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Journal Cover Liver Cancer
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   Full-text available via subscription Subscription journal
   ISSN (Print) 2235-1795 - ISSN (Online) 1664-5553
   Published by Karger Homepage  [120 journals]
  • Short-Term Outcomes following Hepatectomy in Elderly Patients with
           Hepatocellular Carcinoma: An Analysis of 10,805 Septuagenarians and 2,381
           Octo- and Nonagenarians in Japan
    • Abstract: Background: As the population is aging, the indication for hepatocellular carcinoma (HCC) resection in patients aged over 80 years will increase. Japan is facing the most aging society worldwide. We examined the safety of hepatectomy in octogenarians and nonagenarians using large-scale data from the Diagnosis Procedure Combination database, a national administrative database in Japan. Method: We conducted a survey to collect data for all inpatients from 2007 and 2012. We identified 27,094 patients who underwent hepatectomy for HCC. Patients' age was divided into the following five categories: ≤59, 60-69, 70-79, 80-84, and ≥85 years (n = 5,099, 8,809, 10,805, 2,011, and 370, respectively). The primary outcomes of hepatectomy were in-hospital death within 90 days and complications. Logistic regression analyses were performed to analyze the impact of age on the outcomes with the adjustment of other individual-level factors. Results: The mortality and morbidity rates were 2.6 and 23.4%, respectively. Compared with patients in their 70s, the mortality rate was significantly lower in patients aged ≤59 years (odds ratio [OR], 0.34; 95% confidence interval [CI], 0.26-0.45; p < 0.01) and in those in their 60s (OR, 0.63; 95% CI, 0.53-0.74; p < 0.01). However, no significant difference was observed in patients aged 80-84 years (OR, 1.03; 95% CI, 0.78-1.385; p = 0.844) and those aged ≥85 years (OR, 0.95; 95% CI, 0.50-1.79; p = 0.870). Based on the multivariate logistic regression analysis, age ≥70 years, male gender, low hospital volume, and surgical procedure were identified as independent predictors of mortality. Conclusions: The operative risk for hepatectomy gradually increases with age until patients are in their 70s, and it appears to reach a plateau among septuagenarian. Indeed, age over 70 years can also be a risk factor for HCC. By considering the aging risk, surgeons can attain good outcome after hepatectomy even in octo- and nonagenarian patients.
      Liver Cancer
       
  • Management of Hepatocellular Carcinoma in Japan as a World-Leading Model
    • Abstract:
      Liver Cancer
       
  • Association between Loss of Skeletal Muscle Mass and Mortality and Tumor
           Recurrence in Hepatocellular Carcinoma: A Systematic Review and
           Meta-Analysis
    • Abstract: Background: Hepatocellular carcinoma (HCC) has multiple prognostic factors, and there is an increase in knowledge about the body composition and physical status of patients with HCC. The present meta-analysis aimed to explore whether loss of skeletal muscle mass is associated with mortality and tumor recurrence in patients with HCC. Method: A systematic search was conducted for published literature using PubMed, Embase, and Scopus. We included cohort or case-control studies investigating patients with HCC. The primary and secondary outcomes were the associations of loss of skeletal muscle mass with overall survival and tumor recurrence, respectively, expressed by a summary hazard ratio (HR) and 95% confidence interval (CI). Result: A total of 13 studies comprising 3,111 patients were included. The summary HRs calculated by either univariate or multivariate analysis both suggested a significant association between sarcopenia and all-cause mortality (crude HR = 2.04, 95% CI: 1.74-2.38; adjusted HR = 1.95, 95% CI: 1.60-2.37). Similarly, loss of skeletal muscle mass was associated with tumor recurrence (crude HR = 1.85, 95% CI: 1.44-2.37; adjusted HR = 1.76, 95% CI: 1.27-2.45). The stratified analysis showed that treatment types and inclusion of body mass index or body weight in the Cox regression model did not modify both clinical outcomes. With an increase in cut-off values of muscle mass on computed tomography images (especially for male patients), there was an insignificant trend of stronger associations between loss of skeletal muscle mass and all-cause mortality. Conclusion: Loss of skeletal muscle mass is associated with increased all-cause mortality and tumor recurrence in patients with HCC. Further prospective studies incorporating measurements of muscle strength and physical function are warranted to see whether inclusion of both parameters better predicts the outcome than use of muscle mass only.
      Liver Cancer
       
