.7-91.2 months). The 5-year PFS was 39.9% (95% CI, 19.9%-59.9%), and the 5-year OS was 51.3% (95% CI, 31.7%-70.9%). In terms of number of patients, ORRs were 62.5% ([n = 20] 95% CI, 54.2%-68.7%) by RECIST 1.1, 71.9% ([n = 23] 95% CI, 63.7%-79.0%) by mRECIST, and 78.1% ([n = 25] 95% CI, 73.2%-86.7%) by PERCIST. In terms of number of lesions, ORRs were 75.0% ([n = 42] 95% CI, 61.6%-80.8%) by RECIST 1.1, 83.9% ([n = 47] 95% CI, 74.7%-90.6%) by mRECIST, and 87.5% ([n = 49] 95% CI, 81.3%-98.6%) by PERCIST. Twenty patients with 36 lesions received DDLT, of whom 15 patients (75.0%) with 21 lesions (58.3%) exhibited pathologic complete response. Multivariable analyses revealed that pretreatment metabolic tumor volume (MTV) based on ACC (hazard ratio [HR], 1.06 [95% CI, 1.01-1.10]; P = .01) and complete metabolic response (CMR) by PERCIST (HR, 0.31 [95% CI, 0.10-0.96]; P = .04) were associated with PFS, while pretreatment MTV based on ACC (HR, 1.07 [95% CI, 1.03-1.16]; P = .01), total lesion activity based on ACC (HR, 1.01 [95% CI, 1.00-1.02]; P = .02), and CMR by PERCIST (HR, 0.21 [95% CI, 0.07-0.73]; P = .01) were associated with OS. Toxic effects associated with SBRT were reported for 9 patients (28.1%), with 1 grade 3 event. Conclusions and Relevance: This phase 2 nonrandomized controlled trial demonstrated promising survival and safety outcomes of SBRT before DDLT for unresectable HCC. Future randomized clinical trials are warranted.

Child-Pugh Parameters and Platelet Count as an Alternative to ICG Test for Assessing Liver Function for Major Hepatectomy.

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.

Hepatopancreatoduodenectomy for advanced hepatobiliary malignancies: a single-center experience.

BACKGROUND: Hepatopancreatoduodenectomy is a complicated and challenging procedure but necessary for curative resection for advanced hepatobiliary malignancies. This retrospective study was to examine the safety and survival outcomes of hepatopancreatoduodenectomy in our center. METHODS: Prospectively collected data of 12 patients who underwent hepatopancreatoduodenectomy for advanced hepatobiliary malignancies in our hospital from January 1998 to December 2014 were analyzed. The primary endpoints are treatment-related morbidity and mortality and the secondary endpoints are overall survival and disease-free survival. RESULTS: Curative resection was achieved in 11 (91.7%) patients. Complications developed in 10 (83.3%) patients. Three hospital deaths resulted from multiorgan failure secondary to postoperative pancreatic fistula or hepaticojejunostomy leakage. Six of the nine remaining patients had disease recurrence. The nine patients had a median survival of 39.8 (5.3-151.8) months. The 1-, 3- and 5-year overall survival rates were 66.7%, 55.6% and 27.8%, respectively. The corresponding disease-free survival rates were 55.6%, 44.4% and 29.6%, respectively. CONCLUSIONS: Morbidity and mortality after hepatopancreatoduodenectomy were significant. With R0 resection, the 5-year overall survival and disease-free survival rates were 27.8% and 29.6%, respectively.

NLRP3 inflammasome induced liver graft injury through activation of telomere-independent RAP1/KC axis.

