Relationship between lower urinary tract symptoms and frailty.

OBJECTIVE: To elucidate the relationship between frailty and lower urinary tract symptoms (LUTS). METHODS: We longitudinally evaluated the temporal changes and the relationships between frailty and LUTS in 247 community-dwelling adults (45 years or older) at baseline and at a 5-year follow-up. We used the Fried phenotype (phenotype-based frailty), 5-item modified frailty index (5i-mFI; comorbidity-based frailty), and frailty discriminant score (comprehensive frailty assessment) to evaluate frailty. LUTS were evaluated using the international prostate symptom score (IPSS) and overactive bladder symptom score (OABSS). RESULTS: We analyzed 247 participants with a median age of 60 years. The median IPSS and OABSS were significantly increased over the 5 years. The proportion of frail individuals did not increase significantly over the 5 years. Of the three frailty assessment tools, the 5i-mFI score significantly increased between 2014 and 2019. Multiple linear regression analyses showed that the 5i-mFI score was significantly associated with the severity of LUTS in 2014 to 5i-mFI in 2019 but not with 5i-mFI in 2014 to the severity of LUTS in 2019. CONCLUSION: The effect of LUTS on frailty might be greater than the effect of frailty on LUTS. Further large-scale studies are needed to elucidate the relationship between LUTS and frailty.

Altered gut microbiome associated with overactive bladder and daily urinary urgency.

PURPOSE: To explore associations between the gut microbiome and overactive bladder (OAB) with daily urinary urgency among individuals reporting this diagnosis within a single community. METHODS: This cross-sectional study surveyed 1113 individuals who participated in the Iwaki Health Promotion Project in Japan. OAB was defined as urinary urgency at least once per week and an Overactive Bladder Symptom Score (OABSS) of ≥ 3. OAB with urinary urgency at least once a day was defined as daily urgency. The gut microbiomes were assessed by next-generation sequencing of 16S rRNA genes extracted from fecal samples. The participants were divided into two groups: OAB-daily urgency and non-OAB. Cases were selected for inclusion on the basis of 1:1 propensity score matching; we assigned 58 individuals to each group (23 men and 35 women) for our analysis. RESULTS: Individuals reporting OAB with daily urinary urgency demonstrated a lower bacterial diversity between individuals (Bray-Curtis distance 0.48 vs. 0.53, P < 0.001); the results cluster differently in the non-OAB groups. The relative abundance of genus Bifidobacterium was significantly lower among those reporting daily urgency (2.41% vs. 4.23%, P = 0.014). By contrast, the relative abundance of genus Faecalibacterium (9.25% vs. 6.26%, P = 0.006) was significantly higher in this group. CONCLUSION: We observed significant differences in gut microbial contents and specific bacterial genera in association with OAB with daily urgency. Further study will be necessary to assess causal relationships between the gut microbiome and OAB.

The association between serum serotonin levels and overactive bladder: results from a community-based cross-sectional study in Japan.

PURPOSE: To investigate the association between serum serotonin (5-HT) levels and overactive bladder (OAB) in a community-dwelling population. METHODS: This cross-sectional study analyzed 1024 subjects who participated in the Iwaki Health Promotion Project in 2015 in Hirosaki, Japan. OAB was assessed using the Overactive Bladder Symptom Score (OABSS). OAB was defined as an occurrence of urinary urgency at least once a week and an OABSS of ≥ 3. We assessed serum 5-HT levels, laboratory data, and comorbidities of each participants. Participants' mental health status was evaluated using the Center for Epidemiologic Studies Depression (CES-D) scale. The association of serum 5-HT levels and OAB was analyzed by multivariable logistic regression analysis. RESULTS: This study included 394 men and 630 women. Of those, 118 (44 male and 74 female) were OAB sufferers. There were significant group differences in age, history of cardiovascular disease, chronic kidney disease, hypertension, diabetes mellitus, and CES-D score. Participants' serum 5-HT levels in the OAB group were significantly lower than those in the non-OAB group (100 vs. 127 ng/mL, P < 0.001). Multivariable analysis showed that age (odds ratio [OR]; 1.06, 95% confidence interval [CI]; 1.04-1.08, P < 0.001) and log serum 5-HT level (OR; 0.25, 95% CI; 0.10-0.68, P = 0.006) were independently associated with OAB. CONCLUSIONS: Lower serum 5-HT levels could independently be associated with the presence of OAB. Further study is necessary to elucidate a possible causal relationship between serum 5-HT levels and OAB.