  • The Asia Pacific Consensus Statement on Laparoscopic Liver Resection for
           Hepatocellular Carcinoma: A Report from the 7th Asia-Pacific Primary Liver
           Cancer Expert Meeting Held in Hong Kong
    • Abstract: Background: Laparoscopic liver resection has been gaining momentum, and it has become an accepted practice after the two international consensus conferences where experts worked up guidelines to standardize this approach and improve its safety. However, most laparoscopic hepatectomies were performed in patients with liver metastases. The concurrent presence of liver cirrhosis with hepatocellular carcinoma (HCC) poses a great challenge to clinicians trying to establish a routine use of laparoscopic liver resection for HCC. Summary: The first Asia Pacific consensus meeting on laparoscopic liver resection for HCC was held in July 2016 in Hong Kong. A group of expert liver surgeons with experience in both open and laparoscopic hepatectomy for HCC convened to formulate recommendations on the role and perspective of laparoscopic liver resection for primary liver cancer. The recommendations consolidate the most recent evidence pertaining to laparoscopic hepatectomy together with the latest thinking of practicing clinicians involved in laparoscopic hepatectomy, and give detailed guidance on how to deploy the treatment effectively for patients in need. Key Message: The panel of experts gathered evidence and produced recommendations providing guidance on the safe practice of laparoscopic hepatectomy for patients with HCC and cirrhosis. The inherent advantage of the laparoscopic approach may result in less blood loss if the procedure is performed in experienced centers. The laparoscopic approach to minor hepatectomy, particularly left lateral sectionectomy, is a preferred practice for HCC at experienced centers. Laparoscopic major liver resection for HCC remains a technically challenging operation, and it should be carried out in centers of excellence. There is emerging evidence that laparoscopic liver resection produces a better oncological outcome for HCC when compared with radiofrequency ablation, particularly when the lesions are peripherally located. Augmented features in laparoscopic liver resection, including indocyanine green fluorescence, 3D laparoscopy, and robot, will become important tools of surgical treatment in the near future. A combination of all of these features will enhance the experience of the surgeons, which may translate into better surgical outcomes. This is the first consensus workforce on laparoscopic liver resection for HCC, which is a unique condition that occurs in the Asia Pacific region.
      Liver Cancer
       
  • Preoperative Low Muscle Mass and Low Muscle Quality Negatively Impact on
           Pulmonary Function in Patients Undergoing Hepatectomy for Hepatocellular
           Carcinoma
    • Abstract: Background: Sarcopenia is a prognostic factor for mortality in digestive surgery. However, the correlation between preoperative cardiopulmonary function and sarcopenia in patients undergoing hepatectomy for hepatocellular carcinoma (HCC) remains unclear. Methods: The present study investigated the impact of preoperative sarcopenia on cardiopulmonary function in 402 patients who underwent first hepatectomy for HCC between April 2005 and April 2015. The quantity and quality of skeletal muscle were evaluated using psoas muscle index (PMI) and intramuscular adipose tissue content (IMAC), respectively, as determined from preoperative computed tomography imaging. Correlations between preoperative cardiopulmonary function and sarcopenic factors (PMI and IMAC) were evaluated. Results: No significant correlations were found between left ventricular ejection fraction and the two sarcopenic factors. On the other hand, preoperative vital capacity (VC) and forced expiratory volume in 1 s (FEV1) correlated significantly with PMI (p < 0.001 each) in males and with IMAC (p < 0.001 each) in females. Moreover, VC and FEV1 in the preoperative low PMI (p < 0.001 each) and high IMAC (p = 0.002 and p < 0.001, respectively) groups were significantly lower than in the normal group in males. In females, VC and FEV1 were significantly lower in the preoperative high IMAC group than in the normal group (p < 0.001 each). Conclusion: Preoperative low muscle mass in males and low muscle quality in males and females were significantly associated with pulmonary dysfunction.
      Liver Cancer
       
  • Regional Differences in Efficacy, Safety, and Biomarkers for Second-Line
           Axitinib in Patients with Advanced Hepatocellular Carcinoma: From a
           Randomized Phase II Study
    • Abstract: Background: An unmet need exists for treatment of patients with advanced hepatocellular carcinoma (HCC) who progress on or are intolerant to sorafenib. A global randomized phase II trial (ClinicalTrial.gov No. NCT01210495) of axitinib, a vascular endothelial growth factor receptor 1-3 inhibitor, in combination with best supportive care (BSC) did not prolong overall survival (OS) over placebo/BSC, but showed improved progression-free survival in some patients. Subgroup analyses were conducted to identify potential predictive/prognostic factors. Methods: The data from this phase II study were analyzed for the efficacy and safety of axitinib/BSC in patients from Asia versus non-Asia versus Asian subgroups (Japan, Korea, or mainland China/Hong Kong/Taiwan) and predictive/prognostic values of baseline microRNAs and serum soluble proteins, using the Cox proportional hazards model. Results: Of 202 patients, 78 were from non-Asia and 124 from Asia (37 Japanese, 36 Korean, and 51 Chinese). No significant differences in OS were found between axitinib/BSC and placebo/BSC in non-Asians, Asians, or Asian subgroups. However, in an exploratory analysis, axitinib/BSC showed favorable OS in Asians, especially Japanese, when patients intolerant to prior antiangiogenic therapy were excluded from the data set. Axitinib/BSC was well tolerated by non-Asians and Asians alike. The presence of 4 circulating microRNAs, including miR-5684 and miR-1224-5p, or a level lower than or equal to the median protein level of stromal cell-derived factor 1 at baseline was significantly associated with longer OS in axitinib/BSC-treated Asians or non-Asians. Conclusions: Axitinib/BSC did not prolong survival over placebo/BSC in non-Asians, Asians, or Asian subgroups, but favorable OS with axitinib/BSC was observed in a subset of Japanese patients. A patient population that excludes sorafenib-intolerant patients might potentially be more suitable for clinical trials of new agents in advanced HCC. Since these results are very preliminary, further investigation is warranted. The potential predictive/prognostic value of several baseline microRNAs and soluble proteins identified in this study would require validation in prospective studies on a large cohort of patients.
      Liver Cancer
       
