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S. Kitauchi [1] H. Ohata [2] A. Yoshikawa [2] O. Mohara [2] M. Iwane [2] K. Mugitani [2] K. Yanaoka [1] H. Tamai [1] M. Ichinose [1] [10/12] High Risk [...]

A. Shiotani [1] M. Iguchi [2] H. Magari [2] I. Imoue [2] K. Yanaoka [2] I. Inoue [2] [5/01] Associations between Gastric Myoelectrical Activity and Intraluminal Nitric Oxide Background: We [...]

It has recently been demonstrated that nitric oxide (NO) is highly concentrated in the gastric lumen and plays an important role in defending against pathogenic microorganisms in the stomach. NO in the gastric lumen is mainly delivered by extrinsic sources from saliva. We studied whether Helicobacter pylori infection affected intraluminal NO levels in humans. H. pylori infection was diagnosed on the basis of histology and culture or (13C)-urea breath test. Air and gastric juice in the gastric lumen were collected endoscopically. The concentration of intraluminal NO was measured by a chemiluminescence system, using an NO analyzer. The concentration of nitrite in gastric juice was measured by the Griess reaction. The intraluminal concentration of NO in H. pylori-positive patients (198.2 +/- 41 parts per billion [ppb] mean +/- SE; n = 70) was significantly lower than that in H. pylori-negative patients (353.0 +/-57.9ppb; n = 43; P < 0.05). In contrast, the concentration of nitrite in gastric juice in H. pylori-positive patients (57.7 +/- 12.3 RM; n = 70) was significantly higher than that in H. pylori-negative patients (25.9 +/- 6.4 microM; n = 43, P < 0.01). The intraluminal concentration of NO in H. pylori-positive patients was markedly increased and the concentration of nitrite in H. pylori-positive patients was markedly decreased following the completion of eradication therapy. Based on these results, we propose that a decrease in NO and excess nitrite production in the gastric lumen are associated with H. pylori infection and may play an important role in the pathogenesis of H. pylori-related abnormalities. [ABSTRACT FROM AUTHOR]

BACKGROUND: Phase I/II clinical trials of S-1 plus cisplatin for advanced gastric cancer have yielded good responses and the treatment was well tolerated. In this S-1 Plus cisplatin versus S-1 In RCT In the Treatment for Stomach cancer (SPIRITS) trial, we aimed to verify that overall survival was better in patients with advanced gastric cancer treated with S-1 plus cisplatin than with S-1 alone. METHODS: In this phase III trial, chemotherapy-naive patients with advanced gastric cancer were enrolled between March 26, 2002, and Nov 30, 2004, at 38 centres in Japan, and randomly assigned to S-1 plus cisplatin or S-1 alone. In patients assigned to S-1 plus cisplatin, S-1 (40-60 mg depending on patient's body surface area) was given orally, twice daily for 3 consecutive weeks, and 60 mg/m(2) cisplatin was given intravenously on day 8, followed by a 2-week rest period, within a 5-week cycle. Those assigned to S-1 alone received the same dose of S-1 twice daily for 4 consecutive weeks, followed by a 2-week rest period, within a 6-week cycle. The primary endpoint was overall survival. Secondary endpoints were progression-free survival, proportions of responders, and safety. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00150670. FINDINGS: 305 patients were enrolled; seven patients were ineligible or withdrew consent, therefore, 148 patients were assigned to S-1 plus cisplatin and 150 patients were assigned to S-1 alone. Median overall survival was significantly longer in patients assigned to S-1 plus cisplatin (13.0 months [IQR 7.6-21.9]) than in those assigned to S-1 alone (11.0 months [5.6-19.8]; hazard ratio for death, 0.77; 95% CI 0.61-0.98; p=0.04). Progression-free survival was significantly longer in patients assigned to S-1 plus cisplatin than in those assigned to S-1 alone (median progression-free survival 6.0 months [3.3-12.9] vs 4.0 months [2.1-6.8]; p<0.0001). Additionally, of 87 patients assigned S-1 plus cisplatin who had target tumours, one patient had a complete response and 46 patients had partial responses, ie, a total of 54% (range 43-65). Of 106 patients assigned S-1 alone who had target tumours, one patient had a complete response and 32 had partial responses, ie, a total of 31% (23-41). We recorded more grade 3 or 4 adverse events including leucopenia, neutropenia, anaemia, nausea, and anorexia, in the group assigned to S-1 plus cisplatin than in the group assigned to S-1 alone. There were no treatment-related deaths in either group. INTERPRETATION: S-1 plus cisplatin holds promise of becoming a standard first-line treatment for patients with advanced gastric cancer. [ABSTRACT FROM AUTHOR]

