Using prostate-specific membrane antigen positron-emission tomography to guide prostate biopsies and stage men at high-risk of prostate cancer.

OBJECTIVE: To assess whether a diagnostic pathway in which prostate-specific membrane antigen (PSMA) positron-emission tomography (PET)/computed tomography (CT) is used as a single imaging modality is feasible to guide targeted biopsy and to detect clinically significant prostate cancer (csPCa) in biopsy-naïve men at high-risk of disease. PATIENTS AND METHODS: A total of 60 men with a prostate-specific antigen (PSA) level of 20-50 ng/mL underwent 18 F-PSMA(DCFPyL)-PET/CT prior to prostate biopsies in this prospective, non-randomised cohort study. Magnetic resonance imaging (MRI) was not performed. Using a 12-segment mapping model of the prostate, PSMA-guided targeted biopsy was performed along with systematic biopsies. The detection rate of PCa and csPCa was assessed for combined systematic and targeted biopsy, and for targeted biopsy only. csPCa was defined as a prostate biopsy with an International Society of Uropathology (ISUP) Grade Group ≥2. RESULTS: Lesions suspicious for PCa in the prostate gland were observed on all PSMA-PET/CTs. A total of 27/60 men (45%) already had metastatic disease on staging 18 F-PSMA(DCFPyL)-PET/CT. Combined PSMA-guided targeted and systematic biopsies detected PCa in 56/60 (93.3%) patients, with 52 of them (92.9%) having csPCa. PSMA-guided targeted biopsy, if performed as a single biopsy modality, identified PCa in 52/60 men (86.7%) and in 27/27 men (100%) men with metastases. CONCLUSIONS: Using the PSMA-driven single imaging modality pathway in biopsy-naïve men at high-risk of PCa, a substantial number of diagnostic MRI scans could be avoided while at the same time obtaining adequate targeting, staging, and detection of csPCa.

Evaluating machine learning algorithms to Predict 30-day Unplanned REadmission (PURE) in Urology patients.

BACKGROUND: Unplanned hospital readmissions are serious medical adverse events, stressful to patients, and expensive for hospitals. This study aims to develop a probability calculator to predict unplanned readmissions (PURE) within 30-days after discharge from the department of Urology, and evaluate the respective diagnostic performance characteristics of the PURE probability calculator developed with machine learning (ML) algorithms comparing regression versus classification algorithms. METHODS: Eight ML models (i.e. logistic regression, LASSO regression, RIDGE regression, decision tree, bagged trees, boosted trees, XGBoost trees, RandomForest) were trained on 5.323 unique patients with 52 different features, and evaluated on diagnostic performance of PURE within 30 days of discharge from the department of Urology. RESULTS: Our main findings were that performances from classification to regression algorithms had good AUC scores (0.62-0.82), and classification algorithms showed a stronger overall performance as compared to models trained with regression algorithms. Tuning the best model, XGBoost, resulted in an accuracy of 0.83, sensitivity of 0.86, specificity of 0.57, AUC of 0.81, PPV of 0.95, and a NPV of 0.31. CONCLUSIONS: Classification models showed stronger performance than regression models with reliable prediction for patients with high probability of readmission, and should be considered as first choice. The tuned XGBoost model shows performance that indicates safe clinical appliance for discharge management in order to prevent an unplanned readmission at the department of Urology.

