Monitoring Of Hepatocellular Carcinoma Research Articles

Protein induced by vitamin K absence-II for the surveillance and monitoring of hepatocellular carcinoma in Hong Kong.

Protein induced by vitamin K absence-II for the surveillance and monitoring of hepatocellular carcinoma in Hong Kong.

Serum tRF-33-RZYQHQ9M739P0J as a novel biomarker for auxiliary diagnosis and disease course monitoring of hepatocellular carcinoma

ObjectiveIn most cases, patients with hepatocellular carcinoma (HCC) develop advanced disease when diagnosed. Finding new molecules to combine with traditional biomarkers is crucial for HCC early diagnosis. In cancer development, tRNA-derived small RNAs (tsRNA) play a crucial role. Here, we aimed to identify a novel biomarker among tsRNAs that can facilitate HCC diagnosis and monitor its prognosis. MethodsWe screened candidate tsRNAs in 3 pairs of HCC and adjacent tissues through high-throughput sequencing. tRF-33-RZYQQ9M739P0J was screened in tissues, sera, and cells through quantitative real-time polymerase chain reaction (qRT-PCR) for further analysis. tRF-33-RZYQHQ9M739P0J was characterized using agarose gel electrophoresis, Sanger sequencing, and nuclear and cytoplasmic RNA isolation. Experiments at room temperature and repeated freeze-thaw cycles were conducted to evaluate the detection performance of tRF-33-RZYQHQ9M739P0J. We measured the levels of differential expression of tRF-33-RZYQHQ9M739P0J in sera using qRT-PCR. We applied the chi-square test to evaluate the correlation between tRF-33-RZYQHQ9M739P0J expression levels and clinicopathological features, and assessed its prognostic value by plotting Kaplan-Meier curves. The diagnostic efficacy of tRF-33-RZYQHQ9M739P0J was evaluated using the receiver operating characteristic (ROC) curve. Finally, the downstream genes related to tRF-33-RZYQHQ9M739P0J were explored through bioinformatics prediction. ResultstRF-33-RZYQHQ9M739P0J was highly expressed in HCC tissues and sera, and its expression was correlated with metastasis, TNM stage, BCLC stage, and vein invasion. Expression of tRF-33-RZYQHQ9M739P0J were decreased after surgery in patients with HCC. High serum tRF-33-RZYQHQ9M739P0J levels are associated with low survival rates, and they can predict survival times in patients with HCC according to the Kaplan-Meier analysis. Combining tRF-33-RZYQHQ9M739P0J with serum alpha-fetoprotein and prothrombin induced by vitamin K absence II can improve the diagnostic efficiency of HCC, suggesting its potential as a biomarker for HCC. ConclusiontRF-33-RZYQHQ9M739P0J may not only be a promising non-invasive marker for early diagnosis, but also a predictor of liver cancer progression.

Multiparametric magnetic resonance imaging for hepatocellular carcinoma, part1 : Morphology and dynamic perfusion imaging in primary diagnostics and treatment monitoring

Radiology plays akey role in the diagnosis and monitoring of hepatocellular carcinoma (HCC). Ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) are used to identify HCC lesions. Multiparametric MRI provides detailed insights into the tumor biology through the analysis of morphology, perfusion and diffusion. In this way preoperative decisions can be optimized. The guidelines recommend using contrast-enhanced MRI or ultrasound for the diagnosis of HCC. The preferred method is MRI due to its superiority in the detection of small lesions The treatment response is evaluated using modified response evaluation criteria for solid tumors (RECIST) and the European Association for the Study of the Liver (EASL) criteria. The use of multiparametric MRI in conjunction with the liver imaging reporting and data system (LI-RADS) plays overall acentral role in the precise diagnosis and monitoring of the treatment of HCC.

Monitoring of hepatocellular carcinoma.

Screening for hepatocellular carcinoma in patients at risk is an evidence-based approach; however, adherence to the monitoring protocol recommended by international guidelines is difficult. Hence, there is a need to use the best scr-eening options and refine the selection of patients at risk in the future.

