bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of cytokine polymorphisms with subclinical progressive chronic allograft nephropathy in Japanese renal transplant recipients: Preliminary study
Authors: Satoh Shigeru , Saito Mitsuru , Inoue Kazuyuki , Miura Masatomo , Komatsuda Atsushi , Habuchi Tomonori
Published: September 2007

Background:  The present study calculated the risk of developing subclinical progressive chronic/sclerosing allograft nephropathy (CAN) under tacrolimus‐based immunosuppression according to genetic polymorphisms of cytokines and growth factors, and clinical events including delayed graft function (DGF), acute rejection (AR) and cytomegalovirus (CMV) infection.

Methods:  The subjects were 50 recipients with stable graft function more than one year after renal transplantation. The criteria for subclinical progressive CAN were CAN grade 2 or 3 changes on Banff classification and stable serum creatinine (SCr) levels. Ten genetic polymorphisms were assessed.

Results:  Eleven patients (22.0%) developed progressive CAN. The mean ages and SCr levels of recipients with and without progressive CAN were 41.2 and 47.1 years, and 1.46 and 1.22 mg/dL, respectively. There were no significant differences in donor age, number of HLA mismatches, DGF or CMV infection. Although the rate of AR episode seemed to be greater in patients with subclinical progressive CAN, the difference did not reach significance (P = 0.093). The frequencies of the interleukin (IL)‐2 T‐330G TT genotype (P = 0.046) and IL‐4 C‐590T C allele (P = 0.092) were higher in patients with progressive CAN. In univariate analysis, the presence of IL‐2 T‐330G TT (OR 4.57, P = 0.044) was associated with CAN development.

Conclusion:  The presence of IL‐2 T‐330G TT genotype may be a risk factor for CAN. Further studies with a large number of subjects and analyses of many cytokine polymorphisms would contribute to the ability to make prognostic determinations or tailor immunomodulatory regimens after renal transplantation.
Contextualizing Personality Psychology
Authors: Roberts Brent W.
Published: September 2007

ABSTRACT
The issue of how to contextualize personality psychology constructively has been a longstanding dilemma. This special issue brings together personality, social, self, clinical, and cultural psychologists who have attempted to contextualize the self, personality, attachment, and cultural constructs in an integrative fashion, with a focus on broader situations, such as social roles. In this introductory essay, I describe the potential advantages of integrating traditional concepts in personality psychology with social roles and provide an overview of the contributions made to the special issue.
TEMPEST in a Gallimaufry: Applying Multilevel Systems Theory to Person‐in‐Context Research
Authors: Peck Stephen C.
Published: September 2007

ABSTRACTTerminological ambiguity and inattention to personal and contextual multilevel systems undermine personality, self, and identity theories. Hierarchical and heterarchical systems theories are used to describe contents and processes existing within and across three interrelated multilevel systems: levels of organization, representation, and integration. Materially nested levels of organization are used to distinguish persons from contexts and personal from social identity. Functionally nested levels of representation are used to distinguish personal identity from the sense of identity and symbolic (belief) from iconic (schema) systems. Levels of integration are hypothesized to unfold separately but interdependently across levels of representation. Multilevel system configurations clarify alternative conceptualizations of traits and contextualized identity. Methodological implications for measurement and analysis (e.g., integrating variable‐ and pattern‐centered methods) are briefly described.
A Connectionist Approach to the Organization and Continuity of Working Models of Attachment
Authors: Fraley R. Chris
Published: September 2007

ABSTRACTMost research on adult attachment dynamics has been conducted under the assumption that working models are generalized cognitive‐motivational structures that are highly stable and activated in a wide array of circumstances. Recent research, however, suggests that people develop attachment representations that are relationship specific, leading them to hold distinct working models in different kinds of relationships. The objective of this article is to outline a connectionist approach to the working model construct that has the potential to explain how global and relationship‐specific working models are organized within the same mental system and how different learning environments can support continuity in those representations over time.
Biomarkers at the microscopic range: ToF‐SIMS molecular imaging of Archaea‐derived lipids in a microbial mat
Authors: THIEL V. , HEIM C. , ARP G. , HAHMANN U. , SJÖVALL P. , LAUSMAA J.
Published: September 2007