STUDY NEED AND IMPORTANCE: Unplanned readmissions form a consistent problem for many hospitals. Unplanned readmission rates can go up as high as to 35%, and may differ significantly between respective hospital departments. In addition, in the field of Urology readmission rates can be greatly influenced by type of surgery performed and unplanned readmissions in patients can go up as high as 26%. Although predicting unplanned readmissions for individual patients is often complex, due to multiple factors that need to be taken into account (e.g. functional disability, poor overall condition), there is evidence that these can be prevented when discharge management is evaluated with an objective measuring tool that facilitate such risk stratification between high and low risk patients. However, to the best of our knowledge, the latter risk stratification using ML driven probability calculators in the field of Urology have not been evaluated to date. Using ML, calculated risk scores based on analysing complex data patterns on patient level can support safe discharge and inform concerning the risk of having an unplanned readmission. WHAT WE FOUND: Eight ML models were trained on 5.323 unique patients with 52 different features, and evaluated on diagnostic performance. Classification models showed stronger performance than regression models with reliable prediction for patients with high probability of readmission, and should be considered as first choice. The tuned XGBoost model shows performance that indicates safe clinical appliance for discharge management in order to prevent an unplanned readmission at the department of Urology. Limitations of our study were the quality and presence of patient data on features, and how to implement these findings in clinical setting to transition from predicting to preventing unplanned readmissions. INTERPRETATION FOR CLINICIANS: ML models based on classification should be first choice to predict unplanned readmissions, and the XGBoost model showed the strongest results.

Implications of resampling data to address the class imbalance problem (IRCIP): an evaluation of impact on performance between classification algorithms in medical data.

Objective: When correcting for the "class imbalance" problem in medical data, the effects of resampling applied on classifier algorithms remain unclear. We examined the effect on performance over several combinations of classifiers and resampling ratios. Materials and Methods: Multiple classification algorithms were trained on 7 resampled datasets: no correction, random undersampling, 4 ratios of Synthetic Minority Oversampling Technique (SMOTE), and random oversampling with the Adaptive Synthetic algorithm (ADASYN). Performance was evaluated in Area Under the Curve (AUC), precision, recall, Brier score, and calibration metrics. A case study on prediction modeling for 30-day unplanned readmissions in previously admitted Urology patients was presented. Results: For most algorithms, using resampled data showed a significant increase in AUC and precision, ranging from 0.74 (CI: 0.69-0.79) to 0.93 (CI: 0.92-0.94), and 0.35 (CI: 0.12-0.58) to 0.86 (CI: 0.81-0.92) respectively. All classification algorithms showed significant increases in recall, and significant decreases in Brier score with distorted calibration overestimating positives. Discussion: Imbalance correction resulted in an overall improved performance, yet poorly calibrated models. There can still be clinical utility due to a strong discriminating performance, specifically when predicting only low and high risk cases is clinically more relevant. Conclusion: Resampling data resulted in increased performances in classification algorithms, yet produced an overestimation of positive predictions. Based on the findings from our case study, a thoughtful predefinition of the clinical prediction task may guide the use of resampling techniques in future studies aiming to improve clinical decision support tools.

Cancer detection and complications of transperineal prostate biopsy with antibiotics when indicated.

OBJECTIVES: To describe the prostate cancer (PCa) detection rate, including clinically significant prostate cancer (csPCa), in a large cohort of patients who underwent transperineal ultrasonography-guided systematic prostate biopsy (TPB-US) using a probe-mounted transperineal access system, with magnetic resonance imaging (MRI) cognitive fusion in case of a Prostate Imaging-Reporting and Data System grade 3-5 lesion, under local anaesthesia in an outpatient setting. Additionally, to compare the incidence of procedure-related complications with a cohort of patients undergoing transrectal ultrasonography-guided (TRB-US) and transrectal MRI-guided biopsies (TRB-MRI). PATIENTS AND METHODS: This was an observational cohort study in men who underwent TPB-US prostate biopsy in a large teaching hospital. For each participant, prostate-specific antigen level, clinical tumour stage, prostate volume, MRI parameters, number of (targeted) prostate biopsies, biopsy International Society of Uropathology (ISUP) grade and procedure-related complications were assessed. csPCa was defined as ISUP grade ≥2. Antibiotic prophylaxis was only given in those with an increased risk of urinary tract infection. RESULTS: A total of 1288 TPB-US procedures were evaluated. The overall detection rate for PCa in biopsy-naive patients was 73%, and for csPCa it was 63%. The incidence of hospitalization was 1% in TPB-US (13/1288), compared to 4% in TRB-US (8/214) and 3% in TRB-MRI (7/219; P = 0.002). CONCLUSIONS: Contemporary combined systematic and target TPB-US with MRI cognitive fusion is easy to perform in an outpatient setting, with a high detection rate of csPCa and a low incidence of procedure-related complications.