What factors lead children to delay gratification, holding out for larger rewards later instead of taking smaller rewards now? Traditionally, delay of gratification has been associated with effortful control and willpower. However, we propose that delay of gratification may be partially supported by effortless control employed through habits shaped within sociocultural contexts. Specifically, in sociocultural contexts where waiting is rewarding and socially valued, children are more likely to wait for larger, delayed rewards and to form associations between these contexts and waiting for rewards. These acquired habits enable waiting for rewards without requiring substantial cognitive effort. Based on this novel framework, we reconsider why childhood delay of gratification predicts life outcomes, and the role of cognitive, social, and cultural factors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Cognitive control is a hallmark of human cognition. A large number of studies have focused on the plasticity of cognitive control and examined how repeated task experience leads to the improvement of cognitive control in novel task environments. However, it has been demonstrated that training-induced changes are very selective and that transfer occurs within one task paradigm but not across different task paradigms. The current study tested the possibility that cross-paradigm transfer would occur if a common cognitive control strategy is employed across different task paradigms. Specifically, we examined whether prior experience of using reactive control in one task paradigm (i.e., either the cued task-switching paradigm or the AX-CPT) makes adults (N = 137) and 9- to 10-year-olds (N = 126) respond in a reactive way in a subsequent condition of another task paradigm in which proactive control could have been engaged. Bayesian generalized mixed-effects models revealed clear evidence of an absence of cross-paradigm transfer of reactive control in both adults and school-aged children. Based on these findings, we discuss to what extent learned control could be transferred across different task contexts and the task-specificity of proactive/reactive control strategies., (© 2024. The Psychonomic Society, Inc.)

Experience with instances that vary in their surface features helps individuals to form abstract task knowledge, leading to transfer of that knowledge to novel contexts. The current study sought to examine the role of this variability effect in how adults and school-aged children learn to engage cognitive control. We focused on the engagement of cognitive control in advance (proactive control) and in response to conflicts (reactive control) in a cued task-switching paradigm, and conducted four preregistered online experiments with adults (Experiment 1A: N = 100, Experiment 1B: N = 105) and 9- to 10-year-olds (Experiment 2A: N = 98, Experiment 2B: N = 97). It was shown that prior task experience of engaging reactive control makes both adults and 9- to 10-year-olds respond more slowly in a subsequent similar-structured condition with different stimuli in which proactive control could have been engaged. 9- to 10-year-olds (Experiment 2B) exhibited more negative transfer of a reactive control mode when uninformative cue and pre-target stimuli, which do not convey task-relevant information, were changed in each block, compared with when they were fixed. Furthermore, adults showed suggestive evidence of the variability effect both when cue and target stimuli were varied (Experiment 1A) and when uninformative cue and pre-target stimuli were varied (Experiment 1B). The collective findings of these experiments provide important insights into the contribution of stimulus variability to the engagement of cognitive control., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Engaging cognitive control is essential to flexibly adapt to constantly changing environments. However, relatively little is known about how prior task experience impacts on the engagement of cognitive control in novel task environments. We aimed to clarify how individuals learn and transfer the engagement of cognitive control with a focus on the hierarchical and temporal aspects of task knowledge. Highlighting two distinct cognitive control processes, the engagement of cognitive control in advance (proactive control) and in response to conflicts (reactive control), we conducted six preregistered online experiments with both adults (Experiment 1, 3, and 5: N = 71, N = 108, and N = 70) and 9- to 10-year-olds (Experiment 2, 4, 6: N = 69, N = 108, and N = 70). Using two different experimental paradigms, we demonstrated that prior task experience of engaging reactive control makes adults and 9-to 10-year-olds respond in a reactive way in a subsequent similar-structured condition with different stimuli in which proactive control could have been engaged. This indicates that individuals do learn knowledge about the temporal structure of task goal activation and, on occasion, negatively transfer this knowledge. Furthermore, individuals exhibited these negative transfer effects in a similar-structured condition with different task goals and stimuli, indicating that they learn hierarchically-structured task knowledge. The collective findings suggest a new way of understanding how hierarchical and temporal task knowledge influences the engagement of cognitive control and highlight potential mechanisms underlying the near transfer effects observed in cognitive control training., Competing Interests: Declaration of Competing Interest We have no conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Children engage cognitive control reactively when they encounter conflicts; however, they can also resolve conflicts proactively. Recent studies have begun to clarify the mechanisms that support the use of proactive control in children; nonetheless, sufficient knowledge has not been accumulated regarding these mechanisms. Using behavioral and pupillometric measures, we tested the novel possibility that 5-year-old children (N = 58) learn to use proactive control via the acquisition of abstract task knowledge that captures regularities of the task. Participants were assigned to either a proactive training group or a control training group. In the proactive training group, participants engaged in a training phase where using proactive control was encouraged, followed by a test phase using different stimuli where both proactive and reactive control could be used. In the control training group, participants engaged in a training phase where both cognitive control strategies could be used, followed by a similarly-structured test phase using different stimuli. We demonstrated children in the control training group responded more quickly and accurately and showed greater cue-related pupil dilation in the test phase than in the training phase. However, there were no differences in response times, accuracies, and pupil dilation between the proactive and control training groups in the training and test phases. These findings suggest that prior task experience, that goes beyond specific knowledge about the timing of task goal activation, can lead children to engage more proactive control endogenously, even if they are not directly encouraged to do so., (© 2021 John Wiley & Sons Ltd.)

