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Screening and clinical evaluation of dominant peptides of centromere protein F antigen for early diagnosis of hepatocellular carcinoma.
Li, S, Li, X, Xu, A, Zhang, B, He, X, Chen, H, Huang, J
Molecular medicine reports. 2018;(3):4720-4728
Abstract
Tumor-associated antigens, such as centromere protein F (CENP‑F), have been recognized as potential serological biomarkers for early diagnosis of hepatocellular carcinoma (HCC); however, the exact regions corresponding to the dominant peptides of CENP‑F antigen remain to be explored. We aimed to screen and evaluate potential dominant peptides of CENP‑F for early diagnosis of HCC. Dominant peptides of CENP‑F were predicted by BioSun version 3.0, and the corresponding recombinant proteins were prepared. Enzyme‑linked immunosorbent assays were conducted for initial screening of dominant peptides, and selected dominant peptides were subjected to further clinical evaluation. Eight dominant peptides of CENP‑F antigens were predicted at amino acids (a.a) 121‑220, 335‑416, 1100‑1265, 1670‑1791, 1759‑2093, 2075‑2210, 2485‑2592, and 2808‑2960. Initial screening of the predicted peptides in samples of 47 HCC cases showed the highest diagnostic value for 121‑220 a.a and 1670‑1791 a.a peptides with area under the curve (AUC) values of 0.795 [95% confidence interval (CI), 0.706‑0.884] and 0.809 (95% CI, 0.721‑0.896), sensitivity of 58.3 and 85.4%, and specificity of 93.9 and 65.3%, respectively. Further evaluation of the two peptides in 405 samples comprised of 153 HCC, 126 liver cirrhosis and 126 healthy controls, presenting an AUC of 0.743 (95% CI, 0.674‑0.812) for 121‑220 a.a peptide in detecting early‑stage HCCs. Specifically, the 121‑220 a.a peptide showed a complementary effect in combination with α‑fetoprotein (AFP) for the detection of early‑stage HCC with increased AUC value of 0.840 (95% CI, 0.781‑0.899), and sensitivity of 81.4% and specificity of 72.2%. In conclusion, our study identified the 121‑220 a.a dominant peptide as the region of CENP‑F antigen with the highest immunogenicity and demonstrated its value in combination with AFP for diagnosis of early-stage HCC.
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Association of tooth loss with liver cancer incidence and chronic liver disease mortality in a rural Chinese population.
Thistle, JE, Yang, B, Petrick, JL, Fan, JH, Qiao, YL, Abnet, CC, Taylor, PR, McGlynn, KA
PloS one. 2018;(9):e0203926
Abstract
BACKGROUND Tooth loss has been reported to be associated with the risk of liver cancer in several prior studies in economically advantaged countries. Whether this relationship is also evident in economically disadvantaged populations is not known. METHODS We analyzed data from the Nutrition Intervention Trials, two randomized placebo-controlled trials of vitamin/mineral supplementation in Linxian, China. Participants who reported having lost permanent teeth were examined to determine the number of teeth remaining. In the 30-year follow-up period, 329 liver cancers were diagnosed and 368 chronic liver disease deaths occurred. Tooth loss was categorized based on loess smoothed age-specific predicted quartiles. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the two outcomes. RESULTS Overall, persons in the highest quartile of age-specific tooth loss had an increased risk of liver cancer (HR = 1.27, 95%CI: 0.96, 1.67) which was not statistically significant. Results varied by sex and body mass index (BMI), however. Women in the highest quartile of age-specific tooth loss had a significantly increased risk (HR = 1.64, 95%CI: 1.04, 2.59), while men did not (HR = 1.08, 95%CI = 0.75, 1.57), and persons with a BMI > 23.0 kg/m2 (HR = 1.71, 95%CI: 1.00, 2.92) had a significantly increased risk, while persons with a BMI <23.0 kg/m2 did not (HR = 1.14, 95%CI: 0.82, 1.5). No relationships with chronic liver disease mortality were observed. CONCLUSIONS In a rural, economically disadvantaged population, persons with the highest levels of age-specific tooth loss had an increased risk of liver cancer. The results, which were stronger among women and persons with greater BMI, suggest that periodontal disease may increase risk of liver cancer.
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The role of vitamin D in hepatic metastases from colorectal cancer.
