J Gastroenterol Hepatol 2006 Feb; 21(1 Pt 1): 183-90 (Read article online)

Ikeda K, Kobayashi M, Saitoh S, Someya T, Hosaka T, Sezaki H, Suzuki Y, Suzuki F, Akuta N, Arase Y, Kumada H

Background: To elucidate the origin of the neovascular structure found in well-differentiated hepatocellular carcinoma (HCC), an immunohistochemical study was performed on sequential thin section specimens. Method: Eleven surgically resected specimens of well-differentiated HCC were analyzed for neovascular structure using monoclonal alpha-smooth muscle actin (alpha-SMA) antibody. Each paraffin specimen was serially sliced to a thickness of 3 microm for immunohistochemistry. When a ring-shaped structure was found unrelated to portal triads on alpha-SMA staining, it was regarded as abnormal neovascularity (non-triadal vessel or unaccompanied vessel). Results: All of the 11 liver cancers had thin-walled, round- or oval-shaped non-triadal vessels in their well-differentiated parts. Immunohistochemistry of serial thin sections of HCC showed that these non-triadal vessels were connected to portal veins in portal triads in well-differentiated cancer in a total of nine patients (81.8%). This type of neovascular structure found in a well-differentiated cancer seemed to be a surviving portal vein among diminishing and disappearing arteries and bile ducts. All 11 tumors showed isovascular staining on ordinary digital subtraction angiography, and four of the tumors showed negative enhancement on intra-arterial carbon dioxide-enhanced ultrasonography or computerized tomographic (CT) hepatic arteriography, suggesting a relative arterial blood scarcity in the tumor nodules. Conclusion: At an early stage of HCC, non-triadal vessels originate from ordinary portal veins in intratumoral portal triads. This fact sufficiently explains the reason why a well-differentiated liver cancer can sometimes show arterial blood paucity on CT arteriography or enhanced ultrasonography.

Int J Epidemiol 2006 May 18; (Read article online)

Singh GK, Hiatt RA

BACKGROUND: Immigrants are a growing segment of the US population. In 2003, there were 33.5 million immigrants, accounting for 12% of the total US population. Despite a rapid increase in their numbers, little information exists as to how immigrants' health and mortality profile has changed over time. In this study, we analysed trends in social and behavioural characteristics, life expectancy, and mortality patterns of immigrants and the US-born from 1979 to 2003. METHODS: We used national mortality and census data (1979-2003) and 1993 and 2003 National Health Interview Surveys to examine nativity differentials over time in health and social characteristics. Life tables, age-adjusted death rates, and logistic regression were used to examine nativity differentials. RESULTS: During 1979-81, immigrants had 2.3 years longer life expectancy than the US-born (76.2 vs 73.9 years). The difference increased to 3.4 years in 1999-2001 (80.0 vs 76.6 years). Nativity differentials in mortality increased over time for major cancers, cardiovascular diseases, diabetes, respiratory diseases, unintentional injuries, and suicide, with immigrants experiencing generally lower mortality than the US-born in each period. Specifically, in 1999-2001, immigrants had at least 30% lower mortality from lung and oesophageal cancer, COPD, suicide, and HIV/AIDS, but at least 50% higher mortality from stomach and liver cancer than the US-born. Nativity differentials in mortality, health, and behavioural characteristics varied substantially by ethnicity. CONCLUSIONS: Growing ethnic heterogeneity of the immigrant population, and its migration selectivity and continuing advantages in behavioural characteristics may partly explain the overall widening health gaps between immigrants and the US-born.

Dig Liver Dis 2006 May 13; (Read article online)

