Natural history and health care burden of non-curative treatment for muscle-invasive bladder cancer.

OBJECTIVE: Muscle-invasive bladder cancer is an aggressive disease. Yet, many patients, especially those with advanced age and multiple comorbidities, do not receive treatment with curative intent. We evaluated the disease course and health care burden of these patients. MATERIALS AND METHODS: Bi-center, retrospective analysis of patients diagnosed with muscle-invasive bladder cancer who did not undergo curative-intent treatment (radical cystectomy or trimodal therapy) between 2016 and 2021. Patient characteristics and treatment burden were described. Metastasis-free, cancer-specific, and overall survivals were evaluated using the Kaplan-Meier method. RESULTS: Sixty-six patients with a median age of 86 (IQR 78,90) were evaluated. The median follow-up for survivors was 29 months (IQR 9, 44). All patients were diagnosed with muscle-invasive bladder cancer, and 32 (48%) presented with clinical T3 and T4 disease. The median age adjusted Charlson comorbidity index at diagnosis was 7 (IQR 6,8). Treatment with curative intent was not provided due to comorbidities and low-performance status in 58 patients (88%) and patient refusal in 8 (12%). Two-year estimated metastasis-free survival, cancer-specific survival, and overall survival were 11%, 18%, and 12%, respectively. During follow-up, 7 patients (10%) were treated with chemotherapy, 4 (6%) received immunotherapy, 21 (32%) radiation, and 17 (26%) had emergent operations due to hematuria. Twenty-four patients (37%) required nephrostomy tubes, and 39 (59%) required an indwelling urinary catheter for various periods. Forty-three patients (65%) suffered from recurrent hematuria episodes. Overall, median emergency room visits were 4 (IQR 2, 6), and median hospital admission was 16 days (IQR 9, 29). CONCLUSIONS: Untreated muscle-invasive bladder cancer is associated with a limited lifespan and a high disease burden for the patient and health system. These data should be taken into consideration and portrayed to the patient when curative intent treatment is chosen to be avoided.

Revisiting the issue of "beach balls" in holmium laser enucleation of prostate: clinical and histological characterization.

PURPOSE: To clinically and histologically characterize prostatic nodules resistant to morcellation ("beach balls," BBs). PATIENTS AND METHODS: We reviewed a consecutive cohort of 559 holmium laser enucleation of the prostate (HoLEP) procedures performed between January 2020 and November 2023. The BBs group comprised 55 men (10%) and the control group comprised 504 men (90%). The clinical, intraoperative, outcome, and histologic data were statistically processed for the prediction of the presence of BBs and their influence on the perioperative course and outcome. RESULTS: The BBs group in comparison to the controls was older (75 vs 73 years, respectively, p = 0.009) and had higher rates of chronic retention (51 vs 29%, p = 0.001), larger prostates on preoperative abdominal ultrasound (AUS) (140 vs 80 cc, p = 0.006E-16), longer operating time (120 vs 80 min, p = 0.001), higher weights of removed tissue (101 vs 60 gr, p = 0.008E-10), higher complication rates (5 vs 1%, p = 0.03), and longer hospitalization (p = 0.014). A multivariate analysis revealed that larger prostates on preoperative AUS and older age independently predicted the presence of BBs which would prolong operating time. ROC analyses revealed that a threshold of 103 cc on AUS predicted BBs with 94% sensitivity and 84% specificity. BBs were mostly characterized histologically by stromal component (p = 0.005). CONCLUSIONS: BBs are expected in older patients and cases of chronic retention. Prostatic volume is the most reliable predictor of their presence. They contribute to prolonged operating time and increased risk of complications. The predominantly stromal composition of the BBs apparently confers their resistance to morcellation.

Sterile Water Versus Glycine in Transurethral Resection of Bladder Tumors-Immunogenic and Clinical Implications.