A Longitudinal Study of Bidirectional Relationships between Sleep Disorder and Frequency of Nocturia: Results from the Iwaki Health Promotion Project.

INTRODUCTION: The causal relationship between sleep disorder and frequency of nocturia remains unclear. METHODS: We longitudinally evaluated sleep disorder and frequency of nocturia in 547 community-dwelling adults between baseline and 5-year follow-up. We included participants ≥50 years old who have no sleep disorder (the Pittsburgh Sleep Quality Index [PSQI] ≥ 5) nor nocturia (≥1). For 5 years, we evaluated the temporal changes in sleep disorder and nocturia and the bidirectional relationships between sleep disorder and nocturia. RESULTS: Of the 547 participants, we included 268 adults with a median age of 61 years in this study. Median PSQI and nocturia were significantly increased for 5 years from 2 to 3 and from 1 to 2, respectively. New onset of sleep disorder (PSQI > 5) and nocturia >1 was observed in 42 (16%) and 137 (51%) participants, respectively. The cross-lagged panel analysis showed that the path coefficient from PSQI to nocturia (ß = 0.22, p = 0.031) was significantly higher than that from nocturia to PSQI (ß = 0.02, p = 0.941). CONCLUSIONS: Our longitudinal study showed the effect of sleep disorder on nocturia was significant, although nocturia may not significantly worsen sleep disorder in community-dwelling adults.

Prostanoid receptor genes confer poor prognosis in head and neck squamous cell carcinoma via epigenetic inactivation.

BACKGROUND: Chronic inflammation is a risk factor for head and neck squamous cell carcinoma (HNSCC) and other diseases. Prostanoid receptors are clearly involved in the development of many types of cancer. However, their role is not simple and is poorly understood in HNSCC. METHODS: Methylation profiles of prostanoid receptor family genes were generated for tumour samples obtained from 274 patients with HNSCC, including 69 hypopharynx, 51 larynx, 79 oral cavity, and 75 oropharynx tumour samples, by quantitative methylation-specific PCR. Promoter methylation was then evaluated with respect to various clinical characteristics and patient survival. RESULTS: The mean number of methylated genes per sample was 2.05 ± 2.59 (range 0 to 9). Promoters of PTGDR1, PTGDR2, PTGER1, PTGER2, PTGER3, PTGER4, PTGFR, PTGIR, and TBXA2R were methylated in 43.8%, 18.2%, 25.5%, 17.5%, 41.2%, 8.0%, 19.3%, 20.4%, and 11.3% of the samples, respectively. Methylation indices for prostanoid receptor family genes tended to be higher as the number of TET methylation events increased. Patients with 5-9 methylated genes had a significantly lower survival rate than that of patients with 0-4 methylated genes (log-rank test, P= 0.007). In multivariate analyses, PTGDR1 methylation was most highly correlated with recurrence in patients with hypopharyngeal cancer (P = 0.014). A similar correlation was observed for PTGER4 in patients with laryngeal cancer (P = 0.046). Methylation of the PTGIR and TBXA2R promoters was positively correlated with recurrence in oropharyngeal cancer (P = 0.028 and P = 0.006, respectively). Moreover, Patients with 5-9 methylated genes were extremely lower of 5hmC levels (P = 0.035) and was correlated with increasing expression of DNMT3A and DNMT3B (P < 0.05 and P < 0.05, respectively). CONCLUSION: We characterised the relationship between the methylation status of prostanoid receptor genes and recurrence in HNSCC. These results provide new perspectives for the development of molecular targeted treatment approaches.