Acute-phase inflammation plays a critical role in liver graft injury. Inflammasomes, multi-molecular complexes in the cytoplasm, are responsible for initiating inflammation. Here, we aimed to explore the role of inflammasomes in liver graft injury and further to investigate the regulatory mechanism. In a clinical liver transplant cohort, we found that intragraft expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes was significantly up-regulated post-transplantation. Importantly, overexpression of NLRP3 was strongly associated with poor liver function characterized by high levels of ALT, AST, and urea, as well as neutrophil infiltration after transplantation. The significant correlation between NLRP3 and IL-1ß mRNA levels led us to focus on one of the associated upstream regulators, telomere-independent repressor activator protein 1 (RAP1), which was further proved to be co-localized with NLRP3 in neutrophils. In the liver of a mouse model (hepatic ischaemia/reperfusion and hepatectomy model) and isolated neutrophils from RAP1-/- mice, the expression levels of NLRP3 and keratinocyte chemoattractant (KC) were significantly down-regulated in contrast to those in wild types. The levels of ALT and AST, as well as the neutrophil infiltration, were also decreased by RAP1 deficiency. In our clinical validation, intragraft KC expression was associated with NLRP3 and co-localized with RAP1 in neutrophils. Furthermore, NLRP3 inflammasomes were up-regulated by recombinant KC in the isolated neutrophils and liver of the mouse model. Our data demonstrated that NLRP3 inflammasomes, activated by the RAP1/KC axis, played a critical role in initiating inflammation during the early stage of liver graft injury. Targeting RAP1/KC/NLRP3 inflammasomes may offer a new therapeutic strategy against liver graft injury. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Adult-to-adult living donor liver transplantation: Operative techniques to optimize the recipient's outcome.

Adult-to-adult living donor liver transplantation (LDLT) is widely accepted today with good outcomes and safety reported worldwide for both donor and recipient. Nonetheless, it remained a highly demanding technical and complex surgery if undertaken. The last two decades have seen an increased in adult-to-adult LDLT following our first report of right lobe LDLT in overcoming graft size limitation in adults. In this article, we discussed the operative techniques and challenges of adult right lobe LDLT incorporating the middle hepatic vein, which is practiced in our center for the recipient operation. The various issues and challenges faced by the transplant surgeon in ensuring good recipient outcome are explored and discussed here as well. Hence, it is important to understand that a successful recipient operation is dependent of multifactorial events starting at the preoperative stage of planning, understanding the intraoperative technical challenges and the physiology of flow modulation that goes hand-in-hand with the operation. Therefore, one needs to arm oneself with all the possible knowledge in overcoming these technical challenges and the ability to be flexible and adaptable during LDLT by tailoring the needs of each patient individually.

Lipid profiles of donors and recipients of liver transplant: like father like son.

BACKGROUND/PURPOSE: Dyslipidemia is common in liver transplant recipients. This retrospective study investigates whether donors play a role. METHODS: Prospectively collected data of donors and recipients of deceased-donor liver transplantation (DDLT) and living-donor liver transplantation (LDLT) were reviewed. Total cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein (HDL) and fasting glucose were compared between groups. HDL ≥1.6 mmol/L at 2 years after transplant was considered the marker of a favorable post-transplant lipid profile in recipients. Univariate and multivariate analyses were performed to identify predictive factors for this marker. RESULTS: There were 85 DDLTs and 80 LDLTs. LDLT donors were younger (30 vs. 50 years, p < 0.001) and lighter (58.2 vs. 63.4 kg, p = 0.008) and had a lower body mass index (21.2 vs. 23.7, p < 0.001). The DDLT group had more fatty grafts (p = 0.001) and longer cold (375 vs. 103.5 min, p < 0.001) and warm (50.5 vs. 46 min, p = 0.034) ischemia. LDLT donors had lower fasting glucose (4.85 vs. 7.21 mmol/L, p < 0.001) and triglyceride (0.87 vs. 1.22 mmol/L, p = 0.016) but higher HDL (1.58 vs. 1.39 mmol/L, p = 0.022). LDLT recipients also had higher HDL at 1 year (1.48 vs. 1.28 mmol/L, p = 0.026) and 2 years (1.43 vs. 1.21 mmol/L, p = 0.008). Fourteen (16.5%) DDLT recipients and 27 (33.8%) LDLT recipients had HDL ≥1.6 mmol/L at 2 years. On multivariate analysis, donor HDL ≥1.6 mmol/L (RR 4.311, 95% CI 1.666-11.158, p = 0.003) and recipient body mass index <24 (RR 2.753, 95% CI 1.064-7.127, p = 0.037) were the two independent predictive factors. CONCLUSION: LDLT recipients had better lipid profiles than DDLT recipients. The feature of high HDL level in donors was transferred to recipients.

Resection of T4 hepatocellular carcinomas with adjacent structures, is it justified?

