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Since the release of the first global hepatitis elimination targets in 2016, and until the COVID-19 pandemic started in early 2020, many countries and territories were making progress toward hepatitis C virus (HCV) elimination. This study aims to evaluate HCV burden in 2020, and forecast HCV burden by 2030 given current trends.

ABSTRACTIntroductionCholangiocarcinoma (CCA) is a heterogeneous group of aggressive biliary malignancies. While surgery and liver transplantation are the only potentially curative modalities for early-stage disease, limited options are available for most patients with incurable-stage disease. Survival outcomes remain dismal. Recent molecular profiling efforts have led to improved understanding of the genomic landscape of CCA and to the identification of subgroups with distinct diagnostic, prognostic, and therapeutic implications.Areas covered: We provide an updated review and future perspectives on features of cholangiocarcinogenesis that can be translated into therapeutic biomarkers and targets. We highlight the critical studies that have established current systemic chemotherapy and targeted therapeutics, while elaborating on novel targeted and immunotherapeutic approaches in development. Relevant literature and clinical studies were identified by searching PubMed and www.ClinicalTrials.gov.Expert Opinion: While therapies targeting the various molecular subgroups of CCA are rapidly emerging and changing treatment paradigms, their success has been limited by the genetic heterogeneity of CCA and the plasticity of the targets. Novel strategies aiming to combine immunotherapy, chemotherapy, and molecularly targeted therapeutics will be required to offer durable clinical benefit and maximize survival.

Introduction:Serum α-fetoprotein (AFP), Lens culinarisagglutinin-reactive AFP (AFP-L3), and des-γ-carboxy­pro­thrombin (DCP) are useful biomarkers of hepatocellular carcinoma (HCC). However, associations among molecular characteristics and serum biomarkers are unclear. We analyzed RNA expression and DNA variant data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) to examine their associations with serum biomarker levels and clinical data. Methods:From 371 TCGA-LIHC patients, we selected 91 seen at 3 institutions in Korea and the USA and measured AFP, AFP-L3, and DCP from preoperatively obtained serum. We conducted an integrative clinical and molecular analysis, focusing on biomarkers, and validated the findings with the remaining 280 patients in the TCGA-LIHC cohort. Results:Patients were categorized into 4 subgroups: elevated AFP or AFP-L3 alone (↑AFP&L3), elevated DCP alone (↑DCP), elevation of all 3 biomarkers (elevated levels of all 3 biomarkers [↑All]), and reference range values for all biomarkers (RR). CTNNB1variants were frequently observed in ↑DCP patients (53.8%) and RR patients (38.5%), but ↑DCP patients with a CTNNB1variant had worse survival than RR patients. TP53sequence variants were associated with ↑AFP (30.8%) and ↑DCP (30.8%). The Wnt-β-catenin signaling pathway was activated in the ↑AFP&L3, whereas liver-related Wnt signaling was activated in the RR. TGF-β and VEGF signaling were activated in ↑AFP&L3, whereas dysregulated bile acid and fatty acid metabolism were dominant in ↑DCP. We validated these findings by showing similar results between the test cohort and the remainder of the TCGA-LIHC cohort. Conclusions:Serum AFP, AFP-L3, and DCP levels can help predict variants in the genetic profile of HCC, especially for TP53and CTNNB1. These findings may facilitate development of an evidence-based approach to treatment.

Introduction:Small studies from outside of the USA suggest excellent outcomes after surgical resection for hepatocellular carcinoma (HCC) with vascular invasion. The study aims to (1) compare overall survival after surgical resection and systemic therapy among patients with HCC and vascular invasion and (2) determine factors associated with receipt of surgical resection in a US population. Methods:HCC patients with AJCC clinical TNM stage 7th T3BN0M0 diagnosed between 2010 and 2017 from the National Cancer Database were analyzed. Cox and logistic regression analyses identified factors associated with overall survival and receipt of surgical resection. Results:Of 11,259 patients with T3BN0M0 HCC, 325 (2.9%) and 4,268 (37.9%) received surgical resection and systemic therapy, respectively. In multivariable analysis, surgical resection was associated with improved survival compared to systemic therapy (adjusted hazard ratio: 0.496, 95% confidence interval: 0.426–0.578) with a median survival of 21.4 and 8.1 months, respectively. Superiority of surgical resection was observed in noncirrhotic and cirrhotic subgroups and propensity score matching and inverse probability of treatment weighting adjusted analysis. Asians were more likely to receive surgical resection, whereas Charlson comorbidity ≥3, elevated alpha-fetoprotein, smaller tumor size, care in a community cancer program, and the South or West region were associated with a lower likelihood of surgical resection. Conclusion:HCC patients with vascular invasion may benefit from surgical resection compared to systemic therapies. Demographic and clinical features of HCC patients and region and type of treating facility were associated with surgical resection versus systemic treatment.

