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1.  Helicobacter pylori-related chronic gastritis as a risk factor for colonic neoplasms 
To summarize the current views and insights on associations between Helicobacter pylori (H. pylori)-related chronic gastritis and colorectal neoplasm, we reviewed recent studies to clarify whether H. pylori infection/H. pylori-related chronic gastritis is associated with an elevated risk of colorectal neoplasm. Recent studies based on large databases with careful control for confounding variables have clearly demonstrated an increased risk of colorectal neoplasm associated with H. pylori infection. The correlation between H. pylori-related chronic atrophic gastritis (CAG) and colorectal neoplasm has only been examined in a limited number of studies. A recent large study using a national histopathological database, and our study based on the stage of H. pylori-related chronic gastritis as determined by serum levels of H. pylori antibody titer and pepsinogen, indicated that H. pylori-related CAG confers an increased risk of colorectal neoplasm, and more extensive atrophic gastritis will probably be associated with even higher risk of neoplasm. In addition, our study suggested that the activity of H. pylori-related chronic gastritis is correlated with colorectal neoplasm risk. H. pylori-related chronic gastritis could be involved in an increased risk of colorectal neoplasm that appears to be enhanced by the progression of gastric atrophy and the presence of active inflammation.
PMCID: PMC3925856  PMID: 24587623
Colorectal neoplasm; Cancer risk; Pepsinogen; Helicobacter pylori antibody; Atrophic gastritis
2.  Synchronous Bilateral Solid Papillary Carcinomas of the Breast 
Case Reports in Surgery  2013;2013:812129.
We herein report a case of synchronous bilateral solid papillary carcinoma of the breast. A 73-year-old female had a mass that was detected in the right breast on mammography. An ultrasound examination revealed one intracystic tumor in the right breast and two tumors in the left breast. A fine-needle aspiration biopsy of these three tumors was performed, which revealed a diagnosis of malignancy. A magnetic resonance imaging examination of the breasts showed diffuse small nodules surrounding these tumors bilaterally. Bilateral partial mastectomy and a sentinel lymph node biopsy were performed. Lymph node metastasis was detected in the right axilla, and additional lymph node dissection was performed. The pathological diagnosis was synchronous bilateral breast cancer, invasive ductal carcinoma NOS of the right breast, mucinous carcinomas of the left breast, and bilateral SPCs. A wide range of surgical margins were positive for SPCs, and additional bilateral total mastectomy was then performed. To the best of our knowledge, little is known about synchronous bilateral SPCs. Our case indicates that some SPCs can be widely scattered and make up a variety of invasive carcinomas. It is difficult to make a correct preoperative evaluation in such cases.
PMCID: PMC3703433  PMID: 23844308
3.  Does mild cognitive impairment affect the occurrence of radiographic knee osteoarthritis? A 3-year follow-up in the ROAD study 
BMJ Open  2012;2(6):e001520.
To determine whether mild cognitive impairment (MCI) increases the risk of occurrence or progression of radiographic knee osteoarthritis (KOA) in a general population.
Population-based cohort study.
Residents in mountain and seaside areas of Wakayama Prefecture, Japan.
1690 participants (596 men, 1094 women; mean age 65.2 years old) were enrolled from the large-scale cohort for the Research on Osteoarthritis (OA)/osteoporosis Against Disability (ROAD) study initiated in 2005 to investigate epidemiological features of OA in Japan. Of these, 1384 individuals (81.9%; 466 men, 918 women) completed the second survey including knee radiography 3 years later.
Primary outcome measures
Radiographic KOA was defined as Kellgren-Lawrence (KL) grade ≥ 2 using paired x-ray films. Incidence of KOA during follow-up defined on radiographs as KL grade ≥2, progression of KOA defined as a higher KL grade (either knee) at follow-up compared with baseline. MCI defined as a summary mini-mental state examination (MMSE) score ≤23. Associations between MCI and incidence or progression of KOA were analysed.
The annual cumulative incidence of KOA was 3.3%; for progression of OA it was 8.0%. On logistic regression analysis adjusted for age, gender, regional differences, body mass index, grip strength (worse side), smoking, alcohol consumption, regular exercise and history of knee injury, baseline MMSE summary score was significantly associated with the incidence of KOA (+1 MMSE score; OR 0.83, p=0.010). Baseline MCI was also significantly associated with the incidence of KOA (vs non-occurrence of KOA; OR 4.90, p=0.027). There was no significant association between MMSE scores, the presence of MCI and progression of KOA (+1 MMSE score; OR 0.96, p=0.232; vs non-progression of KOA; OR 1.38, p=0.416).
