Display omitted
•Recurrence is frequent within 2 years of surgical resection of hepatocellular carcinoma.•In this large collaboration, we identify readily available, clinical parameters which ...influence early recurrence.•A simple and extensively validated statistical model for estimating early recurrence risk using an online calculator.•This facility will enhance patient counselling and will help in design of adjuvant clinical trials.
Resection is the most widely used potentially curative treatment for patients with early hepatocellular carcinoma (HCC). However, recurrence within 2 years occurs in 30–50% of patients, being the major cause of mortality. Herein, we describe 2 models, both based on widely available clinical data, which permit risk of early recurrence to be assessed before and after resection.
A total of 3,903 patients undergoing surgical resection with curative intent were recruited from 6 different centres. We built 2 models for early recurrence, 1 using preoperative and 1 using pre and post-operative data, which were internally validated in the Hong Kong cohort. The models were then externally validated in European, Chinese and US cohorts. We developed 2 online calculators to permit easy clinical application.
Multivariable analysis identified male gender, large tumour size, multinodular tumour, high albumin-bilirubin (ALBI) grade and high serum alpha-fetoprotein as the key parameters related to early recurrence. Using these variables, a preoperative model (ERASL-pre) gave 3 risk strata for recurrence-free survival (RFS) in the entire cohort – low risk: 2-year RFS 64.8%, intermediate risk: 2-year RFS 42.5% and high risk: 2-year RFS 20.7%. Median survival in each stratum was similar between centres and the discrimination between the 3 strata was enhanced in the post-operative model (ERASL-post) which included ‘microvascular invasion’.
Statistical models that can predict the risk of early HCC recurrence after resection have been developed, extensively validated and shown to be applicable in the international setting. Such models will be valuable in guiding surveillance follow-up and in the design of post-resection adjuvant therapy trials.
The most effective treatment of hepatocellular carcinoma is surgical removal of the tumour but there is often recurrence. In this large international study, we develop a statistical method that allows clinicians to estimate the risk of recurrence in an individual patient. This facility enhances communication with the patient about the likely success of the treatment and will help in designing clinical trials that aim to find drugs that decrease the risk of recurrence.
Background
Approximately one-quarter of patients with Barcelona Clinic Liver Cancer (BCLC) stage 0/A hepatocellular carcinoma (HCC) suffer from tumor relapse within the first year after surgical ...resection. Little data is available for inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI), in predicting the clinical outcome of patients with very early/early stage HCC who underwent curative surgery.
Methods
A retrospective cohort study of 324 patients with BCLC stage 0/A primary HCC undergoing surgical resection was conducted to investigate the prognostic impacts of NLR, PLR, and PNI.
Results
The low-PNI group (<45) had an adverse overall survival (1-year survival rate of 92 vs. 97 %; 5-year survival rate of 57 vs. 82 %;
p
< 0.001) and disease-free survival (1-year survival rate of 69 vs. 85 %; 5-year survival rate of 39 vs. 63 %;
p
< 0.001). It was an independent predictor for disease-specific death, and early and late tumor relapses, with hazard ratios of 2.78 (
p
< 0.001), 1.82 (
p
= 0.011), and 2.55 (
p
= 0.013), respectively. Neither NLR nor PLR had any prognostic significance.
Conclusions
The PNI is a significant prognostic factor for OS and DFS of patients with very early/early stage HCC receiving curative surgery.
Hepatocellular carcinoma (HCC) is the fifth common cancer. The differential expression of microRNAs (miRNAs) has been associated with the prognosis of various cancers. However, limited information is ...available regarding genome-wide miRNA expression profiles in HCC to generate a tumor-specific miRNA signature of prognostic values. In this study, the miRNA profiles in 327 HCC patients, including 327 tumor and 43 adjacent non-tumor tissues, from The Cancer Genome Atlas (TCGA) Liver hepatocellular carcinoma (LIHC) were analyzed. The associations of the differentially expressed miRNAs with patient survival and other clinical characteristics were examined with t-test and Cox proportional regression model. Finally, a tumor-specific miRNA signature was generated and examined with Kaplan-Meier survival, univariate\multivariate Cox regression analyses and KEGG pathway analysis. Results showed that a total of 207 miRNAs were found differentially expressed between tumor and adjacent non-tumor HCC tissues. 78 of them were also discriminatively expressed with gender, race, tumor grade and AJCC tumor stage. Seven miRNAs were significantly associated with survival (P value <0.001). Among the seven significant miRNAs, six (hsa-mir-326, hsa-mir-3677, hsa-mir-511-1, hsa-mir-511-2, hsa-mir-9-1, and hsa-mir-9-2) were negatively associated with overall survival (OS), while the remaining one (hsa-mir-30d) was positively correlated. A tumor-specific 7-miRNAs signature was generated and validated as an independent prognostic predictor. Collectively, we have identified and validated an independent prognostic model based on the expression of seven miRNAs, which can be used to assess patients' survival. Additional work is needed to translate our model into clinical practice.
