Comparison Between 64Cu-PSMA-617 PET/CT and 18F-Choline PET/CT Imaging in Early Diagnosis of Prostate Cancer Biochemical Recurrence.

PURPOSE: To evaluate the diagnostic performance of 64Cu-PSMA-617 positron emission tomography (PET) with computed tomography (CT) for restaging prostate cancer after biochemical recurrence (BCR) and to compare it with 18F-choline PET/CT in a per-patient analysis. PATIENTS AND METHODS: An observational study was performed of 43 patients with BCR after laparoscopic radical prostatectomy who underwent 64Cu-PSMA-617 PET/CT and subsequently 18F-choline PET/CT for restaging. The detection rates (DR) of 64Cu-PSMA-617 PET/CT and of 18F-choline PET/CT were calculated by standardized maximum uptake value (SUVmax) at 4 hours and SUVmax at 1 hour as reference, respectively. Furthermore, univariate logistic regression analysis was carried out to identify independent predictive factors of positivity with 64Cu-PSMA-617 PET/CT. RESULTS: An overall positivity with 64Cu-PSMA-617 PET/CT was found in 32 patients (74.4%) versus 19 (44.2%) with 18F-choline PET/CT. Specifically, after stratifying for prostate-specific antigen (PSA) values, we found a good performance of 64Cu-PSMA-617 PET/CT at low PSA levels compared to 18F-choline PET/CT, with a DR of 57.1% versus 14.3% for PSA 0.2-0.5 ng/mL (P = .031), and of 60% versus 30% with PSA 0.5-1 ng/mL. At univariate binary logistic regression analysis, PSA level was the only independent predictor of 64Cu-PSMA-617 PET/CT positivity. No significant difference in terms of DR for both 64Cu-PSMA-617 PET/CT and 18F-choline PET/CT was found according to different Gleason score subgroups. CONCLUSION: In our study cohort, a better performance was observed for 64Cu-PSMA-617 PET/CT compared to 18F-choline PET/CT in restaging after BCR, especially in patients with low PSA values.

[A cause of acute renal dysfunction: a giant bladder diverticulum].

We describe the case of a previously 77-year-old man who accessed in our Nephrology Unit for acute kidney injury (AKI) on chronic kidney disease (CKD), gastric discomfort and vague urinary symptoms with apparently preserved diuresis and suspected "ascites". Physical examination confirmed the presence of abdominal effusion, even though ultrasound abdominal examination revealed the presence of a giant diverticular urinary bladder with bilateral hydronephrosis. We discuss the diagnostic and therapeutic approach of these rare complications by briefly reviewing the technical aspects and the possible consequences.

A larger detrusor wall thickness increases the risk of non muscle invasive bladder cancer recurrence and progression: result from a multicenter observational study.

BACKGROUND: Recent experimental study showed a higher incidence of bladder cancer in presence of bladder detrusor muscle thickening. The aim of this study is to assess whether a higher detrusor muscle thickness (DWT) may be a risk factor of recurrence of non-muscle invasive urothelial bladder cancer (NMIBC). METHODS: Men with histologically-confirmed diagnosis of NMIBC were prospectively enrolled in 4 centers between December 2015 and April 2017. DWT was measured by ultrasound and DWT>2.5 mm was used as threshold for detrusor muscle thickening. Patients underwent to adjuvant local treatment in according to their progression and recurrence risk computed by European Organization Research and Treatment of Cancer (EORTC) Score for NMIBC. Every three months cystoscopy and urinary cytology were used to detect disease recurrence and progression. The main clinic-pathological variables were compared between patients with DWT≤2.5 mm and DWT>2.5 mm. RESULTS: One hundred patients (49.8%) with DWT >2.5 mm were significantly older, had larger and more tumors and experienced more prior NMIBC than 101 (50.2%) patients with a DWT≤2.5 mm. Recurrence and progression disease occurred more often and briefly in patients with a detrusor muscle thickening. At univariate analysis, DWT>2.5 was a predictive risk factors of cancer recurrence and progression, respectively: OR 4.9 (95% CI: 2.5-9.5) P=0.001 and OR 2.21 (95% CI: 1.71-4.73), P=0.001. Enclosing DWT in EORTC risk calculator significantly increased by 3% and 1% recurrence and progression risk assessment, respectively. CONCLUSIONS: Detrusor muscle thickening may have a role in NMIBC course with a higher recurrence rate, however further confirmatory and elucidating studies are required.