Hsieh CB, Tzao C, Yu CY, Chen CJ, Chang WK, Chu CH, Chou SJ, Tung HJ, Yu JC

BACKGROUND: The Acute Physiology and Chronic Health Evaluation II classification system has been extensively used for predicting the patient mortality in various diseases. However, its utilisation on the pyogenic liver abscess has not yet been well studied. AIMS: The purpose of this study was to validate this system on this high death rate disease. PATIENTS: A retrospective study was conducted to assess 314 patients with pyogenic liver abscesses admitted to tertiary medical centre in past 12 years. METHODS: The outcome measurement was the in-hospital mortality. A multiple logistic regression model was used to assess the association between mortality and Acute Physiology and Chronic Health Evaluation II score while controlling for the potential confounding factors. RESULTS: The overall in-hospital mortality was 8.3%. The mean Acute Physiology and Chronic Health Evaluation II score of the expired patients was higher (P<0.0001). The mortality rate increased rapidly when Acute Physiology and Chronic Health Evaluation II score >/=15. After controlling for the potential confounding factors, patient with high admission Acute Physiology and Chronic Health Evaluation II score >/=15 had a higher chance of in-hospital mortality (P<0.01). In addition, the primary liver cancer history is also a risk factor (P=0.03). CONCLUSIONS: The Acute Physiology and Chronic Health Evaluation II score and the primary liver cancer history predict the in-hospital mortality of the pyogenic liver abscess patient.

Int J Mol Med 2006 Jun; 17(6): 1163-6 (Read article online)

Katoh Y, Katoh M

AREG (Amphiregulin), BTC (beta-cellulin), EGF, EPGN (Epigen), EREG (Epiregulin), HBEGF, NRG1, NRG2, NRG3, NRG4 and TGFA (TGFalpha) constitute EGF family ligands for ERBB family receptors. Cetuximab (Erbitux), Pertuzumab (Omnitarg) and Trastuzumab (Herceptin) are anti-cancer drugs targeted to EGF family ligands, while Gefitinib (Iressa), Erlotinib (Tarceva) and Lapatinib (GW572016) are anti-cancer drugs targeted to ERBB family receptors. AREG and TGFA are biomarkers for Gefitinib non-responders. The TCF/LEF binding sites within the promoter region of human EGF family members were searched for by using bioinformatics and human intelligence (Humint). Because three TCF/LEF-binding sites were identified within the 5'-promoter region of human AREG gene, comparative genomics analyses on AREG orthologs were further performed. The EPGN-EREG-AREG-BTC cluster at human chromosome 4q13.3 was linked to the PPBP-CXCL segmental duplicons. AREG was the paralog of HBEGF at human chromosome 5q31.2. Chimpanzee AREG gene, consisting of six exons, was located within NW_105918.1 genome sequence. Chimpanzee AREG was a type I transmembrane protein showing 98.0% and 71.4% total amino-acid identity with human AREG and mouse Areg, respectively. Three TCF/LEF-binding sites within human AREG promoter were conserved in chimpanzee AREG promoter, but not in rodent Areg promoters. Primate AREG promoters were significantly divergent from rodent Areg promoters. AREG mRNA was expressed in a variety of human tumors, such as colorectal cancer, liver cancer, gastric cancer, breast cancer, prostate cancer, esophageal cancer and myeloma. Because human AREG was characterized as potent target gene of WNT/beta-catenin signaling pathway, WNT signaling activation could lead to Gefitinib resistance through AREG upregulation. AREG is a target of systems medicine in the field of oncology.

MMWR Morb Mortal Wkly Rep 2006 May 12; 55(18): 505-9 (Read article online)

Chronic hepatitis B virus (HBV) infection is the most common cause of cirrhosis and liver cancer worldwide. In Asian and western Pacific countries where HBV is endemic, estimated prevalence of chronic HBV infection ranges from 2.4%-16.0%, and liver cancer is a leading cause of mortality. Although population-based prevalence data for Asians/ Pacific Islanders (A/PIs) living in the United States are lacking, they are believed to constitute a sizeable percentage of persons with chronic HBV infection in the United States, a country of low endemicity. To assess the prevalence of chronic HBV infection among A/PI populations living in New York City, the Asian American Hepatitis B Program (AAHBP) conducted a seroprevalence study among persons who participated in an ongoing hepatitis B screening, evaluation, and treatment program. The results indicated that approximately 15% of participants who had not been previously tested had chronic HBV infection; all were born outside the United States. Screening programs are needed in A/PI communities in the United States to identify persons with chronic HBV infection so that they can be referred for appropriate medical management to prevent cirrhosis and liver cancer and so that their susceptible household and sex contacts can receive hepatitis B vaccine.