Highly Efficient Semi-Continuous Extraction and In-Line Purification of High ß-O-4 Butanosolv Lignin.

Innovative biomass fractionation is of major importance for economically competitive biorefineries. Lignin is currently severely underutilized due to the use of high severity fractionation methodologies that yield complex condensed lignin that limits high-value applicability. Mild lignin fractionation conditions can lead to lignin with a more regular C-O bonded structure that has increased potential for higher value applications. Nevertheless, such extraction methodologies typically suffer from inadequate lignin extraction efficiencies and yield. (Semi)-continuous flow extractions are a promising method to achieve improved extraction efficiency of such C-O linked lignin. Here we show that optimized organosolv extraction in a flow-through setup resulted in 93-96% delignification of 40 g walnut shells (40 wt% lignin content) by applying mild organosolv extraction conditions with a 2 g/min flowrate of a 9:1 n-butanol/water mixture with 0.18 M H2SO4 at 120°C in 2.5 h. 85 wt% of the lignin (corrected for alcohol incorporation, moisture content and carbohydrate impurities) was isolated as a powder with a high retention of the ß-aryl ether (ß-O-4) content of 63 linking motifs per 100 C9 units. Close examination of the isolated lignin showed that the main carbohydrate contamination in the recovered lignin was butyl-xyloside and other butoxylate carbohydrates. The work-up and purification procedure were investigated and improved by the implementation of a caustic soda treatment step and phase separation with a continuous integrated mixer/separator (CINC). This led to a combined 75 wt% yield of the lignin in 3 separate fractions with 3% carbohydrate impurities and a very high ß-O-4 content of 67 linking motifs per 100 C9 units. Analysis of all the mass flows showed that 98% of the carbohydrate content was removed with the inline purification step, which is a significant improvement to the 88% carbohydrate removal for the traditional lignin precipitation work-up procedure. Overall we show a convenient method for inline extraction and purification to obtain high ß-O-4 butanosolv lignin in excellent yields.

Time-of-flight mass spectrometry of particle emission during irradiation with slow, highly charged ions.

We describe a setup for the analysis of secondary ions and neutrals emitted from solid surfaces and two-dimensional materials during irradiation with highly charged ions. The ultrahigh vacuum setup consists of an electron beam ion source to produce bunches of ions with various charge states q (e.g., Xe1+-Xe46+) and thus potential energies, a deceleration/acceleration section to tune the kinetic energy of the ions in the range of 5 keV to 20 × q keV, a sample stage for laser-cleaning and positioning of freestanding as well as supported samples, a pulsed excimer laser for post-ionization of sputtered neutrals, and a reflectron type time-of-flight mass spectrometer, enabling us to analyze mass and velocity distributions of the emitted particles. With our setup, contributions from potential and kinetic energy deposition can be studied independently of each other. Charge dependent experiments conducted at a constant kinetic energy show a clear threshold for the emission of secondary ions from SrTiO3. Data taken with the same projectile charge state, but at a different kinetic energy, reveal a difference in the ratio of emitted particles from MoS2. In addition, first results are presented, demonstrating how velocity distributions can be measured with the new setup.

Inter- and Intraobserver Agreement in Measuring Urolithiasis Density on Nonenhanced Computed Tomography.