This study examined whether or not the number of topic-attributed features affects the speakers' use of metaphor production rather than literal expressions. Across two experiments, participants were asked to produce an expression that best paraphrased a given sentence. The number of features attributed to each topic was manipulated: one feature ("Her sarcasm hurts people"), two features ("Her sarcasm hurts people and is sharp"), and three features ("Her sarcasm hurts people, is sharp, and is piercing to the heart"). Participants' responses were classified into nominal metaphor/simile, literal, other metaphor/simile, and others. In both Experiment 1 and Experiment 2, participants' nominal metaphor responses (e.g., "Her sarcasm is a knife") increased with the number of topic-vehicles that shared significant features in a given sentence. These results suggest that the number of topic-attributed features affects participants' preference for the use of metaphorical expressions. We discussed the results based on the compactness hypothesis (Ortony, Educational Theory, 25: 45-53, 1975) of metaphor production., (© 2022. The Psychonomic Society, Inc.)

Resisting immediate temptations in favor of larger later rewards predicts academic success, socioemotional competence, and health. These links with delaying gratification appear from early childhood and have been explained by cognitive and social factors that help override tendencies toward immediate gratification. However, some tendencies may actually promote delaying gratification. We assessed children's delaying gratification for different rewards across two cultures that differ in customs around waiting. Consistent with our preregistered prediction, results showed that children in Japan ( n = 80) delayed gratification longer for food than for gifts, whereas children in the United States ( n = 58) delayed longer for gifts than for food. This interaction may reflect cultural differences: Waiting to eat is emphasized more in Japan than in the United States, whereas waiting to open gifts is emphasized more in the United States than in Japan. These findings suggest that culturally specific habits support delaying gratification, providing a new way to understand why individuals delay gratification and why this behavior predicts life success.

Our daily lives are composed of several sequential actions that we perform routinely, such as making breakfast, taking a train, and changing clothes. Previous research has demonstrated that a routine system plays a role in performing and controlling repeated sequential actions in familiar situations, and a top-down control system involves the control of the routine system in novel situations. Specifically, most developmental studies have focused on the top-down control system (e.g., executive functions) as a factor enabling the control of goal-directed actions in novel situations. Yet, it has not been thoroughly examined how young children learn, perform, and control repeated sequential actions in familiar contexts. In this review, based on recent computational accounts for adults, we highlight two critical aspects of the routine system from a developmental perspective: (1) automatic flexible changes of contextual representations, which enables humans to select context-dependent actions appropriately; and (2) detection of deviant situations, which signals the need for control to avoid errors. In addition, we propose the developmental mechanism underlying the routine system and its potential driving factors such as statistical regularities and executive functions. Finally, we suggest that an investigation into the interplay between routine and executive functions can form foundations for understanding learning, performing, and controlling repeated sequential actions in young children and discuss future directions in this area., (© 2021 Cognitive Science Society LLC.)

This study examined whether executive functions impact how flexibly children represent task context in performing repeated sequential actions. Japanese children in Experiments 1 (N = 52; 3-6 years) and 2 (N = 50, 4-6 years) performed sequential actions repeatedly; one group received reminders. Experiment 1 indicated that reminders promote flexible changes in contextual representations. Experiment 2 observed such effects in younger children and showed executive functions were associated with the flexible representation of task context. Reminders did not perfectly compensate for the role of executive functions but wiped out individual differences in executive functions that contribute to children's acquisition of routines. Therefore, setting goals before context-dependent actions is necessary, but not sufficient, to modulate contextual representations in routines., (© 2020 Society for Research in Child Development.)

Active maintenance of goal representations is an integral part of our mental regulatory processes. Previous developmental studies have highlighted goal neglect, which is the phenomenon caused by a failure to maintain goal representations, and demonstrated developmental changes of the ability to maintain goal representations among preschoolers. Yet, few studies have explored the cognitive mechanisms underlying preschoolers' development of goal maintenance. The first aim of this study was to test whether working memory capacity and inhibitory control contribute to goal maintenance using a paradigm for measuring goal neglect. Moreover, although recent studies have shown that preschoolers recruit lateral prefrontal regions in performing executive functions tasks, they could not specify the neural underpinnings of goal maintenance. Thus, the second aim was to examine whether lateral prefrontal regions played a key role in maintaining goal representations using functional near-infrared spectroscopy. Our results showed that developmental differences in inhibitory control predicted the degree of goal neglect. It was also demonstrated that activation in the right prefrontal region was associated with children's successful avoidance of goal neglect. These findings offer important insights into the cognitive and neural underpinnings of goal maintenance in preschoolers., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The Hebb repetition paradigm has recently attracted attention as a measure of serial order learning, which underlies word-form learning abilities. Although children are good vocabulary learners, it is surprising that previous Hebb learning studies with young children show rather weak Hebb effects. In this study, we conducted two experiments to identify developmental factors that drive an increase of the size of the Hebb effect in young children. Motivated by evidence from adult work, we focused on an ability to group a sequence into consistent subsequences and on phonological short-term memory (STM) capacity. In Experiment 1 ( N = 98), it was shown that 3- to 5-year-old children with high phonological STM capacity showed a Hebb effect, particularly in the later experimental trials. In Experiment 2 ( N = 97), temporal grouping of the sequences in 2-2 subsequences further encouraged children with high phonological STM capacity to show the Hebb effect even in the earlier experimental trials and children with low STM capacity to show a trend toward a Hebb effect in the later trials. Moreover, across Experiments 1 and 2 we found robust evidence of transfer of the Hebb effect to recall of new sequences that partially overlapped in item-by-item pairings with the Hebb sequence, indicating that children use consistent grouping strategies when learning above-span Hebb sequences. These findings indicate that phonological STM, grouping consistency, and their interaction are developmental requirements for the Hebb effect to emerge. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