Int J Radiat Biol 2006 Apr; 82(4): 231-40 (Read article online)

Sharp GB, Mizuno T, Fukuhara T, Tokuoka S

Purpose: Although previous studies have shown significantly increased risks of liver cirrhosis and chronic liver disease for acute radiation exposure among survivors of the atomic bombings of Hiroshima and Nagasaki, Japan, these studies have not taken into account hepatitis B virus (HBV) infections. Because HBV is associated with both A-bomb radiation and liver cirrhosis, our goal was to investigate the relationship of acute ionizing radiation to liver cirrhosis adjusting for HBV, co-occurring primary liver cancer (PLC), and other potential confounders.Materials and methods: Using a cross-sectional design and pathology review of a cohort of Japanese atomic-bomb survivors, we found that 213 of 335 (63.6%) subjects with PLC and 55 of 776 (7.1%) subjects without PLC had cirrhosis.Results: We found no association between acute exposure to A-bomb radiation and liver cirrhosis. The adjusted odds ratio of cirrhosis per Sv liver irradiation was 0.59 (95% confidence interval: 0.27 - 1.27). Cirrhosis risks for the highest tertile of radiation exposure (mean exposure 0.7 Sv) were also not elevated (0.8, 0.26 - 2.12 and 0.2, 0.03 - 0.98 among subjects with and without PLC.Conclusions: Acute exposure to liver irradiation does not increase risks of liver cirrhosis, regardless of PLC status.

Med Image Comput Comput Assist Interv Int Conf Med Image Comput Comput Assist Interv 2005; 8(Pt 1): 811-8 (Read article online)

Leven J, Burschka D, Kumar R, Zhang G, Blumenkranz S, Dai XD, Awad M, Hager GD, Marohn M, Choti M, Hasser C, Taylor RH

We present daVinci Canvas: a telerobotic surgical system with integrated robot-assisted laparoscopic ultrasound capability. DaVinci Canvas consists of the integration of a rigid laparoscopic ultrasound probe with the daVinci robot, video tracking of ultrasound probe motions, endoscope and ultrasound calibration and registration, autonomous robot motions, and the display of registered 2D and 3D ultrasound images. Although we used laparoscopic liver cancer surgery as a focusing application, our broader aim was the development of a versatile system that would be useful for many procedures.

Toxicol Lett 2006 Apr 18; (Read article online)

Kim WK, In YJ, Kim JH, Cho HJ, Kim JH, Kang S, Lee CY, Lee SC

Dioxin response element (DRE) is a cis-acting DNA sequence mediating the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced gene expression. The present study was undertaken to elucidate TCDD-responsive gene expression profiles and their relationships to the number of DREs in liver cancer cells. Hep3B and HepG2 human hepatocarcinoma cells were exposed to 50-nM TCDD for 0, 1, 2 and 4h in culture, after which gene expression profiles were analyzed by the microarray hybridization using a chip containing 24,000 cDNAs prepared from the human liver. The TCDD-responsive expression levels in each gene were calculated by dividing the densitometric values of the hybridization signal for h1, h2 and h4 by that of h0, followed by transformation of the resulting data into a log scale with the base of 2. Up- and down-regulated gene expressions were defined as >0.585 and <-0.585 by the log scale (>1.5 and <1/1.5 arithmetically), respectively, exhibited at any time after h0. Hep3B and HepG2 cells had 27 and 58 TCDD-responsive, up-regulated genes, respectively, of which 78% (21/27) and 62% (36/58) had one or more DREs. Of these 85, 80 genes were up-regulated exclusively in one of the two lines, with CYP1A1 and PPP1R15A being so regulated in both lines. Expression levels of the up-regulated genes at h1, h2 and h4 were correlated with each other (P<0.01) and the mean of these regressed to the number of DRE(s) in both lines (P<0.01). However, expression of a total of 93 TCDD-responsive, down-regulated genes, of which 46% contained DRE(s), had no relation to the number of DRE(s). In conclusion, results suggest that DREs may cooperatively mediate the expression of TCDD-responsive genes in liver cancer cells.