Systemic Inflammatory Markers and Oncologic Outcomes in Patients with High-risk Non-muscle-invasive Urothelial Bladder Cancer.

BACKGROUND: Serum levels of neutrophils, platelets, and lymphocytes have been recognized as factors related to poor prognosis for many solid tumors, including bladder cancer (BC). OBJECTIVE: To evaluate the prognostic role of the combination of the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and lymphocyte/monocyte ratio (LMR) in patients with high-risk non-muscle-invasive urothelial BC (NIMBC). DESIGN, SETTING, AND PARTICIPANTS: A total of 1151 NMIBC patients who underwent first transurethral resection of the bladder tumor (TURBT) at 13 academic institutions between January 1, 2002 and December 31, 2012 were included in this analysis. The median follow-up was 48 mo. INTERVENTION: TURBT with intravesical chemotherapy or immunotherapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable Cox regression analysis was performed to identify factors predictive of recurrence, progression, cancer-specific mortality, and overall mortality. A systemic inflammatory marker (SIM) score was calculated based on cutoffs for NLR, PLR, and LMR. RESULTS AND LIMITATIONS: The 48-mo recurrence-free survival was 80.8%, 47.35%, 20.67%, and 17.06% for patients with an SIM score of 0, 1, 2, and 3, respectively (p<0.01, log-rank test) while the corresponding 48-mo progression free-survival was 92.0%, 75.67%, 72.85%, and 63.1% (p<0.01, log-rank test). SIM scores of 1, 2, and 3 were associated with recurrence (hazard ratio [HR] 3.73, 7.06, and 7.88) and progression (HR 3.15, 4.41, and 5.83). Limitations include the lack of external validation and comparison to other clinical risk models. CONCLUSIONS: Patients with high-grade T1 stage NMIBC with high SIM scores have worse oncologic outcomes in terms of recurrence and progression. Further studies should be conducted to stratify patients according to SIM scores to identify individuals who might benefit from early cystectomy. PATIENT SUMMARY: In this study, we defined a risk score (the SIM score) based on the measurement of routine systemic inflammatory markers. This score can identify patients with high-grade bladder cancer not invading the muscular layer who are more likely to suffer from tumor recurrence and progression. Therefore, the score could be used to select patients who might benefit from early bladder removal.

Presence and severity of lower urinary tract symptoms are inversely correlated with the risk of prostate cancer on prostate biopsy.

BACKGROUND: The assessment of lower urinary tract symptoms (LUTS) is common part of urological investigation. Furthermore, patients bother of prostate cancer (PCa) when they are affected of LUTS. This study was aimed to determine whether the presence and severity of LUTS, as assessed by the International Prostate Symptoms Score (IPSS), could help to identify patients at higher risk of prostate cancer (PCa) on prostate biopsy (PBx). In this effort, an initial PCa predictive model was calculated and IPSS was subsequently added. The diagnostic accuracy of both models was compared. METHODS: The analysis of prospectively collected data of patients scheduled for PBx at four academic hospitals between January 2012 and June 2015 was performed. Univariate and multivariate analysis assessed the correlation between the IPSS and the risk of being diagnosed with PCa; Receiver operator characteristic curve (ROC) analysis evaluated the predictive models including or not the IPSS. RESULTS: Of the 1366 enrolled patients, 706 (52%) were diagnosed with PCa. Patients with PCa had a significantly lower IPSS (10.6±7.4 vs. 12.7±8.1) than those with benign diagnosis. Multivariate logistic regression analysis showed that age, prostate-specific antigen (PSA), prostate volume and IPSS were the most significant predictors of PBx outcome, (OR 1.61, P=0.001; OR 1.20, P=0.001; OR 0.97, P=0.001; OR 0.74, P=0.004; respectively). ROC curve analysis showed that the addition of IPSS to the predictive model based on age, PSA, DRE and prostate volume significantly improved the model diagnostic accuracy (AUC: 0.776 vs. 0.652; P=0.001). CONCLUSIONS: Presence and severity of LUTS are inversely correlated with the risk of being diagnosed with PCa at PBx. Incorporating the IPSS into predictive models may reduce the risk of unnecessary PBxs.

