Generalization of a clinical diagnosis support tool for lumbar spinal stenosis: Can the ankle brachial pressure index be replaced by palpation of the posterior tibial artery in the lumbar spinal stenosis diagnostic support tool? (DISTO project).

BACKGROUND: The Japanese Society for Spine Surgery and Related Research previously developed a diagnostic support tool for lumbar spinal stenosis (LSS-DST). Using the LSS-DST, general physicians can identify potential cases of LSS. However, in the LSS-DST, measurement of the ankle brachial pressure index (ABI) is required to exclude peripheral artery lesions in the lower limbs. We can expect further application of the LSS-DST if we can identify a simpler and easier method than ABI measurement. Therefore, in this large-scale, multicenter, cross-sectional study, we verified whether palpation of the posterior tibial (PT) artery could be used instead of ABI in the LSS-DST. METHODS: This survey was conducted at 2177 hospitals and included 28,883 participants. The sensitivity and specificity of the original LSS-DST method using the ABI and that of the LSS-DST ver2.0 with PT artery palpation were assessed to screen their ability for diagnosing LSS, using the physicians' final diagnosis based on the patients' history, physical examination and radiographic findings as the gold standard. RESULTS: The sensitivity and specificity [95%CI] of the LSS-DST were 88.2% [87.5, 88.8] and 83.9% [83.4, 84.5], respectively, whereas the sensitivity and specificity of the LSS-DST ver2.0 were 87.7% [87.0, 88.3] and 78.3% [77.7, 78.9], respectively, indicating that LSS-DST ver2.0 is a useful screening tool for LSS with good sensitivity. CONCLUSION: When the item of ABI in the LSS-DST is replaced by palpation of the PT artery (LSS-DST ver2.0), its sensitivity is maintained as a screening tool for LSS. LEVEL OF EVIDENCE: Level 3.

Association of serum s-adenosylmethionine, s-adenosylhomocysteine, and their ratio with the risk of dementia and death in a community.

We examined the association of serum s-adenosylmethionine (SAM), s-adenosylhomocysteine (SAH) (methionine metabolites), and their ratio on the risk of dementia and death in a community-dwelling population of older Japanese individuals. 1371 residents of Hisayama, Japan, aged 65 years or older and without dementia, were followed for a median of 10.2 years (2007-2017). We divided serum SAM, SAH, and SAM/SAH ratio into quartiles. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and their 95% confidence intervals (CIs) of serum SAM, SAH, and SAM/SAH ratio levels on the risk of a composite outcome of all-cause dementia or death, and each outcome. During the follow-up, 635 participants developed all-cause dementia and/or died, of which 379 participants developed dementia and 394 deaths occurred. The multivariable-adjusted HRs of the composite outcome decreased significantly with increasing serum SAM levels (P for trend = 0.01), while they increased significantly with higher serum SAH levels (P for trend = 0.03). Higher serum SAM/SAH ratio levels were significantly associated with a lower risk of the composite outcome (P for trend = 0.002), as well as with lower risk of each outcome. Our findings suggest that the balance of methionine metabolites may closely associate with the risk of dementia and death.

Race and nodal disease status are prognostic factors in patients with stage IVB cervical cancer.

BACKGROUND: Patients presenting with stage IVB cervical cancer pose a significant clinical challenge. While previous studies described several poor prognostic factors, they were limited by small sample sizes. The aim of this study was to identify clinicopathological prognostic factors in a large sample of patients with stage IVB cervical cancer at a single institution. METHODS: Patients with primary stage IVB cervical cancer diagnosed between 1992 and 2011 were extracted from a search of the MD Anderson Cancer Center registry. Clinicopathological data retrieved from their medical records included demographics (age and race), tumor characteristics (primary lesion size, grade, and histology), TNM classification, and metastatic site (nodal/organ). Treatment approach (radiation, chemotherapy, or both) and intent (palliation or curative) were recorded. Survival rates were evaluated using the Kaplan-Meier method. Cox proportional hazards regression was used to model the association between key variables and overall survival (OS). RESULTS: Two hundred sixty-six patients with stage IVB cervical cancer were identified. Their median OS was 12.7 months. The hazard ratio for African-Americans vs. patients with other ethnicities was 1.76 (95% confidence interval [CI], 1.18-2.54, P = 0.0063), and that for patients with para-aortic nodes alone vs. more extensive metastases was 0.37 (95% CI, 0.26-0.51, P < 0.0001). Other clinicopathological factors were not significantly associated with survival. CONCLUSIONS: African-American race was an independent adverse prognostic factor in this cohort. On the other hand, nodal disease in the para-aortic chain alone predicted a favorable prognosis.