Cholangiocarcinoma (CCA) includes a cluster of highly heterogeneous biliary malignant tumours that can arise at any point of the biliary tree. Their incidence is increasing globally, currently accounting for ~15% of all primary liver cancers and ~3% of gastrointestinal malignancies. The silent presentation of these tumours combined with their highly aggressive nature and refractoriness to chemotherapy contribute to their alarming mortality, representing ~2% of all cancer-related deaths worldwide yearly. The current diagnosis of CCA by non-invasive approaches is not accurate enough, and histological confirmation is necessary. Furthermore, the high heterogeneity of CCAs at the genomic, epigenetic and molecular levels severely compromises the efficacy of the available therapies. In the past decade, increasing efforts have been made to understand the complexity of these tumours and to develop new diagnostic tools and therapies that might help to improve patient outcomes. In this expert Consensus Statement, which is endorsed by the European Network for the Study of Cholangiocarcinoma, we aim to summarize and critically discuss the latest advances in CCA, mostly focusing on classification, cells of origin, genetic and epigenetic abnormalities, molecular alterations, biomarker discovery and treatments. Furthermore, the horizon of CCA for the next decade from 2020 onwards is highlighted.

Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDHmutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDHmutant subtype. More broadly, we found that IDHmutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance.

Single-dose neoadjuvant inhibition of phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR)/protein kinase B (AKT) signaling in combination with thermal ablation may represent a candidate therapeutic strategy to prevent local recurrence of hepatocellular carcinoma after ablation.

PURPOSE:We investigated the antitumor effect of the casein kinase II (CK2) inhibitor CX-4945 on cholangiocarcinoma (CCA). METHODS:We assessed the effect of CX-4945 alone and/or in combination with gemcitabine and cisplatin on cell viability, colony formation, and apoptosis of CCA cell lines and on in vivogrowth of HuCCT1 xenografts. RESULTS:CX-4945 dose-dependently decreased viability of HuCCT1, EGI-1, and Liv27 and decreased phospho-AKT/total AKT and phospho-PTEN/total PTEN ratios. CX-4945 significantly increased caspase 3/7 activity in a dose- and time-dependent manner. CX-4945 significantly enhanced the effect of gemcitabine or cisplatin on HuCCT1, EGI-1, and Liv27 cells and inhibited the phosphorylation of DNA repairing enzymes XRCC1 and MDC1. Further, CX-4945 alone significantly inhibited growth of HuCCT1 mouse xenograft tumors. Combining CX-4945 with gemcitabine and cisplatin was more potent than CX-4945 alone or gemcitabine/cisplatin. The effect of CX-4945 on cell proliferation, apoptosis, the PI3K/AKT pathway, and DNA repair was confirmed in the mouse xenografts. CONCLUSION:CX-4945 has an antiproliferative effect on CCA and enhances the effect of gemcitabine and cisplatin through its inhibitory effect on the PI3K/AKT pathway and DNA repair.

Hepatitis C virus (HCV) treatment has changed dramatically in the last few years. Our observations suggest that a minority of HCV infected Somalis are treated. In this study, we aimed to evaluate for treatment and health outcome disparities between Somali and non-Somali patients during the direct acting antiviral (DAA) era.

Moderate heat stress and hepatic laser thermal ablation induce a local protumorigenic microenvironment that stimulates hepatocellular carcinoma growth and may in part be mediated by growth factor–dependent phosphoinositide 3-kinase, mammalian target of rapamycin, and protein kinase B signaling.