Intravesical treatment with highly-concentrated hyaluronic acid and chondroitin sulphate in patients with recurrent urinary tract infections: Results from a multicentre survey.

INTRODUCTION: We assess the effectiveness of intravesical instillation of hyaluronic acid (HA) and chondroitin sulphate (CS) as a non-antibiotic treatment option for prophylaxis of recurrent urinary tract infections (UTIs) in female patients. METHODS: This was a retrospective cohort study involving 7 European institutions. We included patients with recurrent UTIs who received intravesical instillations of Ialuril (IBSA International) (50 mL HA 1.6% and CS 2% solution) between January 2010 and March 2012. Medication schedule, length of follow-up, recurrence infection time, number of UTIs/patients/year, patient quality of life, subjective symptoms score, and treatment-emergent side effects were recorded and analyzed. RESULTS: In total, 157 women (mean age: 54.2 ± 4.1 years) were included in the analysis. All patients had at least 12 months follow-up. After 4 weekly and 5 monthly HA-CS bladder instillations, UTI episodes decreased from 4.13 ± 1.14 to 0.44 ± 0.50 (p = 0.01) at 12 months, while recurrent UTI time prolonged from 94.8 ± 25.1 days to 178.4 ± 37.3 days (p = 0.01) at 12 months. An improvement in symptoms and quality of life was achieved. A medium-depth pain after medication instillation was the most reported side effect. Regression model analysis showed significant risk factors in developing new UTI episodes: being more than 50 years old and having more than 4 UTI episodes per year (OR 3.41; CI 95%; 1.51-7.71, p = 0.003 and OR 3.31; CI 95% 1.51-7.22; p = 0.003, respectively). Retrospective design and lack of a control group represent two main limitations of the study. CONCLUSIONS: Restoring glycosaminoglycans bladder layer therapy is a promising non-antibiotic therapy to prevent recurrent UTIs.

Restoring the glycosaminoglycans layer in recurrent cystitis: experimental and clinical foundations.

Restoring the bladder glycosaminoglycans layer has recently been introduced as prophylactic treatment for recurrent urinary tract infections. Herein, we analyze the latest main clinical and experimental studies to support this therapeutic option. An electronic research was carried out in the most common databases in order to identify any published studies. Retrieved studies were categorized as experimental or clinical according to their setting. For the clinical studies, the evidence level was assigned. A total of 13 laboratory studies showed how bladder glycosaminoglycans instillations act: attenuation of the inflammation process, reduction of bladder contraction amplitude and frequency, reduction of epithelium damage, and lower bacterial growth in urine and tissue samples. Likewise, two randomized clinical trials with grade 2 evidence level and two case series with grade 4 evidence level reported glycosaminoglycans as an alternative to reduce episodes and to prolong recurrence time in patients with recurrent urinary tract infections. At least 12 months of follow up was completed. No serious adverse events were reported. Compared with a placebo, in one randomized study a significantly higher maximum cystometric capacity was obtained, whereas in the other study a significant increase in quality of life scores was reported too. An improvement in the urinary symptoms score was reported by the two randomized trials. Although the clinical use of glycosaminoglycans replacement therapy for recurrent urinary tract infections is supported by a small number of clinical studies with different evidence levels, the laboratory studies show that glycosaminoglycans could have a protective role against inflammatory factors, supporting the idea "to restore the glycosaminoglycans bladder layer to prevent chronic disease course".

Metabolic syndrome correlates with peri-urethral fibrosis secondary to chronic prostate inflammation: evidence of a link in a cohort of patients undergoing radical prostatectomy.