Prognostic implications of HER2 heterogeneity in gastric cancer.

The prognostic implications of human epidermal growth receptor 2 (HER2) heterogeneity in gastric cancer (GC) are not well established. Therefore, the aim of the present study was to determine to the effect of HER2 status on the prognosis of GC patients. We retrieved data on 248 pathologically-confirmed, consecutive patients with primary adenocarcinoma of the stomach or gastro-esophageal junction who underwent surgical resection at Kurume University Medical Center between July 2000 and December 2012. HER2 status was classified as HER2 positive or negative and HER2 heterogeneity or homogeneity. The endpoint was overall survival (OS), which was compared using the generalized Wilcoxon test. HER2 status was positive in 36 patients (14.5%) and negative in 212 patients (85.5%). Among the 36 HER2 positive patients, 25 patients (69.4%) had HER2 heterogeneity and the remaining 11 patients (30.6%) had HER2 homogeneity. Among the 141 patients with stage III or IV disease, the prognosis of the HER2 homogeneity group was significantly worse than that of the HER2 heterogeneity group (p = 0.019; median OS 193 and 831 days, respectively). The prognosis was not significantly different between the HER2 positive group and the HER2 negative group (p = 0.84; median OS 552 and 556 days, respectively). The present study was conducted with small samples, however, the results of the study suggest that HER2 homogeneity but not HER2 positivity may represent a prognostic indicator in GC.

Augmented Association Between Blood Pressure and Proteinuria in Hyperuricemic Patients With Nonnephrotic Chronic Kidney Disease.

BACKGROUND: Hyperuricemia (HU) may enhance susceptibility to hypertensive renal damage via disrupted autoregulation of glomerular hemodynamics. The effect of HU on the association between blood pressure (BP) and proteinuria remains unknown in patients with chronic kidney disease (CKD). METHODS: In total, 109 patients with nonnephrotic CKD (55 men and 54 females) who underwent renal biopsy were recruited. Arteriolar hyalinosis was semiquantitatively assessed via arteriole grading. Correlation between BP and urine protein (UP) level was examined based on the presence of HU, which was defined as the use of urate-lowering drugs or serum uric acid levels of ≥7 and ≥5 mg/dl in males and females, respectively, which were associated with increased risks of hyalinosis in our previous study. RESULTS: Median age, BP, estimated glomerular filtration rate, and UP level were 38 years, 124/74 mm Hg, 82 ml/min/1.73 m2, and 0.8 g/gCr, respectively. In patients with HU (n = 59), log-transformed systolic BP (SBP) was significantly correlated with log-transformed UP level (r = 0.49, P < 0.0001); this was not observed in patients without HU (n = 50). Multiple regression analysis (R2 = 0.21, P = 0.0001) revealed that the interaction between HU and log-transformed SBP with respect to proteinuria was significantly correlated with log-transformed UP level (ß = 7.0, P = 0.03), independent of age, sex, and potential confounding factors; however, this statistical significance was completely eliminated after adjustment for the arteriolar hyalinosis index. CONCLUSIONS: HU potentiates susceptibility to hypertensive glomerular damage via disrupted autoregulation in patients with nonnephrotic CKD.

Risk of malignancies in autoimmune hepatitis type 1 patients with a long-term follow-up in Japan.