Application of ultrasound diagnosis in cardiac and liver diseases

Ultrasonography is a non-invasive imaging modality widely used to evaluate and diagnose many diseases. The purpose of this article is to provide a more detailed overview of the use of ultrasound in the diagnosis of heart and liver disease. In addition to a basic introduction to heart and liver disease, this article will explore specific applications of ultrasound in specific heart and liver diseases. In terms of heart disease, ultrasound plays an important role in the diagnosis of coronary atherosclerotic heart disease, valvular heart disease and congenital heart disease. Ultrasound can assess the degree of narrowing and blood flow in coronary arteries to help determine a patient's cardiovascular risk. For valvular heart disease, ultrasound can detect and evaluate the function and abnormality of the heart valves, providing information about valve stenosis or regurgitation. For congenital heart disease, ultrasound can reveal structural abnormalities and hemodynamic changes in the heart, helping to determine the type and severity of the lesion. In liver disease, ultrasound plays an important role in the evaluation of pathologies such as cirrhosis and hepatocellular carcinoma. Ultrasound can assess the shape, size, and texture of the liver, help detect and diagnose cirrhosis, and assess liver function and disease progression. In addition, ultrasound is also of great significance for the early diagnosis and monitoring of hepatocellular carcinoma, which can reveal the location, size and blood flow of the tumor. The role of ultrasound in diagnosing and monitoring disease will expand further with advances in technologies such as artificial intelligence and elastography. In conclusion, ultrasound plays a key role in the assessment, diagnosis and monitoring of heart and liver diseases and has many advantages. With the further development of technology and the expansion of application, the position of ultrasound in clinical practice will be further strengthened.

Validation of combined AFP, AFP-L3, and PIVKA II for diagnosis and monitoring of hepatocellular carcinoma in Chinese patients

BackgroundIn this study, we aimed to investigate the performance of GALAD, GALAD-C, and GAAP models in Chinese population in comparison to our newly build statistical model. MethodsIn this study, we built the AALP model based on age, α-fetoprotein (AFP), AFP-L3, and prothrombin induced by vitamin K absence-II (PIVKA II) to differentiate between patients with HCC and patients with CLD. We then compared the serum levels of AFP-L3 and PIVKA II in patients with HCC who were defined as remission or progression and showed the prognostic value of combined biomarkers. ResultsThe AUC value of the AALP model for HCC detection was 0.939 and AALP model exhibited a sensitivity of 81 % and a high specificity of 95 %. AALP model also exhibited good performance in the subgroups of patients with CLD. Furthermore, we demonstrated the consistency between imaging results and serum levels of AFP-L3 and PIVKA II. ConclusionsThe AALP model achieved a good diagnostic performance and a high sensitivity for predicting HCC patients. Our research also showed that AFP-L3 and PIVKA II are complementary to each other but irreplaceable in the clinical detection and monitoring of HCC.

Diagnosis and monitoring of hepatocellular carcinoma in Hepatitis C virus patients using attenuated total reflection Fourier transform infrared spectroscopy

