CD3+ and CD8+ T cell-based immune cell score as a prognostic factor in clear-cell renal cell carcinoma.

BACKGROUND AND PURPOSE: Immunoscore® is a prognostic parameter based on densities of lymphocyte populations in the tumor center and invasive margin. Immunoscore® is validated in colorectal cancer as a high Immunoscore® is associated with longer survival. Previous studies have suggested that Immunoscore® may also predict oncological outcomes in clear-cell renal cell carcinoma (ccRCC). This study aims to assess the prognostic role of immune cell score in ccRCC. MATERIAL AND METHODS: All patients with ccRCC undergoing surgery between 2007 and 2020 in Central Finland Central Hospital were retrospectively identified. CD3+ and CD8+ cell densities were calculated from tissue samples to determine the immune cell score using Immunoscore® principles. Receiver-operating characteristic analysis, Kaplan-Meier survival curve, and Cox regression were used to evaluate the association between immune cell score and survival. RESULTS: A total of 203 patients (mean age 66.5 years) were identified. The median follow-up time was 6.2 years. Based on the immune cell score, the patients were divided into three groups: low, intermediate, and high. In Cox regression analysis, adjusted with age, sex, and Charlson Comorbidity Index, no significant differences in disease-specific mortality were observed among the three groups. The hazard ratios (HRs) for disease-specific mortality were 0.93 (95% confidence interval [CI] 0.48-1.79) and 1.12 (0.52-2.37) for intermediate- and high-immune cell score groups when compared to low-immune cell score group, respectively. INTERPRETATION: This study found no association between immune cell score and survival. These results indicate that immune cell score may not serve as a prognostic tool in ccRCC.

Do men adapt to lower urinary tract symptoms? An 11-year longitudinal study of male urinary urgency and associated bother.

OBJECTIVE: The study objective is to evaluate prognosis and predictors of bother caused by urinary urgency among middle-aged and older men. MATERIAL AND METHODS: A population-based sample of men born in 1974, 1964, 1954, 1944, 1934 and 1924 was followed-up from 2004 to 2015. The course of urgency and associated bother was evaluated with the Danish Prostatic Symptom Score at baseline and follow-up. Logistic regression was utilized to explore risk factors of increased bother at follow-up. RESULTS: A total of 2,480 men (39%) who had responded at baseline and follow-up were included in the study. Of them, 1,056 men (43%) had persistent mild urgency and 132 men (5%) persistent moderate or severe urgency at follow-up. The proportions of men experiencing at least moderate bother due to persistent urgency at follow-up were 6% (95% confidence interval 4.5-7.3) of those with mild and 79% (71.7-85.9) of the men with moderate or severe urgency. In multivariable-adjusted logistic regression, moderate to severe urgency was strongly associated with bother (odds ratio, OR 55.2, 95% CI 32.1-95.2). Other predictors of bother included cardiac disease (OR 1.8, 95% CI 1.0-31.1), pulmonary disease (OR 1.9, 95% CI 1.1-3.5) and medical treatment (OR 2.7, 95% CI 1.6-4.6). CONCLUSIONS: Most men with urinary urgency have mild symptoms and bother. Only one out of five men with persistent moderate or severe urgency adapt to the symptoms. Men with a history of medical treatment for lower urinary tract symptoms (LUTS) or impaired cardiopulmonary health are more likely to experience bother from urinary urgency.

Do LUTS Predict Mortality? An Analysis Using Random Forest Algorithms.

Purpose: To evaluate a random forest (RF) algorithm of lower urinary tract symptoms (LUTS) as a predictor of all-cause mortality in a population-based cohort. Materials and Methods: A population-based cohort of 3143 men born in 1924, 1934, and 1944 was evaluated using a mailed questionnaire including the Danish Prostatic Symptom Score (DAN-PSS-1) to assess LUTS as well as questions on medical conditions and behavioral and sociodemographic factors. Surveys were repeated in 1994, 1999, 2004, 2009 and 2015. The cohort was followed-up for vital status until the end of 2018. RF uses an ensemble of classification trees for prediction with a good flexibility and without overfitting. RF algorithms were developed to predict the five-year mortality using LUTS, demographic, medical, and behavioral factors alone and in combinations. Results: A total of 2663 men were included in the study, of whom 917 (34%) died during follow-up (median follow-up time 15.0 years). The LUTS-based RF algorithm showed an area under the curve (AUC) 0.60 (95% CI 0.52-0.69) for five-year mortality. An expanded RF algorithm, including LUTS, medical history, and behavioral and sociodemographic factors, yielded an AUC 0.73 (0.65-0.81), while an algorithm excluding LUTS yielded an AUC 0.71 (0.62-0.78). Conclusion: An exploratory RF algorithm using LUTS can predict all-cause mortality with acceptable discrimination at the group level. In clinical practice, it is unlikely that LUTS will improve the accuracy to predict death if the patient's background is well known.