BACKGROUND AND OBJECTIVE: We compared the oncologic outcomes of patients with non-muscle invasive bladder cancer (NMIBC) who underwent transurethral resection of bladder tumor (TUBRT) using sterile water vs glycine irrigation. The tumoricidal and immunogenic effects of these solutions on urothelial cancer cell lines were investigated. METHODS: The medical records of 530 consecutive patients who underwent TURBT using sterile water or glycine irrigation for NMIBC were reviewed. Recurrence and progression rates were evaluated using time dependent analyses.Bladder cancer cell lines (RT4, T24 and 5637) were treated with glycine and sterile water. Cell viability was evaluated with the XTT assay. Cell membrane calreticulin levels were evaluated with flow cytometry. Extracellular high mobility group box 1 (HMGB1) and heat shock 70 (HSP70) protein levels were evaluated using western blots. KEY FINDINGS AND LIMITATIONS: After propensity score matching each study arm comprised 161 patients. Median follow-up was 13.6 months (IQR 6.2, 24.5). The 2-year recurrence free survival was significantly lower in the sterile water vs glycine group (43% vs 71%, respectively, p<0.0001). Similarly, the 2-years progression free survival was significantly lower in the sterile water vs glycine group (85% vs 94%, respectively, p<0.014). Sterile water treatment resulted in the lowest number of viable cells. Early and late immunogenic cell death markers were markedly elevated in cells treated with glycine. CONCLUSIONS AND CLINICAL IMPLICATIONS: Sterile water compared to glycine irrigation during TURBT for NMIBC was associated with higher recurrence and progression rates. Possible explanation for these findings is the diminished immune response associated with sterile water reflected in a comparatively lesser expression of immune response inducers. PATIENT SUMMARY: We compared two irrigation fluids in non-muscle-invasive bladder cancer surgery: glycine and sterile water. Glycine outperformed sterile water in cancer recurrence, possibly boosting immunogenicity over sterile water.

Mini-HoLEP (MILEP) vs HoLEP: a propensity score-matched analysis.

BACKGROUND AND PURPOSE: Minimal invasiveness improves outcome in many surgical fields including urology. We aimed to assess intraoperative performance and clinical outcome of miniaturized holmium laser enucleation of prostate (MiLEP) (22FR). METHODS: We ran a propensity score-matched analysis among all consecutive laser enucleations of prostate performed between 9/2022 and 2/2023. It resulted in two matched comparison groups: MiLEP 22 FR (n = 40) and holmium laser enucleation of prostate (HoLEP 26 Fr) (n = 40). Statistical analysis was performed. RESULTS: MiLEP was associated with significantly less intraoperative irrigation (20.5 L vs 15 L, p = 0.002E-3), less decrease in body core temperature (0.6°C vs 0.1°C, p = 0.003E-5), and less need for meatal dilation (25% vs 78%, p = 0.01E-3). These parameters were identified as being independent in the multivariate analysis. There was a trend toward less and a shorter period of postoperative stress incontinence (SI) for the MiLEP group compared to the HoLEP group: 15% and 42% (p = 0.01) at 1 month, 8% and 14% (p = 0.07) at 2 months, and 0 and 0.3% (p = 1) at 3 months, respectively. There were no differences in prostatic enucleation effectiveness, operative time, hospital stay, complications, and improvement in the international prostate symptom score and quality of life score. CONCLUSIONS: MiLEP is feasible and provides better maintenance of body core temperature, reduction in amount of fluid irrigation, and decrease in need for meatal dilation without affecting effectiveness in comparison with HoLEP. MiLEP may reduce early postoperative stress incontinence, thereby shortening the recovery period.

En bloc holmium laser enucleation of prostate in octogenarians and nonagenarians: clinical characteristics and outcome.