A wealth of developmental research suggests that preschoolers are capable of reporting, imitating, and performing sequential actions they engage in routinely. However, few studies have explored the developmental and cognitive mechanisms required for learning how to perform such routines. A previous computational model of routines argued that a representation of task contexts underlying routines could change flexibly. This position was supported by the empirical evidence that if adults are interrupted in the course of a routine, they make fewer errors if they are interrupted just before the selection of context-dependent action than if they are interrupted earlier. Another computational model examined how efficiently adults learned to perform routines and suggested the relationship of learning efficacy with executive functions. The present study aimed to examine whether the above-mentioned models and evidence from adults can be extended to preschoolers by using an experimental task, in which children were required to play the role of a baker and repeatedly make toast for either a cat or mouse, with momentary distractions. Experiment 1 showed that earlier interruption tended to cause older children to produce more branch point errors than interruption immediately before the branch points, whereas younger children tended to be vulnerable to both interruptions. Further, across 2 experiments, this study showed that the developmental differences in how young children represent task contexts were associated with their executive functions. These findings indicate that the representational flexibility of task contexts underlies children's performance of repeated sequential actions and its association with executive functions. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Delay of gratification refers to the ability to forgo a small immediate reward to obtain a larger delayed reward. Cognitive mechanisms underlying the delay of gratification in young children have been examined extensively. However, the neural mechanism of this process is largely unknown. The present study examined whether inferior prefrontal regions play an important role in the delay of gratification choice paradigm in young children. Preschool children were given a choice version of a delay of gratification task, and their neural activation during the task was assessed using near-infrared spectroscopy in cross-sectional (Study 1) and longitudinal designs (Study 2). Results revealed the activation of the right inferior prefrontal regions of children during the task in both studies. Specifically, the inferior prefrontal regions of the children were activated during immediate choices but not during delay choices. This study is the first to demonstrate the neural correlates of the delay of gratification in young children. We discuss how the right inferior prefrontal regions of preschool children are activated during the delay of gratification., (© 2018 Wiley Periodicals, Inc.)

The execution of a script often requires detecting and resolving conflict with a goal, particularly in nonroutine situations. To take the example of taking a bus daily to work, if someone's usual bus is delayed and a bus for another destination comes first, the person must inhibit taking it and wait for the usual one. Young children can gradually acquire the ability to control the execution of scripts in such nonroutine situations, but few studies have explored the control process involved. In two experiments, we investigated the role of developments in the maintenance of hierarchical goal representations and in executive functions. We measured the ability to control the execution of scripts using a task in which children helped a doll select items to wear; clothing options were presented in an unexpected order in the nonroutine situations. The younger children (4-year-olds) could not flexibly control their execution of scripts in nonroutine situations, although they could exogenously detect and resolve conflict if they were prompted to maintain a subgoal. The older children (5-year-olds) endogenously controlled script execution based on a main goal, whereas subgoal maintenance led them to rigidly control their performance. In addition, children's inhibition abilities were associated with their control of script execution. These findings indicate that the development of the control process underlying the execution of scripts in nonroutine situations is partially dependent on the ability to maintain hierarchical goal representations., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Autism spectrum disorder (ASD) is characterized by problems with reciprocal social interaction, repetitive behaviours/narrow interests, and impairments in the social cognition and emotional processing necessary for intention-based moral judgements. The aim of this study was to examine the information used by early adolescents with and without ASD when they judge story protagonists as good or bad. We predicted that adolescents with ASD would use protagonists' behaviour, while typically developing (TD) adolescents would use protagonists' characteristics when making the judgements. In Experiment 1, we measured sentence by sentence reading times and percentages for good or bad judgements. In Experiment 2, two story protagonists were presented and the participants determined which protagonist was better or worse. Experiment 1 results showed that the adolescents with ASD used protagonist behaviours and outcomes, whereas the TD adolescents used protagonist characteristics, behaviours, and outcomes. In Experiment 2, TD adolescents used characteristics information when making "bad" judgements. Taken together, in situations in which participants cannot go back and assess (Experiment 1), and in comparable situations in which all information is available (Experiment 2), adolescents with ASD do not rely on information about individual characteristics when making moral judgements.

This research examined the effects of planning and executive functions on young children's (ages 3-to 5-years) strategies in changing scripts. Young children (N = 77) performed a script task (doll task), three executive function tasks (DCCS, red/blue task, and nine box task), a planning task, and a receptive vocabulary task. In the doll task, young children first enacted a "changing clothes" script, and then faced a situation in which some elements of the script were inappropriate. They needed to enact a script by compensating inappropriate items for the other-script items or by changing to the other script in advance. The results showed that shifting, a factor of executive function, had a positive influence on whether young children could compensate inappropriate items. In addition, planning was also an important factor that helped children to change to the other script in advance. These findings suggest that shifting and planning play different roles in using the two strategies appropriately when young children enact scripts in unexpected situations.

