Kentaro Sakamaki

Combined inhibitory effects of soy isoflavones and curcumin on the production of prostate-specific antigen.

Sustained chronic inflammation in the prostate promotes prostate carcinogenesis. Since an elevated level of prostate‐specific antigen (PSA) per se reflects the presence of inflammation in the prostate, intervention to improve the PSA value might potentially have beneficial effects for the prevention of the development of prostate cancer. Isoflavones and curcumin have anti‐inflammatory and anti‐oxidant properties. We examined the biological effects of soy isoflavones and curcumin on LNCaP cells. After that, we conducted a clinical trial for men who received prostate biopsies, but were not found to have prostate cancer, to evaluate the effects of soy isoflavones and curcumin on serum PSA levels.

LINE-1 hypomethylation is associated with a poor prognosis among patients with curatively resected esophageal squamous cell carcinoma.

Objective: To investigate the relationship between the long interspersed nucleotide element-1 (L1/LINE-1) methylation level and the disease-free survival and cancer-specific survival in patients with esophageal squamous cell carcinoma (ESCC). Background: Cancer cells exhibit 2 types of deoxyribonucleic acid (DNA) methylation alterations: global DNA hypomethylation and site-specific CpG island promoter hypermethylation. Global DNA hypomethylation plays a role in genomic instability and carcinogenesis. DNA methylation in the LINE-1 repetitive element is a good indicator of the global DNA methylation level. Although the LINE-1 methylation level is attracting interest as a useful marker for predicting cancer prognosis, the prognostic significance of LINE-1 hypomethylaiton in ESCC remains unclear. Methods: Using 217 curatively resected ESCC specimens, we quantified the LINE-1 methylation by utilizing the bisulfite pyrosequencing technology. Promoter methylation levels of MGMT and MLH1 were also evaluated by pyrosequencing. Results: ESCC showed significantly lower LINE-1 methylation levels in comparison with matched normal esophageal mucosa (P < 0.0001; N = 50). LINE-1 hypomethylation was significantly associated with disease-free survival [log-rank P = 0.0008; univariate hazard ratio (HR): 2.32, 95% confidence interval (CI): 1.38–3.84, P = 0.0017; multivariate HR: 1.81, 95% CI: 1.06–3.05, P = 0.031] and cancer-specific survival (log-rank P = 0.0020; univariate HR: 2.21, 95% CI: 1.33–3.60, P = 0.0026; multivariate HR: 1.87, 95% CI: 1.12–3.08, P = 0.018]. MGMT and MLH1 hypermethylation were not associated with patient prognosis. Conclusions: LINE-1 hypomethylation in ESCC is associated with a shorter survival, thus suggesting that it has potential for use as a prognostic biomarker.

Comparison of the Incidence of Acute Decompensated Heart Failure Before and After the Major Tsunami in Northeast Japan

On March 11, 2011, a huge tsunami attacked the northeastern coast of Japan after a magnitude 9 earthquake. No reports have investigated the impact of tsunamis on the incidence of cardiovascular disease, especially heart failure (HF). We investigated the number and clinical characteristics of hospitalized patients with acute decompensated HF (ADHF) in the east coast of Iwate hit by the tsunami (tsunami area) for a 12-week period around the disaster. For comparison with previous years, numbers of ADHF were surveyed in the corresponding area in 2009 and 2010. In addition, to elucidate the impact of the tsunami, a similar study was performed in a remote area where the tsunami had minimal effect (control area). After the disaster, the number of patients with ADHF in the tsunami area was significantly increased compared to the predisaster period (relative risk 1.97, 95% confidence interval 1.50 to 2.59). The peak was found 3 to 4 weeks after the disaster. In contrast, in the control area, no significant change in ADHF events was observed (relative risk 1.29, 95% confidence interval 0.94 to 1.78). There was a significant correlation between changes in the number of ADHF admissions and percent tsunami flood area (r = 0.73, p <0.001) or the number of shelter evacuees (r = 0.83, p <0.001). In conclusion, these findings suggest that large and sudden changes in daily life and the trauma associated with a devastating tsunami have a significant impact on the incidence of ADHF.

Decreased duration of acute upper respiratory tract infections with daily intake of fermented milk: A multicenter, double-blinded, randomized comparative study in users of day care facilities for the elderly population

BACKGROUND There is insufficient evidence of preventive effect of probiotics on upper respiratory tract infections (URTIs) in an elderly population. METHODS We conducted a multicenter, double-blinded, randomized, placebo-controlled parallel group study. Elderly persons had participated who used day care at 4 facilities in Tokyo. We used fermented milks containing Lactobacillus casei strain Shirota (LcS) and placebo drinks as test drinks. RESULTS A total of 154 subjects was analyzed. The number of persons diagnosed with an acute URTIs was almost identical in both groups (LcS: 31, placebo: 32), whereas the number of acute URTIs events (LcS: 68, placebo: 51) and the symptom score (LcS: 425, placebo: 396) were both higher in the LcS group. Permutation tests performed using the total number of acute URTIs infection events/total days of observation and the total symptom score/total days of observation found no statistically significant difference respectively (P values of .89 and .64, respectively). Comparing the mean duration of infection per infection event found a shorter mean duration in the LcS group (LcS: 3.71 days, placebo: 5.40 days), and the difference was statistically significant. CONCLUSION The results suggest that fermented milk containing LcS probably reduces the duration of acute URTIs.