The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate viral hepatitis by 2030. Although no virological cure exists for hepatitis B virus (HBV) infection, existing therapies to control viral replication and prophylaxis to minimise mother-to-child transmission make elimination of HBV feasible. We aimed to estimate the national, regional, and global prevalence of HBsAg in the general population and in the population aged 5 years in 2016, as well as coverage of prophylaxis, diagnosis, and treatment.

Fibrolamellar carcinoma has a distinctive morphology and immunophenotype, including cytokeratin 7 and CD68 co-expression. Despite the distinct findings, accurate diagnosis of fibrolamellar carcinoma continues to be a challenge. Recently, fibrolamellar carcinomas were found to harbor a characteristic somatic gene fusion, DNAJB1–PRKACA. A break-apart fluorescence in situ hybridization (FISH) assay was designed to detect this fusion event and to examine its diagnostic performance in a large, multicenter, multinational study. Cases initially classified as fibrolamellar carcinoma based on histological features were reviewed from 124 patients. Upon central review, 104 of the 124 cases were classified histologically as typical of fibrolamellar carcinoma, 12 cases as ‘possible fibrolamellar carcinoma’ and 8 cases as ‘unlikely to be fibrolamellar carcinoma’. PRKACA FISH was positive for rearrangement in 102 of 103 (99%) typical fibrolamellar carcinomas, 9 of 12 ‘possible fibrolamellar carcinomas’ and 0 of 8 cases ‘unlikely to be fibrolamellar carcinomas’. Within the morphologically typical group of fibrolamellar carcinomas, two tumors with unusual FISH patterns were also identified. Both cases had the fusion gene DNAJB1–PRKACA, but one also had amplification of the fusion gene and one had heterozygous deletion of the normal PRKACA locus. In addition, 88 conventional hepatocellular carcinomas were evaluated with PRKACA FISH and all were negative. These findings demonstrate that FISH for the PRKACA rearrangement is a clinically useful tool to confirm the diagnosis of fibrolamellar carcinoma, with high sensitivity and specificity. A diagnosis of fibrolamellar carcinoma is more accurate when based on morphology plus confirmatory testing than when based on morphology alone.

ABSTRACTWhile intratumor heterogeneity contributes to disease progression, metastasis, and resistance to chemotherapy, it also provides a route to understanding the evolution and drivers of disease. Defects in epigenetic landscapes are intimately linked to pathogenesis of a variety of human diseases, with epigenetic deregulation promoting tumorigenesis. Understanding epigenetic heterogeneity is crucial in hepatocellular carcinoma (HCC), where epigenetic alterations are frequent, early, and pathogenic events. We determined genome-wide DNA methylation and copy number variation leveraging the Infinium 450K in a series of regenerative nodules from within single patient livers. Bioinformatics strategies were used to ascertain within-patient heterogeneity, link epigenetic changes to clinical features, and determine their relevance to disease pathogenesis. Our data demonstrate that DNA methylation and copy number alterations evolve during the pre-neoplastic phase of HCC and independently segregate regenerative nodules into distinct clusters. Regenerative nodules with a high frequency of epigenetic changes have significantly lower copy number variation, suggesting that individual nodules have differential enrichment of epigenetic and genetic components, with both contributing to disease progression. Regenerative nodules were scored based on ‘epigenetic progression’ with higher scores associated with increased proliferation measured by Ki67 staining. Early events observed in epigenetically ‘aggressive’ nodules are enriched for genes involved in liver cancer. Our study demonstrates that marked epigenetic and genetic heterogeneity exists in early pre-neoplastic liver tissue within individual patients, emphasizing the potential contributions of each mechanism to driving liver disease progression, and it unveils strategies for identifying epigenetic drivers of hepatocellular carcinoma.

The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate hepatitis C virus (HCV) infection by 2030, which can become a reality with the recent launch of direct acting antiviral therapies. Reliable disease burden estimates are required for national strategies. This analysis estimates the global prevalence of viraemic HCV at the end of 2015, an update of—and expansion on—the 2014 analysis, which reported 80 million (95% CI 64–103) viraemic infections in 2013.