The impact of microalbuminuria on overactive bladders: Results from a community-based four-year longitudinal study in Japan.

AIMS: To investigate the longitudinal association of microalbuminuria with overactive bladder (OAB). METHODS: This longitudinal study investigated 561 participants of the Iwaki Health Promotion Project in both 2015 and 2019 in Japan. Microalbuminuria and OAB symptoms were assessed using the urine albuminuria creatinine ratio (ACR) and the overactive bladder symptom score (OABSS), respectively. Urine ACR was defined as high if ≥9.3 mg/gCr. Differences in OABSS between 2015 and 2019 were evaluated as ∆OABSS. Participants were divided into two groups according to ΔOABSS: high (ΔOABSS > 1) and control (≤1). We used baseline data acquired in 2015, such as urine ACR, the Pittsburgh Sleep Quality Index (PSQI), and arterial stiffness expressed by brachial-ankle pulse wave velocity (baPWV). Predictive factors of a ΔOABSS > 1 were assessed by multivariable logistic regression analysis. RESULTS: This study included 332 women and 229 men. Of those, 86 (34 males and 52 females) were classified into the ΔOABSS > 1 group. There were significant group differences in age, renal function, and hemoglobin A1c. Participants in the ΔOABSS > 1 had a higher prevalence of PSQI > 5, baPWV ≥ 1400 seconds/cm, and urine ACR ≥ 9.3 mg/gCr (49% vs 20%, P = .001) than those in the control group. Multivariable analysis revealed that PSQI > 5 (odds ratio [OR], 2.57; 95% confidence interval [CI], 1.15-4.60; P = .002) and urine ACR ≥ 9.3 mg/gCr (OR, 1.93; 95% CI, 1.15-3.23; P = .013) were independent risk factors for ΔOABSS > 1. CONCLUSIONS: Microalbuminuria may be an independent risk indicator for OAB symptom exacerbation.

Survey on attitudes toward brain-dead and living donor transplantation in medical students: a cross-sectional study in Japan.

BACKGROUND: Although a shortage in organ donation is a critical problem in Japan, understanding of and attitude toward organ transplantation in medical students have not been sufficiently reported. METHODS: Between 2013 and 2018, we surveyed 702 medical students in the fifth-year clinical training in our urology department. The survey concerned (1) knowledge of Japanese transplantation law, which was amended in 2010, and (2) whether the respondents had an organ donor card and had agreed to be a brain-dead donor or a living donor in kidney transplantation with specific reasons for their choices. RESULTS: All 702 students answered the survey. Of 657 students who provided valid answers to the first section, 402 (61%) recognized the amendment to the Japanese transplantation law, and only 11 (1.7%) fully understood its contents. Of 702 students, 194 (28%) had a donor card, 384 (55%) agreed to be a brain-dead donor, and 529 (75%) agreed to be a living donor in kidney transplantation. As the specific reasons for their choices, only a few medical students wrote reasons based on their medical standpoint, and more students wrote emotional reasons. CONCLUSIONS: The understanding of and attitude toward organ transplantation were not remarkably high in the fifth-year medical students in Japan. To solve the donor shortage problem, education about organ transplantation may need to be more effective.

Management of elderly patients with head and neck carcinoma: analysis of outcomes for radical versus palliative treatment.