Introduction: Treatment choice for urolithiasis is partially based on measuring stone density in HU on nonenhanced computed tomography (NECT). Interobserver variability in these measurements could have treatment consequences. This study aims to assess the observer agreement of measuring HU and whether the use of a protocol leads to a better agreement. Materials and Methods: We retrospectively included 155 consecutive NECTs of patients with stones ≥4 mm. Five observers (two radiologists, one urologist, one urology resident, and one radiology resident) assessed all anonymized NECTs four times in randomized order. HU was measured without instruction (rounds 1 and 2) and subsequently using two protocols (A and B, rounds 3 and 4). Protocols comprised using bone setting, zoom, and measuring HU without the penumbra, in either three (A) or one (B) axial plane. The inter- and intraobserver agreement was evaluated using the intraclass correlation coefficient (ICC). Results: Interobserver agreement on HU measurement without protocol was as follows: ICC = 0.84 (confidence interval [CI]: 0.79-0.87). Agreement diminished with protocol A, ICC = 0.62 (CI: 0.37-0.76), and improved with protocol B, ICC = 0.90 (CI: 0.86-0.92). Intraobserver agreement without protocol was ICC = 0.87, with protocol A, ICC = 0.87, and with protocol B, ICC = 0.93. The biggest improvement was seen for urologists' agreement from no protocol to protocol B, where ICC improved from 0.81 (CI: 0.70-0.87) to 0.91 (CI: 0.84-0.94). Conclusions: Observer agreement of HU measurement of urolithiasis without protocol is already good but using zoom, bone setting, and measuring in a representative plane is recommended. This protocol results in higher agreement, especially among urologists. Measuring in three axial planes does not increase agreement.

Fluoroquinolone use for uncomplicated urinary tract infections in women: a retrospective cohort study.

OBJECTIVES: The United States Food & Drug Administration released an advisory in 2016 that fluoroquinolones be relegated to second-line agents for uncomplicated urinary tract infections (UTIs) given reports of rare but serious side effects; similar warnings have followed from Health Canada and the European Medicines Agency. The objective was to determine whether alternative non-fluoroquinolone agents are as effective as fluoroquinolones in the treatment of UTIs. METHODS: We conducted a retrospective population-based cohort study using administrative health data from six Canadian provinces. We identified women (n = 1 585 997) receiving antibiotic treatment for episodes of uncomplicated UTIs (n = 2 857 243) between January 1 2005 and December 31 2015. Clinical outcomes within 30 days from the initial antibiotic dispensation were compared among patients treated with a fluoroquinolone versus non-fluoroquinolone agents. High-dimensional propensity score adjustments were used to ensure comparable treatment groups and to minimize residual confounding. RESULTS: Fluoroquinolone use for UTI declined over the study period in five of six Canadian provinces and accounted for 22.3-48.5% of treatments overall. The pooled effect across the provinces indicated that fluoroquinolones were associated with fewer return outpatient visits (OR 0.89, 95%CI 0.87-0.92), emergency department visits (OR 0.74, 95%CI 0.61-0.89), hospitalizations (OR 0.83, 95%CI 0.77-0.88), and repeat antibiotic dispensations (OR 0.77, 95%CI 0.75-0.80) within 30 days. CONCLUSIONS: Fluoroquinolones are associated with improved clinical outcomes among women with uncomplicated UTIs. This benefit must be weighed against the risk of fluoroquinolone resistance and rare but serious fluoroquinolone side effects when selecting first-line treatment for these patients.

Upper Tract Urothelial Carcinoma Grade Prediction Based on the Ureteroscopic Appearance: Caution Should be Taken.

OBJECTIVES: To investigate the diagnostic accuracy, inter-rater and intrarater agreement of grade predictions based on the visual appearance of papillary upper tract urothelial carcinoma (UTUC) during digital ureteroscopy. METHODS: Nine urologists predicted the histopathologic grade of 64 papillary UTUC (low-grade vs high-grade) by assessing the visual appearance of the tumors in videos from digital ureteroscopy. The diagnostic accuracy was estimated by comparing the grade predictions with the histopathology from colocalized biopsies. Inter-rater agreement was assessed by pairwise inter-rater percentage agreement and Fleiss Kappa analysis. The videos were rated in a random order again 30 days after the first assessment to evaluate the intrarater percentage agreement. RESULTS: Low-grade tumors were predicted correctly in 37%-85% of the cases with a median concordance of 59% for questionnaire 1 and 66% for questionnaire 2. High-grade tumors were predicted correctly in 26%-91% of the cases with a median concordance of 52% and 61% for each questionnaire. The median pairwise inter-rater percentage agreement was 66% for both questionnaires with a Fleiss Kappa of 0.29 and 0.38, respectively. The median intrarater percentage agreement was 81%. CONCLUSION: The histopathologic grade of UTUC is essential to the risk-stratification for treatment selection. Predictions of the histopathologic grade based on the visual appearance of papillary UTUC with digital ureteroscopy are often incorrect in comparison with biopsy results and yield low inter-rater agreement. Urologists must be aware of these limitations in the assessment of the tumor grade during digital ureteroscopy to warrant good clinical practice.