AIM: The risk of malignancies in autoimmune diseases is high and is regarded to be due to immunological abnormalities, the use of immunosuppressive agents, and/or chronic inflammation. The aim of this study was to investigate the incidence and risk of malignancies in patients with autoimmune hepatitis (AIH) type 1 in Japan. METHODS: Two hundred and fifty-six patients diagnosed with AIH were enrolled. A person-year calculation was carried out for AIH patients, and the numbers of expected events were clarified using data from "The Monitoring of Cancer Incidence in Japan Project" in order to examine the standard incident rate (SIR) of each type of malignancy. Biochemical data regarding carcinogenesis and its background factors were also examined. RESULTS: Twenty-seven patients (10.5%) developed malignancies; 11 (4.3%) with hepatobiliary cancer and 16 (6.3%) with extrahepatic malignancies. The overall SIR for malignancies in AIH was significantly high at 2.04 (95% confidence interval [CI], 1.34-2.96), and was high among female patients at 2.49 (95% CI, 1.60-3.71). The SIR for hepatobiliary cancer was 14.14 (95% CI, 7.05-25.30), and was markedly high for female patients at 21.83 (95% CI, 10.45-40.16). The SIR for oral/pharyngeal cancer was significantly high for female patients at 14.61 (95% CI, 1.64-52.77). The risk factors for hepatobiliary cancer at the diagnosis of AIH were low levels of alanine aminotransferase (P = 0.0226), low platelet counts (P < 0.0001), and cirrhosis (P = 0.0004). The risk factor for extrahepatic malignancy was relapse of AIH (P = 0.0485). CONCLUSION: The risk of malignancies was generally high among AIH patients. Those with the risk factors of malignancies should be carefully followed up.

Development and validation of a risk assessment tool for gastric cancer in a general Japanese population.

BACKGROUND: There have been very few reports of risk score models for the development of gastric cancer. The aim of this study was to develop and validate a risk assessment tool for discerning future gastric cancer risk in Japanese. METHODS: A total of 2444 subjects aged 40 years or over were followed up for 14 years from 1988 (derivation cohort), and 3204 subjects of the same age group were followed up for 5 years from 2002 (validation cohort). The weighting (risk score) of each risk factor for predicting future gastric cancer in the risk assessment tool was determined based on the coefficients of a Cox proportional hazards model in the derivation cohort. The goodness of fit of the established risk assessment tool was assessed using the c-statistic and the Hosmer-Lemeshow test in the validation cohort. RESULTS: During the follow-up, gastric cancer developed in 90 subjects in the derivation cohort and 35 subjects in the validation cohort. In the derivation cohort, the risk prediction model for gastric cancer was established using significant risk factors: age, sex, the combination of Helicobacter pylori antibody and pepsinogen status, hemoglobin A1c level, and smoking status. The incidence of gastric cancer increased significantly as the sum of risk scores increased (P trend < 0.001). The risk assessment tool was validated internally and showed good discrimination (c-statistic = 0.76) and calibration (Hosmer-Lemeshow test P = 0.43) in the validation cohort. CONCLUSIONS: We developed a risk assessment tool for gastric cancer that provides a useful guide for stratifying an individual's risk of future gastric cancer.

Nocturnal Polyuria and Hypertension in Patients with Lifestyle Related Diseases and Overactive Bladder.