Time‐of‐Flight Secondary Ion Mass Spectrometry (ToF‐SIMS) with a bismuth cluster primary ion source was used for analysing microbial lipid biomarkers in 10‐µm‐thick microscopic cryosections of methanotrophic microbial mats from the Black Sea. Without further sample preparation, archaeal isopranyl glycerol di‐ and tetraether core lipids, together with their intact diglycoside (gentiobiosyl‐) derivatives, were simultaneously identified by exact mass determination. Utilizing the imaging capability of ToF‐SIMS, the spatial distributions of these biomarkers were mapped at a lateral resolution of < 5 µm in 500 × 500 µm2 areas on the mat sections. Using cluster projectiles in the burst alignment mode, it was possible to reach a lateral resolution of 1 µm on an area of 233 × 233 µm, thus approaching the typical size of microbial cells. The mappings showed different ‘provenances’ within the sections that are distinguished by individual lipid fingerprints, namely (A) the diethers archaeol and hydroxyarchaeol co‐occurring with glycerol dialkyl glycerol tetraethers (GDGT), (B) hydroxyarchaeol and dihydroxyarchaeol, and (C) GDGT and gentiobiosyl‐GDGT. Because ToF‐SIMS is a virtually nondestructive technique affecting only the outermost layers of the sample surface (typically 10–100 nm), it was possible to further examine the studied areas using conventional microscopy, and associate the individual lipid patterns with specific morphological traits. This showed that provenance (B) was frequently associated with irregular, methane‐derived CaCO3 crystallites, whereas provenance (C) revealed a population of fluorescent, filamentous microorganisms showing the morphology of known methanotrophic ANME‐1 archaea. The direct coupling of imaging mass spectrometry with microscopic techniques reveals interesting perspectives for the in‐situ study of lipids in geobiology, microbial ecology, and organic geochemistry. After further developing protocols for handling different kinds of environmental samples, ToF‐SIMS could be used as a tool to attack many challenging problems in these fields, such as the attribution of biological source(s) to particular biomarkers in question, or the high‐resolution tracking of biogeochemical processes in modern and ancient natural environments.
Molecular characterization of microbial communities in deep coal seam groundwater of northern Japan
Authors: SHIMIZU S. , AKIYAMA M. , NAGANUMA T. , FUJIOKA M. , NAKO M. , ISHIJIMA Y.
Published: September 2007

We investigated microbial methanogenesis and community structure based on 16S rRNA gene sequences from a coal seam aquifer located 843–907 m below ground level in northern Japan; additionally, we studied the δ13C and δ2H (δD) of coal‐bed gases and other physicochemical parameters. Although isotopic analysis suggested a thermocatalytic origin for the gases, the microbial activity and community structure strongly implied the existence of methanogenic microbial communities in situ. Methane was generated in the enrichment cultures of the hydrogenotrophic and methylotrophic microorganisms obtained from coal seam groundwater. Methanogen clones dominated the archaeal 16S rRNA gene libraries and were mostly related to the hydrogenotrophic genus Methanoculleus and the methylotrophic genus Methanolobus. Bacterial 16S rRNA gene libraries were dominated by the clones related to the genera Acetobacterium and Syntrophus which have a symbiotic association with methanogens. LIBSHUFF analysis revealed that N2 gas injected into the coal seam (for enhanced methane production) does not affect the coverage of archaeal and bacterial populations. However, amova analysis does provide evidence for a change in the genetic diversity of archaeal populations that are dominated by methanogens. Therefore, N2 injection into the coal seam might affect the cycling of matter by methanogens in situ.
Early colonization of thermal niches in a silica‐depositing hot spring in central Tibet
Authors: LAU C. Y. , AITCHISON J. C. , POINTING S. B.
Published: September 2007

Thermophilic microbial mats dominated by the anoxygenic phototroph Roseiflexus castenholzii commonly develop around sinter‐depositing geysers in the Daggyai Tso geothermal field of central Tibet. In this study we used morphological and molecular genetic techniques to reveal a diverse pioneer biofilm community including both archaea and bacteria involved in early colonization of such thermal niches at temperatures ranging from 46 to 77 °C. Sinter precipitation and biomineralization were evident at all locations, but the latter was selective between taxa and most evident on filamentous cells. Evidence for possible indirect biosignatures from biofilms overwhelmed by sinter deposition was found. Succession to a mature community appeared to relate to the growth rate for key taxa outpacing that of silicification within an optimum temperature range of 54–61 °C. The thin surface layer of silicification‐resistant cyanobacteria that developed on the surface of mature mats may play a role in preventing biomineralization of the susceptible R. castenholzii beneath within these communities.
The Precambrian emergence of animal life: a geobiological perspective
Authors: GAIDOS E. , DUBUC T. , DUNFORD M. , MCANDREW P. , PADILLA‐GAMIÑO J. , STUDER B. , WEERSING K. , STANLEY S.
Published: September 2007

The earliest record of animals (Metazoa) consists of trace and body fossils restricted to the last 35 Myr of the Precambrian. It has been proposed that animals arose much earlier and underwent significant evolution as a cryptic fauna; however, the need for any unrecorded prelude of significant duration has been disputed. In this context, we consider recent published research on the nature and chronology of the earliest fossil record of metazoans and on the molecular‐based analysis that yielded older dates for the appearance of major animal groups. We review recent work on the climatic, geochemical, and ecological events that preceded animal fossils and consider their portent for metazoan evolution. We also discuss inferences about the physiology and gene content of the last common ancestor of animals and their closest unicellular relatives. We propose that the recorded Precambrian evolution of animals includes three intervals of advancement that begin with sponge‐grade organisms, and that any preceding cryptic fauna would be no more complex than sponges. The molecular data do not require that more complex animals appeared well before the recognized fossil record; nor, however, do they rule the possibility out, particularly if the interval of simpler metazoan ancestors lasted no more than about 100 or 200 Myr. The geological record of abrupt changes in climate, biogeochemistry, and phytoplankton diversity can be taken to be the result of changes in the carbon cycle triggered by the appearance and diversification of metazoans in an organic carbon‐rich ocean, but as yet no compelling evidence exists for this interpretation. By the end of this cryptic period, animals would already have possessed sophisticated systems of cell–cell signalling, adhesion, apoptosis, and segregated germ cells, possibly with a rudimentary body plan based on anterior–posterior organization. The controls on the timing and tempo of the earliest steps in metazoan evolution are unknown, but it seems likely that oxygen was a key factor in later diversification and increase in body size. We consider several recent scenarios describing how oxygen increased near the end of the Precambrian and propose that grazing and filter‐feeding animals depleted a marine reservoir of suspended organic matter, releasing a microbial ‘clamp’ on atmospheric oxygen.
The problem of power and the politics of landscape: stopping the Greater Cairo ring road
Authors: Rose Mitch
Published: September 2007