Lung cancer care trajectory at a Canadian centre: an evaluation of how wait times affect clinical outcomes.

BACKGROUND: Lung cancer continues to be one of the most common cancers in Canada, with approximately 28,400 new cases diagnosed each year. Although timely care can contribute substantially to quality of life for patients, it remains unclear whether it also improves patient outcomes. In this work, we used a set of quality indicators that aim to describe the quality of care in lung cancer patients. We assessed adherence with existing guidelines for timeliness of lung cancer care and concordance with existing standards of treatment, and we examined the association between timeliness of care and lung cancer survival. METHODS: Patients with lung cancer diagnosed between 2010 and 2015 were identified from the Pulmonary Division Lung Cancer Registry at our centre. RESULTS: We demonstrated that the interdisciplinary pulmonary oncology service successfully treated most of its patients within the recommended wait times. However, there is still work to be done to decrease variation in wait time. Our results demonstrate a significant association between wait time and survival, supporting the need for clinicians to optimize the patient care trajectory. INTERPRETATION: It would be helpful for Canadian clinicians treating patients with lung cancer to have wait time guidelines for all treatment modalities, together with standard definitions for all time intervals. Any reductions in wait times should be balanced against the need for thorough investigation before initiating treatment. We believe that our unique model of care leads to an acceleration of diagnostic steps. Avoiding any delay associated with referral to a medical oncologist for treatment could be an acceptable strategy with respect to reducing wait time.

Applying the Care Group model to tuberculosis control: findings from a community-based project in Mozambique.

BACKGROUND: We describe the effectiveness of an innovative community-based social mobilization approach called Care Groups to improve the effectiveness of the national tuberculosis (TB) program by increasing TB testing and improving treatment outcomes in six districts of rural Mozambique. METHODS: The Care Group approach, which was implemented in a population of 218 191, enabled a facilitator to meet every 6 months with 10-12 community health volunteers (forming a Care Group) to share key TB messages and then for them to convey these messages over the subsequent 6 months to 10-12 households. Three household surveys were performed over 5 years to measure population-level changes in knowledge and behaviors. Data from village TB, laboratory, and district registers were also used to monitor activities and outcomes. RESULTS: There were substantial improvements in TB-related knowledge and behaviors in the number of patients initiating treatment, in the percentage of patients receiving directly observed treatment, in treatment success, and in TB-related mortality. CONCLUSION: Care Groups are uniquely suited to address some of the challenges of TB control. This project sheds light on a new strategy for engaging communities to address not only TB, but other health priorities as well.

Dipeptidyl peptidase-4 inhibitors and the risk of community-acquired pneumonia in patients with type 2 diabetes.

AIMS: To determine whether the use of dipeptidyl peptidase-4 (DPP-4) inhibitors is associated with an increased risk of community-acquired pneumonia. METHODS: The UK Clinical Practice Research Datalink and the Hospital Episodes Statistics database were used to conduct a nested case-control analysis within a cohort of new users of antidiabetic drugs between 2007 and 2012. Incident cases of hospitalization for community-acquired pneumonia were matched with up to 20 controls on age, duration of treated diabetes, calendar year and duration of follow-up. Conditional logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for hospitalization for community-acquired pneumonia associated with current use of DPP-4 inhibitors compared with current use of two or more oral antidiabetic drugs. RESULTS: The cohort included 49,653 patients, of whom 562 were hospitalized for community-acquired pneumonia during follow-up (incidence rate 5.2/1000 person-years). Compared with current use of two or more oral antidiabetic drugs, current use of DPP-4 inhibitors was not associated with an increased risk of hospitalized community-acquired pneumonia overall (adjusted OR 0.80, 95% CI 0.50-1.29) or according to duration of use (p for trend = 0.57). CONCLUSIONS: The use of DPP-4 inhibitors was not associated with an increased risk of hospitalization for community-acquired pneumonia. Additional research is needed to assess the association between these drugs and other serious infections.