OBJECTIVES: To investigate the pathological relationship between metabolic syndrome and peri-urethral fibrosis status secondary to chronic prostate inflammation. METHODS: Peri-urethral prostate tissue from 80 consecutive patients who underwent retropubic radical prostatectomy for prostate cancer was analyzed. Patients were divided in two groups according to whether or not they had a diagnosis of metabolic syndrome. A 16-peri-urethral core bench biopsy was carried out on each radical prostatectomy specimen to evaluate the extent of peri-urethral inflammatory infiltrate, and collagen and elastin amount. Spearman's correlation analysis was used to test the association between variables. Furthermore, the data were used to define a bivariate logistic regression model in which the presence (>50% collagen amount for each patients) or absence (≤50% collagen amount) of fibrosis was analyzed after adjusting for clinical and pathological variables. RESULTS: A significant difference was found between the two groups in terms of International Prostatic Symptoms Score (P < 0.05) and urodynamics findings (all P < 0.05). Patients with metabolic syndrome showed a more extended inflammatory infiltrate and higher peri-urethral collagen amount, along with a lower peri-urethral elastin amount (all P < 0.05). A positive correlation was observed between inflammation, International Prostatic Symptoms Score, Bladder Outlet Obstruction Index and collagen amount, whereas inflammation was inversely correlated with elastin amount. On multivariate logistic regression analysis, prostate inflammation and metabolic syndrome were the only independent predictors of peri-urethral fibrosis (OR 1.73, 1.52, respectively). CONCLUSIONS: The present findings suggest that metabolic syndrome might represent an independent risk factor for prostate inflammation and fibrotic changes secondary to inflammation within the peri-urethral prostatic tissue.

Prevention of recurrent urinary tract infections by intravesical administration of hyaluronic acid and chondroitin sulphate: a placebo-controlled randomised trial.

BACKGROUND: Urinary tract infection (UTI) is a prevalent condition in women during their lifetime with a high rate of recurrence within 3-6 mo. OBJECTIVES: Our aim was to investigate the efficacy and tolerability of the intravesical administration of combined hyaluronic acid (HA) and chondroitin sulphate (CS) in female patients with a history of recurrent UTI. DESIGN, SETTING, AND PARTICIPANTS: We conducted a prospective, randomised, double-blind, placebo-controlled study comparing the intravesical instillation of HA-CS with placebo in women with recurrent UTI. INTERVENTION: Participants were randomised to receive 50 ml of sterile sodium HA 1.6% and CS 2.0% solution (IALURIL(®)) weekly for 4 wk and then monthly for 5 mo. MEASUREMENTS: The primary end point of the study was defined as the mean number of UTI per patient per year. Participants were evaluated addressing UTI status/urinary symptoms and with a general health-related quality-of-life (QoL) questionnaire at baseline and after 3, 6, 9, and 12 mo. RESULTS AND LIMITATIONS: In the intention-to-treat analysis, 57 women were randomly allocated to HA-CS (n=28) or placebo (n=29). The UTI rate per patient per year at the end of the study (12 mo) (mean±SD: -86.6%±47.6 vs -9.6%±24.6; mean difference: 77%; 95% confidence interval, 72.3-80.8; p=0.0002) and the mean time to UTI recurrence (52.7±33.4 vs 185.2±78.7 d; p<0.001) were significantly reduced after treatment with HA-CS compared with placebo. Overall urinary symptoms and QoL measured by questionnaires significantly improved compared with placebo (Pelvic Pain and Urgency/Frequency questionnaire symptom score: 14.53±4.32 vs 9.88±6.77; p=0.004; SF-36 QoL score: 78.6±6.44 vs 53.1±4.72; p<0.001). No serious adverse event was reported. CONCLUSIONS: Compared with placebo, HA-CS intravesical instillations significantly reduced UTI rate without severe side effects while improving symptoms and QoL over a 12-mo period in patients with recurrent UTI. TRIAL REGISTRATION: ISRCTN 76354426.