BackgroundCurrent diagnostic methods for assessment of hepatitis C virus related hepatocellular carcinoma and subsequent categorization of hepatocellular carcinoma into non-angio-invasive hepatocellular carcinoma and angio-invasive hepatocellular carcinoma, to establish appropriate treatment strategies, are costly, invasive and requires multiple screening steps. This demands alternative diagnostic approaches that are cost-effective, time-efficient, and minimally invasive, while maintaining their efficacy for screening of hepatitis c virus related hepatocellular carcinoma. In this study, we propose that attenuated total reflection Fourier transform infrared in conjunction with principal component analysis – linear discriminant analysis and support vector machine multivariate algorithms holds a potential as a sensitive tool for the detection of hepatitis C virus-related hepatocellular carcinoma and the subsequent categorization of hepatocellular carcinoma into non-angio-invasive hepatocellular carcinoma and angio-invasive hepatocellular carcinoma. MethodsFreeze-dried sera samples collected from 31 hepatitis c virus related hepatocellular carcinoma patients and 30 healthy individuals, were used to acquire mid-infrared absorbance spectra (3500–900 cm-1) using attenuated total reflection Fourier transform infrared. Chemometric machine learning techniques were utilized to build principal component analysis – linear discriminant analysis and support vector machine discriminant models for the spectral data of hepatocellular carcinoma patients and healthy individuals. Sensitivity, specificity, and external validation on blind samples were calculated. ResultsMajor variations were observed in the two spectral regions i.e., 3500–2800 and 1800–900 cm-1. IR spectral signatures of hepatocellular carcinoma were reliably different from healthy individuals. Principal component analysis – linear discriminant analysis and support vector machine models computed 100% accuracy for diagnosing hepatocellular carcinoma. To classify the non-angio-invasive hepatocellular carcinoma/ angio-invasive hepatocellular carcinoma status, diagnostic accuracy of 86.21% was achieved for principal component analysis – linear discriminant analysis. While the support vector machine showed a training accuracy of 98.28% and a cross-validation accuracy of 82.75%. External validation for support vector machine based classification observed 100% sensitivity and specificity for accurately classifying the freeze-dried sera samples for all categories. ConclusionsWe present the specific spectral signatures for non-angio-invasive hepatocellular carcinoma and angio-invasive hepatocellular carcinoma, which were prominently differentiated from healthy individuals. This study provides an initial insight into the potential of attenuated total reflection Fourier transform infrared to diagnose hepatitis C virus related hepatocellular carcinoma but also to further categorize into non-angio-invasive and angio-invasive hepatocellular carcinoma.

Utility of combining PIVKA-II and AFP in the surveillance and monitoring of hepatocellular carcinoma in the Asia-Pacific region.

Even though the combined use of ultrasound (US) and alpha-fetoprotein (AFP) is recommended for the surveillance of hepatocellular carcinoma (HCC), the utilization of AFP has its challenges, including accuracy dependent on its cut-off levels, degree of liver necroinflammation, and etiology of liver disease. Though various studies have demonstrated the utility of protein induced by vitamin K absence II (PIVKA-II) in surveillance, treatment monitoring, and predicting recurrence, it is still not recommended as a routine biomarker test. A panel of 17 experts from Asia-Pacific, gathered to discuss and reach a consensus on the clinical usefulness and value of PIVKA-II for the surveillance and treatment monitoring of HCC, based on six predetermined statements. The experts agreed that PIVKA-II was valuable in the detection of HCC in AFP-negative patients, and could potentially benefit detection of early HCC in combination with AFP. PIVKA-II is clinically useful for monitoring curative and intra-arterial locoregional treatments, outcomes, and recurrence, and could potentially predict microvascular invasion risk and facilitate patient selection for liver transplant. However, combining PIVKA-II with US and AFP for HCC surveillance, including small HCC, still requires more evidence, whilst its role in detecting AFP-negative HCC will potentially increase as more patients are treated for hepatitis-related HCC. PIVKA-II in combination with AFP and US has a clinical role in the Asia-Pacific region for surveillance. However, implementation of PIVKA-II in the region will have some challenges, such as requiring standardization of cut-off values, its cost-effectiveness and improving awareness among healthcare providers.

Validation of the GALAD model for early diagnosis and monitoring of hepatocellular carcinoma in Chinese multicenter study.