Extended longevity leads to greater numbers of elderly patients with benign prostatic hyperplasia (BPH) who seek surgical solutions. We assessed the clinical characteristics and outcomes of octogenarians and nonagenarians with BPH who underwent en bloc holmium laser enucleation of prostate (HoLEP). Retrospective cohort of all consecutive HoLEP patients treated in our medical center between January 2020 and January 2023. Cohort was divided into group aged < 80 years (n = 290) and group aged ≥ 80 years (n = 77). Their demographics, presentations, indications, and outcomes were compared. Octogenarians and nonagenarians had higher rates of indwelling catheters (p = 0.00001), chronic retention (p = 0.00006), larger prostates (p = 0.03), higher American Anesthesiology Association scores (p = 0.000001), and more antiplatelet medications (p = 0.0003) at presentation. They had longer operations (median 115 vs 90 min, respectively, p = 0.0008), longer hospital stay (median 2 vs 1 day, p = 0.01E-7), a higher complication rate (17% vs 7%, p = 0.02), and a higher transitory urinary incontinence (TUI) rate (54% vs 9%, p = 0.00001). TUI was more prevalent in the older group with indwelling catheters (61% vs, 13%, p = 0.00001). The functional outcome was similar for both age groups, and all patients could void spontaneously after the procedure. En-bloc HoLEP improves urinary symptoms and quality of life in patients ≥ 80 years of age despite larger prostates, more comorbidities, and higher complications rate, compared to younger men. HoLEP bestows a significant improvement in urologic quality of life regardless of age.

The role of serum and urinary markers in predicting obstructing ureteral stones and reducing unjustified non-contrast computerized tomographic scans in emergency departments.

INTRODUCTION: The reported yield of non-contrast computed tomography (NCCT) in assessing flank pain and obstructive urolithiasis (OU) in emergency departments (EDs) is only ~ 50%. We investigated the potential capability of serum and urinary markers to predict OU and improve the yield of NCCT in EDs. METHODS: All consecutive ED patients with acute flank pain suggestive of OU and assessed by NCCT between December 2019 and February 2020 were enrolled. Serum white blood cells (WBC), C-reactive protein (CRP) and creatinine (Cr) levels, and urine dipstick results were analyzed for association with OU, and unjustified NCCT scan rates were calculated. RESULTS: NCCTs diagnosed OU in 108 of the 200 study patients (54%). The median WBC, CRP, and Cr values were 9,100/µL, 4.3 mg/L, and 1 mg/dL, respectively. Using ROC curves, WBC = 10,000/µL and Cr = 0.95 mg/dl were the most accurate thresholds to predict OU. Only WBC ≥ 10,000/µL (OR = 3.7, 95% CI 1.6-8.3, p = 0.002) and Cr ≥ 0.95 mg/dl (OR = 5, 95% CI 2.3-11, p < 0.001) were associated with OU. Positive predictive value and specificity for detecting OU among patients with combined WBC ≥ 10,000 and Cr ≥ 0.95 were 83% and 89%, respectively. Patients negative to the serum markers criteria underwent significantly more unjustified NCCTs (p = 0.03). The negative predictive value of the serum criteria for justified NCCT scanning was 81%. CONCLUSIONS: WBC and Cr may be valuable serum markers in predicting OU among patients presenting to EDs with acute flank pain. They may potentially reduce the number of unjustified NCCT scans in the ED setting.

Association between early change in neutrophil-to-lymphocyte ratio after radical cystectomy and treatment outcomes.