Objective:Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related mortality worldwide, and a rising cause of cancer mortality in the U.S. Liver cirrhosis is the major risk factor for HCC. Surveillance of persons with cirrhosis facilitates early detection and improves outcomes. We assessed the surveillance rate for HCC within a major academic health system and identified factors influencing surveillance. Patients and Methods:We examined the surveillance rate for HCC using liver ultrasound, CT, or MRI, and factors influencing surveillance in a cohort of 369 Minnesota residents with cirrhosis seen at the Mayo Clinic between 2007 and 2009. Results:Ninety-three percent of cirrhosis patients received at least one surveillance study, but only 14% received the recommended uninterrupted semiannual surveillance. Thirty percent received ≥75% of recommended surveillance, and 59% received ≥50% of recommended surveillance. Factors increasing surveillance included gastroenterology or hepatology specialist visits (p < 0.0001), advanced liver disease as assessed by hepatic encephalopathy (p = 0.0008), and comorbid illness as assessed by diabetes mellitus (p = 0.02). Age, sex, race, residence, cirrhosis etiology, or number of primary care visits did not significantly affect the rate of surveillance. Conclusions:While the rate of surveillance in a major academic health system was higher than reported in other studies, surveillance was heavily dependent on visits to a subspecialist. This suggests a major and urgent national need to improve identification of individuals at risk for HCC in the primary care setting and the initiation and maintenance of surveillance by primary care practitioners.

Hepatocellular carcinoma is a leading cause of cancer-related death in Africa, but there is still no comprehensive description of the current status of its epidemiology in Africa. We therefore initiated an African hepatocellular carcinoma consortium aiming to describe the clinical presentation, management, and outcomes of patients with hepatocellular carcinoma in Africa.

ABSTRACTHigh-fat diet consumption and sedentary lifestyle elevates risk for obesity, non-alcoholic fatty liver disease, and cancer. Exercise training conveys health benefits in populations with or without these chronic conditions. Diet and exercise regulate gene expression by mediating epigenetic mechanisms in many tissues; however, such effects are poorly documented in the liver, a central metabolic organ. To dissect the consequences of diet and exercise on the liver epigenome, we measured DNA methylation, using reduced representation bisulfite sequencing, and transcription, using RNA-seq, in mice maintained on a fast food diet with sedentary lifestyle or exercise, compared with control diet with and without exercise. Our analyses reveal that genome-wide differential DNA methylation and expression of gene clusters are induced by diet and/or exercise. A combination of fast food and exercise triggers extensive gene alterations, with enrichment of carbohydrate/lipid metabolic pathways and muscle developmental processes. Through evaluation of putative protective effects of exercise on diet-induced DNA methylation, we show that hypermethylation is effectively prevented, especially at promoters and enhancers, whereas hypomethylation is only partially attenuated. We assessed diet-induced DNA methylation changes associated with liver cancer-related epigenetic modifications and identified significant increases at liver-specific enhancers in fast food groups, suggesting partial loss of liver cell identity. Hypermethylation at a subset of gene promoters was associated with inhibition of tissue development and promotion of carcinogenic processes. Our study demonstrates extensive reprogramming of the epigenome by diet and exercise, emphasizing the functional relevance of epigenetic mechanisms as an interface between lifestyle modifications and phenotypic alterations.

The 2016 World Health Assembly endorsed the elimination of hepatitis B virus (HBV) infection as a public health threat by 2030; existing therapies and prophylaxis measures make such elimination feasible, even in the absence of a virological cure. We aimed to estimate the national, regional, and global prevalence of HBV in the general population and among children aged 5 years and younger, as well as the rates of diagnosis, treatment, prophylaxis, and the future burden globally.