GALAD is an algorithm model estimating the presence of hepatocellular carcinoma (HCC). However, the participants enrolled in the GALAD differ from those of Chinese subjects whose HCCs are mainly hepatitis B virus infection related. Therefore, the cross-sectional as well as longitudinal multicenter study was designed to assess the clinical performances of GALAD in the Chinese population. A case-control study of 602 patients with HCC (34.10% within Barcelona Clinic Liver Cancer 0-A stage) and 923 subjects without HCC from five Chinese medical centres was conducted. Longitudinally the performances of GALAD identifying HCC were assessed using receiver operating characteristic curves analyses. Furthermore, the surveillance performance of GALAD for 204 HCC patients after radical surgery and for the early detection of HCC prospectively in an independent cohort of chronic hepatitis B were analysed, respectively. We found the GALAD identified early stage HCC at an area under the receiver operating characteristic curve (AUC) above 0.85 and outperformed significantly than AFP, PIVKAII, AFP-L3 and BALAD-2 respectively. Meanwhile the GALAD could stratify HCC into two distinct subgroups with high or low risks of overall survival and recurrence. The GALAD could detection HCC 24 (AUC: 0.848) or even 48 (AUC: 0.833) weeks before clinical diagnosis. Our study indicates that the GALAD exhibits outstanding performance in the early diagnosis, prognosis prediction as well as risk monitoring of HCC in our cross-sectional and longitudinal multicenter study of 1561 patients. GALAD should be implanted into clinical practice early so as to improve the clinical efficacy of individual biomarkers in HCC early monitoring and prognosis prediction.

Microbubble-enhanced ultrasound for the antivascular treatment and monitoring of hepatocellular carcinoma.

Background and Objective: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, and its current management relies heavily on locoregional therapy for curative therapy, bridge to transplant, and palliative therapy. Locoregional therapies include ablation and hepatic artery therapies such as embolization and radioembolization. In this study we evaluate the feasibility of using novel antivascular ultrasound (AVUS) as a noninvasive locoregional therapy to reduce perfusion in HCC lesions in a rat model and, monitor the effect with contrast-enhanced ultrasound imaging.Methods: HCC was induced in 36 Wistar rats by the ingestion of 0.01% diethylnitrosamine (DEN) for 12 weeks. Two therapy regimens of AVUS were evaluated. A primary regimen (n = 19) utilized 2-W/cm2, 3-MHz ultrasound (US) for 6 minutes insonation with 0.7 ml of microbubbles administered as an intravenous bolus. An alternate dose at half the primary intensity, sonication time, and contrast concentration was evaluated in 11 rats to assess the efficacy of a reduced dose. A control group (n = 6) received a sham therapy. Tumor perfusion was measured before and after AVUS with nonlinear contrast ultrasound (NLC) and power Doppler (PD). The quantitative perfusion measures included perfusion index (PI), peak enhancement (PE), time to peak (TTP), and perfusion area from NLC and PD scans. Total tumor area perfused during the scan was measured by a postprocessing algorithm called delta projection. Tumor histology was evaluated for signs of tissue injury and for vascular changes using CD31 immunohistochemistry.Results: DEN exposure induced autochthonous hepatocellular carcinoma lesions in all rats. Across all groups prior to therapy, there were no significant differences in the nonlinear contrast observations of peak enhancement and perfusion index. In the control group, there were no significant differences in any of the parameters after sham treatment. After the primary AVUS regimen, there were significant changes in all parameters (p ≤ 0.05) indicating substantial decreases in tumor perfusion. Peak enhancement in nonlinear contrast scans showed a 37.9% ± 10.1% decrease in tumor perfusion. Following reduced-dose AVUS, there were no significant changes in perfusion parameters, although there was a trend for the nonlinear contrast observations of peak enhancement and perfusion index to increase.Conclusion: This study translated low-intensity AVUS therapy into a realistic in vivo model of HCC and evaluated its effects on the tumor vasculature. The primary dose of AVUS tested resulted in significant vascular disruption and a corresponding reduction in tumor perfusion. A reduced dose of AVUS, on the other hand, was ineffective at disrupting perfusion but demonstrated the potential for enhancing tumor blood flow. Theranostic ultrasound, where acoustic energy and microbubbles are used to monitor the tumor neovasculature as well as disrupt the vasculature and treat lesions, could serve as a potent tool for delivering noninvasive, locoregional therapy for hepatocellular carcinoma.