LINE-1 Hypomethylation, DNA Copy Number Alterations, and CDK6 Amplification in Esophageal Squamous Cell Carcinoma

Purpose: Global DNA hypomethylation plays a crucial role in genomic instability and carcinogenesis. DNA methylation of the long interspersed nucleotide element-1, L1 (LINE-1) repetitive element is a good indicator of the global DNA methylation level, and is attracting interest as a useful marker for predicting cancer prognosis. Our previous study using more than 200 esophageal squamous cell carcinoma (ESCC) specimens demonstrated the significant relationship between LINE-1 hypomethylation and poor prognosis. However, the mechanism by which LINE-1 hypomethylation affects aggressive tumor behavior has yet to be revealed. Experimental Design: To examine the relationship between LINE-1 hypomethylation and DNA copy number variations, we investigated LINE-1–hypomethylated and LINE-1–hypermethylated ESCC tumors by comparative genomic hybridization array. Results: LINE-1–hypomethylated tumors showed highly frequent genomic gains at various loci containing candidate oncogenes such as CDK6. LINE-1 methylation levels were significantly associated with CDK6 mRNA and CDK6 protein expression levels in ESCC specimens. In our cohort of 129 patients with ESCC, cases with CDK6-positive expression experienced worse clinical outcome compared with those with CDK6-negative expression, supporting the oncogenic role of CDK6 in ESCC. In addition, we found that the prognostic impact of LINE-1 hypomethylation might be attenuated by CDK6 expression. Conclusion: LINE-1 hypomethylation (i.e., global DNA hypomethylation) in ESCC might contribute to the acquisition of aggressive tumor behavior through genomic gains of oncogenes such as CDK6. Clin Cancer Res; 20(5); 1114–24. ©2014 AACR.

Pregnancy Outcomes Based on Pre-Pregnancy Body Mass Index in Japanese Women

Objective To verify whether body mass index (BMI) classification proposed by the Institute of Medicine (IOM) is valid in Japanese women. Method A study was conducted in 97,157 women with singleton pregnancies registered in the Japan Society of Obstetrics and Gynecology (JSOG) Successive Pregnancy Birth Registry System between January 2013 and December 2013, to examine pregnancy outcomes in four groups stratified by pre-pregnancy BMI category according to the 2009 criteria recommended by the Institute of Medicine (IOM). The groups comprised 17,724 underweight women with BMI <18.5, 69,126 normal weight women with BMI 18.5–24.9, 7,502 overweight women with BMI 25–29.9, and 2,805 obese women with BMI ≥30. The pregnancy outcomes were also compared among subgroups stratified by a gestational weight gain below, within, and above the optimal weight gain. Results The higher the pre-pregnancy BMI, the higher the incidences of pregnancy-induced hypertension, gestational diabetes mellitus, macrosomia, cesarean delivery, postpartum hemorrhage, and post-term birth, but the lower the incidence of small for gestational age (SGA). In all pre-pregnancy BMI category groups, excess gestational weight gain was associated with a higher frequency of large for gestational age and macrosomia; poor weight gain correlated with a higher frequency of SGA, preterm birth, preterm premature rupture of membranes, and spontaneous preterm birth; and optimal weight gain within the recommended range was associated with a better outcome. Conclusion The BMI classification by the IOM was demonstrated to be valid in Japanese women.

Development and internal validation of a nomogram for predicting stone-free status after flexible ureteroscopy for renal stones.

To develop and internally validate a preoperative nomogram for predicting stone‐free status (SF) after flexible ureteroscopy (fURS) for renal stones, as there is a need to predict the outcome of fURS for the treatment of renal stone disease.