PURPOSE: The objective of this multicenter cross-sectional study was to investigate the relationship of nocturnal polyuria in patients with common lifestyle related diseases and overactive bladder, with special attention to hypertension. MATERIALS AND METHODS: After baseline assessment, patients recorded 24-hour urinary frequency/volume, blood pressure and heart rate for 3 days. They were stratified into 4 groups based on mean blood pressure, including no hypertension, and controllable, untreated and uncontrolled hypertension, respectively. RESULTS: The 2,353 eligible patients, who had urinary urgency once or more per week and 1 or more nocturnal toilet visits, were enrolled from 543 sites in Japan. Of these patients complete data, including the 24-hour frequency volume chart, were collected from 1,271. Multivariable analyses showed a statistically significant association of nocturnal polyuria with increasing age (OR 1.04, 95% CI 1.02-1.05, p <0.001) and gender (women vs men OR 0.75, 95% CI 0.59-0.96, p = 0.02), and for controllable (OR 1.10, 95% CI 0.83-1.460), untreated (OR 2.62, 95% CI 1.55-4.45) and uncontrolled (OR 1.15, 95% CI 0.81-1.62) hypertension vs no hypertension (p = 0.005). However, when assessed separately in men and women, hypertension and heart rate were significantly associated with nocturnal polyuria in women alone (p = 0.01 and 0.03, respectively). Lower urinary tract symptoms suggestive of benign prostatic hyperplasia were significantly associated with nocturnal polyuria in men alone (p <0.001). CONCLUSIONS: The current study demonstrates that nocturnal polyuria was significantly associated with age, male gender, and untreated hypertension in patients with lifestyle related diseases and overactive bladder. The association between hypertension and nocturnal polyuria was significant in women alone.

Injury to the endometrium prior to the frozen-thawed embryo transfer cycle improves pregnancy rates in patients with repeated implantation failure.

AIM: This retrospective cohort study evaluated the effectiveness of injury to the endometrium prior to the frozen-thawed embryo transfer (FET) cycle in patients with repeated implantation failure (RIF) in our clinic. METHODS: Included in this study were 173 patients, aged ≤ 41 years, who failed to become pregnant after repeating fair and/or good embryo transfer more than twice between February 2012 and February 2015. The patients were divided into three groups: Group A (n = 38) underwent soft curettage to the endometrium twice, prior to the FET cycle; Group B (n = 45) underwent hysteroscopy prior to the FET cycle, with no significant factors, such as endometrial polyp; and Group C (n = 90) was the no-treatment group. RESULTS: The clinical pregnancy rate per transfer was found to be statistically significant between Group A at 42.1% (16/38) and Group C at 22.2% (20/90). The crude and adjusted odds ratios (OR) were 2.55 and 2.49 (95% confidence intervals 1.13-5.78, P = 0.03 and 1.01-6.17, P = 0.048) respectively. Group B with only hysteroscopy had a higher pregnancy rate of 35.6% (16/45) than Group C, but showed no statistical significance (P = 0.103). CONCLUSION: These results suggest that injuring the endometrium has a positive effect on pregnancy.

Sedentary bout durations and metabolic syndrome among working adults: a prospective cohort study.

BACKGROUND: This study aimed to examine the associations between time spent in prolonged and non-prolonged sedentary bouts and the development of metabolic syndrome. METHODS: We used data from a prospective study of Japanese workers. Baseline examination was conducted between 2010 and 2011. A total of 430 office workers (58 women) aged 40-64 years without metabolic syndrome were followed up by annual health checkups until 2014. Metabolic syndrome was defined as having ≥ 3 out of 5 diagnostic criteria from the Joint Interim Statement 2009 definition. Sedentary time was assessed using a tri-axial accelerometer. Time spent in total, prolonged (accumulated ≥ 30 min) and non-prolonged sedentary bouts (accumulated < 30 min) was calculated. Cox proportional hazards models were used to estimate the risk of developing metabolic syndrome. RESULTS: During a median follow-up of 3 years, 83 participants developed metabolic syndrome. After adjustment for age, sex, education, smoking, and family income, positive associations were observed between time spent in prolonged sedentary bouts and the development of metabolic syndrome. After additional adjustment for moderate-to-vigorous physical activity, those in the three highest quartiles of time spent in prolonged sedentary bouts showed higher risk of metabolic syndrome compared to the lowest quartile group, with adjusted hazard ratios (95 % confidence intervals) of 2.72 (1.30 - 5.73), 2.42 (1.11 - 5.50), and 2.85 (1.31 - 6.18), respectively. No associations were seen for time spent in total and non-prolonged sedentary bouts. CONCLUSIONS: Sedentary behavior accumulated in a prolonged manner was associated with an increased risk of metabolic syndrome. In devising public health recommendations for the prevention of metabolic disease, the avoidance of prolonged uninterrupted periods of sedentary behavior should be considered.