This paper reconceptualises the politics of landscape as the precarious art of managing the unexpected. By telling the story of a campaign to stop the construction of a road through the Giza plateau in Egypt, the paper elucidates how political power is characterised not only by triumphal coalitions but also by insecurity, blindly grasped chances and pure luck. The paper elaborates on this story by presenting a conception of power not predicated on forces, consequences or effects but rather on the fundamental problem of temporal uncertainty. Through an engagement with Nietzsche, Deleuze and Derrida, the paper conceptualises time as the origin of uncertainty and, thus, the advent of politics itself.
The effects of party mobilisation strategies on the vote: The PSOE and the PP in the 1996 Spanish election
Authors: CRIADO HENAR
Published: September 2007

Abstract.  In this article, the author analyses the impact of parties' mobilisation strategies at the district level on their vote share in the Spanish 1996 general elections. In order to do this, the author has estimated a multilevel model to test the impact of aggregate mobilisation variables at the district level controlling for voters' individual characteristics. The efforts made by the two main Spanish parties increased their share of the vote. Moreover, their strategies seem to be more efficient for some profiles of voters than for others. The mobilisation of the PSOE especially affected those who had clear political preferences, whereas the PP's mobilisation had stronger effects on less politically aware voters.
The frog pond beauty contest: Physical attractiveness and electoral success of the constituency candidates at the North Rhine‐Westphalia state election of 2005
Authors: ROSAR ULRICH , KLEIN MARKUS , BECKERS TILO
Published: September 2007

Abstract.  Voters usually do not know much about the biography and political agenda of the local candidates for parliament in their constituency. Since posters with photographs of these candidates are omnipresent on the streets during the election campaign, many voters are at least familiar with their facial appearance. As a consequence, the attractiveness of the constituency candidates substantially influences voter behaviour. This is shown by the example of the North Rhine‐Westphalia state election of 2005. Judgments about the attractiveness of the constituency candidates were collected by means of a web survey among members of an online access panel. Respondents were confronted with portrait photographs of local candidates and asked to rate their attractiveness. According to the truth‐of‐consensus method, the attractiveness score of a candidate is computed by averaging across the different ratings he or she has received. Voter behaviour is captured by the real‐life election results in the constituencies.
Conceptual and Design Essentials for Evaluating Mechanisms of Change
Authors: Nock Matthew K.
Published: September 2007

Background:  Considerable progress has been made toward the development of evidence‐based treatments for a wide range of psychological disorders; however, little is known about the mechanisms through which these treatments actually lead to clinical change. Although the use of traditional randomized controlled treatment designs and tests of statistical mediation have significantly advanced understanding of psychological treatments, they are insufficient to test mechanisms of change.

Method:  This article outlines the conceptual and methodological requirements for evaluating mechanisms of change, highlights the importance of such a focus, and offers specific recommendations for research aimed at elucidating change mechanisms.

Results and Conclusions:  Conceptualizing and conducting studies that test mechanisms of change requires substantial modifications to traditional research designs, but doing so will significantly enhance scientific understanding as well as the efficiency and effectiveness of clinical interventions.
The Search for Mechanisms of Change in Behavioral Treatments for Alcohol Use Disorders: A Commentary
Authors: Longabaugh Richard
Published: September 2007

Background:  Definitive results from efforts to identify mechanisms of change in behavioral treatments for alcohol use disorders have been elusive. The working hypothesis guiding this paper is that one of the reasons for this elusiveness is that the models we hypothesize to account for treatments effectiveness are unnecessarily restricted and too simple.

Methods:  This paper aims to accomplish 3 things. First, a typography for locating potential mediators of change will be presented. In the course of doing so, a nomenclature will be proposed with the hope that this will facilitate communications among alcohol treatment researchers studying mechanisms of change. Second, alternatives to the classic test of mediation of alcohol treatment effects will be considered and one such alternative described. Third, alternative ways of conceptualizing, constructing and analyzing variables to measure mediators will be suggested.

Results:  It is hoped that this commentary will facilitate research on mechanisms of change in behavioral treatments for alcohol use disorders.