G Chir 2006 Mar; 27(3): 113-8 (Read article online)

Monaco M, Scisca C, Pavia R, Sibilio M, La Rocca A, Familiari D, Pavone A, Surleti S, Monaco F, Mondello B

Versione italiana Introduzione: Purtroppo ancora oggi la maggior parte dei tumori polmonari sono inoperabili al momento della diagnosi; la chemio- e la radioterapia hanno in questi casi un ruolo importante, ma palliativo, determinando un modesto miglioramento della sopravvivenza, ma non sono prive di effetti tossici, soprattutto in caso di patologie concomitanti, ridotta funzionalità cardiorespiratoria o età avanzata. Di conseguenza sono state applicate in tali patologie tecniche mininvasive di ablazione termica, già impiegate nella terapia dei tumori epatici a scopo adiuvante od in sostituzione del trattamento chirurgico. Obiettivo: Scopo dello studio è definire l?attuale stato dell?arte in tema di ablazione con radiofrequenza (RFA) dei tumori polmonari non operabili, attraverso una revisione della letteratura internazionale da cui si evincano obiettivi, indicazioni, tecnica, efficacia, sicurezza, complicanze e risultati della metodica, anche in termini di eventuale miglioramento della qualità di vita e/o della sopravvivenza. Pazienti e metodi: I pazienti sono adeguatamente selezionati; i noduli polmonari vengono sottoposti a termoablazione percutanea TC o ecoguidata e quindi a follow-up radiologico e clinico, talora istopatologico. Risultati: Le dimensioni del nodulo RFA-trattato sono il fattore da cui dipendono l?estensione (completa o parziale) della necrosi e, conseguentemente, la sopravvivenza media. Conclusioni: E necessario disporre di casistiche più ampie ed omogenee, nonché di metodiche standard di follow-up (TC e/o prelievi istopatologici). Tuttavia la letteratura è concorde nel ritenere l?RFA una procedura sicura ed efficace nel trattamento alternativo o complementare delle neoplasie polmonari inoperabili. I migliori risultati si ottengono nel caso di tumori di diametro inferiore a 3 cm; nel caso di neoplasie più grandi, l?RFA, effettuata prima della chemio- e/o della radioterapia, ha un ruolo neoadiuvante, riducendo il volume tumorale e attenuando la sintomatologia. English version Background: Unfortunately, as of yet, most lung cancers are not operable as soon as diagnosis is available; in these situations chemo- and radio-therapy still play a key role, albeit palliative, improving survival rate moderately, but are not lacking in toxic effects, especially in case of concurrent pathology, reduced cardio-respiratory functionality or being advanced in years. Therefore thermal ablation mini-invasive techniques, already employed as ancillary treatments of hepatic cancer or in place of surgery, have been performed for these pathologies. Aim: Aim of this work is to define the current state of the art for Radio-Frequency Ablation (RFA) to be performed on non-resectable lung cancer, also by means of a thorough review of international literature, from which to infer purposes, suggestions, methodologies, effectiveness, safety, complications and achievements, also in terms of the possible improvement of life quality and/or survival expectancy. Patients and methods: Patients have been carefully selected. Pulmonary nodules have been treated with TC or echo-guided percutaneous thermal ablation and, afterwards, evaluated by radiological and clinical (sometimes histopathological) follow-up. Results: The size of the RFA-treated nodules is necessary in order to evaluate full or partial necrosis extent and, therefore, average survival rate. Conclusions: Availability of more extensive and homogeneous case histories, as well as standard follow-up (TC and/or histopathological sampling) methodologies, is required. Nevertheless several authors agree that RFA is a safe and effective technique within the framework of a substitutive or complementary treatment of non-operable lung cancer. The best results can be achieved for cancers less than 3 cm wide; RFA, performed before chemo- and/or radio-therapy, plays a neoadjuvant role for larger cancers, decreasing cancer volume and weakening the symptoms.