Identification of appropriate cone length to avoid positive cone margin in high grade cervical intraepithelial neoplasia.

OBJECTIVE: To identify key factors for predicting positive cone margin and appropriate cone length. METHODS: We retrospectively reviewed the margin status of patients who received conization with high grade cervical intraepithelial neoplasia, along with other factors such as patient age, parity, preoperative cytology, size of disease, type of transformation zone, and cone length from patient records. Cut-off value of cone length was analyzed in women younger than 40 years old because we design conization with minimum length especially for women who wish for future pregnancy. Cut-off value of cone length was defined as length corresponds to estimated probability of positive cone margin equal to 0.1 by logistic regression analysis with variables selected by stepwise methods. RESULTS: Among 300 patients, 75 patients had positive cone margin. Multivariable analysis revealed that squamous cell carcinoma at preoperative cytology (p=0.001), 2 or more quadrant disease (p=0.011), and shorter cone length (p<0.001) were risk factors for positive cone margin. Stepwise methods identified cone length and size of lesion as important variables. With this condition, cut-off value of cone length was estimated as 15 mm in single quadrant disease and 20 mm in 2 or more quadrant disease, respectively. CONCLUSION: We identified the independent risk factors of positive cone margin and identified the cut-off value of cone length to avoid positive cone margin in women younger than 40 years old. Conization should be performed not only according to colposcopic findings including type of transformation zone but size of disease and cone length.

Combination of Helicobacter pylori Antibody and Serum Pepsinogen as a Good Predictive Tool of Gastric Cancer Incidence: 20-Year Prospective Data From the Hisayama Study.

BACKGROUND: There is little information regarding whether the combination of Helicobacter pylori (H. pylori) antibody and serum pepsinogen (sPG), which is a marker of the degree of atrophic gastritis, has a discriminatory ability for detecting incident gastric cancer. We examined this issue in a long-term prospective cohort study of a Japanese population. METHODS: A total of 2446 Japanese community-dwelling individuals aged ≥40 years were stratified into four groups according to baseline H. pylori serological status and sPG: Group A (H. pylori[-], sPG[-]), Group B (H. pylori[+], sPG[-]), Group C (H. pylori[+], sPG[+]), and Group D (H. pylori[-], sPG[+]), and participants were followed up prospectively for 20 years. RESULTS: During the follow-up, 123 subjects developed gastric cancer. Compared with that in Group A, the cumulative incidence of gastric cancer was significantly increased in Groups B, C, and D, whereas no significant difference was found between Groups C and D. The multivariable-adjusted risk of gastric cancer was significantly increased in Group B (hazard ratio [HR], 4.08; 95% confidence interval [CI], 1.62-10.28) and in Groups C and D combined (HR 11.1; 95% CI, 4.45-27.46). When the multivariable model with H. pylori antibody was changed into that with the combination of H. pylori antibody and sPG, the C statistics for developing gastric cancer increased significantly (0.773 vs 0.732, P = 0.005), and the continuous net reclassification improvement value was 0.591 (P < 0.001). CONCLUSIONS: Our findings suggest that the combination of H. pylori antibody and sPG is a useful tool for predicting the development of gastric cancer.

Relationship between lumbar spinal stenosis and psychosocial factors: a multicenter cross-sectional study (DISTO project).