BACKGROUND: There are no universally accepted treatment recommendations for elderly patients with head and neck carcinomas. This study investigated whether radical treatment in elderly patients resulted in better survival compared with palliative treatment. METHODS: We retrospectively reviewed the medical records of 724 patients aged > 60 years who underwent treatment for primary head and neck carcinomas at Hamamatsu University Hospital. We evaluated the impact of the following: age, sex, the clinical stage, smoking history, alcohol use history, primary tumor site, performance status, and Osaka Head and Neck Comorbidity Index score on overall survival using a Cox proportional hazards model. RESULTS: The 5-year overall survival rate was significantly greater for the 646 patients initially treated with radical (curative) therapy than for the 78 patients treated with palliative therapy (p < 0.01). Patients who received palliative treatment in all age groups were more likely to die than were those in the radical treatment group, after controlling for age, sex, and clinical stage of the cancer. Information on the survival status of patients was obtained after a mean follow-up period of 46 months (range 6-205 months). CONCLUSIONS: In the absence of contraindications associated with comorbidities, radical treatment protocols should be recommended for elderly patients with head and neck carcinomas because they confer better survival.

Influence of pretreatment quality of life on prognosis in patients with urothelial carcinoma.

BACKGROUND: We investigated the association between the pretreatment quality of life (QOL) and overall survival (OS) in patients with urothelial carcinoma (UC), as the influence of pretreatment QOL on prognosis remains unclear in patients with localized and metastatic UC. METHODS: Between June 2013 and May 2019, we retrospectively investigated 205 patients with UC who received radical cystectomy or nephroureterectomy for non-metastatic UC (M0 group) or systemic chemotherapy for metastatic UC (M1 group). Patients answered the European Organization for the Research and Treatment of Cancer Quality-of-Life Questionnaire C30 (QLQ-C30) before the treatments. Patients were stratified into two groups: QOL high and low according to the optimal cutoff scores which were defined by receiver operating characteristic curve. Inverse probability of treatment weighting (IPTW)-adjusted multivariate Cox regression analyses were performed to investigate the clinical implication of pretreatment QOL score on OS in patients with UC. RESULTS: The number of patients in the M0 and M1 groups was 125 and 80, respectively. Optimal cutoff values in global, fatigue, pain, appetite loss, physical, and role scores were < 50, > 33, > 33, > 16, < 80, and < 67, respectively. IPTW-adjusted multivariate Cox regression analyses revealed that appetite loss score indicated a significantly poorer OS in the M1 group. No significant association of QOL with OS was observed in the M0 group. CONCLUSION: Pretreatment QOL of appetite loss may predict poor prognosis of patients with metastatic UC.

STone Episode Prediction: Development and validation of the prediction nomogram for urolithiasis.

OBJECTIVES: To develop and validate a nomogram predicting the occurrence of a stone episode, given the lack of such predicting risk tools for urolithiasis. METHODS: We retrospectively analyzed 1305 patients with urolithiasis and 2800 community-dwelling individuals who underwent a comprehensive health survey. The STone Episode Prediction nomogram was created based on data from the medical records of 600 patients with urolithiasis and 1300 controls, and was validated using a different population of 705 patients with urolithiasis and 1500 controls. Logistic regression analysis was used to construct a model to predict the potential candidate for a stone episode. The predictive ability of the model was evaluated using the results of the area under the receiver operating characteristics curve (area under the curve). RESULTS: Age, sex, diabetes mellitus, renal function, serum albumin, and serum uric acid were found to be significantly associated with urolithiasis in the training set and were included in the STone Episode Prediction nomogram. The optimal cut-off value for the probability of a stone episode using the nomogram was >28% with a sensitivity of 79%, a specificity of 76%, and area under the curve of 0.860. In the validation test, area under the curve for the detection of urolithiasis was 0.815 with a sensitivity of 81% and specificity of 63%. CONCLUSIONS: Herein, we developed and validated the STone Episode Prediction nomogram that can predict a potential candidate for an episode of urolithiasis. This nomogram might be beneficial for the first step in stone screening in individuals with lifestyle-related diseases.

Geriatric 8 screening of frailty in patients with prostate cancer.