MCI significantly increases the risk of incident radiographic KOA, but not the progression of KOA.
PMCID: PMC3532983  PMID: 23166128
4.  Elevated risk of recurrent colorectal neoplasia with Helicobacter pylori-associated chronic atrophic gastritis: A follow-up study of patients with endoscopically resected colorectal neoplasia 
In a previous population-based case-control study, we demonstrated an elevated risk of colorectal neoplasia with Helicobacter pylori (H. pylori) infection. The present study investigated the effects of H. pylori-associated chronic gastritis on the development of colorectal neoplasia by analyzing the recurrence of colorectal neoplasia subsequent to endoscopic resection. Ninety-nine patients who had undergone endoscopic resection of colorectal neoplasia were monitored under colonoscopy, and the recurrence of colorectal neoplasia was prospectively investigated. The stage of H. pylori-associated chronic gastritis in each subject was evaluated using a combination of two serum tests: H. pylori antibody and pepsinogen. In the present cohort, colorectal neoplasia recurred at a rate of 15,296/100,000 person-years during the study period. After adjusting for the confounding factors, chronic atrophic gastritis (CAG) was identified as an independent risk factor [adjusted hazard ratio (HR), 2.72; 95% confidence interval, 1.33–5.57], while H. pylori-infected non-atrophic gastritis was not identified as an independent risk factor for recurrent colorectal neoplasia. Colorectal neoplasia recurred earlier and was significantly more frequent in patients with CAG (22,573/100,000 person-years) compared to patients without CAG (11,089/100,000 person-years; P=0.029, log-rank test). Patients with more extensive CAG showed a higher risk of recurrence. These results demonstrated a significant elevation of the risk of recurrent colorectal neoplasia with the establishment and progression of CAG, indicating the involvement of H. pylori infection in the development of colorectal neoplasia. The two serum tests were useful clinical markers for noninvasively evaluating the risk of each individual for recurrent colorectal neoplasia subsequent to endoscopic resection.
PMCID: PMC3956255  PMID: 24649126
colorectal neoplasia; recurrence; pepsinogen; chronic atrophic gastritis; cohort study
To assess the prevalence and correlates of regional pain and associated disability in four groups of Japanese workers.
As part of a large international survey of musculoskeletal symptoms (the CUPID study), samples of nurses, office workers, sales/marketing personnel and transportation operatives in Japan completed a self-administered questionnaire (response rate 83%). The questionnaire covered experience of pain in six anatomical regions, associated disability and sickness absence, and various possible occupational and psychosocial risk factors for these outcomes. Associations with risk factors were assessed by logistic regression.
Analysis was based on 2290 subjects. Rates of regional pain were generally less than have been reported in the UK, with a particularly low prevalence of wrist/hand pain among office workers (6% in the past month). The strongest and most consistent risk factor for regional pain in the past month was tendency to somatise (odds ratios (95% confidence intervals) for report of ≥2 v 0 distressing somatic symptoms 3.1 (2.4-4.0) for low back pain, 2.8 (2.1-3.8) for shoulder pain, and 2.5 (1.6-4.1) for wrist/hand pain). Sickness absence for regional pain complaints in the past year was reported by 5% of participants, the major risk factor for this outcome being absence during the same period for other medical reasons (OR 3.7, 95%CI 2.4-5.8).
Japanese office workers have markedly lower rates of wrist/hand pain than their UK counterparts. In Japan, as in Western Europe, somatising tendency is a major risk factor for regional pain. Sickness absence attributed to regional pain complaints appears to be much less common in Japan than in the UK, and to be driven principally by a general propensity to take sickness absence.