Conclusions:  Behavioral change is a complex process, and the models that we develop to account for this process need to reflect this complexity. Advances in statistical approaches for testing mediation, along with a better understanding as to how to use these tools should help in moving toward this goal.
Client Language as a Mediator of Motivational Interviewing Efficacy: Where Is the Evidence?
Authors: Moyers Theresa B. , Martin Tim , Christopher Paulette J. , Houck Jon M. , Tonigan J. Scott , Amrhein Paul C.
Published: September 2007

Background:  Identifying in‐session indicators of client outcomes is important in determining the mechanisms of psychotherapeutic treatments, including Motivational Interviewing (MI). The current studies sought to determine if clinician behavior influences client speech, and the extent to which client speech predicted treatment outcome in clients receiving treatment for substance abuse.

Methods:  Study 1 examined 38 sessions from 5 sites in Project MATCH. Sessions were coded using the Sequential Code for Process Exchanges (SCOPE) behavioral coding system. Transition probabilities and inter‐rater reliability were calculated. Study 2 examined 45 sessions from the New Mexico site in Project MATCH. Sessions were coded using the MISC 1.0 behavioral coding system. Distal outcome measures were calculated for proportion of days abstinent (PDA) and drinks per drinking day (DDD). Hierarchical multiple regression and hierarchical logistic regression were used to characterize the relationship between client speech and outcome.

Results:  In Study 1, inter‐rater reliability estimates indicate that coders reliably distinguished between the categories within the SCOPE. Behaviors consistent with MI (MICO) were significantly likely to be followed by client Change Talk (CT) and behaviors inconsistent with MI (MIIN) were significantly likely to be followed by Counterchange Talk (CCT). There was also a significant negative transition probability between MICO and CCT. In Study 2, CT was found to account for significant portions of outcome variability beyond that attributable to baseline measures of problem severity.

Conclusions:  Client speech during early therapy sessions appears to be a powerful predictor of substance abuse outcome. The pattern of therapist behaviors and subsequent client language found in this data supports the intervention test in the causal chain we have described for motivational interviewing. These studies provide preliminary support for a causal chain between therapist behaviors, subsequent client speech, and drinking outcomes within motivational interviewing sessions. The results of both studies provide further support to the proposition that client speech impacts the likelihood of behavioral change, and that the occurrence of such speech is influenced by the therapist.
Advances in Causal Chain Development and Testing in Alcohol Research: Mediation, Suppression, Moderation, Mediated Moderation, and Moderated Mediation
Authors: Wirtz Philip W.
Published: September 2007

Background:  While causal modeling is generally well known to alcohol researchers, several causal structures (including suppression, mediated moderation, and moderated mediation) are often poorly understood and seldom employed when investigators seek to model the complex mechanisms of behavior change, despite their widespread applicability to the field.

Methods:  This paper compares and contrasts five basic structures of causal modeling in the context of contemporary alcohol research and demonstrates how mechanisms of behavior change can be conceptualized and tested as parallel and serial sequences of these basic causal structures, forming causal chains.

Conclusion:  Recent methodological developments, while representing an important advancement for the field, fail to adequately address the complexities of alcohol dependence phenomena. A differentiation between frequently combined forms of these causal structures is proposed that would better address the needs of the field.
Treatment Processes and Mediators of Substance Use Disorders Treatment Effects: The Benefits of Side Road Excursions
Authors: Finney John W.
Published: September 2007

Background:  This article provides some commentary on six brief presentations on treatment processes and mediators of substance use disorder (SUD) treatment effects that were made at the 2005 Research Society on Alcoholism Satellite Preconference on “The Search for Mechanisms of Change in Evidence‐Based Behavioral Treatments.”

Methods:  Six presentations are discussed.

Results:  The foci of the presentations ranged from the linkages of intermediate outcomes of cognitive‐behavioral and 12‐step treatment (e.g., spirituality) to posttreatment substance use to the relationship between treatment completion of brief motivational interviewing and treatment outcome. None of the six presentations met all or even most of the criteria for analyses of mediation of intervention effects outlined by Kazdin and Nock. In fact, some did not examine mediation at all. However, the presentations were valuable in illustrating that important new knowledge can be gained from addressing SUD treatment processes and mechanisms of treatment change.

Conclusions:  Given the paucity of extant research on mediation of SUD treatment effects, correlational explorations of treatment processes and treatment mediators are useful at this point, even though most mediational analyses do not meet many of the criteria listed by Kazdin and Nock. More attention should be devoted to assessing mediators before the assessment of outcome variables (e.g., during treatment) in order to address temporal precedence. Only after reasonable evidence has accrued regarding statistical mediation (expected associations, temporal precedence, reduction in treatment effects when putative mediator is controlled) does it make sense to mount expensive studies with experimental designs to examine causal mediation effects.
A Broader View of Change in Drinking Behavior
Authors: Willenbring Mark L.
Published: September 2007

Most research concerning change in drinking behavior has taken place within the context of specialized treatment for a help‐seeking population. However, treatment approaches with different purported mechanisms of action yield very similar results, suggesting that common elements, rather than specific mechanisms, may be responsible for the bulk of the individual change process. Mechanisms of change have not been explicitly examined. Other factors such as social pressure may be more important mediators of change, which may occur prior to treatment entry. Also, most change occurs outside the context of specific treatment. A broader perspective focusing on mechanisms of change will need to account for change occurring both with and without professional treatment. Future research must be interdisciplinary in nature, seeking to relate social, behavioral, and neurophysiologic correlates of behavior change.
In Situ Synthesis of Porous Silicon Carbide (SiC) Ceramics Decorated with SiC Nanowires
Authors: Yoon Byung‐Ho , Park Chee‐Sung , Kim Hyoun‐Ee , Koh Young‐Hag
Published: September 2007