MMWR Morb Mortal Wkly Rep 2006 May 12; 55(18): 509-11 (Read article online)

Hepatitis B virus (HBV) infection is a major cause of cirrhosis and liver cancer in the United States. The Advisory Committee on Immunization Practices (ACIP) has recommended a comprehensive strategy to eliminate HBV transmission, including prevention of perinatal HBV transmission; universal vaccination of infants; catch-up vaccination of unvaccinated children and adolescents; and vaccination of unvaccinated adults at increased risk for infection. The incidence of acute hepatitis B has declined 75%, from 8.5 per 100,000 population in 1990 to 2.1 per 100,000 population in 2004, with the greatest declines (94%) among children and adolescents. Incidence remains highest among adults, who accounted for approximately 95% of the estimated 60,000 new infections in 2004. To measure hepatitis B vaccination coverage among adults, data were analyzed from the 2004 National Health Interview Survey (NHIS). This report summarizes the results of that analysis, which indicated that, during 2004, 34.6% of adults aged 18-49 years reported receiving hepatitis B vaccine, including 45.4% of adults at high risk for HBV infection. To accelerate elimination of HBV transmission in the United States, public health programs and clinical care providers should implement strategies to ensure that adults at high risk are offered hepatitis B vaccine.

J Gastroenterol 2006 Mar; 41(3): 250-6 (Read article online)

Nanashima A, Sumida Y, Abo T, Shindou H, Fukuoka H, Takeshita H, Hidaka S, Tanaka K, Sawai T, Yasutake T, Nagayasu T, Omagari K, Mine M

BACKGROUND: We previously reported the effectiveness of the modified Cancer of the Liver Italian Program (CLIP) score in hepatocellular carcinoma (HCC) staging. To determine the best predictive staging system for HCC patients, we conducted a comparative analysis of prognosis using multivariate analysis in 230 Japanese HCC patients following hepatic resection. METHODS: We compared overall survival as predicted by different staging systems: the tumor node metastasis (TNM) system by the Liver Cancer Study Group of Japan, the Japan Integrated Staging (JIS) score (Japanese TNM and Child-Pugh classification), the modified JIS score using liver damage grade, the CLIP score, and our modified CLIP score using protein induced by vitamin K absence or the antagonist II (PIVKA-II). RESULTS: By a univariate analysis the PIVKA-II level (cut-off level, 400 mAU/ml) was significantly associated with patient survival (P = 0.031); however, alpha-fetoprotein level was not related to survival. Liver damage grade was significantly associated with patient survival (P = 0.039), although Child-Pugh classification was not related to survival. Univariate analysis showed that prediction of survival, according to disease stage, was better with the modified JIS score than with the TNM system, CLIP, modified CLIP, or JIS score. Multivariate analysis showed the modified JIS score showed the best ability to predict overall survival according to disease stage (Hazard ratio, 1.77; P = 0.002), and its Akaike information criteria statistic was the lowest (634.3). CONCLUSIONS: The modified JIS score, a staging system that combines tumor factors and hepatic function, is a better predictor of prognosis than other systems in HCC patients who have undergone hepatic resection.

Hepatobiliary Pancreat Dis Int 2006 May; 5(2): 246-51 (Read article online)

Qin JM, Yan HX, Liu SQ, Wan XW, Zeng JZ, Cao HF, Qiu XH, Wu MC, Wang HY

BACKGROUND: Signal regulatory protein (Sirp) is a recently isolated, cloned and identified inhibitor receptor distributed in the membrane of hematopoietic and nonhematopoietic cells. Sirp alpha1 (Sirpalpha1) is a member of Sirp families. Sirpalpha1 can bind SHP-2 in the form of tyrosine phosphorylation by SH2 effect and negatively regulate growth factor, oncogene, or insulin-induced responses as its substrate. This study aimed to preliminarily clarify the negatively regulating proliferation mechanism of Sirpalpha1 in liver cancer. METHODS: pLXSN, Sirpalpha1 and Sirpalpha1P4Y2 plasmids were respectively transfected into Sk-Hep1 liver cancer cell line, and various stable Sk-Hep1 cell lines were obtained with screening agent of G418 (1200 mug/ml). The expressing levels of cyclin D1, CDK4, Fas, beta-catenin and gankyrin in various cell lines were determined with Western blotting. Cell cycles were determined at 0, 12 and 24 hours with flow cytometry after various synchronous cell lines were cultured without serum for 72. Cell apoptosis induced with agent of TNF-alpha (50 ng/ml) was determined with flow cytometry at 0, 0.5, 1, 3, 6 and 12 hours. RESULTS: Sirpalpha1 could significantly decrease the expression of cyclin D1, beta-catenin and gankyrin, but it couldn't affect the expression level of CDK4 and Fas. When synchronous cells were cultured for 12 hours, S phase Sk-Hep1 cell transfected with Sirpalpha1 plasmid was the lowest [(31.92+/-0.22)% vs. other cell lines, P<0.05], and the cell line was highly sensitive to TNF-alpha agent for 1 hour. (59.31+/-0.59)% of apoptotic cells occurred (vs. the other time points, P<0.05). CONCLUSIONS: Sirpalpha1 might block the cell cycle of liver cancer, inhibit cell proliferation, promote cell apoptosis by decreasing the expression of cyclin D1, beta-catenin and gankyrin. It is one of the important mechanisms inhibiting the occurrence and development of hepatocellular carcinoma.