Lower Urinary Tract Symptoms and Mortality among Finnish Men: The Roles of Symptom Severity and Bother.

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.

Sauna habits/bathing and changes in lower urinary tract symptoms - Tampere Ageing Male Urologic Study (TAMUS).

OBJECTIVE: To evaluate the effect of sauna bathing on lower urinary tract symptoms (LUTS) in a Finnish population-based cohort. METHODS: A mail survey was sent to a population-based cohort of 50-, 60-, and 70-year-old men in 1994 followed by repeat questionnaires in 1999 and 2004. The evaluation of ten different types of LUTS was based on Danish Prostatic Symptom Score (DAN-PSS-1). The weekly frequency of sauna bathing was assessed in the first questionnaire and divided into three subgroups (0-1, 2, and ≥3). The prevalence, incidence, and remission rate of each LUTS was assessed based on the initial and follow-up assessments. In addition, the mean DAN-PSS-1 symptoms score, medication for LUTS, and operative treatment were determined at each time-point. Chi-square test, a linear-by-linear test, and binary logistic regression analysis were used to assess statistical significance. RESULTS: The population-based cohort included initially 3,163, men of whom 1,306 (41.3%) responded to all three questionnaire rounds and were included in the analysis. There was no clear association between sauna bathing frequency and prevalence of the nine LUTS, nor with incidence and remission rates. The only exception was feelings of incomplete emptying, with lower prevalence associated with frequent sauna bathing. There were no clear differences in the medications or operations for LUTS by sauna bathing habits. CONCLUSION: Based on our results, sauna bathing does not affect LUTS development or natural history in the long-term.

Seasonal changes in occurrence and severity of lower urinary tract symptoms-Tampere Aging Male Urologic Study (TAMUS).

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.

Impact of lower urinary tract symptoms on mortality: a 21-year follow-up among middle-aged and elderly Finnish men.

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 time-dependent Cox regression adjusted for the year of birth and comorbidities using variable values updated every 5 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 relevant and persistent symptoms, often associated with ill health. Accordingly, men with daytime frequency or nocturia exhibit a 1.4-fold risk of death and therefore, should be evaluated for underlying comorbidity.

Severity and bother of lower urinary tract symptoms among men aged 30-80 years: Tampere Ageing Male Urological Study (TAMUS).

OBJECTIVE: The aim of this study was to determine the severity and bother of lower urinary tract symptoms (LUTS) and evaluate the burden of each symptom in a male population. MATERIALS AND METHODS: Postal questionnaires were sent to 7470 men aged 30-80 years. The Danish Prostatic Symptom Score (DAN-PSS-1) was used to determine the severity, bother and total symptom score for each symptom. To assess the total burden of each symptom at the population level, the total symptom scores were weighted by the prevalence they represented. RESULTS: The overall response rate was 58.7% (4384/7470 men). Urgency caused the greatest burden to men aged 30-80, with a prevalence-weighted symptom score of 0.712. Urgency affected 66.2% of men and 5.1% experienced moderate symptoms with moderate bother. Post-micturition dribble caused the second greatest burden, with a prevalence-weighted score of 0.704, affecting 58.7% of men and with 31.1% reporting mild bother from it. Nocturia and feeling of incomplete emptying caused the third and fourth greatest burdens, respectively. In young men (aged 30 and 40 years), post-micturition dribble caused the greatest burden, as moderate symptoms were common and caused mild bother to 11.4%. Among retired (70 and 80 years) and middle-aged (50 and 60 years) men, urgency was the most burdensome symptom. CONCLUSIONS: The most burdensome LUTS in men aged 30-80 years was urgency, followed by post-micturition dribble, nocturia and feeling of incomplete emptying. Urgency and nocturia were prominent in old men and post-micturition dribble was noted in young men.

CIP2A expression and prognostic role in patients with esophageal adenocarcinoma.

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.