  • APPLE News
    • Abstract:
      Liver Cancer 2017;6:380
       
  • The APPLE Association President's Message
    • Abstract:
      Liver Cancer 2017;6:381
       
  • Efficacy and Safety of Systemic Therapies for Advanced Hepatocellular
           Carcinoma: A Network Meta-Analysis of Phase III Trials
    • Abstract: Aim/Background: After the introduction of sorafenib in the treatment of advanced hepatocellular carcinoma (HCC), different studies tried to evaluate whether other systemic therapies can improve survival. To provide a comprehensive indirect treatment comparison of efficacy and safety of novel drugs, a network meta-analysis (NMA) of phase III randomized controlled trials was performed. Methods: After pertinent literature search up to November 1, 2016, 6 studies were eligible for the analysis including 4,812 individual patients with advanced HCC: 2,454 received sorafenib, 577 received brivanib, 530 received sunitinib, 514 received linifanib, 358 received sorafenib + erlotinib and 379 received placebo. Frequentist NMA was used to compare treatments within a single analytical framework. Results: NMA showed that sorafenib alone, regardless of combination with erlotinib, and linifanib provide a significant survival advantage over placebo (p < 0.05) but without any significant difference between each other. Conversely, all regimens significantly ameliorate progression-free survival versus placebo (p < 0.05). The rank order of efficacy was: sorafenib ± erlotinib, linifanib, brivanib, sunitinib, and placebo. Sorafenib ± erlotinib was the regimen with the fewest number of adverse events that required discontinuation of treatment, whereas linifanib and brivanib resulted in the most adverse events. The risk-benefit summary identified one cluster of therapies with a similar balance between efficacy and safety which included sorafenib alone or in combination with erlotinib, having, at the same time, the highest efficacy and safety. Conclusions: Sorafenib remains the best systemic treatment for advanced HCC; linifanib also resulted in survival advantages over placebo but with a lower safety profile.
      Liver Cancer 2017;6:337-348
       
  • Prospective Comparison of Gd-EOB-DTPA-Enhanced MRI with Dynamic CT for
           Detecting Recurrence of HCC after Radiofrequency Ablation
    • Abstract: Background: We prospectively compared the efficacy of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) with that of dynamic multidetector computed tomography (MDCT) for detection of recurrent hypervascular hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA). Methods: Institutional review board approval and written informed consent were obtained for this multicenter study. Ninety-seven HCC patients treated with curative RFA underwent both Gd-EOB-DTPA-enhanced MRI and dynamic MDCT every 3-4 months. HCC diagnosis was made based on the typical enhancement pattern of HCC on MRI and/or CT by on-site consensus reading. Two blinded observers independently assessed image datasets to compare diagnostic accuracy, sensitivity, specificity, and the areas under the receiver operating characteristic curve (AUROC). Results: Recurrence was observed in 48 of 97 patients. Among these, 22 were diagnosed by both Gd-EOB-DTPA-enhanced MRI and MDCT; the remainder were diagnosed by only one of these 2 modalities. Recurrence was diagnosed in more patients by Gd-EOB-DTPA-enhanced MRI than by MDCT (44 vs. 26 patients, p < 0.001). Patient-based analysis revealed that the accuracy, sensitivity, and AUROC of Gd-EOB-DTPA-enhanced MRI were significantly higher than those of MDCT for both observers (p < 0.005). The AUROC of Gd-EOB-DTPA- enhanced MRI and MDCT was 0.95 and 0.76 for observer 1 and 0.90 and 0.74 for observer 2, respectively. The #x03BA; values for MRI and MDCT were 0.83 and 0.70, respectively. Conclusions: Compared with dynamic MDCT, Gd-EOB-DTPA-enhanced MRI had higher diagnostic accuracy and sensitivity for detection of recurrent hypervascular HCC and may be a better tool for following patients after RFA.
      Liver Cancer 2017;6:349-359
       
 
 
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