OBJECTIVES: To evaluate the association between the score of the Geriatric 8 screening tool and treatment by disease stages in patients with prostate cancer. METHODS: Between January 2017 and June 2019, we prospectively evaluated the Geriatric 8 in 540 prostate cancer patients who were treated with robot-assisted radical prostatectomy, radiotherapy, androgen deprivation therapy alone and standard of care for metastatic hormone-naïve prostate cancer or castration-resistant prostate cancer. The primary purpose was the association between frailty (Geriatric 8 ≤14) and robot-assisted radical prostatectomy, radiotherapy, androgen deprivation therapy alone, and metastatic diseases. Secondary purposes included a comparison of the Geriatric 8 scores among the disease status and the influence of Geriatric 8 score on overall survival. RESULTS: The median age was 75 years. Geriatric 8 scores ≤14 were seen in 36% of robot-assisted radical prostatectomy (n = 78/214), 57% of radiotherapy (n = 119/209), 91% of androgen deprivation therapy alone (n = 19/21) and 70% of metastatic diseases (n = 67/96). The median Geriatric 8 score in patients treated with robot-assisted radical prostatectomy, radiotherapy, androgen deprivation therapy alone and metastatic diseases was 15.0, 14.0, 12.0 and 12.8, respectively. The median Geriatric 8 score was significantly higher in the metastatic disease than that in localized disease (14.5 vs 12.8, respectively). Robot-assisted radical prostatectomy patients had a significantly higher Geriatric 8 score than radiotherapy patients, with the cut-off value of <14.5. The overall survival was significantly different between Geriatric 8 scores ≤13 and >13 in metastatic hormone-naïve prostate cancer patients, and between Geriatric 8 scores ≤12 and >12 in castration-resistant prostate cancer patients. CONCLUSION: The Geriatric 8 score is significantly associated with treatment by disease stages in patients with prostate cancer.

Relationship between oxidative stress and lower urinary tract symptoms: results from a community health survey in Japan.

OBJECTIVE: To investigate the relationship between oxidative stress and lower urinary tract symptoms (LUTS) in a community-dwelling population. MATERIALS AND METHODS: The cross-sectional study included 1 113 people who participated in the Iwaki Health Promotion Project of 2015 in Hirosaki, Japan. LUTS were assessed using structured questionnaires, including the International Prostate Symptom Score (IPSS) and the Overactive Bladder Symptom Score (OABSS). IPSS > 7, OABSS > 5, nocturia score > 1, or urge incontinence score > 1 were defined as moderate to severe symptoms. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) and advanced glycation end products (AGEs) were measured by urine analysis and skin autofluorescence, respectively. The relationship between oxidative stress and LUTS was investigated using logistic regression analyses. RESULTS: This study included 431 men and 682 women. AGEs and 8-OHdG levels were significantly higher in severe forms of LUTS. Multivariate logistic regression analyses showed that AGE levels were significantly associated with a higher frequency of nocturia but were not associated with IPSS, OABSS or urge incontinence. No significant association was observed between LUTS and 8-OHdG levels. CONCLUSIONS: We observed a significant association between AGE levels and nocturia score > 1. Further research is necessary to clarify a possible causal relationship between oxidative stress and nocturia.

The Relationship Between Gait Function and Erectile Dysfunction: Results from a Community-Based Cross-Sectional Study in Japan.