OBJECTIVES:As most hepatocellular carcinoma (HCC) patients have cirrhosis, the association between diabetes and HCC may be confounded by the fact that diabetes is common in patients with cirrhosis. The aim of this study is to investigate whether diabetes increases the risk of HCC in patients with cirrhosis and whether the etiology of liver disease modifies the association between diabetes and HCC.METHODS:All liver cirrhosis patients who had repeated radiographic evaluation of the liver (that is, ultrasound, computed tomography, or magnetic resonance image) at Mayo Clinic Rochester between January 2006 and December 2011 were included. The Cox proportional hazard regression analysis was used to investigate the effect of diabetes on the risk of HCC.RESULTS:A total of 739 patients met the eligibility criteria, of whom 253 (34%) had diabetes. After a median follow-up of 38 months, 69 (9%) patients developed HCC. In patients without hepatitis C virus (HCV) infection, diabetes was significantly associated with the risk of developing HCC (hazard ratio (HR)=2.1, 95% confidence interval (CI)=1.1–4.1), whereas in patients with HCV, there was no association (HR=0.8, 95% CI=0.4–1.8). When adjusted for covariates, the interaction between HCV and diabetes remained significant (HR for non-HCV=1.9, 95% CI=0.9–3.7; HR for HCV=0.6, 95% CI=0.2–1.3). Lack of association between diabetes and HCC was externally validated in 410 patients with HCV cirrhosis enrolled in the HALT-C trial.CONCLUSIONS:Diabetes increases the risk of HCC in patients with non-HCV cirrhosis. In HCV cirrhosis patients who already have very high risk, diabetes may not increase the risk any further.

To determine whether daily measurement of Model for End-Stage Liver Disease (MELD) score adds prognostic value to the initial MELD score in predicting mortality among patients with cirrhosis admitted to the intensive care unit (ICU).

An analytic approximation for the critical clearing time (CCT) metric is derived from direct methods for power system stability. The formula has been designed to incorporate as many features of transient stability analysis as possible such as different fault locations and different post-fault network states. The purpose of this metric is to analyze trends in stability (in terms of CCT) of power systems under the variation of a system parameter. The performance of this metric to measure stability trends is demonstrated on an aggregated power network, the so-called two machine infinite bus network, by varying load parameters in the full bus admittance matrix using numerical continuation. The metric is compared to two other expressions for the CCT which incorporate additional nonlinearities present in the model.

Fibrolamellar carcinoma is a distinct subtype of hepatocellular carcinoma that predominantly affects young patients without underlying cirrhosis. A recurrent DNAJB1-PRKACA fusion has recently been reported in fibrolamellar carcinomas. To determine the specificity of this fusion and to develop routinely available clinical methods of detection, we developed an RT-PCR assay for paraffin-embedded tissues and a FISH probe for detection of the rearrangements of the PRKACA locus. We also developed an RNA in situ hybridization assay to assess expression levels of the total chimeric transcript and wild-type transcripts. A total of 106 primary liver tumors were studied by RT-PCR, including 26 fibrolamellar carcinomas (4 of which were metastases to the abdominal wall or lymph nodes), 25 conventional hepatocellular carcinomas, 25 cholangiocarcinomas, 25 hepatic adenomas, and 5 hepatoblastomas. RT-PCR was successful in 92% of tested fibrolamellar carcinoma cases (24/26) and the DNAJB1-PRKACA fusion transcript was found in all fibrolamellar carcinomas but not in other tumor types. FISH was tested in 19 fibrolamellar carcinomas and in 6 scirrhous hepatocellular carcinomas, which can closely mimic fibrolamellar carcinoma. Rearrangements of the PRKACA locus was seen in all 19 fibrolamellar carcinoma specimens, but in none of the scirrhous hepatocellular carcinomas. Finally, a RNA in situ hybridization strategy was positive in 7/7 successfully hybridized cases, and showed mRNA over-expression in all of the fibrolamellar carcinomas. In addition, the stromal cells embedded in the characteristic intratumoral fibrosis of fibrolamellar carcinomas and the background liver tissues were negative for the DNAJB1-PRKACA fusion by all tested methods. In conclusion, detection of DNAJB1-PRKACA is a very sensitive and specific finding in support of the diagnosis of fibrolamellar carcinoma.