J Am Acad Nurse Pract 2006 May; 18(5): 203-15 (Read article online)

Perrillo R

Purpose: To address the clinical management of chronic hepatitis B virus (HBV) infection. Data sources: Studies from the National Library of Medicine that examine the natural history, prevention, and antiviral therapy of chronic HBV infection, with emphasis on recent studies. Conclusions: Chronic infection with HBV is a frequent cause of cirrhosis, liver cancer, and liver-related mortality worldwide. Strategies to prevent infection, screen for liver cancer in HBV carriers, and treat chronic hepatitis B are all important in managing this disorder. Implications for practice: Much can be done to prevent and treat infection. Both classes of drugs to treat hepatitis B, nucleoside analogues and interferons, have advantages and disadvantages. Selection of therapy should be based on biochemical, histological, and virological parameters as well as consideration of several practical issues.

Zhonghua Yi Xue Za Zhi 2006 Mar 28; 86(12): 850-3 (Read article online)

Ma Y, Hua YP, Chen ZB, Zhang JX

OBJECTIVE: To explore the inducing method for hepatic carcinoma in rats and the operative technique in establishment of orthotopic liver transplantation (OLT) model in rats with induced hepatic tumor. METHODS: Hepatic carcinoma was induced by diethylnitrosamine (DENA) in rats. Then OLT was performed, using a two-cuff vessel anastomosis method modified from that introduced by Kamada, with reconstruction of hepatic artery. RESULTS: At the observation time point (18 weeks) after the initiation of carcinogenesis, the one-month survival rate in OLT group was higher than that in non-OLT group, 56.3% and 21.4% respectively, P < 0.05. The operative successful rate in tumor rats group and control group was 87.5% and 90.0%, respectively. In OLT rats with hepatic carcinoma group, metastasis mainly occurred in lung and abdomen, while only 2 cases of intrahepatic recurrence were observed. There was significant difference between the tumor rats group and control group in cum survival rate. CONCLUSION: DENA can wholesale induce stable rat model for hepatic carcinoma. OLT can markedly elevate survival rate in rats with liver cancer. In rats with induced hepatic tumor, OLT model, suggested by the author, was established with hepatic arterial reconstruction and it offers a satisfied method with more similar pattern of physiological setting and carcinoma development situation.

Ai Zheng 2006 May; 25(5): 651-6 (Read article online)

Chen LD, Li Y, Yuan HY, Pang DW

Quantum dots are semiconductor nanocrystals with physical dimensions smaller than the exciton Bohr radius. As their fluorescence emissions are size-tunable, we can acquire any spectrum from ultraviolet (UV) to near-infrared by changing the particles;radiuses. The large Stokes shifts of quantum dots can be used to further improve detection sensitivity. The luminescence intensity is high and stable. Single quantum dots have longer excited state lifetimes, and they appear 10-20 times brighter than organic fluorescent dyes. And they have good biocompatibility because quantum dots with appropriate shells don;t interfere with physiological processes, such as growth, development, signaling and motility. With the development of optical labeling and imaging technology, many present conventional biomedical methods have limitations in microcosmic direct real-time researches of bio-molecular interactions and early diagnosis of malignant tumors. The invention of quantum dots and their biomedical applications make them as good markers for tumor cell tracing and targeting in cancer research, such as prostate cancer, mammary cancer, cervical cancer, basal cell carcinoma, liver cancer, and melanoma. The current research is focused on tumor markers imaging and molecular interaction based on tangible carriers such as cells and tissues. The next research orientation would be to tap the potential of this highly sensitive technology to image tumor biomarkers in serum and other body fluids, so as to increase the early diagnosis rate of malignant tumors.