INTRODUCTION: Although physical activity is associated with a decreased risk of erectile dysfunction (ED), the association of ED with physical function remains unclear. AIM: To investigate the relationship between gait function and ED in a community-dwelling population. METHODS: This cross-sectional study analyzed 324 men who participated in the Iwaki Health Promotion Project in 2015 in Hirosaki, Japan. ED was assessed with the 5-Item International Index of Erectile Function (IIEF-5). The participants were divided into 2 groups: low IIEF-5 score (≤16) and high IIEF-5 score (>16). We evaluated physical function, including gait function and grip strength. Gait function was evaluated by 10-meter gait speed and 2-step score (the ratio of the maximum length of 2 strides to height). We assessed daily physical activity, comorbidities, mental status, and laboratory data. The association between physical function and a low IIEF-5 score was analyzed by multivariate logistic regression analysis. MAIN OUTCOME MEASURE: The main outcome measure was to assess whether gait function was an independent indicator for erectile dysfunction. RESULTS: Of 324 men, 154 (48%) had a low IIEF-5 score. Grip strength, 2-step score, and 10-meter gait speed in the low IIEF-5 group were significantly inferior to those in the high IIEF-5 group. Multivariate analysis showed that the 2-step score (odds ratio = 0.08), age, and total testosterone were independently associated with a low IIEF-5. CLINICAL IMPLICATIONS: This study may motivate clinicians to investigate predictive values of physical function for ED. STRENGTHS & LIMITATIONS: The strength of this study was the use of simple, objective, and feasible tests for gait function to assess its association with ED. The limitations of this study were selection bias, regional bias, and nature of the cross-sectional study. CONCLUSIONS: Of the gait functional tests, not the 10-meter gait speed but 2-step score was an independent indicator for the presence of ED. Okamoto T, Hatakeyama S, Imai A, et al. The Relationship Between Gait Function and Erectile Dysfunction: Results from a Community-Based Cross-Sectional Study in Japan. J Sex Med 2019; 16:1922-1929.

Relevance of Level IIb Neck Dissection in Patients with Head and Neck Squamous Cell Carcinomas.

BACKGROUND: Cervical nodal metastasis is the most important prognostic factor in patients with head and neck cancers. Unfortunately, nodal dissection at level IIb carries a risk of damage to the spinal accessory nerve. We aimed to determine the prevalence of level IIb metastasis and the relevance of nodal dissection at level IIb in patients with head and neck squamous cell carcinomas. METHODS: During neck dissection, level IIb lymph nodes obtained from 181 patients with head and neck squamous cell carcinomas were removed, processed, and histopathologically examined. All specimens were divided into two groups according to the side (affected and unaffected sides). The number of dissected lymph nodes and prevalence of level IIb metastasis in each group were then determined and compared according to the preoperative clinical N stage (cN0 and cN+). RESULTS: The study included 158 men and 23 women with a median age of 65 years (range, 17-89 years). The prevalence of pathologically confirmed level IIb metastasis was 0% for clinically node-negative (cN0) necks on the unaffected side and 10.34% for clinically node-positive necks (cN+), with an overall prevalence of 2.4%. There was a significant association between clinically determined and pathologically confirmed node negativity at level IIb. CONCLUSION: Our findings suggest that level IIb neck dissection in patients with head and neck squamous cell carcinomas may be required only if preoperative examination reveals multilevel or level IIa metastasis or suspicious level IIb metastasis.

Impact of distance between donor and recipient hospitals on cadaveric kidney transplantation outcomes.

BACKGROUND: The impact of distance between donor and recipient hospitals on outcomes in cadaveric kidney transplantations is unknown. We investigated the association between inter-hospital distance and outcomes in cadaveric kidney transplantations in Japan. METHODS: We retrospectively analyzed 363 cadaveric kidney transplantations between 2002 and 2017 in Japan. Inter-hospital distance, graft transport time, total ischemic time (TIT), and graft survival were compared between our hospital and national transplantation cohort in Japan. Estimated glomerular filtration rate (eGFR) 1 month and 1 year after transplantation was compared between cadaveric and living-donor kidney transplantations in our hospitals. Additionally, inter-hospital distances among the seven geographical regions in Japan were assessed. RESULTS: There were 12 and 351 cadaveric kidney transplantations at our hospital and in Japan, respectively. Mean inter-hospital distance at our hospital (217 ± 121 km) was significantly longer than that of the national cohort (53 ± 80 km; P < 0.001). Mean TIT and graft survival for our hospital and national cohort were 539 ± 200 min and 91% and 491 ± 193 min and 81%, respectively. Mean eGFRs 1 year after cadaveric and living-donor transplantations at our hospitals were comparable (47 ± 16 vs. 47 ± 15 mL/min/1.73 m2). The comparison among seven regions in Japan indicated a regional difference in inter-hospital distance with an association between area (km2) and inter-hospital distance (km). CONCLUSIONS: Despite the longer inter-hospital distance at our hospital, TIT and transplant outcomes were acceptable in our cases. In addition, geographical inequity in graft allocation in Japan was suggested.