INTRODUCTION: Lumbar spinal stenosis (LSS) is a lumbar spinal disorder that causes leg symptoms and intermittent claudication. It is reported that the risk factors for low back pain include age, family history, smoking, obesity, work-related physical load, exercise, and depression. This was a multicenter, cross-sectional survey, and the aim of this study was to investigate the prevalence of LSS by age and the relationships between LSS and psychosocial factors and job satisfaction. METHODS: This study enrolled subjects aged 50 years and over from a survey of LSS in 2177 hospitals and general practices nationwide. The clinical characteristics of the LSS and non-LSS groups were compared using the χ2 test, and the multivariate logistic regression analysis was performed to examine associations between exercise, perceived stress, strenuous use of the low back or legs, job satisfaction, and LSS. RESULTS: In total, 18,642 patients (8338 males, 10,267 females) were analyzed. The rate of LSS was 38.3% and it increased with age. Regular exercise was less common among those in the LSS group than those in the non-LSS group (p<0.001). Satisfaction in all job-related items was less in the LSS group than in the non-LSS group (p<0.001). The odds for having LSS were higher in subjects having perceived stress and strenuous use of the low back or legs (p=0.001). The odds ratios of heart diseases and hypertension (p<0.001) were higher in the LSS group. CONCLUSION: This study investigated factors associated with LSS. The prevalence of LSS increased with age. Perceived stress and strenuous use of the low back or legs might be associated with LSS, and job satisfaction was lower with LSS.

Neoplastic spindle cells are an independent prognostic factor in pancreatic cancer.

OBJECTIVE: Several reports showed that neoplastic spindle cells (NSCs) may be strongly involved in the invasion, metastasis, and poor prognosis, as well as in epithelial-mesenchymal transition (EMT). It has not yet been investigated that NSCs relate to the recurrence and prognosis in various cancers. Furthermore, NSCs participate in EMT in pancreatic cancer (PC) too. We clinicopathologically investigated the association between NSCs and the recurrence, prognosis, and EMT in PC. METHODS: We studied 68 PC patients. Cancer cells with a spindle or oval shape that do not exhibit luminal structures were defined as NSCs. We graded NSCs regarding to an area of NSCs at hematoxylin and eosin stain (NSC grade) and examined the participation in NSCs and EMT by immunohistostaining of snail antibody and E-cadherin antibody. RESULTS: In multivariate analysis, NSC grade was an independent risk factor for disease-free survival and overall survival. This was independent of TNM stage and histological grade. Neoplastic spindle cells were related to EMT pattern in immunohistostaining significantly. CONCLUSIONS: Neoplastic spindle cell grade significantly related to the recurrence and prognosis of PC. The NSC grade assessment can be not only performed inexpensively and conveniently, but also used to guide future individualized therapeutic approaches. Furthermore, NSCs were found to relate to EMT profoundly.

Angiotensin I-converting enzyme gene polymorphism enhances the effect of hypercholesterolemia on the risk of coronary heart disease in a general Japanese population: the hisayama study.

AIM: The angiotensin I-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism has been reported to be implicated in susceptibility to coronary heart disease (CHD). However, this association remains inconclusive. The purpose of this study was to clarify the association between the I/D polymorphism of the ACE gene and the development of CHD in a Japanese general population and investigate whether the effects of traditional risk factors on the risk of CHD are heterogeneous among ACE genotypes. METHODS: The subjects included 2,125 community-dwelling individuals 40 years of age or older without cardiovascular disease for whom genetic information was available. All patients were prospectively followed for 19 years, and the association between the ACE polymorphism and the incidence of CHD was examined based on the interactions with traditional risk factors, such as hypercholesterolemia, hypertension, diabetes and smoking. RESULTS: A total of 161 CHD events occurred during the follow-up period. The age- and sex-adjusted incidence of CHD was not significantly different among the genotypes (5.8, 5.2, and 6.9 per 1,000person-years for genotypes II, ID and DD, respectively). In a stratified analysis, however, the ACE DD genotype was found to significantly accelerate the risk of developing CHD by hypercholesterolemia (hazard ratio [HR]=4.50, 95% confidence interval=2.02-10.04 for hypercholesterolemia with the DD genotype; HR=1.48, 95% CI=1.04-2.12 for hypercholesterolemia with the ID＋II genotype; P for interaction=0.01), even after adjusting for other confounding factors, whereas no such associations were observed for hypertension, diabetes or smoking. CONCLUSIONS: The current findings suggest that the ACE DD genotype enhances the effect of hypercholesterolemia on the development of CHD in the general Japanese population.