Validated gene expression biomarker analysis for biopsy-based clinical trials in ulcerative colitis.

BACKGROUND: Accurate and reproducible measurement of expression of pro-inflammatory cytokines in colonic biopsies from patients with ulcerative colitis (UC) is essential for proof-of-concept and mechanism-of-action studies. Few studies have rigorously established the number of biopsies required for accurate and reproducible biomarker measurements. AIM: To validate methods for measuring changes in gene expression in colonic biopsy samples. METHODS: Twelve colonic biopsies were obtained from each of six healthy controls, six patients with inactive UC and seven patients with active UC. Mayo endoscopic scores were used as a clinical reference standard. Quantitative PCR was used to assess mRNA expression of eight known inflammatory genes. The power to detect a reduction in gene expression in active vs. inactive UC was calculated using a linear mixed effect model. RESULTS: mRNA analysis of colonic biopsies is a sensitive and feasible approach for measuring inflammatory gene expression in colonic biopsies. Inflammatory biomarkers correlate with Mayo endoscopic subscores for each colonic region. For most genes, three rectal biopsies from two to four patients are required to detect changes in gene expression corresponding to active vs. inactive UC to achieve a power of 80% with an alpha of 0.05. CONCLUSION: Our data suggest that systematic measurement of inflammatory biomarkers at the mRNA level can be a valuable tool for hypothesis testing, and assessment of clinical activity and response to therapy in ulcerative colitis.

The optimal duration of frequency-volume charts related to compliance and reliability.

AIMS: To assess Frequency-volume charts (FVCs) for the yield of additional recorded days and the ideal duration of recording related to compliance and reliability. METHODS: Of 500 consecutive urologic outpatients willing to complete a 7-day FVC, 378 FVCs were evaluable. During seven consecutive days every voiding time and volume were recorded. Missed entries were indicated with a coded letter, thereby assessing the true frequency and compliance. Reliability is the agreement of the day-to-day FVC parameters with the 7-day FVC pattern. Single-day reliability was assessed and used in the Spearman-Brown formula. RESULTS: FVCs of 228 male and 150 females were evaluated. Mean age was 55.2 years (standard deviation [SD]: 16.2 years), and mean 24-hr urine production was 1,856 ml (SD: 828 ml). The percentage of patients with complete FVCs decreased from 78% on day 2 to 58% on day 7, and dropped below 70% after 4 days. Single-day reliability was r = 0.63 for nocturnal urine production, r = 0.72 for 24-hr urine production, and r = 0.80 for mean voided volume. At 5 days, reliability of 90% was achieved for all parameters. CONCLUSIONS: With each additional day, FVCs showed a decrease in compliance and an increase in reliability. At day 3, reliability of 80% was achieved for all FVC parameters, but compliance dropped to 73%. Beyond 5 days, the yield of additional recorded days was limited. We advocate an FVC duration of 3 days, but the duration may be shortened or extended depending on the goal of the FVC.

Can RENAL and PADUA nephrometry indices predict complications of laparoscopic cryoablation for clinical stage T1 renal tumors?