Aim:   Continuation of pegylated interferon (PEG-IFN) plus ribavirin at the recommended dose is difficult in elderly patients and/or patients with cytopenia or complications. Whether the therapeutic efficacy of low-dose PEG-IFN plus ribavirin therapy could be predicted based on virological response within 2 weeks of therapy initiation was evaluated., Methods:   A total of 106 patients with a high viral load of genotype-1b hepatitis C virus (HCV) underwent low-dose PEG-IFN plus ribavirin therapy. PEG-IFN alpha 2b (0.75 µg/kg per week) and ribavirin (600-800 mg/day) were administered for 48 weeks., Results:   Sustained virological response (SVR) was achieved in 37%, and treatment was discontinued in 9%. On univariate analysis of SVR-contributing factors, significant differences were noted in the white blood cell count, platelet count, fibrosis markers, and viral reduction within 2 weeks from therapy initiation. On multivariate analysis, the platelet count and the reduction in the HCV core antigen level at week 2 were independent factors. The positive predictive value (PPV) and the negative predictive value (NPV) for SVR based on a 1-log or greater HCV-RNA level reduction at week 2 were 65% and 90%, respectively, and those based on HCV core antigen level at week 2 were 64% and 97%, respectively. PPV and NPV based on a 2-log or greater reduction of the RNA level were 86% and 67%, respectively, and those based on the core antigen level were 93% and 69%, respectively., Conclusion:   Evaluation of viral reduction at week 2 after therapy initiation is useful for predicting SVR to low-dose PEG-IFN plus ribavirin therapy., (© 2011 The Japan Society of Hepatology.)

This study investigated correlations between Helicobacter pylori infection or chronic atrophic gastritis (CAG) and risk of colorectal adenoma in a population-based case-control study. Subjects comprised asymptomatic, middle-aged, male Japanese factory workers who participated in an annual health check-up program, including cancer screening with colonoscopy. We selected 239 colorectal adenoma cases based on histological evaluation and 239 age-matched adenoma-free controls, and evaluated colorectal adenoma risk according to stage of H. pylori-related chronic gastritis as determined by serum tests for H. pylori antibody titer and pepsinogen. Subjects with colorectal adenoma were more likely to be smokers and have hypercholesterolemia. H. pylori infection was a risk factor for adenoma as a whole (crude odds ratio [OR]: 2.26, 95% confidence interval [CI]: 1.44-3.55). Analysis of distal adenoma cases showed that adenoma risk was significantly increased in the presence of H. pylori infection, but there was no further increase in risk with CAG. In contrast, proximal adenoma risk increased stepwise with the presence and progression of H. pylori-related chronic gastritis and showed a maximal and significant increase with CAG (crude OR: 4.51, 95% CI: 1.43-14.2). Subjects with more extensive and severe gastritis showed still higher risk not only for proximal but also for distal adenoma. H. pylori-related chronic gastritis is likely to be involved in the development of colorectal neoplasms, and its progression appears to increase the risk, particularly for proximal adenomas. Knowing the H. pylori-related chronic gastritis stage will probably be useful for evaluation of risk for colorectal neoplasia., (Copyright © 2011 UICC.)

Aim:   To clarify the clinical features of and risk factors for extrahepatic seeding, a major complication following radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC)., Methods:   Our prospective database of 351 nodules in 257 patients with HCC who had undergone RFA between April 2001 and April 2008 was reviewed. The following variables were assessed to identify the risk factors for extrahepatic seeding: age, sex, viral markers, Child-Pugh class, tumor size, number of tumors, RFA indication (tumor size ≤3 cm, number of tumors ≤3), tumor biopsy prior to RFA, degree of histological differentiation, tumor markers, tumor location, number of sessions, and combined transcatheter arterial chemoembolization., Results:   The median follow-up period was 36.5 months, during which the rate of seeding after was 5.1% and the 5-year cumulative seeding rate was 8.4%. The survival rate after neoplastic seeding was 21% at 5 years. Univariate analysis of the risk factors for neoplastic seeding showed significant differences in tumor size, RFA indication, subcapsular lesion, number of sessions, tumor biopsy prior to RFA, and des-gamma-carboxy prothrombin value. However, multivariate analysis showed that the only independent risk factor was RFA indication., Conclusions:   The prognosis of patients with neoplastic seeding was poor. In particular, RFA performed for HCC not satisfying the RFA indication showed a high risk of seeding, and careful consideration should be given to the optimal treatment method and avoiding direct puncture of subcapsular tumors., (© 2011 The Japan Society of Hepatology.)

Purpose: To establish a method of assessing the malignant potential of hepatocellular carcinoma (HCC) using magnetic resonance imaging (MRI)., Methods: For 69 nodules [12 Edmondson (Ed)-I, 48 Ed-II, 9 Ed-III] in 54 HCC patients, signal intensity patterns and enhancement patterns of gadopentate dimeglumine (Gd-DTPA) dynamic studies were correlated with histological differentiation and serum lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3) level, which is an indicator of poor prognosis., Results: Hypointensity on T1-weighted imaging was seen in 17, 72, and 89% of Ed-I, Ed-II, and Ed-III HCCs, respectively (P < 0.001). Meanwhile, hyperintensity on T2-weighted imaging was seen in 42, 88, and 89% (P < 0.005). Tumor stain during the arterial phase of Gd dynamic MRI was seen in 75, 86, and 89%. Tumor stain washout during the portal phase was seen in 43% of Ed-II and 100% of Ed-III HCCs (P < 0.005). In the Ed-II and Ed-III HCCs, hypointensity on T1-weighted imaging was seen in 65% of AFP-L3-negative HCCs and 90% of AFP-L3-positive HCCs (P = 0.071). Washout of tumor stain during the portal phase was seen in 39% of AFP-L3-negative HCCs and 75% of AFP-L3-positive HCCs (P < 0.05)., Conclusions: Although hyperintensity of tumor on T2-weighted imaging and arterial hypervascularity of tumor are considered to be useful for differential diagnosis between well differentiated HCCs and moderately/poorly differentiated HCCs, hypointensity of tumor on T1-weighted imaging and tumor stain washout during the portal phase of Gd-DTPA dynamic MRI reflected poorer histological differentiation of HCCs and correlated with AFP-L3 levels.