Abstract 1734: Absolute quantification of circulating tumor cell RNA enables high specificity detection of hepatocellular carcinoma

Abstract Background: Although liver cancer has the second-highest mortality rate among cancers internationally, accurate and scalable assays for the early detection and longitudinal monitoring of hepatocellular carcinoma are lacking. Circulating tumor cells are released from invasive cancers into the blood stream, but the difficulty inherent in isolating, identifying, and characterizing these ultra-rare cells has precluded their widespread implementation as a biomarker. By combining a high-throughput microfluidic negative depletion CTC isolation strategy with the absolute quantification of lineage-specific RNAs, we report the highly specific detection of hepatocellular carcinoma CTCs from patient blood draws. Methods: Blood draws from 48 hepatocellular carcinoma patients, 31 chronic liver disease patients, 25 healthy donors, and 44 patients with primary cancers other than hepatocellular carcinoma were processed through the microfluidic device (CTC-iChip). RNA was extracted, whole-transcriptome amplified, and quantified using droplet digital PCR. Transcript counts were used to fit a logistic regression model to integrate distinct transcript levels into a single CTC-score. The technical feasibility of utilizing RNA sequencing for identification of novel CTC transcripts of interest was also demonstrated with a liver cancer cell line spike-in study. Results: 9 of the 16 untreated HCC patients were successfully detected, while only 1/31 chronic liver disease patients were incorrectly classified. HCC patients undergoing treatment showed a significant decrease in their CTC-score; only 9/32 patients actively receiving treatment were positive. The CTC-score was not correlated with the HCC serum biomarker alpha-fetoprotein, and combining these two orthogonal measures led to estimated positive and negative predictive values of 80% and 86%, respectively, in a high-risk cohort. RNAseq analysis of cell line spike-in data revealed the potential of RNA sequencing for uncovering novel transcripts of interest. Conclusion: Coupling microfluidic depletion with droplet digital PCR allows for the highly specific detection of hepatocellular carcinoma. The CTC-score generated from these data tracks with clinical intervention and is orthogonal to the existing biomarker AFP; combining these two assays has the potential to provide superior detection compared to either individual approach. Citation Format: Mark Kalinich, Irun Bhan, Tanya T. Kwan, David T. Miyamoto, Sarah Javaid, Joseph A. LiCausi, John D. Milner, Xin Hong, Lipika Goyal, Srinjoy Sil, Melissa Choz, Ravi Kapur, Alona Muzikansky, Huidan Zhang, David A. Weitz, Lecia V. Sequist, David P. Ryan, Raymond Chung, Andrew X. Zhu, Kurt J. Isselbacher, David T. Ting, Mehmet Toner, Shyamala Maheswaran, Daniel A. Haber. Absolute quantification of circulating tumor cell RNA enables high specificity detection of hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1734. doi:10.1158/1538-7445.AM2017-1734

Cancer-associated circulating large extracellular vesicles in cholangiocarcinoma and hepatocellular carcinoma