BACKGROUND: T4 hepatocellular carcinoma (HCC) with invasion to adjacent structure(s) may require resection of not only the tumor but also the invaded structure(s). This study aims to assess whether such combined resection for T4 HCC is justifiable. METHODS: Adult patients with T4 HCC were divided into three groups. Group 1: tumors and invaded adjacent structures were resected together if histopathologically confirmed tumor invasion; group 2: same as group 1 but histopathologically confirmed tumor adhesion; group 3: tumor resection only. Group comparisons were made. RESULTS: Totally 144 patients were included in the study. There were 71, 14 and 59 patients in groups 1, 2 and 3, respectively. The groups were comparable in demographics, complication and survival. Ten hospital deaths occurred (5, 0 and 5 in groups 1, 2 and 3, respectively; P=0.533). The 5-year overall survival (hospital mortality excluded) was 17.8% in group 1, 14.3% in group 2, and 28.9% in group 3 (P=0.191). The 5-year disease-free survival was 10.4% in group 1 and 14.5% in group 3 (no data for group 2 yet) (P=0.565). On multivariate analysis, macrovascular invasion and poor differentiation were risk factors for survival whereas combined resection did not impact patients' survival. CONCLUSIONS: Combined resection achieved survival outcomes similar to tumor resection only. Patients with tumor invasion and those with tumor adhesion had comparable survival after combined resection. At centers with the required expertise, combined resection should be attempted to treat T4 HCCs with clinically suspected invasion of adjacent structures.

Comparable Short- and Long-term Outcomes in Living Donor and Deceased Donor Liver Transplantations for Patients With Model for End-stage Liver Disease Scores ≥35 in a Hepatitis-B Endemic Area.

OBJECTIVE: To evaluate if living donor liver transplantation (LDLT) should be offered to patients with Model for End-stage Liver Disease (MELD) scores ≥35. BACKGROUND: No data was available to support LDLT of such patients. METHODS: 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. RESULTS: The LDLT group (n = 54) had younger (33 yrs vs 50 yrs, P < 0.001) and lighter (56 Kg vs 65 Kg, P = 0.004) donors, lighter grafts (627.5 g vs 1252.5 g, P < 0.001), lower graft-weight-to-recipient-standard-liver-volume rates (51.28% vs 99.76%, P < 0.001), shorter cold ischemic time (106.5 min vs 389 min, P < 0.001), and longer operation time (681.5 min vs 534 min, P < 0.001). 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. CONCLUSIONS: 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.

Serum and urinary biomarkers that predict hepatorenal syndrome in patients with advanced cirrhosis.

BACKGROUND: Prediction of hepatorenal syndrome (HRS) remains difficult in advanced cirrhotic patients. AIMS: To evaluate use of serum and urine biomarkers to predict HRS. METHODS: We prospectively recruited Child's B or C cirrhotic patients with normal serum creatinine, and followed them for 12 weeks for the development of HRS. Serum Cystatin C (CysC), serum and urine Neutrophil Gelatinase-Associated Lipocalin (NGAL), serum and urine IL-18, serum N-acetyl-ß-d glucosaminidase (NAG), urine kidney injury molecule-1 (KIM-1) and urine liver-type fatty acid binding protein (LFABP) were measured at recruitment (baseline), and their relationship with subsequent HRS investigated. RESULTS: 43 patients were included. 12 (27.9%) developed HRS at 7.3±5.1 weeks from baseline. Logistic regression analysis showed that baseline urinary NGAL and urinary KIM-1 were significantly associated with the development of HRS (RR 1.007, 95% CI 1.001-1.012, p=0.014; RR 1.973, 95% CI 1.002-3.886, p=0.049). The cut-off values for NGAL and KIM-1 to predict HRS were 18.72ng/mL and 1.499ng/mL respectively (AUCs 0.84, p=0.005; and 0.78, p=0.008). CONCLUSION: Urinary NGAL and KIM-1 could serve as biomarkers to predict HRS in advanced cirrhotic patients.

Lowered Immune Cell Function in Liver Recipients Recovered From Posttransplant Lymphoproliferative Disease Who Developed Graft Tolerance.