Aim: To evaluate the association of Helicobacter pylori (H.pylori)-related chronic gastritis stage with upper gastrointestinal symptoms and gastroesophageal reflux disease (GERD)., Methods: Subjects underwent upper gastrointestinal endoscopy, a questionnaire using a frequency scale for symptoms of GERD (FSSG), and measurements of serum H.pylori-antibody and pepsinogen (PG) levels. They were classified into the following 4 groups in terms of H.pylori-related chronic gastritis stage: Group A (n = 219), H.pylori(-)PG(-); Group B (n = 310), H.pylori(+)PG(-); Group C (n = 279), H.pylori(+)PG(+); and Group D (n = 17), H.pylori(-)PG(+)., Results: Reflux esophagitis occurred in 30.6% of Group A, 14.5% of Group B, 6.8% of Group C, and 0% of Group D (P < 0.001). Scores for acid reflux symptoms decreased significantly with chronic gastritis stage (from Group A to D) (P < 0.05), while scores for dysmotility symptoms did not differ significantly. The prevalence of non-erosive reflux disease (NERD) did not differ among groups. However, in subjects with GERD, the prevalence of NERD tended to increase with chronic gastritis stage (P = 0.081)., Conclusion: Acid reflux symptoms and the prevalence of reflux esophagitis can be assessed by measuring both serum H.pylori-antibody and PG levels.

Aim:   Evaluation of malignant potential is important to determine the treatment strategy for small hepatocellular carcinoma (HCC). The aim of the present study was to establish a method of assessing the malignant potential of small hypervascular HCC using B-mode ultrasonography., Methods:   One hundred and thirteen arterial hypervascular HCC nodules under 3 cm diagnosed by biopsy or surgical resection (20.5 ± 6.3 mm) were classified into two groups ultrasonographically: type 1 with (n = 27) and type 2 without (n = 86) a halo. Type 2 was categorized into three subgroups: type 2a, homogenous hyperechoic (n = 9); type 2b, hypoechoic with a smooth margin (n = 35); and type 2c, hypoechoic with an irregular or unclear margin (n = 42)., Results:   The mean diameter of type 2a nodules was significantly smaller than that of other HCC types (P < 0.05). Overall, moderately differentiated HCC was the predominant histological type, except for type 2a, all of which were well-differentiated HCC. The percentage of poorly differentiated HCC was significantly higher in type 2c nodules (19%) than in other HCC types (P < 0.01). The percentage of Lens culinaris agglutinin-reactive α-fetoprotein (AFP-L3) positivity was significantly higher in type 2c nodules (55%) than in other HCC types (P < 0.01). Classification on B-mode ultrasonography was correlated with the histological differentiation and serum level, an indicator of a poor prognosis., Conclusion:   The malignant potential of type 2a is the lowest and that of type 2c is the highest, both histologically and serologically. Assessment of the malignant potential of small, hypervascular HCC is possible by B-mode ultrasonography., (© 2011 The Japan Society of Hepatology.)

A 53-year-old woman was admitted because of a giant pancreatic tumor. Hypercalcemia and a high serum parathyroid hormone-related peptide (PTHrP) level were observed. A hypoglycemic attack occurred during pancreatectomy, and the surgical specimen revealed a PTHrP-secreting glucagonoma. Liver metastases developed 1 and 5.5 years later, and bone metastases appeared 6 years after surgery. Her serum PTHrP concentrations remained normal after surgery, despite re-elevation of the serum glucagon concentration after recurrence. The clinical course of this case illustrates the process of development of neuroendocrine tumors secreting two or more hormones.

Initial identification of populations at high risk of gastric cancer (GC) is important for endoscopic screening of GC. As serum pepsinogen (PG) test-positive subjects with progression of chronic atrophic gastritis (CAG) show a high likelihood of future cancer development, this population warrants careful follow-up observation as a high-risk GC group. By combining the PG test with Helicobacter pylori (HP) antibody titers, the HP-related chronic gastritis stage can be classified, thus identifying not only a GC high-risk group but also a low-risk group. Among PG test-negative patients without CAG, those with high serum PG II levels and HP antibody titers are thought to have severe gastric mucosal inflammation and the risk of diffuse-type GC is also high. Meanwhile, in gastric mucosae obtained by endoscopic biopsy, HP infection induces aberrant DNA methylation in CpG islands in multiple gene regions and the extent of methylation clearly correlates with GC risk. By quantifying aberrant DNA methylation in suitable gene markers, we can determine the extent of the epigenetic field for cancerization. These novel concepts and risk markers will have many clinical applications in gastrointestinal endoscopy, including more efficient endoscopic GC screening and a strategic approach to metachronous multiple GCs after endoscopic treatment.