Elevated depressive symptoms in metabolic syndrome in a general population of Japanese men: a cross-sectional study.

BACKGROUND: Uncertainty still surrounds the association between metabolic syndrome (MetS) and depression. We aimed to evaluate the association between MetS and elevated depressive symptoms in a general Japanese population. METHODS: This is a cross-sectional survey of 3,113 community-dwelling individuals aged 40 years or over. MetS was defined according to the joint interim statement. MetS was diagnosed when a subject had three or more of the following components: 1) central obesity (waist circumference ≥ 90 cm for men, ≥ 80 cm in for women); 2) elevated blood pressure (≥ 130/85 mmHg or current use of antihypertensive medication); 3) hypertriglyceridemia (≥ 1.7 mmol/L); 4) low HDL cholesterol (< 1.0 mmol/L for men, < 1.3 mmol/L for women); and 5) elevated fasting plasma glucose (≥ 5.55 mmol/L or current use of antidiabetic medication). Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). The age- and multivariable-adjusted odds ratio (OR) and 95% confidence interval (CI) were estimated using a logistic regression model. RESULTS: Elevated depressive symptoms were observed in 4.3% of male and 6.3% of female participants. In men, the age-adjusted prevalence of elevated depressive symptoms was significantly higher in subjects with MetS than in those without (7.1% versus 3.6%, p = 0.04). The prevalence of elevated depressive symptoms rose progressively as the number of MetS components increased (3.5%, 3.6%, 5.8%, and 9.2% in male subjects with 0-1, 2, 3, and ≥ 4 components, respectively; p = 0.02 for trend). This association remained significant even after adjustment for age, marital status, history of cardiovascular disease, smoking habit, alcohol intake, and regular exercise. In women, on the other hand, there was no clear association between MetS and depressive symptoms. CONCLUSIONS: MetS was associated with elevated depressive symptoms in a general population of Japanese men.

RECQL1 DNA repair helicase: a potential therapeutic target and a proliferative marker against ovarian cancer.

OBJECTIVE: This study analyzed the clinicopathological correlation between ovarian cancer (OC) and RECQL1 DNA helicase to assess its therapeutic potential. METHODS: Surgically resected OC from 118 retrospective cases, for which paraffin blocks and all clinical data were complete, were used in this study. RECQL1 and Ki-67 immunostaining were performed on sections to correlate RECQL1 staining with subtype and patient survival. Ten OC and two normal cell lines were then examined for RECQL1 expression and were treated with siRNA against RECQL1 to assess its effect on cell proliferation. RESULTS: Of the 118 cases of adenocarcinoma (50, serous; 26, endometrioid; 21, clear cell; 15, mucinous; 6, other histology), 104 (90%) showed varying levels of RECQL1 expression in the nuclei of OC cells. The Cox hazards model confirmed that diffuse and strong staining of RECQL1 was correlated with histological type. However, RECQL1 expression did not correlate with overall patient survival or FIGO stage. In vitro, RECQL1 expression was exceptionally high in rapidly growing OC cell lines, as compared with normal cells. Using a time-course analysis of RECQL1-siRNA transfection, we observed a significant inhibition in cell proliferation. CONCLUSIONS: RECQL1 DNA helicase is a marker of highly proliferative cells. RECQL1-siRNA may offer a new therapeutic strategy against various subtypes of OC, including platinum-resistant cancers, or in recurrent cancers that gain platinum resistance.

Secular trends in cardiovascular disease and its risk factors in Japanese: half-century data from the Hisayama Study (1961-2009).