Shaw, E, Massaro, N, Brockton, NT
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. 2018;(3):259-273
Abstract
Colorectal cancer (CRC) represents a significant health burden worldwide, comprising approximately 10% of annual cancer cases globally. Hepatic metastases are the most common site of CRC metastasis, and are the leading cause of death in CRC patients. There is strong epidemiologic evidence for an inverse association between vitamin D status and risk of CRC; however, the role of vitamin D in the natural history of liver metastases has not yet been investigated. Several researchers have proposed hallmarks of metastases; crucially, metastases can be blocked by interrupting just one rate-limiting step. Vitamin D status has been implicated in each proposed hallmark of metastasis. The aim of this review is to examine the potential role for vitamin D in reducing the development of hepatic metastases from CRC and outline the candidate mechanisms by which vitamin D may mediate these effects. The results of ongoing randomised intervention trials are eagerly awaited to determine whether addressing vitamin D insufficiency in CRC patients could reduce the occurrence of liver metastases, and the consequent morbidity and mortality.
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Which is the best combination of TACE and Sorafenib for advanced hepatocellular carcinoma treatment? A systematic review and network meta-analysis.
Feng, F, Jiang, Q, Jia, H, Sun, H, Chai, Y, Li, X, Rong, G, Zhang, Y, Li, Z
Pharmacological research. 2018;:89-101
Abstract
The aim of this study was to assess the comparative efficacy and safety of combination therapy with transarterial chemoembolization (TACE) and Sorafenib for patients with advanced hepatocellular carcinoma (HCC) through a systematic review and network meta-analysis and identify the best combination of TACE and Sorafenib. We searched databases for publications prior to May 2018. The prespecified efficacy outcomes were the objective response rate, overall survival rate, and time to progression. adverse effects included dermatologic, gastrointestinal, and general disorders. Subgroup analyses, meta-regression, and a network meta-analysis regarding two types of outcomes by different chemotherapy agents in TACE (5-fluorouracil, Adriamycin, Platinum, mitomycin C, hydroxycamptothecin) were included. The study is registered with PROSPERO (CRD42018098541). For efficacy outcomes, subgroups which included 5-fluorouracil and hydroxycamptothecin ranked higher than other chemotherapy agents, while mitomycin C ranked the lowest. For advanced effects, the use of mitomycin C or 5-fluorouracil as the chemotherapy agent ranked higher, while hydroxycamptothecin ranked the lowest. Therefore, we excluded 5-Fu and Mitomycin C in subsequent studies. Additionally, in the evaluation of primary adverse effects by the network meta-analysis, Platinum ranked the highest while hydroxycamptothecin ranked the lowest. Therefore, we excluded Platinum this time. Furthermore, all types of Adriamycin are not same, and some studies included two types of Adriamycin. The network meta-analysis results showed that the TACE (hydroxycamptothecin + pirarubicin) +Sorafenib arm and TACE (hydroxycamptothecin + epirubicin) +Sorafenib arm had significant efficacy differences. In conclusion, for patients with advanced HCC, combination therapy with HCPT plus THP/EPI in TACE and Sorfenib may be used as a first-line treatment.
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Evidence Supporting LI-RADS Major Features for CT- and MR Imaging-based Diagnosis of Hepatocellular Carcinoma: A Systematic Review.
Tang, A, Bashir, MR, Corwin, MT, Cruite, I, Dietrich, CF, Do, RKG, Ehman, EC, Fowler, KJ, Hussain, HK, Jha, RC, et al
Radiology. 2018;(1):29-48
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Abstract
The Liver Imaging Reporting and Data System (LI-RADS) standardizes the interpretation, reporting, and data collection for imaging examinations in patients at risk for hepatocellular carcinoma (HCC). It assigns category codes reflecting relative probability of HCC to imaging-detected liver observations based on major and ancillary imaging features. LI-RADS also includes imaging features suggesting malignancy other than HCC. Supported and endorsed by the American College of Radiology (ACR), the system has been developed by a committee of radiologists, hepatologists, pathologists, surgeons, lexicon experts, and ACR staff, with input from the American Association for the Study of Liver Diseases and the Organ Procurement Transplantation Network/United Network for Organ Sharing. Development of LI-RADS has been based on literature review, expert opinion, rounds of testing and iteration, and feedback from users. This article summarizes and assesses the quality of evidence supporting each LI-RADS major feature for diagnosis of HCC, as well as of the LI-RADS imaging features suggesting malignancy other than HCC. Based on the evidence, recommendations are provided for or against their continued inclusion in LI-RADS. © RSNA, 2017 Online supplemental material is available for this article.