OBJECTIVES: To evaluate the associations of peri-operative neutrophil-to-lymphocyte ratio (NLR) and change in NLR with survival after radical cystectomy. PATIENTS AND METHODS: We retrospectively reviewed a multicentre cohort of patients with bladder cancer who underwent radical cystectomy between 2010 and 2020. Preoperative NLR, postoperative NLR, delta-NLR (postoperative minus preoperative NLR) and NLR change (postoperative divided by preoperative NLR) were calculated. Patients were stratified based on elevation of preoperative and/ or postoperative NLR above the median values. Multivariable Cox regression models were used to evaluate the associations of peri-operative NLR and NLR change with survival. RESULTS: The study cohort included 346 patients with a median age of 69 years. The median (interquartile range) preoperative NLR, postoperative NLR, delta-NLR and NLR change were 2.55 (1.83, 3.90), 3.33 (2.21, 5.20), 0.43 (-0.50, 2.08) and 1.2 (0.82, 1.96), respectively. Both preoperative and postoperative NLR were elevated in 110 patients (32%), 126 patients (36%) had an elevated preoperative or postoperative NLR, and 110 patients (32%) did not have an elevated NLR. On multivariable analysis, increased preoperative and postoperative NLR were significantly associated with decreased survival. While delta-NLR and NLR change were not associated with outcome, patients with elevations in both preoperative and postoperative NLR had the worst overall (hazard ratio [HR] 2.97, 95% confidence interval [CI] 1.78, 4.95; P < 0.001) and cancer-specific survival rates (HR 2.41, 95% CI 1.3, 4.4; P = 0.004). CONCLUSIONS: Preoperative and postoperative NLR are significant predictors of survival after radical cystectomy; patients in whom both NLR measures were elevated had the worst outcomes. Future studies should evaluate whether an increase in NLR during long-term follow-up may precede disease recurrence.

Querying the significance of patient position during computerized tomography on the reliability of pre-percutaneous nephrolithotomy planning.

BACKGROUND: Computerized tomography (CT) is considered indispensable in percutaneous nephrolithotomy (PCNL) planning. We aimed to define the reliability of pre-PCNL CT for planning renal access by assessing renal positional changes between supine and prone CTs. SUBJECTS AND METHODS: CT urographies (CTU) of 30 consecutive patients were reviewed for distances upper pole (UP)-diaphragm, UP-diaphragm attachment, renal pelvis (RP)-lateral body wall, RP- posterior body wall, and lower pole (LP)- anterior-superior iliac spine (ASIS). The posterior and lateral renal axes angles were also calculated. RESULTS: The most consistent overall movement in transition from prone to supine was backward rotation, as demonstrated by a decrease in distance UP-posterior body wall (p = 0.010) and increase in the posterior renal angle (p < 0.0001). This finding correlated with the patient's body mass index (BMI) (p = 0.029). The left kidney was more mobile than the right one, moving significantly for five of the measured parameters compared to the right kidney which moved significantly for only two parameters. The UP-diaphragm distance of the left kidney correlated with age (p = 0.014), the RP-lateral wall distance correlated with previous abdominal surgery (p = 0.006), and the RP-posterior wall distance with BMI (p = 0.017). On the right, the UP-diaphragm distance correlated with gender (p = 0.002) and the lateral renal rotation was smaller (p = 0.046). CONCLUSIONS: Kidneys present significant mobility between supine and prone positions. CT assessment should be performed in the position expected during surgery and should be interpreted with caution, while a real-time imaging modality should be used in the operating room.

Cardiovascular Proteomics: A Post Hoc Analysis from a Phase II Randomized Clinical Trial Comparing GnRH Antagonist vs GnRH Agonist among Men with Advanced Prostate Cancer.