Portal vein tumor thrombosis(PVTT) is a common phenomenon in hepatocellular carcinoma(HCC). Compared to HCC without PVTT, HCC with PVTT is characterized by an aggressive disease course, worse hepatic ...function, a higher chance of complications related to portal hypertension and poorer tolerance to treatment. Conventionally, HCC with PVTT is grouped together with metastatic HCC during the planning of its management, and most patients are offered palliative treatment with sorafenib or other systemic agents. As a result, most data on the management of HCC with PVTT comes from subgroup analyses or retrospective series. In the past few years, there have been several updates on management of HCC with PVTT. First, it is evident that HCC with PVTT consists of heterogeneous subgroups with different prognoses. Different classifications have been proposed to stage the degree of portal vein invasion/thrombosis, suggesting that different treatment modalities may be individualized to patients with different risks. Second, more studies indicate that more aggressive treatment, including surgical resection or locoregional treatment, may benefit select HCC patients with PVTT. In this review, we aim to discussthe recent conceptual changes and summarize the data on the management of HCC with PVTT.
The popular sense of the word “cure” implies that a patient treated for a specific disease will return to have the same life expectancy as if he/she had never had the disease. In analytic terms, it ...translates into the concept of statistical cure which occurs when a group of patients returns to having similar mortality to a reference population. The aim of this study was to assess the probability of being cured from hepatocellular carcinoma (HCC) by hepatic resection.
Data from 2,523 patients undergoing resection for HCC were used to fit statistical cure models, to compare disease-free survival (DFS) after surgery to the survival expected for patients with chronic hepatitis and/or cirrhosis and the general population, matched by sex, age, race/ethnicity and year of diagnosis.
The probability of resection enabling patients with HCC to achieve the same life expectancy as those with chronic hepatitis and/or cirrhosis was 26.3%. The conditional probability of achieving this result was time-dependent, requiring about 8.9 years to be accomplished with 95% certainty. Considering the general population as a reference, the cure fraction decreased to 17.1%. Uncured patients had a median DFS of 1.5 years. In multivariable analysis, patient's age and the risk of early HCC recurrence (within 2 years) were independent determinants of the chance of cure (p <0.001). The chances of being cured ranged between 36.0% for individuals at low risk of early recurrence to approximately 3.6% for those at high risk.
Estimates of the chance of being cured of HCC by resection showed that cure is achievable, and its likelihood increases with the passing of recurrence-free time. The data presented herein can be used to inform decision making and to provide patients with accurate information.
Data from 2,523 patients who underwent resection for hepatocellular carcinoma were used to estimate the probability that resection would enable treated patients to achieve the same life expectancy as patients with chronic hepatitis and/or cirrhosis, and the general population. Herein, the cure model suggests that in patients with hepatocellular carcinoma, resection can enable patients to achieve the same life expectancy as those with chronic liver disease in 26.3% of cases and as the general population in 17.1% of cases.
Display omitted
•DFS in resected patients with HCC was compared to DFS in those with chronic liver disease w/o HCC, and the general population.•Resected patients with HCC could achieve the same life expectancy as those with chronic liver disease in 26.3% of cases.•Resection enables patients with HCC to achieve the same life expectancy as the general population in 17.1% of cases.•Patients resected in more recent years had higher cure probabilities, probably due to effective antiviral therapies.
Treatment of hepatocellular carcinoma (HCC) is predicated on early diagnosis such that 'curative therapies' can be successfully applied. The term 'curative' is, however, poorly quantitated. We aimed ...to complement our previous work by developing a statistical model to predict cure after ablation and to use this analysis to compare the true curative potential of the various 'curative' therapies.
We accessed data from 1571 HCC patients treated in 5 centres receiving radiofrequency (RFA) or microwave (MWA) ablation and used flexible parametric modelling to determine the curative fraction. The results of this analysis were then combined with our previous estimations to provide a simple calculator applicable to all patients undergoing potentially curative therapies.
The cure fraction was 18.3% rising to about 40% in patients with good liver function and very small tumours.
Cure for HCC treated with ablation occurs in the order of 20% to 30%, similar to that achievable by resection but much inferior to transplantation where the analogous figure is >70%. We provide a 'calculator' that permits clinicians to estimate the chance of cure for any individual patient, based on readily available clinical features.
Background
The development of robotic system may help to relieve the difficulties encountered during laparoscopic hepatectomy. A difficulty scoring system (DSS) was developed to assess the difficulty ...of various laparoscopic liver resection procedures. The aim of this study is to explore if the DSS is applicable in robotic hepatectomy and to compare the outcomes of robotic hepatectomy and laparoscopic hepatectomy among different difficulty levels.