Neutrophil-to-lymphocyte ratio is a prognostic marker in bladder cancer patients after radical cystectomy

BackgroundThere is no reliable biomarker for predicting the prognosis of patients who undergo radical cystectomy for bladder cancer. Recent studies have shown that the neutrophil-to-lymphocyte ratio (NLR) could function as a useful prognostic factor in several types of malignancies. This study aimed to assess the usefulness of NLR in bladder cancer.MethodsA total of 74 patients who underwent radical cystectomy in our institutions from 1999 to 2014 were analyzed. The NLR was calculated using the patients’ neutrophil and lymphocyte counts before radical cystectomy. An immunohistochemical analysis was also performed to detect tumor infiltrating neutrophils (CD66b) and lymphocytes (CD8) in bladder cancer specimens.ResultsA univariate analysis showed that the patients with a high NLR (≥2.38; HR = 4.84; p = 0.007), high C-reactive protein level (>0.08; HR = 10.06; p = 0.030), or pathological lymph node metastasis (HR = 4.73; p = 0.030) had a significantly higher risk of cancer-specific mortality. Kaplan-Meier and log-rank tests further revealed that NLR was strongly correlated with overall survival (p = 0.018), but not progression-free survival (p = 0.137). In a multivariate analysis, all of these were found to be independent risk factors (HR = 4.62, 10.8, and 12.35, respectively). The number of CD8-positive lymphocytes was significantly increased in high-grade (p = 0.001) and muscle-invasive (p = 0.012) tumors, in comparison to low-grade and non-muscle-invasive tumors, respectively.ConclusionsThe NLR predicted the prognosis of patients who underwent radical cystectomy and might therefore function as a reliable biomarker in cases of invasive bladder cancer.

Hepatocellular Carcinoma: Concomitant Sorafenib Promotes Necrosis after Radiofrequency Ablation—Propensity Score Matching Analysis

PURPOSE To retrospectively compare radiofrequency ablation (RFA) combined with the multikinase inhibitor sorafenib (hereafter, sorafenib-RFA) and RFA alone in the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS Institutional review board approval and informed consent were obtained. Between January 2007 and December 2011, 16 patients (mean age, 72.8 years; age range 52-84 years; 10 men, six women) with HCC tumors less than 3 cm in diameter were included in the sorafenib-RFA group, and 136 patients (mean age, 72.1 years; age range, 51-86 years; 92 men, 44 women) with HCC tumors less than 3 cm in diameter were included in the RFA alone (control) group. Mean diameters of the greatest long-axis dimensions of HCC were 22.8 mm ± 4.6 (standard deviation) in the sorafenib-RFA group and 18.1 mm ± 4.4 in the control group. RFA was performed immediately after the 7-day administration of sorafenib. Propensity score matching analysis was used to adjust for potential biases. RESULTS Fifteen of the 16 patients in the sorafenib-RFA group and 30 of the 136 patients in the control group were selected during propensity score matching. No significant differences between the sorafenib-RFA group (n = 15) and the control group (n = 30) were observed with regard to age, sex, etiology, Child-Pugh class, tumor size, puncture number, needle size, location at the liver margin, or location adjacent to a main vessel. The respective mean diameters of the greatest long- and short-axis dimensions of the RFA-induced ablated area were 46.3 mm ± 10.3 and 33.0 mm ± 6.9 in the sorafenib-RFA group and 32.9 mm ± 7.6 and 25.6 mm ± 5.7 in the control group; both of these dimensions were significantly larger in the sorafenib-RFA group (both P < .001). CONCLUSION Sorafenib-RFA may be superior to standard RFA alone in the treatment of HCC tumors smaller than 3 cm in diameter.

Use of color Doppler ultrasonography for evaluating vascularity of small intestinal lesions in Crohn's disease: correlation with endoscopic and surgical macroscopic findings

Abstract Objective. Ultrasonography (US) is a simple, inexpensive and minimally invasive method. We evaluated the vascularity of small intestinal lesions in Crohns disease using color Doppler US (CD-US) and retrospectively compared them with endoscopic and surgical macroscopic findings. Material and methods. In order to compare CD-US and endoscopic findings, 108 Crohns disease patients who underwent examination of the terminal ileum by both colonoscopy and CD-US were included in the study. Vascularity was evaluated in CD-US using a semiquantitative method, the Limberg score. We analyzed correlations between Limberg score and simple endoscopic score for Crohns disease (SES-CD), an index reflecting endoscopic activity. Scores of SES-CD 3 and higher were defined as endoscopically active. For comparison with surgical macroscopic findings, 22 Crohns disease patients who received CD-US and subsequent iliectomies were included. Lesions with apparent open ulcers were defined as active, and those without as non-active. These findings were compared with the Limberg score. Results. A substantial positive correlation was observed between Limberg scores and SES-CD (ρ = 0.709 [p < 0.001]). Notably, all 27 cases with a Limberg score of 3 or 4 were classified as endoscopically active. Compared to surgical macroscopic activity, Limberg scores of active lesions were significantly higher than those of non-active lesions (p = 0.005). In particular, all 11 cases with a Limberg score of 3 or 4 were classified as active lesions. Conclusion. Vascularity of small intestinal lesions of Crohns disease evaluated by CD-US with Limberg score is well correlated with endoscopic and surgical macroscopic findings.