Am J Clin Nutr 2006 May; 83(5): 1199-203 (Read article online)

El-Nezami HS, Polychronaki NN, Ma J, Zhu H, Ling W, Salminen EK, Juvonen RO, Salminen SJ, Poussa T, Mykkänen HM

BACKGROUND: In vitro and in vivo studies suggest that selected strains of probiotic bacteria can form tight complexes with aflatoxin B(1) and other carcinogens. OBJECTIVE: The aim of the present study was to determine whether administration of probiotic bacteria could block the intestinal absorption of aflatoxin B(1) and thereby lead to reduced urinary excretion of aflatoxin B(1)-N(7)-guanine (AFB-N(7)-guanine), a marker for a biologically effective dose of aflatoxin exposure. Elevated urinary excretion of this aflatoxin-DNA adduct is associated with an increased risk of liver cancer. DESIGN: Ninety healthy young men from Guangzhou, China, were randomly assigned to 2 groups; one group received a mixture of Lactobacillus rhamnosus LC705 and Propionibacterium freudenreichii subsp. shermanii strains 2 times/d for 5 wk, and the other group received a placebo preparation. The subjects provided 4 urine samples: at baseline, at 3 and 5 wk after starting the supplementation, and at the end of the 5-wk postintervention period. RESULTS: The percentage of samples with negative AFB-N(7)-guanine values tended to be higher in the probiotic group than in the placebo group during the 5-wk intervention period (odds ratio: 2.63, P = 0.052), and a statistically significant decrease in the concentration of urinary AFB-N(7)-guanine was observed in the probiotic group. The reduction was 36% at week 3 and 55% at week 5. The geometric means for the probiotic and placebo groups were 0.24 and 0.49 ng AFB-N(7)-guanine/mL, respectively, during the intervention period (P = 0.005). CONCLUSION: A probiotic supplement reduces the biologically effective dose of aflatoxin exposure and may thereby offer an effective dietary approach to decrease the risk of liver cancer.

Carcinogenesis 2006 May 5; (Read article online)

Kirk GD, Bah E, Montesano R

Human liver cancer, primarily hepatocellular carcinoma (HCC), is both common and lethal. Notable variation in HCC incidence rates worldwide corresponds to the prevalence and pattern of the primary etiologic factors. In summary of decades of collaborative research centered in The Gambia, West Africa, this review explores the independent and combined effects of hepatitis B virus (HBV), hepatitis C virus (HCV) and dietary aflatoxin exposure in the etiology of HCC. Through population surveys, field trials and a series of HCC case-control studies, the patterns and natural history of HBV, HCV and aflatoxin exposures have been defined within this population. These investigations have paralleled and informed the development of molecular biomarkers of these etiologic agents and contributed to understanding the complex mechanisms involved in hepatocarcinogenesis. We discuss preventive approaches to reduce the global burden of HCC, emphasizing the Gambia Hepatitis Intervention Study, a country-wide randomized controlled trial designed to document the efficacy of HB vaccination in preventing HBV infections and HBV-related HCC. By recognizing the synergy of applying molecular techniques to population-based epidemiological studies, the portfolio of Gambian research projects presented provides a model for partnering etiologic and mechanistic investigations with applied research.

Zhonghua Liu Xing Bing Xue Za Zhi 2005 Dec; 26(12): 934-8 (Read article online)

Yang GH, Wang JF, Wan X, Wang LJ, Chen AP

OBJECTIVE: To explain trend of death in Chinese by quantitative analysis of demographic and non-demographic factors and estimate the proportion of contribution of non-demographic and demographic factors. METHODS: Using census data and death causes data of National Disease Surveillance Points at 1991 and 2000 to calculate the proportion of contribution of demographic and non-demographic factors and to change on various death causes from 1991 to 2000 by methods of decomposing the differences of death rates. RESULTS: The death rate showed a rapid decrease during 1950 - 1975, mainly owing to the contribution of non-demographic factors, including economic development, popularization of education and health service, especially the "patriotic hygiene movement". During 1991 - 2000, the death causes of lung cancer, liver cancer, breast cancer, chronic heart disease, stroke, diabetes and traffic accident had been increasing. The increase of deaths caused by these diseases were contributed to the non-demographic factors including 63% of the increase on lung cancer and 88% of increase on death rate of traffic accidents. CONCLUSION: The study showed that the risk factors had contributed to the increase of death rates, including behavioral risk factors described in the preceding 5 papers as smoking and passive smoking, unhealthy diet, sedentary life style, violating traffic regulation etc. In order to reduce the death rates on cancer, heart diseases, diabetes, traffic accidents, emphasis should be also laid on the change of unhealthy behaviors.