A 79-year-old woman complaining of epigastric pain was examined by her local physician, who found an abdominal mass and referred the patient to our department. Abdominal plain computed tomography revealed a mass, 50 mm in size, with slight calcification on the ventral side of the head of the pancreas. On abdominal ultrasound, the mass lesion consisted of an aggregation of hypoechoic masses, with a heterogeneous hyperechoic region at its center. On contrast ultrasonography, only the hyperechoic region was stained. (18)F-Fluorodeoxyglucose-positron emission tomography (FDG-PET) revealed FDG accumulation in the same region. It was difficult to differentiate between a malignant pancreatic tumor and an inflammatory disease on imaging, but since QuantiFERON TB2G testing was positive, pancreatic tuberculosis was suspected, and endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) was performed to obtain a definitive diagnosis. Samples from the hypoechoic region consisted of necrotic tissue, while those from the hyperechoic region consisted of pancreatic tissue together with granulation tissue. BCG immunostaining was positive, and a diagnosis of pancreatic tuberculosis was made. If EUS-FNA is performed on stained areas seen on contrast ultrasonography, this will probably enable a more accurate diagnosis of pancreatic tuberculosis with low invasiveness.

The present study investigated the preventive effects of etodolac, a selective cyclo-oxygenase (COX)-2 inhibitor, on metachronous cancer development after endoscopic resection of early gastric cancer. Among 267 early gastric cancer patients who underwent endoscopic resection, 47 patients with extensive metaplastic gastritis were selected based on endoscopic findings and our previously described criteria of serum pepsinogen (PG) test-positive and Helicobacter pylori antibody-negative conditions. Nonrandomized etodolac treatment (300 mg/day) was administered to 26 patients (Group A), while the remaining 21 patients were untreated (Group B). No significant differences in age, sex distribution, lifestyle factors or extent of metaplastic gastritis at baseline were identified between groups. Patients were followed for metachronous cancer development with endoscopy every 6-12 months for up to 5 years. Mean (standard deviation) follow-up period was 4.2 (0.9) years. In Group B, 5 cancers developed (incidence rate = 6,266/100,000 person-years), significantly more than the 1 cancer in Group A (incidence rate = 898/100,000 person-years; p < 0.05). Long-term etodolac treatment did not influence the extent of metaplastic gastritis as revealed by endoscopic findings or by serum PG levels, but effectively reduced metachronous cancer development in patients with extensive metaplastic gastritis. These results strongly suggest that chemoprevention of cancer in the metaplastic stomach is possible by controlling COX-2 expression.

A longitudinal cohort study was conducted in Helicobactor pylori-infected middle-aged Japanese males to evaluate the preventive effects of H. pylori eradication on the development of gastric cancer according to the extent of chronic atrophic gastritis (CAG). The extent of CAG was monitored by baseline serum pepsinogen (PG) levels. We followed 3,656 subjects with persistent H. pylori infection and 473 subjects with successful H. pylori eradication for cancer development for a mean (SD) of 9.3 (0.7) years. Groups with and without extensive CAG were categorized based on PG test-positive criteria to detect extensive CAG of PG I

Two patients developed segmental, diffuse intrahepatic recurrence after percutaneous radiofrequency ablation (RFA) to treat a primary, solitary, and small (2.5 cm) hepatocellular carcinoma (HCC). Despite the size of the HCC, levels of the tumor markers (α-fetoprotein, α-fetoprotein-L3%, and des-γ-carboxyprothrombin) were all elevated before RFA, and tumors in both patients were contiguous with a major branch of the portal vein. Tumor biopsies of both patients revealed moderately differentiated HCC but diagnostic imaging showed an area of reduced tumor blood flow, suggesting a poorly differentiated component. Since early detection of post-RFA malignancies by standard ultrasonography and contrast-enhanced computed tomography was difficult, the most sensitive indicator of recurrence in these two patients was the elevated tumor markers. The diffuse intrahepatic recurrence was thought to be caused by increased intratumoral pressure during RFA, resulting in the dissemination of cancer cells through the contiguous portal vein. The clinical course of these tumors indicate that the choice of RFA should be carefully considered when treating specific subtype of HCC that is adjacent to main portal vein branch and involves a possible poorly differentiated component and that surgical resection or combinations of RFA with other treatment modalities such as transcatheter arterial chemoembolization should be considered as alternative treatment strategies.

To clarify the alterations in lower intestinal microflora induced by gastric acid reduction, the dynamics of 12 major genera or groups of bacteria comprising the microflora in feces and colonic contents were examined by quantitative real-time PCR in proton pump inhibitor-treated rats and in asymptomatic human subjects with hypochlorhydria. In both rat and human experiments, most genera or groups of intestinal microflora (facultative and obligate anaerobes) proliferated by gastric acid reduction, and marked and significant increases in the Lactobacilli group and Veillonella, oropharyngeal bacteria, were observed. In rats, potent gastric acid inhibition led to a marked and significant increase of intestinal bacteria, including the Bacteroidesfragilis group, while Bifidobacterium, a beneficial bacterial species, remained at a constant level. These results strongly indicate that the gastric acid barrier not only controls the colonization and growth of oropharyngeal bacteria, but also regulates the population and composition of lower intestinal microflora.