PURPOSE: Recent studies demonstrated reduced cardiovascular (CV) risk with gonadotropin-releasing hormone (GnRH) antagonist, yet the underlying mechanism remains undetermined. The objective of this study was to examine longitudinal changes over time in established CV related proteins among men treated with GnRH agonists vs GnRH antagonist. MATERIALS AND METHODS: We performed a proteomics analysis of serum samples collected during a phase II randomized study among 80 men with advanced prostate cancer and preexisting CV disease who were randomized to receive a GnRH agonist (39) or GnRH antagonist (41) for 1 year. Serum samples were collected at baseline and at 3, 6 and 12 months following treatment, and analyzed levels of 188 proteins using the CV panel II and III of the Olink Multiplex platform (Olink Proteomics AB, Uppsala, Sweden). We fitted a linear mixed effects model to assess evidence of a treatment effect across CV related protein values. This included terms for treatment arm, protein levels and time-by-treatment interaction. Results were corrected for multiple testing using the Benjamini-Hochberg method. RESULTS: The CV proteomics analysis included 283 samples from 78 subjects. We identified 5 proteins with distinct patterns over time depending on study arm: human chitotriosidase, macrophage receptor with collagenous structure, cathepsin D, superoxide dismutase 2 and hydroxyacid oxidase 1. All 5 are associated with plaque stability and demonstrated an increased level among subjects in the GnRH antagonist arm compared to agonist. CONCLUSIONS: We compared longitudinal changes in CV proteins among men using androgen deprivation therapy. Our results support a direct protective effect of GnRH antagonist on plaque stability rather than a hazardous consequence of GnRH agonists on plaque rupture. This is a hypothesis generating study, and requires further confirmation.

Role of Metabolic Syndrome in Prostate Cancer Development.

Prostate cancer and metabolic syndrome are common among men in the Western world. As the population grows older and life expectancy increases, the rates of both diseases are expected to increase. We now recognize that metabolic syndrome and prostate cancer interact. Metabolic syndrome may be a risk factor for prostate cancer and may also worsen outcomes. At the same time, treatment for prostate cancer may exacerbate metabolic syndrome and cardiac disease. This mini-review summarizes current evidence and puts it into clinical prospective. PATIENT SUMMARY: Metabolic syndrome is now a global epidemic. It is characterized by obesity, insulin resistance, high blood pressure, and high blood lipids. There is a complex interaction between metabolic syndrome and the risk of prostate cancer, as treatment of one disease may affect the other.

Current data on acute haematogenous osteomyelitis in children in Southern Israel: epidemiology, microbiology, clinics and therapeutic consequences.

BACKGROUND: Acute haematogenous osteomyelities (AHO) is the most common form of osteomyelitis, occurring when bone is infected secondary to transient bacteremia. The prevalence, aetiology and outcome of AHO may vary from region to region and period to period. The study objectives were to define the epidemiology, clinical, laboratory and imaging characteristics and treatment consequences of AHO in children in southern Israel. METHODS: This was a retrospective cohort study, enrolling all children <16 years of age hospitalized with AHO. Epidemiologic, clinical, laboratory and imaging data were recorded from medical charts. RESULTS: Ninety-one patients were diagnosed with AHO (52.7 % <4 years of age). Most children (80.24 %) did not receive antibiotic treatment prior to diagnosis. During 2005-2012 the AHO incidence was 5.6:100,000; the AHO incidence in the Bedouin and Jewish population was 7.3 and 4.1:100,000, respectively. Fifty-four (57.8 %) patients were afebrile at admission and 34 (37.4 %) showed leukocytosis >15,000/mm(3). The most involved bone was tibia (39.6 %), followed by femur (19.8 %), humerus (8.8 %) and pelvis (8.8 %). Positive cultures were reported in 26 (28.6 %) patients. The most common pathogen was methicillin-susceptible Staphylococcus aureus (MSSA, 18 patients, 19.8 %). There was only one case of MRSA. More positive cultures were recorded among children requiring surgery compared to children treated conservatively (P < 0.01). MSSA representation in cases requiring surgical intervention was higher than in cases treated conservatively (P = 0.01). There were nine bone biopsies and 33 bone aspirations (MSSA in 44.4 % and 24.2 %, respectively). The longest hospitalization was observed in patients with humerus-AHO (14.8 ± 12.2 days). There was no difference in the number of days of hospitalization between patients who received previous antibiotics compared with children who did not receive antibiotics before admission. CONCLUSIONS: Tibia was the most frequently involved bone, but humeral AHO required more surgical intervention and longer hospitalization. Negative cultures were frequent, MSSA was the most commonly involved pathogen and MRSA was rare. Culture positive AHO was associated with higher requirement for surgical intervention.