The Impact of Glycosylation of Osteopontin on Urinary Stone Formation.

Osteopontin (OPN) is a matrix glycoprotein of urinary calculi. This study aims to identify the role of aberrant glycosylation of OPN in urolithiasis. We retrospectively measured urinary glycosylated OPN normalized by urinary full-length-OPN levels in 110 urolithiasis patients and 157 healthy volunteers and 21 patients were prospectively longitudinal follow-up during stone treatment. The urinary full-length-OPN levels were measured using enzyme-linked immunosorbent assay and glycosylated OPN was measured using a lectin array and lectin blotting. The assays were evaluated using the area under the receiver operating characteristics curve to discriminate stone forming urolithiasis patients. In the retrospective cohort, urinary Gal3C-S lectin reactive- (Gal3C-S-) OPN/full-length-OPN, was significantly higher in the stone forming urolithiasis patients than in the healthy volunteers (p < 0.0001), with good discrimination (AUC, 0.953), 90% sensitivity, and 92% specificity. The Lycopersicon esculentum lectin analysis of urinary full-length-OPN showed that urinary full-length-OPN in stone forming urolithiasis patients had a polyLacNAc structure that was not observed in healthy volunteers. In the prospective longitudinal follow-up study, 92.8% of the stone-free urolithiasis group had Gal3C-S-OPN/full-length-OPN levels below the cutoff value after ureteroscopic lithotripsy (URS), whereas 71.4% of the residual-stone urolithiasis group did not show decreased levels after URS. Therefore, Gal3C-S-OPN/full-length-OPN levels could be used as a urolithiasis biomarker.

Risk and prognostic factors for multiple primary carcinomas in patients with head and neck cancer.

BACKGROUND: Unexpected multiple primary carcinomas (MPCs) that develop in patients with head and neck carcinomas complicate approaches to their management. We therefore investigated the clinical factors associated with survival outcomes after the treatment of MPCs. METHODS: We performed a retrospective review of records of 1104 patients who underwent treatment for primary head and neck carcinoma at Hamamatsu University Hospital. We evaluated clinical staging, age, sex, smoking, alcohol consumption, the primary tumor site (particularly the involvement of the mucosal epithelial lining of the aerodigestive tract), and overall survival (OS) as determined by Kaplan-Meier analysis. Information on patients' survival status was obtained after a mean follow-up period of 43.8 months (range, 1-144 months). RESULTS: Among 566 patients with mucosa-associated carcinoma arising in the epithelial lining, the 5- and 10-year OS rates (68.49% and 58.96%, respectively) were significantly shorter than those of patients with mucosa non-associated carcinoma (74.22%, and 66.76%, respectively) (log-rank P = 0.0219). Older age (P = 0.016) and male sex (P < 0.001) were likely independent risk factors for developing MPCs; smoking (P < 0.001) and alcohol consumption (P < 0.001) were also significant risk factors. CONCLUSION: Mucosa-associated carcinomas arising in the epithelial lining of the aerodigestive tract in the head and neck are a significant risk factor for developing MPC and are a poor prognostic factor. Careful follow-up and more frequent examinations of the aerodigestive tracts of these patients are recommended.

Significance of preoperative butyrylcholinesterase level as an independent predictor of survival in patients with upper urinary tract urothelial carcinoma treated with nephroureterectomy.