UNLABELLED: Tolerance after treatment and recovery from posttransplant lymphoproliferative disease (PTLD) have been described but little is known about the immunology. The objective of this study is to evaluate the immunity of pediatric recipients who recovered from PTLD. MATERIALS AND METHODS: Pediatric recipients who recovered from PTLD after liver transplant and twice the number of recipients who never had PTLD were recruited. Their immune statuses were measured by ImmuKnow (measurement of adenosine 5-triphospate level produced CD4+ T helper cells), and the results were divided into 3 groups, "low" (≤225 ng/mL), "moderate" (226 to 524 ng/mL), and "high" (≥525 ng/mL). The results of both groups were compared and analyzed. RESULTS: Nine PTLD recipients and 20 non-PTLD recipients were recruited. There were no significant differences in terms of sex and age between the 2 groups. The majority of PTLD recipients (88.9%) had "low" immune status responses, and none of them had "high" responses. For non-PTLD recipients, more than half (55%) had "moderate" immune status responses. The median value of adenosine 5-triphospate levels was significantly lower in the PTLD group (119 ng/mL vs 380.5 ng/mL P = 0.014), and their trough immunosuppressant level was also lower (3.8 µg/L vs 7.7 µg/L; P = 0.004). None of the patients in either group had abnormal liver enzymes (aspartate aminotransferase/alanine aminotransferase) to suggest graft rejection. CONCLUSIONS: Patients who recovered from PTLD have a lower CD4 T-cell activity compared with those who have not suffered from PTLD. Under careful monitoring, their immunosuppressant levels can be kept at low levels to prevent recurrence of PTLD.

Short- and long-term impact of reoperation for complications after major hepatectomy for hepatocellular carcinoma.

BACKGROUND: The impact of reoperation for complications after major liver resection for hepatocellular carcinoma was evaluated. METHODS: In this retrospective study covering 25 years, patients with reoperation for complications after major liver resection for hepatocellular carcinoma were compared with patients without reoperation in terms of demographics, tumor characteristics, operative details, postoperative results, oncologic outcomes, and survival. Reasons for reoperation were also investigated. RESULTS: Forty-nine out of 1,092 patients underwent reoperation within a median of 0.2 days (range, 0-6.9 days) after hepatectomy. Patients with and without reoperation had similar baseline characteristics and liver function. Nonetheless, patients with reoperation had a higher indocyanine green retention rate at 15 minutes (12.55% vs 10.5%, P = .015), more operative blood loss (1.4 L vs 1 L, P = .012), a higher blood transfusion rate (44.9% vs 29.2%, P = .029), longer hospital stay (21 days vs 11 days, P < .001), a higher hospital mortality (38.8% vs 3.0%, P < .001), and a higher 90-day mortality (38.8% vs 4.7%, P < .001). Hemorrhage was the most common cause for reoperation (26/49, 53.1%), mainly resulting from coagulopathic bleeding from raw areas (12/26, 46.2%) and bleeding from diaphragmatic veins (6/26, 23.1%). However, reoperation did not affect 5-year overall survival (50.2% vs 48.3%, P = .468). CONCLUSION: Postoperative hemorrhage was associated with a high mortality, signifying the importance of meticulous hemostasis and careful perioperative management. Oncologic outcomes, however, were not affected by reoperation.

The effect of wide resection margin in patients with intrahepatic cholangiocarcinoma: A single-center experience.

INTRODUCTION: Prognosis of intrahepatic cholangiocarcinoma (ICC) remained poor despite the multitude advancement of medical care. Resection margin status is one of the few modifiable factors that a surgeon could possibly manipulate to alter the disease outcome. However, the significance of margin status and margin width is still controversial. This study serves to further elucidate the role of them. METHOD: This is a retrospective cohort from the Queen Mary Hospital, The University of Hong Kong. Consecutive patients diagnosed to have ICC and with surgical resection performed in curative intent were retrieved, while patients with cholangiohepatocellular carcinoma, Klaskin tumor, tumor of extrahepatic bile duct, and uncertain tumor pathology were excluded. RESULTS: From 1991 to 2013, there were 107 patients underwent hepatectomy for ICC. Gender predilection was not observed with 58 males and 49 females, median age of the patients was 61. The median tumor size was 6 cm and most of them (43%) were moderately differentiated adenocarcinoma. Clear resection margin were achieved in 95 patients (88.8%) and the median margin width was 0.5 cm. The hospital length of stay and operative mortality were 11 days and 3%, respectively. The disease-free survival and overall survival were 17.5 and 25.1 months, respectively. Multivariate analysis showed that margin width was an independent factor associated with disease-free survival (P = 0.015, 95% confidence interval [CI] 0.4-0.9). Subgroup analysis in patients with solitary tumor showed that margin width is an independent factor affecting overall survival (P = 0.048; odds ratio: 0.577; 95% CI: 0.334-0.996). Discriminant analysis showed that the overall survival increased from 36 to 185 months when margin width was >0.9 cm (P = 0.025) in patients with solitary tumor. CONCLUSION: Aggressive resection to achieve resection margin of at least 1 cm maximizes chance of cure in patients with early ICC.