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Metronomic capecitabine as second-line treatment for hepatocellular carcinoma after sorafenib discontinuation.
Trevisani, F, Brandi, G, Garuti, F, Barbera, MA, Tortora, R, Casadei Gardini, A, Granito, A, Tovoli, F, De Lorenzo, S, Inghilesi, AL, et al
Journal of cancer research and clinical oncology. 2018;(2):403-414
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Abstract
PURPOSE Metronomic capecitabine (MC) is a well-tolerated systemic treatment showing promising results in one retrospective study, as second-line therapy after sorafenib failure, in patients with hepatocellular carcinoma (HCC). METHODS 117 patients undergoing MC were compared to 112 patients, eligible for this treatment, but undergoing best supportive care (BSC) after sorafenib discontinuation for toxicity or HCC progression. The two groups were compared for demographic and clinical features. A multivariate regression analysis was conducted to detect independent prognostic factors. To balance confounding factors between the two groups, a propensity score model based on independent prognosticators (performance status, neoplastic thrombosis, causes of sorafenib discontinuation and pre-sorafenib treatment) was performed. RESULTS Patients undergoing MC showed better performance status, lower tumor burden, lower prevalence of portal vein thrombosis, and better cancer stage. Median (95% CI) post-sorafenib survival (PSS) was longer in MC than in BSC patients [9.5 (7.5-11.6) vs 5.0 (4.2-5.7) months (p < 0.001)]. Neoplastic thrombosis, cause of sorafenib discontinuation, pre-sorafenib treatment and MC were independent prognosticators. The benefit of capecitabine was confirmed in patients after matching with propensity score [PSS: 9.9 (6.8-12.9) vs. 5.8 (4.8-6.8) months, (p = 0.001)]. MC lowered the mortality risk by about 40%. MC achieved better results in patients who stopped sorafenib for adverse events than in those who progressed during it [PSS: 17.3 (10.5-24.1) vs. 7.8 (5.2-10.1) months, (p = 0.035)]. Treatment toxicity was low and easily manageable with dose modulation. CONCLUSIONS MC may be an efficient and safe second-line systemic therapy for HCC patients who discontinued sorafenib for toxicity or tumor progression.
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Contrast enhanced ultrasound for focal liver lesions: how accurate is it?
Barr, RG
Abdominal radiology (New York). 2018;(5):1128-1133
Abstract
With the recent FDA approval for characterization of focal liver lesions (FLL) in both pediatric and adult patients using Lumason (sulfur hexafluoride microbubbles), increased use of ultrasound contrast for routine clinical use is expected. This agent has been available for many years in Europe and Asia, and a large body of literature is available regarding the sensitivity and specificity of this agent. In addition, a few studies have directly compared CEUS to CECT and CEMRI for the characterization of focal liver lesions. This paper reviews the literature to provide a background to investigators in the United States as to the accuracy of CEUS in the characterization of FLL. This paper reviews the literature regarding sulfur hexafluoride microbubbles (Lumason in the USA and Sonovue in the rest of the world) since it is the only FDA approved agent in the USA for characterization of FLL. The results of other ultrasound contrast agents which are not FDA approved for abdominal indications (approval for cardiac indications) most likely will have similar results.
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Sustained complete response of advanced hepatocellular carcinoma with metronomic capecitabine: a report of three cases.
Brandi, G, Venturi, M, De Lorenzo, S, Garuti, F, Frega, G, Palloni, A, Garajovà, I, Abbati, F, Saccoccio, G, Golfieri, R, et al
Cancer communications (London, England). 2018;(1):41
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Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is one of the most frequent causes of cancer-related death. Sorafenib, a multitarget angiogenesis inhibitor, is an approved frontline treatment for advanced HCC in Western countries, although a complete response (CR) to treatment is infrequently reported. Capecitabine, an oral fluoropyrimidine, has been shown to be effect in both treatment-naïve patients and those previously treated with sorafenib. To date, however, only one case of sustained CR to metronomic capecitabine has been reported. CASE PRESENTATION We describe three cases of advanced HCC treated with metronomic capecitabine where a CR was obtained. In the first case, capecitabine was administered as first line therapy; in the second case, capecitabine was used after intolerance to sorafenib; while in the third case, capecitabine was administered after sorafenib failure. CONCLUSION Capecitabine is a potentially important treatment option for patients with advanced HCC and may even represent a cure in certain cases.
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Automatic spectral imaging protocol and iterative reconstruction for radiation dose reduction in typical hepatic hemangioma computed tomography with reduced iodine load: a preliminary study.