Methods
Clinical data from all consecutive patients who underwent robotic and conventional laparoscopic hepatectomy at the Prince of Wales Hospital, Hong Kong, were prospectively collected and reviewed. The difficulty level of operations was graded using the DSS. Perioperative outcomes of robotic and conventional laparoscopic hepatectomy were compared at each difficulty level.
Results
A total of 107 and 94 patients underwent robotic and laparoscopic hepatectomy during the study period, respectively. Among them, 16 and 2 patients were operated for recurrent pyogenic cholangitis, respectively, and were excluded because no mark for tumour location can be assigned. For robotic hepatectomy, a higher DSS was significantly correlated with higher minor complication rate (
p
= 0.001), more intraoperative blood loss (
p
= 0.002), longer operation time (
p
< 0.001) and longer post-operative hospital stay (
p
< 0.001). The mean DSS scores of robotic and laparoscopic hepatectomy were 4.5 and 3.6, respectively. (
p
= 0.004). For cases with low (DSS 1–3) and intermediate (DSS 4–6) difficulty level, there was no significant difference in operative blood loss, operation time and overall complications rate. Only 2 cases (2.2%) with high difficulty level were operated with laparoscopic approach while 20% of patients operated with robotic approach had DSS > 6.
Conclusions
DSS significantly correlated with surgical outcomes in patient who underwent robotic hepatectomy. Perioperative outcomes following robotic and conventional laparoscopic hepatectomy were similar in cases with low and intermediate difficulty. However, robotic system allowed minimally invasive approach in cases with higher difficulty level.
To date, identification of nonislet-specific transcriptional factors in the regulation of insulin gene expression has been little studied. Here, we report that the expression level of the ...transcription factor YY1 is increased dramatically in both human and mouse pancreatic β-cells after birth. Nevertheless, the physiological role of YY1 during β-cell development and its regulatory mechanism in β-cell function remain largely unknown. After β-cell ablation of Yy1, we observed rapid onset of hyperglycemia, impaired glucose tolerance, and reduced β-cell mass in neonatal and adult mice. These mice also had hypoinsulinemia with normal insulin sensitivity compared with their wild-type littermates, manifesting as a type 1 diabetic phenotype. Mechanistically, genome-wide RNA sequencing has defined dysregulated insulin signaling and defective glucose responsiveness in β-cells devoid of YY1. Integrative analyses coupled with chromatin immunoprecipitation assays targeting YY1, and histone modifications, including H3K4me1, H3K27ac, and H3K27me3, have further identified Ins1 and Ins2 as direct gene targets of YY1. Luciferase reporter assays and loss- and gain-of-function experiments also demonstrated that YY1 binds to the enhancer regions in exon 2 of Ins1 and Ins2, activating insulin transcription and, therefore, proinsulin and insulin production in pancreatic β-cells. YY1 also directly interacts with RNA polymerase II, potentially stabilizing the enhancer-promoter interaction in the multiprotein-DNA complex during transcription initiation. Taken together, our findings suggest a role for YY1 as a transcriptional activator of insulin gene expression, assisting β-cell maturation and function after birth. These analyses may advance our understanding of β-cell biology and provide clinically relevant insights targeting the pathophysiological origins of diabetes.
Application of curative therapy for hepatocellular carcinoma is crucially dependent on underlying liver function. Using the recently described ALBI grade we examined the long-term impact of liver ...dysfunction on survival of early-stage hepatocellular carcinoma (HCC) patients.
This cohort study comprised 2559 HCC patients from different geographic regions, all treated with curative intent. We also examined the relation between indocyanine green (ICG) clearance and ALBI score. Survival was measured from the date of treatment to the date of death or last follow-up.
The ALBI score correlated well with ICG clearance. Among those undergoing surgical resection, patients with ALBI grade-1 (good liver function) survived approximately twice as long as those with ALBI grade-2 (less good liver function), although more than 90% of these patients were classified as Child-Pugh (C-P) grade A. In the cohort receiving ablative therapies, there was a similar difference in survival between ALBI grade-1 and grade-2. Cox regression analysis confirmed that the ALBI score along with age, gender, aetiology and tumour factors (AFP, tumour size/number and vascular invasion) independently influenced survival in HCC patients receiving curative treatments.
The ALBI score represents a simple approach to the assessment of liver function in patients with HCC. After potentially curative therapy, those with ALBI grade-1 survived approximately twice as long as those with ALBI grade-2. These data suggest that ALBI grade-1 patients are appropriately treated with surgical resection whereas ALBI grade-2 patients may, where the option exists, be more suitable for liver transplantation or the less invasive curative ablative therapies.
PDF