PMCID: PMC3088869  PMID: 20833762
Musculoskeletal; pain; disability; sickness absence; somatising
6.  Alternative use of multiple exons 1 of aromatase gene in cancerous and normal breast tissues from women over the age of 80 years 
Peripherally localized aromatase, which converts circulating androgens into estrogens, is important in the pathogenesis of postmenopausal breast carcinomas. We have previously shown that aromatase mRNA levels are higher in elderly breast carcinomas (EldCa) than breast carcinomas of the control group (ContCa) or normal breast tissues. Aromatase expression has been reported to be regulated through the alternative use of multiple exons 1 (exons 1a-1f and so on); however, the preferential usage of exons 1 in elderly breast tissue has never been systematically examined. In order to properly treat and protect against EldCa, the regulation mechanism of aromatase expression in elderly breast tissues should be elucidated. The aim of the present study is to elucidate whether there are any specific patterns in use of multiple exons 1 in elderly breast tissue.
Usage of multiple exons 1 of the aromatase gene and mRNA levels of aromatase were examined by reverse transcription-polymerase chain reaction analysis in breast tissues of 38 elderly patients with breast cancer (age 80–99), and the results were compared with those in 35 patients of the control group (age 37–70). One-factor analysis of variance and the Scheffé test were used for the comparison of aromatase mRNA levels. Patterns of preferential utilization of multiple exons 1 of the aromatase gene were compared by χ2 test for independence or Fisher exact test for independence using a contingency table.
Exon 1d was utilized much more frequently in elderly tissue than in the control group irrespective of cancerous or normal tissue (EldCa, 36/38, 95% versus ContCa, 7/35, 20%, P < 0.0001; normal tissue of the elderly, EldNorm, 30/34, 88% versus normal tissue of controls, ContNorm, 2/29, 7%, P < 0.0001). Twenty EldCa (53%) and 12 EldNorm (35%) used both exons 1c and 1d; however, their dominance was reversed (EldCa, all 1d > 1c; EldNorm, all 1c > 1d).
Elderly breast tissues exhibited specific patterns in use of multiple exons 1, which at least partly explained the higher aromatase levels in EldCa. The mechanisms of how these specific patterns occur during aging and carcinogenesis should be further examined.
PMCID: PMC2750107  PMID: 19589174
7.  Intratumoural mRNA expression of genes from the oestradiol metabolic pathway and clinical and histopathological parameters of breast cancer 
Breast Cancer Research  2003;6(2):R46-R55.
The expression of the oestrogen receptor (ER) is one of the more important clinical parameters of breast cancer. However, the relationship between the ER and its ligand, oestradiol, and the enzymes that synthesise it are not well understood. The expression of mRNA transcripts of members of the oestradiol metabolic and signalling pathways including the ER was studied in detail.
mRNA transcripts for aromatase (CYP19), 17-β-hydroxysteroid dehydrogenase I, 17-β-hydroxysteroid dehydrogenase II, ERα, ERβ, steroid sulfatase (STS), oestradiol sulfotransferase (EST), cyclin D1 (CYCLD1) and ERBB2 were fluorometrically quantified by competitive RT-PCR using an internal standard in 155 breast carcinomas. In addition, the transcripts of CYP19 were analysed for alternative splicing/usage of exon 1 and an alternative poly A tail.
A great variability of expression was observed, ranging from 0 to 2376 amol/mg RNA. The highest levels were observed for STS and EST, and the lowest levels (close to zero) were observed for the 17-β-hydroxysteroid dehydrogenase isoenzymes. The levels of mRNA expression were analysed with respect to clinical and histopathological parameters as well as for disease-free survival. High correlation of the mRNA expression of STS, EST and 17-β-hydroxysteroid dehydrogenase in the tumours suggested a common regulation, possibly by their common metabolite (oestradiol). Hierarchical clustering analysis in the 155 patients resulted in two main clusters, representing the ERα-negative and ERα-positive breast cancer cases. The mRNA expression of the oestradiol metabolising enzymes did not follow the expression of the ERα in all cases, leading to the formation of several subclasses of tumours. Patients with no expression of CYP19 and patients with high levels of expression of STS had significantly shorter disease-free survival time (P > 0.0005 and P < 0.03, respectively). Expression of ERβ mRNA was a better prognostic factor than that of ERα in this material.
Our results indicate the importance of CYP19 and the enzymes regulating the oestrone sulfate metabolism as factors of disease-free survival in breast cancer, in addition to the well-known factors ER and ERBB2.
PMCID: PMC400649  PMID: 14979917
breast cancer; clustering analysis; disease-free survival; oestradiol metabolism; signalling

Results 1-7 (7)