Pure Laparoscopic Hepatectomy Versus Open Hepatectomy for Hepatocellular Carcinoma in 110 Patients With Liver Cirrhosis: A Propensity Analysis at a Single Center.

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 gathered from small numbers of patients. METHODS: Data of patients diagnosed with HCC and cirrhosis treated by hepatectomy were reviewed. The outcomes of pure laparoscopic hepatectomy were compared with those of open hepatectomy. Propensity score matching of patients in a ratio of 1:3 was conducted. RESULTS: There were 110 patients and 330 patients in the laparoscopic group and the open group, respectively. The laparoscopic group had less blood loss (150 vs 400 mL; P < 0.001), shorter operation time (185 vs 255 minutes; P < 0.001), and shorter hospital stay (4vs 7 days; P < 0.001). The median overall survival was 136 months in the laparoscopic group and 120 months in the open group. The 1, 3, and 5-year overall survival rates were 98.9%, 89.8%, and 83.7%, respectively, in the laparoscopic group, and 94%, 79.3%, and 67.4%, respectively, in the open group (P = 0.033). The median disease-free survival was 66.37 months in the laparoscopic group and 52.4 months in the open group. The 1, 3, and 5-year disease-free survival rates were 87.7%, 65.8%, and 52.2%, respectively, in the laparoscopic group, and 75.2%, 56.3%, and 47.9%, respectively, in the open group (P = 0.141). CONCLUSIONS: Pure laparoscopic hepatectomy for HCC can be carried out safely with favorable short-term and long-term outcomes even in cirrhotic patients at high-volume liver cancer centers.

Technical note on ALPPS for a patient with advanced hepatocellular carcinoma associated with invasion of the inferior vena cava.

Patients with hepatocellular carcinoma have a very short life expectancy if they receive no surgical intervention. A relatively new surgical technique termed "Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy" (ALPPS) has been employed for inducing rapid hypertrophy of the future liver remnant for patients waiting for hepatectomy. As portal vein embolization may not result in satisfactory hypertrophy before tumor progression occurs, ALPPS can be an alternative for patients with advanced hepatocellular carcinoma. Herein we describe an ALPPS procedure with tumor thrombectomy for a patient who had a small left liver lobe and a large hepatocellular carcinoma involving the whole right liver lobe and the middle hepatic vein and extending into the inferior vena cava. In the first-stage operation, the right portal vein was controlled and divided with a Hemolock. The right hepatic artery was well protected. Hepatic transection was performed with a 1-cm margin from the tumor. The middle hepatic vein trunk was preserved. Ten days afterwards, there was significant hypertrophy of the left lateral section of the liver, and the second-stage operation was conducted. Extended right hepatectomy and tumor thrombectomy were performed under sternotomy and total vascular exclusion. The patient had good recovery and was free of disease 10 months after the operation. ALPPS may be a good treatment option even for patients with advanced disease if carried out at high-volume centers.

Early-phase circulating miRNAs predict tumor recurrence and survival of hepatocellular carcinoma patients after liver transplantation.

Post-liver transplantation tumor recurrence is a major challenge for hepatocellular carcinoma (HCC) recipients. We aimed to identify early-phase circulating microRNAs after liver transplantation for predicting tumor recurrence and survival of HCC recipients. Circulating microRNA profiles at early-phase (2-hour after portal vein reperfusion) after liver transplantation were compared between HCC recipients with (n=4) and without tumor recurrence (n=8) by microarray analyses. Candidate microRNAs were validated in 62 HCC recipients by quantitative RT-PCR. The prognostic values of microRNAs for tumor recurrence and survival were examined. Simulated in vitro ischemia-reperfusion injury models were employed to characterize the possible mechanism of up-regulation of circulating microRNAs. Our results showed that up-regulation of circulating miR-148a, miR-1246 or miR-1290 at early-phase was significantly associated with HCC recurrence after liver transplantation. Among them, miR-148a (p=0.030) and miR-1246 (p=0.009) were significant predictors of HCC recurrence. MiR-1246 was an independent predictor of overall (p=0.023) and disease-free survival (p=0.020) of HCC recipients. The level of early-phase circulating miR-1246 was positively correlated with serum AST and ALT levels in HCC recipients after liver transplantation. The expression of hepatic miR-1246 was positively correlated with TNFα mRNA. In vitro experiments indicated that injury-induced activation and differentiation of macrophages significantly elevated the expression and secretion of miR-1246. In conclusion, early-phase circulating miR-1246 is an indicator of hepatic injury and a novel prognostic biomarker for tumor recurrence and survival of HCC recipients after liver transplantation.