Large extracellular vesicles, specifically AnnexinV+ EpCAM+ CD147+ tumour-associated microparticles (taMPs), facilitate the detection of colorectal carcinoma (CRC), non-small cell lung carcinoma (NSCLC) as well as pancreas carcinoma (PaCa). Here we assess the diagnostic value of taMPs for detection and monitoring of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Specifically, the aim of this study was to differentiate liver taMPs from other cancer taMPs, such as CRC and NSCLC. Fluorescence-activated cell scanning (FACS) was applied to detect various taMP populations in patients' sera that were associated with the presence of a tumour (AnnexinV+ EpCAM+ CD147+ taMPs) or could discriminate between cirrhosis (due to HCV or HBV) and liver cancers (AnnexinV+ EpCAM+ ASGPR1+ taMPs). In total 172 patients with liver cancer (HCC or CCA), 54 with cirrhosis and no liver neoplasia, and 202 control subjects were enrolled. The results indicate that AnnexinV+ EpCAM+ CD147+ taMPs were elevated in HCC and CCA. Furthermore, AnnexinV+ EpCAM+ ASGPR1+ CD133+ taMPs allowed the distinction of liver malignancies (HCC or CCA) and cirrhosis from tumour-free individuals and, more importantly, from patients carrying other non-liver cancers. In addition, AnnexinV+ EpCAM+ ASGPR1+ taMPs were increased in liver cancer-bearing patients compared to patients with cirrhosis that lacked any detectable liver malignancy. The smallest sizes of successfully detected cancers were ranging between 11-15mm. AnnexinV+ EpCAM+ ASGPR1+ taMPs decreased at 7days after curative R0 tumour resection suggesting close correlations with tumour presence. ROC values, sensitivity/specificity scores and positive/negative predictive values (>78%) indicated a potent diagnostic accuracy of AnnexinV+ EpCAM+ ASGPR1+ taMPs. These data provide strong evidence that AnnexinV+ EpCAM+ ASGPR1+ taMPs are a novel biomarker of HCC and CCA liquid biopsy that permit a non-invasive assessment of the presence and possible extent of these cancers in patients with advanced liver diseases. Microparticles (MPs) are small vesicles that bleb from the membrane of every cell, including cancer cells, and are released to circulate in the bloodstream. Since their surface composition is similar to the surface of their underlying parental cell, MPs from the bloodstream can be isolated and by screening their surface components, the presence of their parental cells can be identified. This way, it was possible to detect and discriminate between patients bearing liver cancer and chronic liver cirrhosis.

Second cancer risk after diagnostic and monitoring radiation exposure with computed tomography in patients with hepatocellular carcinoma.

238 Background: Contrast-enhanced dynamic computed tomography (CT) is preferred for initial diagnosis and post-treatment monitoring of hepatocellular carcinoma (HCC). The risk of a second cancer with diagnostic and monitoring CT radiation exposure in HCC patients is unclear. Methods: We analyzed cumulative radiation dose (CRD) for diagnostic and monitoring CT with/without transarterial chemoembolization (TACE) in patients with HCC alone (HA group) and HCC patients with a second cancer (SC group), using the big dataset of the National Health Insurance of South Korea. We performed survival analysis, with death treated as a competing risk. Results: A total of 20,073 patients with HCC were enrolled. With a median follow-up of 5.7 years, the SC group comprised 2,005 patients, resulting in a standardized incidence ratio of 1.5 (95% confidence interval [CI], 1.4-1.6) in men and 1.7 (95% CI, 1.6-1.9) in women, as compared with the general population. Use of CT/positron emission tomography (PET) was significantly higher in the SC group (p<0.001). However, the CRD of CT/PET was not significantly different between the SC group and the alive HA group (median effective dose [ED], 93 mSv for the SC group and alive HA group, respectively, p=0.510). After including TACE (n= 9,004 [44.9%], median frequency 2), total CRD was not significantly different between the SC group and the alive HA group. CRD >300 mSv significantly increased the risk of second malignant neoplasms in the subgroup with >7 years of follow-up (YFU) (hazard ratio [HR] 2.01, 95% CI 1.38-2.92, p<0.001). Second cancers in digestive organs and respiratory-intrathoracic organs were significantly increased by CRD in the subgroup with >300 mSv and over 7 YFU (HR 2.41, 95% CI 1.26-4.62; HR 5.69, 95% CI 1.62-20.04, respectively, p<0.01). TACE did not affect the increased risk of second cancers in digestive and respiratory organs in the subgroup >300 mSv and over 7 YFU. Conclusions: The risk of second cancers increased in HCC patients who survived over 7 years with CRD >300 mSv. Consideration of alternative monitoring tests and guidelines for reducing radiation exposure is crucial for long-term HCC survivors.

