Background: The usefulness of lower urinary tract symptoms (LUTS) as mortality risk factors remains unclear. Repeated assessments are required to take into account symptom fluctuation and de novo symptom appearance. The study objective was to evaluate mortality in relation to three urinary storage symptoms-urgency, daytime frequency and nocturia-in middle-aged and elderly men, considering also other time-varying factors during follow-up. Methods: A mail survey of a population-based cohort of men initially aged 50, 60 and 70 years was conducted in Finland in 1994, 1999, 2004 and 2009. The questionnaire included assessments of LUTS based on the Danish Prostatic Symptom Score and comorbidities. The men were followed up for mortality through the population registry through 2014. LUTS-related hazard ratios (HR) were analyzed with timedependent Cox regression adjusted for the year of birth and comorbidities using variable values updated every five years. Sensitivity analyses were conducted using values of all variables fixed to the baseline assessment of 1994. Results: Of the 1332 eligible men with data on LUTS from each preceding survey, 514 (38.6%) died during the 21-year follow-up. In time-dependent analyses, daytime frequency and nocturia were significantly associated with increased mortality: the adjusted HR was 1.42 (95%CI 1.11-1.83) for daytime frequency, 1.38 (1.07-1.79) for nocturia and 1.19 (0.94-1.50) for urgency. In sensitivity analyses with fixed baseline characteristics, only nocturia was suggestively associated with an increased risk of death: the adjusted HR was 1.09 (0.84-1.42) for daytime frequency, 1.41 (0.99-2.02) for nocturia and 0.94 (0.52-1.68) for urgency. Conclusions: Among aging men, LUTS are more accurate predictors of short-term than longer-term mortality risk. Repeated assessments are needed to detect clinically 3 ill health. Accordingly, men relevant and persistent symptoms, often associated with with daytime frequency or nocturia exhibit a 1.4-fold risk of death and therefore, should be evaluated for underlying comorbidity.

CIP2A is overexpressed in many cancers, including esophageal squamous cell carcinoma. The regulation of c-MYC and CIP2A expression is characterized by a positive feedback mechanism facilitating the expression of both of them and accelerating cancer cell proliferation in gastric cancer. Increased CIP2A expression is a predictor of poor survival in some cancers. The incidence of positive CIP2A immunostaining and its association with c-MYC and its predictive value in esophageal adenocarcinoma are unknown. All esophageal adenocarcinoma patients from 1990 to 2007 with sufficient material for analysis of CIP2A and c-MYC in two university hospitals were included in the study. In addition, biopsies from Barrett's epithelium from the cancer patients and control tissue from normal esophageal mucosa adjacent to the tumor were included. CIP2A was moderately or strongly positive in 77.9 %, and c-MYC in 93.8 % of the cancer specimens. These frequencies were statistically different from the expression in normal esophageal epithelium. In addition, there was a positive correlation between CIP2A and c-MYC expression (p = 0.018). According to adjusted Cox regression survival analysis, CIP2A and c-MYC had no effect on survival. However, among patients with stage IVA-IVB cancer, there was a trend toward poor prognosis in CIP2A-positive patients. The expression of CIP2A and c-MYC was associated with each other, and their overexpression was found in most cases of esophageal adenocarcinoma. However, CIP2A and c-MYC had no effect on survival.

Purpose:The utility of male lower urinary tract symptoms (LUTS) as mortality risk factors remains unclear. We explored LUTS-associated mortality among Finnish men, evaluating the association of symptom severity and bother with risk of death.Materials and Methods:A questionnaire including the Danish Prostatic Symptom Score was mailed to a population-based cohort of 3,143 men aged 50, 60 and 70 years in 1994, with repeat surveys in 1999, 2004, 2009 and 2015. The men were followed until the end of 2018. Mortality associated with LUTS was analyzed using time-dependent Cox regression adjusted for age and comorbidity, updating symptom data every 5 years, including interaction terms between symptoms and associated bother.Results:Of the 1,167 men in the analysis, 591 (50.6%) died during the 24-year followup. In analyses of moderate and severe symptoms disregarding bother, overall voiding and storage LUTS, daytime frequency and urgency incontinence were associated with increased mortality: the multivariable-adjusted hazard ratios were 1.19 (95% CI 1.00–1.40), 1.35 (1.13–1.62), 1.31 (1.09–1.58) and 2.19 (1.42–3.37), respectively. In analyses disregarding symptom severity and bother, voiding LUTS were associated with decreased mortality, while daytime frequency and nocturia were associated with increased mortality: the HRs were 0.82 (95% CI 0.67–1.00), 1.31 (95% CI 1.09–1.58) and 1.52 (95% CI 1.21–1.91), respectively. Excess mortality associated with bothersome daytime frequency and nocturia tended to be slightly higher: the HRs were 1.86 (95% CI 1.41–2.47) and 1.88 (95% CI 1.38–2.58), respectively. No significant interactions were found between symptoms and associated bother, however.Conclusions:Moderate and severe LUTS are potential risk factors for mortality, independently of their bother.

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Objectives To determine if lower urinary tract symptoms (LUTS) involve seasonal variation and how this affects the severity of LUTS. Methods A total of 3163 men aged 50 to 70 years were mailed a questionnaire on urinary symptoms. The overall response rate was 65.3% (2064 out of 3163 men). The men were asked whether their urinary symptoms showed variation in degree of difficulty according to time of year and if yes, when LUTS were the worst and the mildest. Ten different LUTS were evaluated with four response options for the severity of symptoms. Mean symptom scores and the proportions of symptomatic men were evaluated according to the presence of seasonal changes in different symptoms. Results Overall, 17.1% of men reported seasonal variation in severity of LUTS, older men more frequently than younger men. Worse LUTS during winter were reported by 81% of the men reporting seasonal variation, and 93% reported that LUTS were relieved in summer. More seasonal variation was reported by men with comorbidities (stroke, neurological disease) and those with medical treatment for LUTS or operative treatment for benign prostatic hyperplasia. Men with more severe LUTS were more likely to report seasonal changes. Conclusions One out of six men reported seasonal changes in LUTS, with winter worsening and summer relieving the symptoms. Men with seasonal variation in LUTS had more severe LUTS in all 10 symptom groups that were investigated.

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