Acute pancreatitis induced by transarterial chemoembolization: a single-center experience of over 1500 cases.

BACKGROUND: Acute pancreatitis is a relatively rare but potentially lethal complication after transarterial chemotherapy. This study aimed to review the complications such as acute pancreatitis after transarterial chemotherapy with or without embolization for hepatocellular carcinoma. METHODS: A total of 1632 patients with hepatocellular carcinoma who had undergone transarterial chemoembolization from January 2000 to February 2014 in a single-center were reviewed retrospectively. We investigated the potential complications of transarterial chemoembolization, such as acute pancreatitis and acute pancreatitis-related complications. RESULTS: Of the 1632 patients with hepatocellular carcinoma who had undergone 5434 transarterial chemoembolizations, 1328 were male and 304 female. The median age of these patients was 61 years. Most (79.6%) of the patients suffered from HBV-related hepatocellular carcinoma. The median tumor size was 5.2 cm. Of the 1632 patients, 145 patients underwent transarterial chemoembolization with doxorubicin eluting bead, making up a total of 538 episodes. The remaining patients underwent transarterial chemoembolization with cisplatin. Seven (0.4%) patients suffered from acute pancreatitis post-chemoembolization. Six patients had chemoembolization with doxorubicin and one had chemoembolization with cisplatin. Patients who received doxorubicin eluting bead had a higher risk of acute pancreatitis [6/145 (4.1%) vs 1/1487 (0.1%), P<0.0001]. Two patients had anatomical arterial variations. Four patients developed acute pancreatitis-related complications including necrotizing pancreatitis (n=3) and pseudocyst formation (n=1). All of the 4 patients resolved after the use of antibiotics and other conservative treatment. Three patients had further transarterial chemoembolization without any complication. CONCLUSIONS: Acute pancreatitis after transarterial chemoembolization could result in serious complications, especially after treatment with doxorubicin eluting bead. Continuation of current treatment with transarterial chemoembolization after acute pancreatitis is feasible providing the initial attack is completely resolved.

Does hepatitis B seroconversion affect survival outcome in patients with hepatitis B related hepatocellular carcinoma?

BACKGROUND: Little is known about whether hepatitis B surface antigen (HBsAg) seroconversion (SC) contributes to any survival benefits for patients with hepatocellular carcinoma (HCC). METHODS: All patients with hepatitis B-related HCC and HBsAg seroclearance between 1989 and 2013 were identified. Case- and control-groups were matched according to their stage of disease and mode of treatment. Baseline demographics, liver function, and overall survivals (OS) were compared between these two groups. RESULTS: Thirty-nine HCC cases with HBsAg SC were identified, and 312 non-seroconversion (NSC) HCC cases were matched. Forty-eight percent of patients had curative resections, 14% were treated with ablation and 38% were for palliation. Age of patients in SC group was older than those in NSC group (P=0.026). Although there was significantly better liver function in SC vs. NSC groups in terms of bilirubin (P=0.027), albumin (P=0.003), AST (P=0.001) and ALT (P<0.001), there was no overall difference in Child-Pugh grade among the two groups. In regarding tumour pathology, SC commonly presented with solitary tumour nodule as compared to multiple nodules in NSC (P=0.027), and was also frequently associated with a normal background liver parenchyma (P<0.001). Although no survival benefit was confirmed in log-rank analysis between SC and NSC, the absolute 5-year survival of SC group was better in resection (72.2% vs. 55.3%), ablation (83.3% vs. 57.4%) and palliation (24.4% vs. 14.4%). CONCLUSIONS: HCC patients with HBsAg SC are associated with a better background liver parenchyma and function, and might contribute to an improved long-term survival.