Magnetic Resonance Imaging in Diagnosis and Monitoring of Hepatocellular Carcinoma in Liver Transplantation: A Comprehensive Review.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. One of the most important risk factors of HCC is cirrhosis. The optimal treatment of HCC is liver transplantation, since it treats both the underlying cirrhosis and the cancer. Patients that have risk factors should be included in surveillance programs since HCC can be cured only during the early stages. Surveillance can be performed by ultrasonography (US), which is an inexpensive, non-invasive, and widely available technique, but it is considered to have a low sensitivity. If a suspicious lesion is detected on US exam, computerized tomography (CT) or magnetic resonance imaging (MRI) can be used to further evaluate this lesion. MRI is considered to be superior to CT because it has greater contrast resolution and tissue characterization. In this article, we present a review of MRI for HCC in liver transplantation (LT) with a focus on characteristic MR features of this tumor and current guidelines.

Evaluation of alpha-fetoprotein as a screening marker for hepatocellular carcinoma in hepatitis prevalent areas

The objective of this study was to establish modified cutoff values of serum alpha-fetoprotein (AFP) according to hepatitis status. While AFP is used as a serum marker in the diagnosis or monitoring of hepatocellular carcinoma (HCC), its use as a screening method to the general population is controversial. We evaluated its screening performance in a hepatitis prevalent East Asian population, and suggest different cutoff values according to the individual’s hepatitis status. We evaluated the performance of AFP as a screening test in 48,123 consecutive Koreans during the period from March, 2012 to August, 2013 who underwent routine health checks at a single institution. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated with fixed cutoff and with modified cutoffs according the individual’s hepatitis status. A total of 24 out of 48,123 subject (0.05%) were newly diagnosed with HCC after screening. Among the 1,874 subject with positive hepatitis B virus surface antigen (HBsAg), 17 (0.91%) developed HCC, compared with two out of 393 (0.51%) individuals with hepatitis C virus antibody (anti-HCV). Five out of 45,855 (0.01%) subject with neither HBsAg nor anti-HCV developed HCC. Compared to the performance of a fixed cutoff, specificity, PPV, and NPV improved without sacrificing sensitivity when applying modified cutoff. In conclusion, our findings suggest that AFP with modified cutoffs according to the individual’s hepatitis status might be a useful screening marker for HCC in hepatitis prevalent areas.

Hepatocellular carcinoma: can circulating tumor cells and radiogenomics deliver personalized care?

The 'omics revolution is facilitating a personalized approach to improving outcome by refining diagnosis, staging, treatment, and monitoring of hepatocellular carcinoma. Furthermore, the promise of being able to target a range of specific tumor drivers at a molecular level offers exciting new therapy prospects for a disease that is notoriously difficult to treat. We provide a unique perspective combining our understanding of the molecular mechanisms of hepatocellular carcinoma development with the potential of circulating tumor cells and radiogenomics to change the drivers of decision-making used in current practice.

Tumor Markers and Hepatocellular Carcinoma

survival rate of patients. Measurement of Alfa-Fetoprotein (AFP) in combination with iconography and liver biopsy are commonly used in the diagnosis of liver cancer as well as HCC. Despite the wide use of AFP in HCC diagnosis and introducing this tumor marker as the gold standard biomarker for HCC detection, the specificity and sensitivity of AFP used in screening for HCC is very controversial. In recent years, along with development of molecular biology and extensive research about ethnology of cancers and simultaneously advances in technology, researchers identified new tumor markers in this disease. In the latest researches various biomarkers including embryonic antigen, protein antigens, cytokines, enzymes and isoenzymes and related genes for effective early diagnosis and monitoring of hepatocellular carcinoma are introduced. In this review, a summary of the data of various studies that discuss new tumor markers involved in hepatocellular carcinoma and classification of these biomarkers was investigated Recently, use of different nanoparticle metal oxides for preventing the spread of microorganisms has reached to the expanding field of nanomaterial research. The objective of this study is to validate combined ultrasound and CuO or MgO noparticle treatments for inactivating Staphylococcus aureus and Pseudomonas aeruginosa. Results showed that nanoparticles of different materials vary in their effectiveness. Ultrasound increased the antibacterial effect of CuO nanoparticles more than the increased antibacterial effect of MgO. These results indicated that CuO or MgO nanoparticles exhibited antibacterial properties that could be additionally enhanced in the presence of ultrasound and, thus, should be further studied for a wide range of medical device anti-infection applications.