OBJECTIVE: Assessment of anatomical complexity with the RENAL (radius; exophytic/endophytic; nearness; anterior/posterior; location) and preoperative aspects and dimensions used for anatomical classification (PADUA) nephrometry indices is used to predict complications related to surgical extirpation treatment for patients with clinical T1a/b renal mass. This single center study aims to investigate the value of these indices to predict complications in a cohort of patients treated with laparoscopic cryoablation (LCA) for cT1 renal mass. MATERIALS AND METHODS: Single institution data from consecutive LCA procedures were prospectively collected from December 2006 to April 2013. Renal mass anatomical complexity was categorized according to RENAL and PADUA indices. Comorbidity was assessed by the Charlson-index. Intraoperative complications (IOCs) were reviewed and categorized: blood loss >100 mL, conversion, tumor fracture, and incomplete ablation. Postoperative complications (POCs) were graded using the modified Clavien-index. Univariate and multivariate logistic regression models addressed the risk for complications. RESULTS: Ninety-nine LCA procedures were included. The median RENAL-score was 7.0 (standard deviation [SD] 1.7), and the median PADUA-score was 8.0 (SD 1.6). IOC occurred in 19 procedures (19%). The risk for IOC was significantly correlated (p<0.05) with tumor diameter (mm), surface, volume, the RENAL domains "R-size," "N-nearness to collecting system," "RENAL score," and the PADUA domain "diameter." In multivariate analysis with surgical complication as the independent variable, tumor diameter, surface, and volume were determining factors. A threshold was set for 35 mm tumor diameter, it being predictive for an increased risk for IOC performing LCA. Twenty-three POC occurred in 20 patients. On univariate analysis, the RENAL domain "nearness to collecting system," and no PADUA domains, had a significant association with POC. CONCLUSION: The RENAL score, and not the PADUA score, is associated with a higher risk for IOC. A noncategorized method of scoring tumor diameter showed a more significant correlation with the risk for IOC than the categorized method of the nephrometry indices. As a result a threshold diameter of 35 mm was established.

The effect of gender and age on kidney cancer survival: younger age is an independent prognostic factor in women with renal cell carcinoma.

OBJECTIVE: Gender-specific differences in incidence of renal cell carcinoma (RCC) and its outcome have previously been reported. We used age as a surrogate to test whether this might be hormone-related in a large international RCC cohort. METHODS AND MATERIALS: This study included patients treated by nephrectomy at 10 international academic centers. Clinicopathologic features were assessed using chi-square and the Student t-tests. Kaplan-Meier survival estimates and Cox proportional hazards models addressed the effect of gender and age on disease-specific survival. RESULTS: Of the 5,654 patients, 3,777 (67%) were men and 1,877 (33%) were women. Generally, women presented at lower T stages (P<0.001), had fewer metastases (P<0.001), and had lower-grade tumors (P<0.001). Women more frequently had clear-cell (87% vs. 82%) and less frequently had papillary RCC (7% vs. 12%) than men (P<0.001). Women had a 19% reduced risk of death from RCC than men (hazard ratio 0.81, 95% confidence interval 0.73-0.90, P<0.001). The survival advantage for women was present to the greatest degree in the age group<42 years (P = 0.0136) and in women aged 42 to 58 years (P<0.001), but was not apparent in patients aged 59 years and older (P = 0.248). Age was an independent predictor of disease-specific survival in women (hazard ratio 1.011, 95% confidence interval 1.004-1.019, P = 0.004), but not in men. CONCLUSIONS: As a group, women present with less advanced tumors, leading to a 19% reduced risk of RCC-specific death compared with men. This survival difference is present only in patients aged<59 years. Because this gender-based survival difference is not related to pathologic features, the role of hormonal effects on the development and progression of RCC needs to be investigated.

A cutoff value based on analysis of a reference population decreases overestimation of the prevalence of nocturnal polyuria.

PURPOSE: We sought criteria for nocturnal polyuria in asymptomatic, nonurological adults of all ages by reporting reference values of the ratio of daytime and nighttime urine volumes, and finding nocturia predictors. MATERIALS AND METHODS: Data from a database of frequency-volume charts from a reference population of 894 nonurological, asymptomatic volunteers of all age groups were analyzed. The nocturnal polyuria index and the nocturia index were calculated and factors influencing these values were determined by multivariate analysis. RESULTS: The nocturnal polyuria index had wide variation but a normal distribution with a mean ± SD of 30% ± 12%. The 95th percentile of the values was 53%. Above this cutoff a patient had nocturnal polyuria. This value contrasts with the International Continence Society definition of 33% but agrees with several other reports. On multivariate regression analysis with the nocturnal polyuria index as the dependent variable sleeping time, maximum voided volume and age were the covariates. However, the increase in the nocturnal polyuria index by age was small. Excluding polyuria and nocturia from analysis did not alter the results in a relevant way. The nocturnal voiding frequency depended on sleeping time and maximum voided volume but most of all on the nocturia index. CONCLUSIONS: The prevalence of nocturnal polyuria is overestimated. We suggest a new cutoff value for the nocturnal polyuria index, that is nocturnal polyuria exists when the nocturnal polyuria index exceeds 53%. The nocturia index is the best predictor of nocturia.