Li, W, Li, A, Wang, B, Niu, X, Cao, X, Wang, X, Shi, H
The British journal of radiology. 2018;(1087):20170978
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Abstract
OBJECTIVE To evaluate the effect of automatic spectral imaging protocol selection (ASIS) and adaptive statistical iterative reconstruction (ASiR) technique in the reduction of radiation and contrast medium dose in typical hepatic hemangioma (HH) dual energy spectral CT (DEsCT). METHODS 62 patients with suspected HH were randomly divided into two groups equally: Group A, conventional 120-kVp CT with standard iodine load; Group B, DEsCT with ASIS technique and reduced iodine load, two sets of monochromatic spectral images were reconstructed: 69 keV level with 30% ASiR (Group B1) and 52 keV level with 50% ASiR (Group B2). The radiation and total iodine dose, quantitative analysis (standard deviation value, contrast-to-noise and contrast enhancement ratio) and qualitative analysis were evaluated. RESULTS No difference was observed in the standard deviation values, subjective image noise, and the diagnostic acceptability score among the three groups (p > 0.05). Contrast to noise [Group B2 vs A, B1 in arterial phase (AP): 19.51 ± 6.29 vs 15.77 ± 5.93, 11.46 ± 2.84; Group B2 vs A, B1 in portal venous phase (PVP): 9.96 ± 2.18 vs 8.19 ± 3.04, 6.01 ± 1.82], contrast enhancement ratio (Group B2 vs A, B1 in AP: 6.88 ± 2.01 vs 5.47 ± 2.01, 4.15 ± 1.28; Group B2 vs A, B1 in PVP: 5.58 ± 1.02 vs 4.54 ± 1.13, 3.49 ± 0.83), and the lesion conspicuity score (Group B2 vs A, B1 in AP: 3.93 ± 0.26 vs 3.45 ± 0.51, 3.10 ± 0.49; Group B2 vs A, B1 in PVP: 3.90 ± 0.31 vs 3.48 ± 0.57, 3.14 ± 0.44) for Group B2 were higher than those in Group A and B1 (p < 0.05). Compared to Group A, the radiation dose and total iodine dose in Group B were reduced by 30 and 41%, respectively (radiation dose in Group B vs A: 5.53 ± 1.59 vs 7.91± 2.71 mSv; iodine dose in Group B vs A: 18.85 ± 2.88 vs 31.78±3.89 ml; p < 0.05). CONCLUSION DEsCT with ASIS and ASiR technique can reduce the radiation dose without image quality degradation as compared to the conventional 120-kVp CT. The monochromatic spectral images at 52 keV level with 50% ASiR allows the reduction in total iodine dose without deteriorating diagnostic performance. Advances in knowledge: ASIS combined with ASiR technique, by using monochromatic spectral images at 52 keV level, represents a feasible imaging protocol to reduce the radiation and total iodine dose in assessment of typical HH.
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Effectiveness and safety of robotic-assisted versus laparoscopic hepatectomy for liver neoplasms: A meta-analysis of retrospective studies.
Hu, L, Yao, L, Li, X, Jin, P, Yang, K, Guo, T
Asian journal of surgery. 2018;(5):401-416
Abstract
This meta-analysis aimed to investigate the effectiveness and safety of RAH and LLR for liver neoplasms. A systematic search was performed in PubMed, EMbase, the Cochrane Library, Web of science, and China Biology Medicine disc up to July 2016 for studies that provided comparisons between the surgical outcomes of RAH and LLR for liver neoplasms. WMD, OR and 95% CI were calculated and data combined using the random-effect model. The quality of the evidence was assessed using GRADE methods. A total of 17 studies were included in the meta-analysis, in which 487 patients were in the RAH group and 902 patients were in the LLR group. The meta-analysis results indicated: compared to LLR, RAH was associated with more estimated blood loss, longer operative time, and longer time to first nutritional intake (p < 0.05). There was no significant difference in length of hospital stay, conversion rate during operation, R0 resection rate, complications and mortality (p > 0.05). Three studies reported the total cost, and the result showed a higher cost in the RAH group when compared with the LLR group (p < 0.05). This meta-analysis indicated that RAH and LLR display similar effectiveness and safety in hepatectomy. Considering the lack of high quality original studies, prospective clinical trials should be conducted to provide strong evidence for clinical guidelines formation, and the insurance coverage policies should be established to promote the application of robotic surgery in the future.