We fabricated highly aligned porous silicon carbide (SiC) ceramics decorated with SiC nanowires by the unidirectional freeze casting of SiC/camphene slurries with various polycarbosilane (PCS) contents, ranging from 0 to 20 wt% in relation to the SiC powders, in which the PCS preceramic was used as a binder and source for the in situ growth of the SiC nanowires. In this method, aligned pore channels were formed as a replica of the unidirectionally grown camphene dendrites, while SiC nanowires were formed within the pores in situ via a vapor–liquid–solid (VLS) mechanism during the heat treatment of the porous green bodies at 1400°C for 1 h in a flowing Ar atmosphere. The pore channels were well decorated with single‐crystalline SiC nanowires. It was also observed that the growth of the SiC nanowires was strongly affected by the initial PCS content and heat‐treatment temperature.
A Novel Route Involving an In Situ Chemical Reduction Process to the One‐Dimensional Nanostructures of Bismuth Trioxide
Authors: Sardar Kripasindhu , Fang Tsang‐Tse , Yang Tsao‐Wei
Published: September 2007

A bismuth citrate precursor has been used to yield bismuth trioxide with single‐crystalline one‐dimensional (1D) morphologies in the temperature range of 400°–600°C. The growth process of the nanorods has been investigated using a series of experiments wherein different polymorphs of Bi2O3 are developed along with the nonstoichiometric bismuth oxides. The nonstoichiometric oxides are generated in situ and facilitate the formation of metastable polymorphs and 1D nanostructures of Bi2O3.
Preparation and Microstructure of a ZrB2–SiC Composite Fabricated by the Spark Plasma Sintering–Reactive Synthesis (SPS–RS) Method
Authors: Zhao Yuan , Wang Lian‐Jun , Zhang Guo‐Jun , Jiang Wan , Chen Li‐Dong
Published: September 2007

A mixture of Zr, B4C, and Si powders was adopted to synthesize a ZrB2–SiC composite using the spark plasma sintering–reactive synthesis (SPS–RS) method. SPS treatments were carried out in the temperature range of 1350°–1500°C under a varying pressure of 20–65 MPa with a 3‐min holding time. A dense (∼98.5%) ZrB2–SiC composite was successfully fabricated at 1450°C for 3 min under 30 MPa. The microstructure of the composite was investigated. The in situ formed ZrB2 and SiC phases dispersed homogeneously on the whole. The grain size of ZrB2 and SiC was <5 and 1 μm, respectively. A number of in situ formed ultrafine SiC particles were observed entrapped in the ZrB2 grains.
IDENTIFYING THE PSYCHOLOGICAL FACTORS THAT MEDIATE THE ASSOCIATION BETWEEN PARENTING PRACTICES AND DELINQUENCY*
Authors: SIMONS RONALD L. , SIMONS LESLIE GORDON , CHEN YI‐FU , BRODY GENE H. , LIN KUEI‐HSIU
Published: September 2007

Past research has largely ignored the developmental changes within the child that account for the association between parenting and risk for delinquency. We used structural equation modeling and data from a longitudinal study of several hundred African‐American families to test the contentions of various theories regarding the sociocognitive and emotional factors that mediate the impact of parental behavior on a youth's risk for delinquency. Our findings largely supported the theories. The impact of monitoring/discipline was indirect through low self‐control and acceptance of deviant norms, whereas the effect of hostility/ rejection was indirect through low self‐control, hostile view of relationships, and acceptance of deviant norms. These two dimensions of parenting were no longer related either to affiliation with deviant peers or to conduct problems once the effects of these psychological characteristics were taken into account; the impact of these parenting practices was completely mediated by these four cognitive/affective variables. Contrary to expectation, however, these psychological factors did not mediate any of the relationship between caretaker involvement in antisocial behavior and child conduct problems.
Epidemiology of hepatocellular carcinoma in Japan
Authors: Umemura Takeji , Kiyosawa Kendo
Published: September 2007

Primary liver cancer, 95% of which is hepatocellular carcinoma (HCC), has ranked third in men and fifth in women as a cause of death from malignant neoplasm in Japan. Although the number of deaths and death rates from HCC increased until 2002 in Japan, annual deaths (34 089) and the death rate (27.0/100 000) from liver cancer decreased in 2003. Hepatitis C virus (HCV)‐related HCC represents 75% of all HCC in Japan. The incidence of HCC without hepatitis B surface antigen (HBsAg) or anti‐HCV accounted for 7–12% of HCC in Japan andhalf of non‐B non‐C‐HCC was of unknown origin. Geographically, HCC is more frequent in western than eastern Japan, and the death rates from HCC in each prefecture correlate with the prevalence of anti‐HCV, but not with HBsAg prevalence. Interferon therapy for chronic hepatitis C has reduced the risk factors for development of HCC, especially among patients with sustained response.
Liver cancer in Korea
Authors: Han Kwang‐Hyub , Kim Ja Kyung
Published: September 2007