BACKGROUND: Changes in lifestyle and advances in medical technology during the past half century are likely to have affected the incidence and mortality of cardiovascular disease and the prevalence of its risk factors in Japan. METHODS AND RESULTS: We established 5 cohorts consisting of residents aged ≥40 years in a Japanese community, in 1961 (n=1618), 1974 (n=2038), 1983 (n=2459), 1993 (n=1983), and 2002 (n=3108), and followed up each cohort for 7 years. The age-adjusted incidence of stroke decreased greatly, by 51% in men and by 43% in women, from the 1960s to the 1970s, but this decreasing trend slowed from the 1970s to the 2000s. Among the stroke subtypes, ischemic stroke in both sexes and intracerebral hemorrhage in men showed a similar pattern. Stroke mortality decreased as a result of the decline in incidence and a significant improvement in survival rate. Although the incidence of acute myocardial infarction did not change in either sex, disease mortality declined slightly in women. From the 1960s to the 2000s, blood pressure control among hypertensive individuals improved significantly and the smoking rate decreased, but the prevalence of glucose intolerance, hypercholesterolemia, and obesity increased steeply. CONCLUSIONS: Our findings suggest that in Japanese, the decreasing trends in the incidence of ischemic stroke have recently slowed down, and there has been no clear change in the incidence of acute myocardial infarction, probably because the benefits of hypertension control and smoking cessation have been negated by increasing metabolic risk factors.

A phase II study of a personalized peptide vaccination for chemotherapy-resistant advanced pancreatic cancer patients.

Pancreatic cancer is one of the most aggressive cancers with a median survival time (MST) of <6 months in chemotherapy-resistant patients. Therefore, the development of novel treatment modalities is needed. In the present study, a phase II study of personalized peptide vaccination (PPV) was conducted, in which vaccine antigens were selected and administered based on the pre-existing IgG responses to 31 different pooled peptides, for 41 chemotherapy-resistant advanced pancreatic cancer patients. No vaccine-related severe adverse events were observed. IgG responses specific to at least one of the vaccine peptides were augmented in 14 of 36 patients (39%) and in 18 of 19 patients (95%) tested after the 5th and 11th vaccination, respectively. MST from the first vaccination was 7.9 months with a 1-year survival rate of 26.8%. Higher serum amyloid A (SAA) and C-reactive protein (CRP) levels in pre-vaccination plasma were unfavorable factors for overall survival (OS). Due to the safety profile and the potential clinical efficacy, the conduction of additional clinical trials of PPV for chemotherapy-resistant advanced pancreatic cancer patients is warranted.

Optimal cutoff value of the serum pepsinogen level for prediction of gastric cancer incidence: the Hisayama Study.

BACKGROUND: Serum pepsinogen (sPG) levels have been established as a good marker of chronic atrophic gastritis and the sequential occurrence of gastric cancer. However, there have been few prospective investigations which investigated the predictive performance of sPG for future gastric cancer incidence. SUBJECTS AND METHODS: We prospectively followed-up a total of 2446 community-dwelling Japanese aged ≥ 40 years for 10 years and used the Youden's index to determine the cutoff values of the pepsinogen I level and pepsinogen I/II ratio to accurately discriminate gastric cancer events. Predictive performance of sPG was assessed by ROC curve. RESULTS: During the follow-up, 69 subjects developed gastric cancer. The most predictive sPG test criteria were determined to be a pepsinogen I level ≤ 59 ng/ml and pepsinogen I/II ratio ≤ 3.9. The sensitivity and specificity of these criteria to discriminate the actual occurrence of gastric cancer were 71.0% and 69.2%, respectively. The area under the ROC curve for gastric cancer occurrence increased significantly by adding the sPG test to the model that included the status of Helicobater pylori infection and other potential risk factors (from 0.742 to 0.809; p for difference in the area < 0.001). CONCLUSIONS: This study determined the optimal sPG test criteria for predicting gastric cancer occurrence over 10 years in a general Japanese population. These criteria would be effective to screen for individuals at high risk of this disease.