A total of 5,209 asymptomatic, middle-aged subjects, whose serum pepsinogen (PG) and Helicobacter pylori antibody levels had been assessed, were followed for 10 years. Subjects with positive serum H. pylori antibodies (>50 U/mL) had an increased cancer risk (HR = 3.48, 95% CI = 1.26-9.64). Risk of gastric cancer increased as the antibody level increased; the H. pylori-positive group with antibody levels >500 U/mL had the highest incidence rate (325/100,000 person-years). Cancer development also increased with a reduced serum PG I level or a reduced PG I/II ratio; the risk was significantly elevated with serum PG I level or=30 ng/mL (HR = 3.81, 95% CI = 1.10-13.21). Using H. pylori antibody and PG levels, subgroups with an especially high or low cancer incidence rate could be identified. H. pylori-negative or indeterminate subjects with low PG level (PG I 500 U/mL and a low PG level were among the subgroups with a high cancer incidence rate (over 400/100,000 person-years). In contrast, H. pylori-negative subjects with a PG I level >70 ng/mL or a PG I/II ratio >3.0 had the lowest risk; none of these subjects developed cancer. Thus, serum PG levels and/or H. pylori antibody levels can be used to predict the risk of cancer in individuals with H. pylori-related gastritis from the general population., ((c) 2008 Wiley-Liss, Inc.)

Background: Gastric cancer screening using the pepsinogen filter test is receiving wide recognition in Japan owing to convenience, freedom from discomfort or risk, efficiency, and economy. Because the long-term outcomes of cancer development in extensive atrophic gastritis detected by pepsinogen test are unclear, test-positive and test-negative subjects were investigated in a longitudinal cohort study., Methods: Subjects comprised 5,209 middle-aged men with measured serum pepsinogen levels who were followed for 10 years. Cancer development based on "atrophy-positive" and "atrophy-negative" criteria used for cancer screening was investigated., Results: During the study, 63 cases of cancer developed in the cohort, representing an incidence rate of 125 per 100,000 person-years. Pepsinogen test screening using the most widely used atrophy-positive criterion (pepsinogen I, < or =70 ng/mL; pepsinogen I/II ratio, < or =3.0) displayed 58.7% sensitivity, 73.4% specificity, and 2.6% positive predictive value. Cancer incidence rate was 276 per 100,000 person-years for the atrophy-positive group and 70 per 100,000 person-years for the atrophy-negative group. Incidence rate was higher in groups fulfilling stricter positive criteria detecting more extensive atrophy, reaching 424 per 100,000 person-years. In addition, 9.2% of atrophy-negative subjects with pepsinogen I of >70 ng/mL and pepsinogen I/II ratio of < or =3.0 (reflecting putative inflammation-based high pepsinogen II level) are at high risk for cancer, particularly diffuse-type cancer, with a cancer incidence rate comparable with atrophy-positive subjects (216 per 100,000 person-years)., Conclusion: Atrophy-positive subjects by pepsinogen filter test, particularly those fulfilling stricter criteria, and atrophy-negative subjects with low pepsinogen I/II ratio reflecting putative extensive active inflammation constitute populations at high risk for gastric cancer, requiring thorough endoscopic examination.

Aims: To compare twice-daily interferon (IFN)-beta administration and once-daily IFN-alpha-2b administration as induction therapy in ribavirin combination therapy in chronic hepatitis C with a high viral load of genotype-1b hepatitis C virus (HCV)., Methods: Sixty-one chronic hepatitis patients with a high viral load of genotype-1b HCV were randomly divided into three groups: group A was given IFN-beta 6 MU induction therapy twice daily for 2 weeks; group B was given IFN-alpha-2b 6 MU induction therapy once daily for 2 weeks; and group C was given no induction therapy. All three groups were then given IFN-alpha-2b 6 MU 3 days/week for the rest of the 24-week study period. Ribavirin was given for the entire 24-week study period., Results: Although the cumulative HCV-RNA negative rates tended to be higher in group A than in group B, the differencewas not significant. The HCV-RNA negative rate at week 2 was significantly higher in groups A and B than in group C (P < 0.05). The sustained virological response (SVR) rate was 16% overall, 21% for groups A and B, and 5% for group C; the SVR rate of groups A plus B tended to be higher than that of group C (P = 0.093)., Conclusions: There was no difference between the effects of the two induction therapies; potent induction therapy does achieve higher early viral clearance but not a higher SVR rate.

Since the 1990's, the test for serum pepsinogen as a marker for chronic atrophic gastritis has been incorporated into gastric cancer screening programs, on a trial basis, to identify people at high risk for gastric cancer. The addition of the serum test to the cancer screening program has been shown to improve the detection rate of cancer and pepsinogen testing is useful in detecting early-stage gastric cancers arising from atrophic gastric mucosa, which macroscopically tend to be elevated and histologically differentiated. Furthermore, the cost for the detection of a single cancer case is much less than that for conventional screening. Thus, with the introduction of pepsinogen testing, complimenting barium X-ray, a more efficient screening system is available.