Hepatocellular carcinoma (HCC) is a highly malignant cancer and third major cause of death in Korean. It is more prevalent among men in the sixth to seventh decades. HCC is particularly prevalent in Korea where the age‐standardized incidence rate is 45.0/100 000 population in males and 12.0/100 000 population in females. The death rate from HCC is 20.0/100 000 population. Approximately 65–75% of HCC patients were positive for hepatitis B surface antigen (HBsAg), where 10–20% of patients were anti‐hepatitis C virus (HCV) positive. The high incidence rate of HCC in Korea is thought to be related to the high carrier rate of hepatitis B virus (HBV) in the general population. For primary prevention, a nationwide HBV vaccination program has been conducted since the late1980s in Korea. Although advances have been made in the various methods of management of HCC, there has been little overall survival improvement during the past 20 years. Only few patients are candidates for potentially curative forms of treatment. Therefore, the early detection of HCC is a key issue. When compared with clinical outcomes of HCC based on recent 10‐year institutional data, our screening and surveillance programs might enable early detection and increased applicability of curative treatments.
Pathogenesis of HCV‐associated HCC: Dual‐pass carcinogenesis through activation of oxidative stress and intracellular signaling
Authors: Koike Kazuhiko
Published: September 2007

Overwhelming lines of epidemiological evidence have indicated that persistent infection with hepatitis C virus (HCV) is a major risk toward development of hepatocellular carcinoma (HCC). It remains controversial, however, in the pathogenesis of HCC associated with HCV, whether the virus plays a direct role or merely an indirect one. The studies using transgenic mouse models by us and others, in which the core protein of HCV has oncogenic potential, indicate that HCV is directly involved in hepatocarcinogenesis, albeit other factors such as continued cell death and regeneration associated with inflammation would play a role, as well. The downstream events of the core protein are segregated into two components. One is the augmented production of oxidative stress along with the activation of scavenging system including catalase and glutathion (GSH) in the putative preneoplastic stage with steatosis in the liver. Thus, oxidative stress production in the absence of inflammation by the core protein would partly contribute to the development of HCC. The generation of oxidative stress is estimated to originate from mitochondrial dysfunction in hepatocytes by HCV infection. The other is the alteration of intracellular signaling cascade of MAPK (JNK),AP‐1, cyclin D1, and CDK4. The combination of these pathways, collective with HCV‐associated alterations in lipid and glucose metabolism, would lead to the frequent development of HCC in persistent HCV infection. Our results suggest that there would be a mechanism for hepatocarcinogenesis in persistent HCV infection that is distinct from those for other cancers. Similar to the pathogenesis of other cancers, the accumulation of a set of genetic aberrations may also be necessary for multistage development of HCC. However, HCV core protein, to which an oncogenic potential is ascribed, may allow some of the multiple steps to be bypassed in hepatocarcinogenesis. Therefore, unlike other cancers, HCV infection can elicit HCC in the absence of a complete set of genetic aberrations. Such a scenario, “non‐Vogelstein‐type” carcinogenesis, would explain the unusually high incidence and multicentric nature of HCC development in HCV infection.
Diagnostic discrepancy of early hepatocellular carcinoma between Japan and West
Authors: Kojiro Masamichi
Published: September 2007

The diagnoses for a range of hepatocellular neoplastic lesions amongst Japanese and Western pathologists show a striking lack of consistency, especially in distinguishing dysplastic nodules (DN) from very well‐differentiated hepatocellular carcinomas (HCC). Namely, very well‐differentiated HCC showing a vaguely nodular appearance diagnosed by Japanese pathologists tends to be diagnosed as high‐grade DN by Western pathologists. Both Japanese and Western pathologists agreed that “stromal invasion”, which is tumor cell invasion into the intra‐tumoral portal tracts, is considered the most helpful morphologic clue to distinguish high‐grade DN from well‐differentiated HCC.
Hepatocellular dysplastic nodules
Authors: Roncalli Massimo , Borzio Mauro , Di Tommaso Luca
Published: September 2007

The multistep process of hepatic carcinogenesis is mirrored by the morphologic classification of lesions detectable in cirrhosis, which include large regenerative nodules (LRN), low grade dysplastic nodules (LGDN), and high grade dysplastic nodules (HGDN). The latter belong to the “bordeline malignancy” category requiring accurate distinction from well‐differentiated and early hepatocellular carcinoma (HCC). Nodules in cirrhosis are usually detected by non‐invasive imaging techniques, which are unable to discriminate malignant from non‐malignant forms, particularly in the 1–2‐cm sized group. Liver biopsy is essential in providing practical diagnostic information to hepathologists in the management of cirrhotic patients with ultrasound (US)‐detectable nodules. Histologic diagnosis on liver samples is based on the accurate search of a set of cyto‐architectural features (e.g. cell atypia, cell crowding, trabecular thickness, microacini) and by a supplement of histochemical (Gomori staining) and immunocytochemical stainings. The latter rely upon the search of both well established and novel markers, targeted to evaluate stromal invasion (CK7/19), the vascular pattern (ASMA and CD34), or tumor markers (including HSP70 and glipican‐3). Still, the diagnostic sensitivity is limited by the type and size of sampling and by its representativity of the entire lesion. Thus, the best diagnostic approach requires the integration ofclinical, morphological, and immunocytochemical information with imaging data (i.e. US pattern, perfusional pattern, helical computed tomography/magnetic resonance pattern). Molecular data are still under evaluation as to their diagnostic efficacy in this controversial field. Discrepancies have emerged recently between Eastern and Western interpretation of these lesions, particularly in the category of “borderline” nodules that are mostly labelled as early, well differentiated HCC by Eastern pathologists and as HGDN by Western pathologsts. Novel and more objective phenotypical and molecular markers are needed to discriminate within the grey area of borderline lesions that, epidemiologically, are likely distinct between Eastern and Western geographic areas. These tools might allow a better understanding of the boundaries of the process going from high grade dysplasia to in situ HCC and from the latter to microinvasive HCC and advanced HCC, for proper clinical management and optimal therapy.
International consensus on histologic diagnosis of early hepatocellular neoplasia
Authors: Wanless Ian R.
Published: September 2007