Ultrasound Med Biol 2006 May; 32(5): 641-7 (Read article online)

Li J, Dong B, Yu X, Li C

To evaluate the characteristics of portal blood supply of hepatic tumors by ultrasonographic portography (USP), an in vivo model was studied using SonoVuetrade mark, a second-generation ultrasound contrast agent (UCA) and low mechanical index (MI), gray-scale harmonic imaging. SonoVuetrade mark (0.05 mL) was administrated through catheter placed into the main trunk of portal vein at laparotomy, followed by a 0.5 mL saline flush, in 12 rabbits with hepatic VX2 tumor, implanted by VX2 tumor tissue cubes of approximately 1 mm(3) from carrier rabbit. Results showed that low MI gray-scale imaging delineated clearly the dynamic enhancement of tumors and liver parenchyma. Among 22 tumors, seven tumors were diffusely increased, with the intensity of enhancement weaker than that of the surrounding liver parenchyma. The UCA was washed out earlier from tumors than from surrounding liver parenchyma. Three tumors showed the branches of portal vein. Five tumors showed peripheral contrast enhancement and a central coarse unenhanced hypoechoic area. Seven tumors displayed no actual enhancement. All lesions (100% [22 of 22]) were depicted clearly in the whole duration of enhancement, especially in the early and late phase, regardless of enhancement pattern, and portal blood flow was manifested in 15 of 22 (68%) tumors, by USP. The enhancement pattern of the tumors corresponded to the pathologic findings. The results indicated that ultrasonographic portography, combined with low MI levels and second-generation UCA, is a sensitive and safe method to study portal blood supply for liver cancer. It may contribute to improvement of the detectability and diagnostic ability and assist the choice of a therapeutic strategy for treatment of liver cancer. However, applicability of the method to human may be problematic because of high invasiveness and great difficulty in administering contrast medium. (E-mail: ).

Cardiovasc Intervent Radiol 2006 Apr 29; (Read article online)

Sato K, Lewandowski RJ, Bui JT, Omary R, Hunter RD, Kulik L, Mulcahy M, Liu D, Chrisman H, Resnick S, Nemcek AA, Vogelzang R, Salem R

In Canada and Europe, yttrium-90 microspheres (TheraSphere((R)); MDS Nordion, Ottawa, Canada) are a primary treatment option for primary and secondary hepatic malignancies. We present data from 30 patients with hepatocellular carcinoma (HCC) and metastatic liver disease treated with TheraSphere from a single academic institution to evaluate the angiographically evident embolization that follows treatment. Seven interventional radiologists from one treatment center compared pretreatment and posttreatment angiograms. The reviewers were blinded to the timing of the studies. The incidence of postembolization syndrome (PES) was determined as well as objective tumor response rates by the World Health Organization (WHO), Response Evaluation Criteria in Solid Tumors (RECIST), and European Association for the Study of the Liver (EASL) criteria. There were 420 independent angiographic observations that were assessed using the chi-squared statistic. The pretreatment and posttreatment angiograms could not be correctly identified on average more than 43% of the time (p = 0.0004). The postprocedure arterial patency rate was 100%. The objective tumor response rates for all patients were 24%, 31%, and 72% for WHO, RECIST, and EASL criteria, respectively. All of the patients tolerated the procedure without complications and were treated on an outpatient basis, and four patients had evidence of PES. This treatment method does not result in macroscopic embolization of the hepatic arteries, thereby maintaining hepatic tissue perfusion. These data support the principle that the favorable response rates reported with TheraSphere are likely due to radiation and microscopic embolization rather than flow-related macroscopic embolization and ischemia.