The international prostate symptom score overestimates nocturia assessed by frequency-volume charts.

PURPOSE: We analyzed differences in nocturia, as estimated by the International Prostate Symptom Score and 7-day frequency-volume charts. MATERIALS AND METHODS: A total of 398 forms were collected from 500 consecutive urological outpatients willing to record a 7-day frequency-volume chart. All patients completed a general questionnaire, an International Prostate Symptom Score, and a bladder symptom and bother score. Missed recordings were indicated by a coded letter. Patients who lacked essential data, bedtimes or an International Prostate Symptom Score, or who recorded the frequency-volume chart for less than 5 days were excluded from study. RESULTS: A total of 186 men and 115 women with a mean age of 56 years were evaluable. In 10.6% of patients no nocturia occurred. Of those with nocturia 70% and 34% experienced nocturia a mean of 1 or more and 2 or more times, respectively. In 43% of patients the International Prostate Symptom Score equaled calculated categorized nocturia while 50% had a higher International Prostate Symptom Score nocturia score than calculated nocturia. On univariate analysis the correlation of International Prostate Symptom Score question 7 with mean nocturia increased with frequency-volume chart duration (day 1 r = 0.52 to day 3 r = 0.63). On longer duration frequency-volume charts the correlation showed no further increase. Multivariate regression analysis revealed that the nocturia score was determined by mean nocturia in the frequency-volume chart, the nocturia bother score and patient age. CONCLUSIONS: The International Prostate Symptom Score nocturia score overestimated nocturia in most patients, as derived from a 7-day frequency-volume chart. When scoring International Prostate Symptom Score nocturia question 7, patients included a degree of bother. The correlation of question 7 with mean nocturia increased with frequency-volume chart duration until day 3.

Spontaneous autoimmune gastritis and hypochlorhydria are manifest in the ileitis-prone SAMP1/YitFcs mice.

SAMP1/YitFcs mice serve as a model of Crohn's disease, and we have used them to assess gastritis. Gastritis was compared in SAMP1/YitFcs, AKR, and C57BL/6 mice by histology, immunohistochemistry, and flow cytometry. Gastric acid secretion was measured in ligated stomachs, while anti-parietal cell antibodies were assayed by immunofluorescence and enzyme-linked immunosorbent spot assay. SAMP1/YitFcs mice display a corpus-dominant, chronic gastritis with multifocal aggregates of mononuclear cells consisting of T and B lymphocytes. Relatively few aggregates were observed elsewhere in the stomach. The infiltrates in the oxyntic mucosa were associated with the loss of parietal cell mass. AKR mice, the founder strain of the SAMP1/YitFcs, also have gastritis, although they do not develop ileitis. Genetic studies using SAMP1/YitFcs-C57BL/6 congenic mice showed that the genetic regions regulating ileitis had comparable effects on gastritis. The majority of the cells in the aggregates expressed the T cell marker CD3 or the B cell marker B220. Adoptive transfer of SAMP1/YitFcs CD4(+) T helper cells, with or without B cells, into immunodeficient recipients induced a pangastritis and duodenitis. SAMP1/YitFcs and AKR mice manifest hypochlorhydria and anti-parietal cell antibodies. These data suggest that common genetic factors controlling gastroenteric disease in SAMP1/YitFcs mice regulate distinct pathogenic mechanisms causing inflammation in separate sites within the digestive tract.