1. The precursor lesions for the development of hepatocellular carcinoma are believed to be high‐grade dysplastic nodules. These lesions have atypical and proliferative features that distinguish them from normal or cirrhotic liver but are not sufficient for the diagnosis of carcinoma.

2. Individual HGDN are often heterogeneous and complete sampling may reveal regions of carcinoma within these otherwise benign lesions.

3. Invasion of stroma is considered a definitive feature of HCC. However, this feature is not always present in early HCC and is seldom found in needle biopsies.

4. Accurate diagnosis of dysplastic nodules and well‐differentiated HCC requires skill and experience. However, accurate diagnosis with needle biopsies may be impossible if the highest grade of atypia is not sampled. Fine needle aspiration is not appropriate for small lesions that are expected to be early hepatic neoplasia. This technique should be reserved for suspected moderate‐ or poorly differentiated HCC.
Doppler and harmonic ultrasound for hepatocellular carcinoma
Authors: Choi Byung Ihn
Published: September 2007

Ultrasound (US) is the imaging method most frequently used for the detection and diagnosis of hepatocellular carcinoma (HCC). US image quality has greatly improved in recent years, with advances in transducer, beam‐former technology and sophisticated image processing. In addition, the recent availability of US contrast agents including first‐ and second‐generation contrast agents and the remarkable advances in US technology have led to the rapid development of new imaging methods such as low and high mechanical index (MI) imaging technology for the vascular phase and parenchymal phase of the liver. In terms of contrast agent, most reported studies in Asian countries have used a very fragile, first‐generation microbubble agent. Nowadays, more stable,second‐generation contrast agents are developing and used in clinical application to the liver. In the future, better results can be obtained in the diagnosis of HCC, decision of treatment method and assessment of therapeutic response if more durable contrast agents are used with advanced US techniques. In this article, the principles, methods, imaging findings and potential roles of new diagnostic US techniques with contrast agents in the diagnosis of HCC are discussed.
New sonographic techniques for the diagnosis and treatment of hepatocellular carcinoma
Authors: Kudo Masatoshi
Published: September 2007

Ultrasound (US) contrast agents such as Levovist and Sonazoid are now commercially available in Japan. Innovative contrast agents and ultrasound technologies have dramatically changed both diagnostic and treatment strategies for hepatocellular carcinoma (HCC). Contrast‐enhanced US is extremely useful in the differential diagnosis of hepatic tumors as well as in evaluation of post‐treatment response of HCC after lipiodol transarterial chemoembolization and radio frequency ablation. Harmonic US sensitively detects residual cancer cells in HCC patients after treatment, to facilitate accurate guidance for needle insertion for US monitoring; no other imaging modalities, including computed tomography (CT) or magnetic resonance imaging (MRI), have such capability. In 2005, the breakthrough technology of pure arterial phase imaging, which depicts only intranodular arterial accumulated maximum intensity projection images, was developed from advanced raw data storing and accumulation technologies. This technique can clearly identify whether blood supplyin the tumor is of arterial or portal origin, to facilitate the non‐invasive characterization of nodular lesions associated with liver cirrhosis. Again, CT or MRI do not have such capabilities. This innovative technique can help differentiate premalignant lesions from overt HCC. Concurrent real‐time imaging of multi‐detector CT and US, known as real‐time virtual sonography, has recently become available. This technique greatly facilitates the treatment guidance for HCC. These newly introduced sonographic techniques are dramatically changing the diagnostic and therapeutic strategies for HCC, which are expected to improve the prognosis of HCC patients.
Imaging of multistep human hepatocarcinogenesis
Authors: Matsui Osamu , Gabata Tosifumi , Kobayashi Satoshi , Terayama Noboru , Sanada Junn‐ichiro , Kouda Wataru , Kawashima Hiroko
Published: September 2007

In Japan, there are approximately 32 000 deaths (∼30 deaths per 100 000) per year due to hepatocellular carcinoma (HCC), and it is the third most common cancer in men and fifth in women. Approximately 90% of them are associated with chronic liver diseases due to hepatitis C or B virus infection. Therefore, it has become possible to detect small early stage HCC by the periodic screening in these high‐risk patients group. During the screening imaging diagnosis of HCC, various kinds of hepatocellular nodules are also frequentlydetected. To characterize them is very important for the early diagnosis and treatment of HCC. For this purpose, it is necessary to understand the concept of multistep hepatocarcinogenesis and the sequential changes of imaging findings.
Cancer of the Liver Italian Program (CLIP) score for staging hepatocellular carcinoma
Authors: Daniele Bruno , Annunziata Mena , Barletta Emiddio , Tinessa Vincenza , Di Maio Massimo
Published: September 2007

Aim:  To assess the prognostic ability of the Cancer of the Liver Italian Program (CLIP) score in patients with hepatocellular carcinoma after a longer follow up.