OBJECTIVES: Butyrylcholinesterase (BChE) is an alpha-glycoprotein synthesized in the liver. Its serum levels are reportedly correlated with disease activity in patients with cancer. The aim of this study was to estimate the potential prognostic significance of preoperative serum BChE levels in patients with upper urinary tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU). METHODS: Of the 220 patients with UTUC who underwent RNU between 1995 and 2016 at Hirosaki University Hospital, 149 patients with available laboratory data were included for analysis. Covariates included age, sex, preoperative laboratory data, clinical T and N grades, tumor grade, tumor location and preoperative chemotherapy. Univariate and multivariate analyses were performed to identify clinical factors associated with overall survival (OS) and disease-free survival (DFS). Univariate analysis was performed using the Kaplan-Meier and log-rank methods, and the multivariate analysis was performed using a Cox proportional hazard model. RESULTS: The median BChE level was 276 U/l and the optimal cut-off point for the serum BChE level was determined to be 218 IU/ml. The 5-year OS and DFS rates were 81.0% and 73.7%, respectively. The 5-year OS and DFS rates were significantly greater in the BChE ≥ 218 than <218 U/l groups (86.6% vs. 53.7%, P < 0.001 and 76.4% vs. 58.3%, P = 0.049, respectively). In multivariate analysis, BChE levels were most significantly associated with OS, whereas BChE level and tumor grade were significantly associated with DFS. CONCLUSIONS: This study validated preoperative serum BChE levels as an independent prognostic factor for UTUC after RNU.

A Trunk Stabilization Exercise Warm-up May Reduce Ankle Injuries in Junior Soccer Players.

The aim of this study was to investigate the efficacy of a trunk stabilization exercise warm-up program in reducing the incidence of lower extremity injuries among male junior soccer players. Two junior soccer teams participated in this study. The intervention (INT) team performed three trunk stabilization exercises before practice sessions and games, while a control (CON) team performed their usual warm-up without trunk exercises. Both teams engaged in regular soccer training and games, and were followed for the incidence of injury. As a result, overall injury incidence rates (IRs) were 2.65 injuries/1,000 h and 4.94 injuries/1,000 h in the INT and CON teams, respectively (incidence rate ratio [IRR]=0.54, 95% confidence interval [CI]=0.32-0.89, p=0.013). The IR of acute injuries was significantly lower in the INT team (1.91 injuries/1,000 h) than in the CON team (4.06 injuries/1,000 h) (IRR=0.47, 95%CI=0.26-0.84, p=0.009). Regarding injury sites, the IRs of ankle injuries in the INT team (0.32 injuries/1,000 h) were significantly lower than that in the CON team (2.28 injuries/1,000 h) (IRR=0.14, 95%CI=0.04-0.47, p<0.001). These results suggest that a warm-up program comprising trunk stabilization exercises alone can prevent acute injuries, especially ankle injuries.

Aberrant Epigenetic Regulation in Head and Neck Cancer Due to Distinct EZH2 Overexpression and DNA Hypermethylation.

Enhancer of Zeste homologue 2 (EZH2) overexpression is associated with tumor proliferation, metastasis, and poor prognosis. Targeting and inhibition of EZH2 is a potentially effective therapeutic strategy for head and neck squamous cell carcinoma (HNSCC). We analyzed EZH2 mRNA expression in a well-characterized dataset of 230 (110 original and 120 validation cohorts) human head and neck cancer samples. This study aimed to investigate the effects of inhibiting EZH2, either via RNA interference or via pharmacotherapy, on HNSCC growth. EZH2 upregulation was significantly correlated with recurrence (p < 0.001) and the methylation index of tumor suppressor genes (p < 0.05). DNMT3A was significantly upregulated upon EZH2 upregulation (p = 0.043). Univariate analysis revealed that EZH2 upregulation was associated with poor disease-free survival (log-rank test, p < 0.001). In multivariate analysis, EZH2 upregulation was evaluated as a significant independent prognostic factor of disease-free survival (hazard ratio: 2.085, 95% confidence interval: 1.390⁻3.127; p < 0.001). Cells treated with RNA interference and DZNep, an EZH2 inhibitor, showed the most dramatic changes in expression, accompanied with a reduction in the growth and survival of FaDu cells. These findings suggest that EZH2 upregulation is correlated with tumor aggressiveness and adverse patient outcomes in HNSCC. Evaluation of EZH2 expression might help predict the prognosis of HNSCC patients.