Fibrolamellar carcinoma is a distinct subtype of hepatocellular carcinoma that predominantly affects young patients without underlying cirrhosis. A recurrent DNAJB1-PRKACAfusion has recently been reported in fibrolamellar carcinomas. To determine the specificity of this fusion and to develop routinely available clinical methods of detection, we developed an RT-PCR assay for paraffin-embedded tissues and a FISH probe for detection of the rearrangements of the PRKACAlocus. We also developed an RNA in situhybridization assay to assess expression levels of the total chimeric transcript and wild-type transcripts. A total of 106 primary liver tumors were studied by RT-PCR, including 26 fibrolamellar carcinomas (4 of which were metastases to the abdominal wall or lymph nodes), 25 conventional hepatocellular carcinomas, 25 cholangiocarcinomas, 25 hepatic adenomas, and 5 hepatoblastomas. RT-PCR was successful in 92% of tested fibrolamellar carcinoma cases (24/26) and the DNAJB1-PRKACAfusion transcript was found in all fibrolamellar carcinomas but not in other tumor types. FISH was tested in 19 fibrolamellar carcinomas and in 6 scirrhous hepatocellular carcinomas, which can closely mimic fibrolamellar carcinoma. Rearrangements of the PRKACAlocus was seen in all 19 fibrolamellar carcinoma specimens, but in none of the scirrhous hepatocellular carcinomas. Finally, a RNA in situhybridization strategy was positive in 7/7 successfully hybridized cases, and showed mRNA over-expression in all of the fibrolamellar carcinomas. In addition, the stromal cells embedded in the characteristic intratumoral fibrosis of fibrolamellar carcinomas and the background liver tissues were negative for the DNAJB1-PRKACAfusion by all tested methods. In conclusion, detection of DNAJB1-PRKACAis a very sensitive and specific finding in support of the diagnosis of fibrolamellar carcinoma.

We present a new and computationally efficient method for characterizing very low-mass companions using low-resolution (R? 30), near-infrared (YJH) spectra from high-contrast imaging campaigns with integral field spectrograph (IFS) units. We conduct a detailed quantitative comparison of the efficacy of this method through tests on simulated data comparable in spectral coverage and resolution to the currently operating direct-imaging systems around the world. In particular, we simulate Project 1640 data as an example of the use, accuracy, and precision of this technique. We present results from comparing simulated spectra of M, L, and T dwarfs with a large and finely sampled grid of synthetic spectra using Markov-chain Monte Carlo techniques. We determine the precision and accuracy of effective temperature and surface gravity inferred from fits to PHOENIXdustyand cond, which we find reproduce the low-resolution spectra of all objects within the adopted flux uncertainties. Uncertainties in effective temperature decrease from ± 100-500 K for M dwarfs to as small as ± 30 K for some L and T spectral types. Surface gravity is constrained to within 0.2-0.4 dex for mid-L through T dwarfs, but uncertainties are as large as 1.0 dex or more for M dwarfs. Results for effective temperature from low-resolution YJHspectra generally match predictions from published spectral type-temperature relationships except for L-T transition objects and young objects. Single-band spectra (i.e., narrower wavelength coverage) result in larger uncertainties and often discrepant results, suggesting that high-contrast IFS observing campaigns can compensate for low spectral resolution by expanding the wavelength coverage for reliable characterization of detected companions. We find that S/N ? 10 is sufficient to characterize temperature and gravity as well as possible given the model grid. Most relevant for direct-imaging campaigns targeting young primary stars is our finding that low-resolution near-infrared spectra of known young objects, compared to field objects of the same spectral type, result in similar best-fit surface gravities but lower effective temperatures, highlighting the need for better observational and theoretical understanding of the entangled effects of temperature, gravity, and dust on near-infrared spectra in cool low-gravity atmospheres.

Classification and staging of hepatocellular carcinoma in a way that allows optimal treatment selection is challenging. This article summarizes some of the classification and staging schemes and discusses the conceptual framework that guides optimal treatment selection for each patient. The article does not exhaustively discuss each staging system proposed in the last three decades, but rather reviews the most commonly used staging systems, evaluates the rationale behind some of the newer staging systems, and compares them focusing on their use in clinical decision-making, notably choice of therapy.

Aims were to assess the prevalence of Papanicolaou (Pap) abnormalities found with cervical cancer screening in Agogo and Nkawie, communities in the Ashanti region of Ghana, and compare the correlation between Pap readings performed at the Komfo Anokye Teaching Hospital in Kumasi, Ghana, and at the Mayo Clinic cytology laboratory in Rochester, MN. Demographic data was collected and Pap tests were performed on women recruited for screening in the communities of Agogo (n=119) and Nkawie (n=255). The Pap tests were assessed by pathology laboratory staff at Komfo Anokye Teaching Hospital and Mayo Clinic. There was a significant difference in prevalence of abnormal cytology between the sites with a rate of 12.6 in Agogo and 3.5 in Nkawie (P=0.016). Demographic differences were noted in education level (P<0.001), occupation (P<0.001), religion (P=0.002), and marital status (P<0.001). The Cohen correlation coefficient between the two pathology departments interpreting samples was 0.185, which indicates a significant degree of discordance (P<0.001). Currently Ghana does not have a national cervical cancer screening program. Identifying higher risk communities and patients as a priority for screening may be useful with limited resources. Accurate identification of Pap abnormalities is necessary to implement an effective screening program.