Methods:  The updated survival data were derived from an analysis that was performed on two joined sets of data. The first set was collected retrospectively in 1995 and was used to perform an exploratory prognostic factor analysis (the CLIP‐03 study), that produced the CLIP score. The second set of data was collected prospectively for the CLIP‐01 randomized clinical trial.

Results:  Out of 912 overall patients, analysis was performed on 650 patients whose records contained all informationregarding prognostic factors. The median survival of the whole group of patients was 17.7 months and the 5‐year survival rate was 10.7%. The median survival of the patients was inversely proportional to the CLIP score: the higher the CLIP score the worse the survival.

Conclusions:  The CLIP score keeps good prognostic and discriminative abilities after a longer follow up and remains one the most useful prognostic system for hepatocellular carcinoma.
International comparison of treatment outcomes based on staging systems
Authors: Kudo Masatoshi
Published: September 2007

Treatment outcomes were compared among several countries based on different staging systems. Data were collected from published data. Treatment outcomes based on Cancer of the Liver Italian Program (CLIP) scores 0–3 were best in Japan when compared among several countries. Furthermore, treatment outcomes in Japan based on Japan Integrated Staging (JIS) scores 0–3 were much better than in the USA. However, Barcelona Clinic Liver Cancer (BCLC) staging was not useful forinternational comparison, suggesting that BCLC staging is not helpful for prognostic staging but for treatment allocation staging. This is an extremely important point, which should be kept in mind.
Repeated radiofrequency ablation for the distant recurrence in the liver in patients with chronic hepatitis C virus infection achieving long‐term survival
Authors: Izumi Namiki , Asahina Yasuhiro , Tsuchiya Kaoru , Kurosaki Masayuki , Nakanishi Hiroyuki , Kitamura Takatoshi , Uchihara Masakatsu , Miyake Schozo
Published: September 2007

Recurrence of hepatocellular carcinoma (HCC) is frequently observed in patients with hepatitis C virus (HCV) infection and the incidence of HCC recurrence is as high as 20% in these patients even after a complete curative treatment is given for the HCC nodules. We report a 57‐year‐old female who was referred to our hospital for the treatment of a HCC nodule of 1.8 cm diameter in S5 and having liver cirrhosis of Child–Pugh A classification with HCV infection in April 1999. The HCC nodule showed hypervascularity by computed tomography during hepatic arteriography (CTHA) and was coagulated by microwave under peritoneoscopy. Complete necrosis was confirmed by enhanced‐CT scan after microwave coagulation. Thereafter, interferon alfa‐2b (3MU, twice weekly) was given but HCV RNA continued to be positive. Thereafter, recurrence of HCC was noted five times in S1, S2, S6; treatment by radiofrequency ablation was given four times; and transarterial chemoembolization was carried out once. Since January 2004, peg‐interferon alfa‐2a (90 µm/week) has been administered, and no recurrence has been detected until August 2005. She is currently 63 years old, and quite well. Five‐year‐survival rate in HCC patients treated by radiofrequency ablation is 62.7% in our hospital, however, the recurrence rate is as high as 26.4% per year in the patients with chronic HCV infection. It is a point of controversy when liver transplantation should be recommended in HCC patients with liver cirrhosis of Child‐Pugh A classification having chronic HCV infection because of the high incidence of recurrence.
Expanded criteria for liver transplantation in patients with hepatocellular carcinoma
Authors: Yao Francis Y.
Published: September 2007

Following the seminal publication by the group from Milan, Italy using a restrictive set of criteria for orthotopic liver transplantation in patients with hepatocellular carcinoma to limit the risk for tumor recurrence, excellent 5‐year patient survival of greater than 70% after liver transplantation has been reported from many centers using criteria similar to or slightly exceeding the Milan criteria (single lesion of ≤5 cm, or 2–3 lesions of ≤3 cm). The growing experience and success of orthotopic liver transplantation for HCC have also fueled controversies related to expansion of conventional criteria for cadaveric or living‐donor liver transplantation based on tumor size and number. The limitations of imaging studies, exemplified by tumor under‐staging in up to 25% of patients,have been a major concern for liberalizing the current criteria for liver transplantation. The University of California, San Francisco criteria (single lesion of ≤6.5 cm, or 2–3 lesions of ≤4.5 cm with a total tumor diameter ≤8 cm) have been independently tested in several studies, and undergone prospective evaluation based on preoperative imaging. This article provides an in‐depth review of published data on expansion of current criteria for liver transplantation.