6655 The emerging role of the novel serum marker GOLPH2 in detecting and monitoring of hepatocellular carcinoma

6655 The emerging role of the novel serum marker GOLPH2 in detecting and monitoring of hepatocellular carcinoma

Progressive familial intrahepatic cholestasis

Progressive familial intrahepatic cholestasis (PFIC) refers to heterogeneous group of autosomal recessive disorders of childhood that disrupt bile formation and present with cholestasis of hepatocellular origin. The exact prevalence remains unknown, but the estimated incidence varies between 1/50,000 and 1/100,000 births.Three types of PFIC have been identified and related to mutations in hepatocellular transport system genes involved in bile formation. PFIC1 and PFIC2 usually appear in the first months of life, whereas onset of PFIC3 may also occur later in infancy, in childhood or even during young adulthood. Main clinical manifestations include cholestasis, pruritus and jaundice. PFIC patients usually develop fibrosis and end-stage liver disease before adulthood. Serum gamma-glutamyltransferase (GGT) activity is normal in PFIC1 and PFIC2 patients, but is elevated in PFIC3 patients. Both PFIC1 and PFIC2 are caused by impaired bile salt secretion due respectively to defects in ATP8B1 encoding the FIC1 protein, and in ABCB11 encoding the bile salt export pump protein (BSEP). Defects in ABCB4, encoding the multi-drug resistant 3 protein (MDR3), impair biliary phospholipid secretion resulting in PFIC3.Diagnosis is based on clinical manifestations, liver ultrasonography, cholangiography and liver histology, as well as on specific tests for excluding other causes of childhood cholestasis. MDR3 and BSEP liver immunostaining, and analysis of biliary lipid composition should help to select PFIC candidates in whom genotyping could be proposed to confirm the diagnosis. Antenatal diagnosis can be proposed for affected families in which a mutation has been identified. Ursodeoxycholic acid (UDCA) therapy should be initiated in all patients to prevent liver damage. In some PFIC1 or PFIC2 patients, biliary diversion can also relieve pruritus and slow disease progression. However, most PFIC patients are ultimately candidates for liver transplantation. Monitoring of hepatocellular carcinoma, especially in PFIC2 patients, should be offered from the first year of life. Hepatocyte transplantation, gene therapy or specific targeted pharmacotherapy may represent alternative treatments in the future.

Monitoring of hepatocellular carcinoma, following proton radiotherapy, with contrast-enhanced color Doppler ultrasonography

We have reported that proton radiotherapy for hepatocellular carcinoma (HCC) is a safe and effective therapeutic option. However, it is difficult to evaluate its effect in certain cases. Recently, it has been reported that the usage of contrast-enhanced color Doppler ultrasonography (CECDU) can improve diagnostic accuracy, both in terms of the presence of hepatic tumor and in the evaluation of treatment. The aim of this study was to determine the usefulness of CECDU in assessing the therapeutic response of HCC treated with proton radiotherapy. Twenty-two patients treated with the proton radiotherapy were studied. We inspected HCC lesions by CECDU, before and after the irradiation, over time. The magnitude of blood flow in the HCC was quantified on still images by CECDU. The ratio of the number of color pixels against that of the total number of pixels in the tumor area was defined as the tumor blood flow ratio (TBFR). Immediately after the proton treatment, a transient increase of blood flow in the tumor was recognized in more than half of the patients, while the TBFR was unchanged or decreased in the remaining patients. At longer periods after irradiation, the TBFR in all HCCs gradually decreased, and this reduction of TBFR was statistically significant from 9 months after irradiation. These findings are consistent with those obtained previously by computed tomography (CT) as well as magnetic resonance imaging (MRI). We propose CECDU as a useful diagnostic option for the evaluation of HCC treated with proton radiotherapy.