Hepatocellular carcinoma (HCC) is the third most common cause of death from cancer. The incidence and mortality of HCC are increasing in most Western countries as a result of an ageing cohort infected with chronic hepatitis C, and are expected to continue to rise as a consequence of the obesity epidemic. Chemopreventive strategies aimed at decreasing the risk or delaying the onset of HCC are needed. Universal immunization against HBV and antiviral therapy against HBV and HCV in patients with established disease has consistently been associated with reduced HCC risk, especially in patients who achieve sustained virologic response. However, the cost-effectiveness of antiviral therapy for primary HCC prevention is not known. Several commonly prescribed medications seem promising as chemopreventive agents against HCC, including statins, antidiabetic medications and aspirin. Dietary agents such as coffee, vitamin E and fish oil as well as phytochemicals might also be associated with reduced risk of HCC. Though randomized controlled trials are ideally needed to firmly establish efficacy, such chemoprevention trials are logistically and ethically challenging. Well-designed, prospective, population-based cohort studies might provide the best evidence for chemopreventive efficacy of these agents.

The objective of this study was to quantitatively compare tumor imaging by magnetic resonance imaging (MRI) and molecular bioluminescence imaging (BLI) and test the feasibility of monitoring the effect of MRI-guided laser ablation on tumor viability by 2-dimensional BLI and 3-dimensional diffuse luminescence tomography (3D DLIT) in an orthotopic rat model of hepatocellular carcinoma.

Extremely large optical telescopes are being designed with primary mirrors composed of hundreds of segments. The “out-of-plane” piston, tip, and tilt degrees of freedom of each segment are actively controlled using feedback from relative height measurements between neighboring segments. The “in-plane” segment translations and clocking (rotation) are not actively controlled; however, in-plane motions affect the active control problem in several important ways, and thus need to be considered. We extend earlier analyses by constructing the “full” interaction matrix that relates the height, gap, and shear motion at sensor locations to all six degrees of freedom of segment motion, and use this to consider three effects. First, in-plane segment clocking results in height discontinuities between neighboring segments that can lead to a global control system response. Second, knowledge of the in-plane motion is required both to compensate for this effect and to compensate for sensor installation errors, and thus, we next consider the estimation of in-plane motion and the associated noise propagation characteristics. In-plane motion can be accurately estimated using measurements of the gap between segments, but with one unobservable mode in which every segment clocks by an equal amount. Finally, we examine whether in-plane measurements (gap and/or shear) can be used to estimate out-of-plane segment motion; these measurements can improve the noise multiplier for the “focus-mode” of the segmented-mirror array, which involves pure dihedral angle changes between segments and is not observable with only height measurements.

To analyze longitudinal trends in the incidence, etiology, and treatment of hepatocellular carcinoma (HCC) in community residents in Olmsted County, Minnesota, and their survival.

To study the frequencies of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, and their associations with hepatocellular carcinoma (HCC) in immigrant Somalis seen at Mayo Clinic in Rochester, Minnesota.

AbstractLiver cancer, the most common form of which is hepatocellular carcinoma (HCC), is one of the most deadly cancers worldwide. As of 2008, in men, HCC was the fifth most common cancer (approximately 450,000 new cases per year) and the second most frequent cause of death from cancer (around 416,000 deaths per year), whereas in women, it was the seventh most frequently diagnosed cancer (150,000 new cases per year) and the sixth most frequent cause of cancer deaths (140,000 deaths per year) [1]. Overall, HCC is the third leading cause of death from cancer globally [2, 3]. Worldwide, the incidence of HCC in males is more than twice that in females. The etiology of HCC is diverse; however, approximately 80 of HCCs occur secondary to chronic infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) [4]. The geographic distribution of HCC is such that the high-incidence regions of Eastern Asia and sub-Saharan Africa bear a disproportionate HCC burden, amounting to more than 80 of the global burden [4]. However, even in areas considered low-incidence regions—North America and Europe—the incidence of HCC is on the rise [4]. In the US, HCC incidence has risen more than threefold in the past 30 years, and it is now the ninth most frequent cause of death from cancer. The major reasons for the increased incidence of HCC in the US are the increasing prevalence of chronic HCV infection, increased immigration from high-incidence countries in Asia and Africa, and the increase in the number of individuals with cirrhosis due to obesity-related fatty liver disease. Most HCCs are diagnosed at an advanced stage for which there is no curative option. Sorafenib, the only agent specifically approved for HCC treatment, is of limited efficacy in this setting. Therefore, an urgent need for improved HCC therapy exists. In this review, we discuss the available data on the development and use of immunotherapy for HCC, with a particular focus on recent results and novel approaches.Copyright © 2012 S. Karger AG, Basel

Shack-Hartmann (S-H) phasing of segmented telescopes is based upon a physical optics generalization of the geometrical optics Shack-Hartmann test, in which each S-H lenslet straddles an intersegment edge. For the extremely large segmented telescopes currently in the design stages, one is led naturally to very large pupil demagnifications for the S-H phasing cameras. This in turn implies rather small Fresnel numbers F for the lenslets; the nominal design for the Thirty Meter Telescope calls for F=0.6. For such small Fresnel numbers, it may be possible to eliminate the lenslets entirely, replacing them with a simple mask containing a sparse array of clear subapertures and thereby also eliminating a number of manufacturing problems and experimental complications associated with lenslets. We present laboratory results that demonstrate the validity of this approach.

Zodiac II is a proposed balloon-borne science investigation of debris disks around nearby stars. Debris disks are analogs of the Asteroid Belt (mainly rocky) and Kuiper Belt (mainly icy) in our Solar System. Zodiac II will measure the size, shape, brightness, and color of a statistically significant sample of disks. These measurements will enable us to probe these fundamental questions: what do debris disks tell us about the evolution of planetary systems; how are debris disks produced; how are debris disks shaped by planets; what materials are debris disks made of; how much dust do debris disks make as they grind down; and how long do debris disks live? In addition, Zodiac II will observe hot, young exoplanets as targets of opportunity. The Zodiac II instrument is a 1.1-m diameter SiC telescope and an imaging coronagraph on a gondola carried by a stratospheric balloon. Its data product is a set of images of each targeted debris disk in four broad visiblewavelength bands. Zodiac II will address its science questions by taking high-resolution, multi-wavelength images of the debris disks around tens of nearby stars. Mid-latitude flights are considered: overnight test flights within the United States followed by half-global flights in the Southern Hemisphere. These longer flights are required to fully explore the set of known debris disks accessible only to Zodiac II. On these targets, it will be 100 times more sensitive than the Hubble Space Telescope's Advanced Camera for Surveys (HST/ACS); no existing telescope can match the Zodiac II contrast and resolution performance. A second objective of Zodiac II is to use the near-space environment to raise the Technology Readiness Level (TRL) of SiC mirrors, internal coronagraphs, deformable mirrors, and wavefront sensing and control, all potentially needed for a future space-based telescope for high-contrast exoplanet imaging.

The Thirty Meter Telescope primary mirror is composed of 492 segments that are controlled to high precision in the presence of wind and vibration disturbances, despite the interaction with structural dynamics. The higher bandwidth and larger number of segments compared with the Keck telescopes requires greater attention to modeling to ensure success. We focus here on the development and validation of a suite of quasi-static and dynamic modeling tools required to support the design process, including robustness verification, performance estimation, and requirements flowdown. Models are used to predict the dynamic response due to wind and vibration disturbances, estimate achievable bandwidth in the presence of control-structure-interaction (CSI) and uncertainty in the interaction matrix, and simulate and analyze control algorithms and strategies, e.g. for control of focus-mode, and sensor calibration. Representative results illustrate TMT performance scaling with parameters, but the emphasis is on the modeling framework itself.