The transcriptional and regulatory identity of erythropoietin producing cells.

Erythropoietin (Epo) is the master regulator of erythropoiesis and oxygen homeostasis. Despite its physiological importance, the molecular and genomic contexts of the cells responsible for renal Epo production remain unclear, limiting more-effective therapies for anemia. Here, we performed single-cell RNA and transposase-accessible chromatin (ATAC) sequencing of an Epo reporter mouse to molecularly identify Epo-producing cells under hypoxic conditions. Our data indicate that a distinct population of kidney stroma, which we term Norn cells, is the major source of endocrine Epo production in mice. We use these datasets to identify the markers, signaling pathways and transcriptional circuits characteristic of Norn cells. Using single-cell RNA sequencing and RNA in situ hybridization in human kidney tissues, we further provide evidence that this cell population is conserved in humans. These preliminary findings open new avenues to functionally dissect EPO gene regulation in health and disease and may serve as groundwork to improve erythropoiesis-stimulating therapies.

The DNA methylome of human vascular endothelium and its use in liquid biopsies.

BACKGROUND: Vascular endothelial cells (VECs) are an essential component of each tissue, contribute to multiple pathologies, and are targeted by important drugs. Yet, there is a shortage of biomarkers to assess VEC turnover. METHODS: To develop DNA methylation-based liquid biopsies for VECs, we determined the methylome of VECs isolated from freshly dissociated human tissues. FINDINGS: A comparison with a human cell-type methylome atlas yielded thousands of loci that are uniquely unmethylated in VECs. These sites are typically gene enhancers, often residing adjacent to VEC-specific genes. We also identified hundreds of genomic loci that are differentially methylated in organotypic VECs, indicating that VECs feeding specific organs are distinct cell types with a stable epigenetic identity. We established universal and lung-specific VEC markers and evaluated their presence in circulating cell-free DNA (cfDNA). Nearly 2.5% of cfDNA in the plasma of healthy individuals originates from VECs. Sepsis, graft versus host disease, and cardiac catheterization are associated with elevated levels of VEC-derived cfDNA, indicative of vascular damage. Lung-specific VEC cfDNA is selectively elevated in patients with chronic obstructive pulmonary disease (COPD) or lung cancer, revealing tissue-specific vascular turnover. CONCLUSIONS: VEC cfDNA biomarkers inform vascular dynamics in health and disease, potentially contributing to early diagnosis and monitoring of pathologies, and assessment of drug activity. FUNDING: This work was supported by the Beutler Research Program, Helmsley Charitable Trust, JDRF, Grail and the DON Foundation (to Y.D.). Y.D holds the Walter & Greta Stiel Chair in heart studies. B.G., R.S., J.M., D.N., T.K., and Y.D. filed patents on cfDNA analysis.

A DNA methylation atlas of normal human cell types.

DNA methylation is a fundamental epigenetic mark that governs gene expression and chromatin organization, thus providing a window into cellular identity and developmental processes1. Current datasets typically include only a fraction of methylation sites and are often based either on cell lines that underwent massive changes in culture or on tissues containing unspecified mixtures of cells2-5. Here we describe a human methylome atlas, based on deep whole-genome bisulfite sequencing, allowing fragment-level analysis across thousands of unique markers for 39 cell types sorted from 205 healthy tissue samples. Replicates of the same cell type are more than 99.5% identical, demonstrating the robustness of cell identity programmes to environmental perturbation. Unsupervised clustering of the atlas recapitulates key elements of tissue ontogeny and identifies methylation patterns retained since embryonic development. Loci uniquely unmethylated in an individual cell type often reside in transcriptional enhancers and contain DNA binding sites for tissue-specific transcriptional regulators. Uniquely hypermethylated loci are rare and are enriched for CpG islands, Polycomb targets and CTCF binding sites, suggesting a new role in shaping cell-type-specific chromatin looping. The atlas provides an essential resource for study of gene regulation and disease-associated genetic variants, and a wealth of potential tissue-specific biomarkers for use in liquid biopsies.

High mannose level in bladder cancer enhances type 1 fimbria-mediated attachment of uropathogenic E. coli.

Bladder cancer is the 4th leading cancer in men. Tumor resection followed by bladder instillation of Bacillus Calmette-Guérin (BCG) is the primary treatment for high-risk patients with Non-Muscle Invasive Bladder Cancer (NMIBC) to prevent recurrence and progression to muscle-invasive disease. This treatment, however, lacks efficiency and causes severe adverse effects. Mannose residues are expressed on bladder surfaces and their levels were indicated to be higher in bladder cancer. Intravesical instillations of a recombinant Pseudomonas aeruginosa (PA) overexpressing the mannose-sensitive hemagglutination fimbriae (PA-MSHA), and of a mannose-specific lectin-drug conjugate showed efficiency against NMIBC in murine models of bladder cancer. Urothelial mannosylation facilitates bladder colonization by Uropathogenic E. coli (UPEC) via the interaction with the FimH mannose lectin, positioned at the tip of type 1 fimbria. A recombinant BCG strain overexpressing FimH on its outer surface, exhibited higher attachment and internalization to bladder cancer cells and increased effectivity in treating bladder cancer in mice. Investigating the pattern of mannose expression in NMIBC is important for improving treatment. Here, using tissue microarrays containing multiple normal and cancerous bladder samples, and lectins, we confirm that human bladder cancer cells express high mannose levels. Using UPEC mutants lacking or overexpressing type 1 fimbria, we also demonstrate that tumor-induced hypermannosylation increases type 1 fimbria mediated UPEC attachment to human and mouse bladder cancer. Our results provide an explanation for the effectiveness of PA-MSHA and the FimH-overexpressing BCG and support the hypothesis that mannose-targeted therapy holds potential for improving bladder cancer treatment.

False Positive Findings of [18F]PSMA-1007 PET/CT in Patients After Radical Prostatectomy with Undetectable Serum PSA Levels.

Background: PET-CT using prostate-specific membrane antigen (PSMA)-targeting radiopharmaceuticals labeled with 68Ga or 18F has emerged as the most sensitive staging tool in prostate cancer (PC). Nonetheless, the occurrence of false positive (FP) findings presents a major concern of this approach. In this prospective study, we investigated the frequency and pattern of false-positive findings of [18F]PSMA-1007 PET/CT in patients after radical prostatectomy with undetectable serum PSA levels. Any discrete non-physiological accumulation of [18F]PSMA-1007 in this population is by definition FP. Methods: Seventeen men after radical prostatectomy, whose serum PSA levels were <0.05 ng/mL at 2-24 months after surgery were prospectively recruited. PET/CT was acquired at both 1 and 2 h after injection of [18F]PSMA-1007. Findings: Three studies (18%) were interpreted as completely normal. Thirty-five foci of "non-physiological" uptake were observed in the remaining 14 (82%) patients, including a single skeletal focus in four patients, multiple skeletal foci in five patients and soft tissue uptake in eight, including in a desmoid tumor and in pelvic lymphocele. The SUVmax of all lesions was in the range of 1-7, except for the desmoid tumor which measured 12.7. All foci were visible in both the 1- and the 2 h studies, presenting a minor (<10%), statistically insignificant increase of SUVmax during this time-interval. Interpretation: FP [18F]PSMA-1007-avid foci are found in about 80% of patients with undetectable serum PSA levels. Thus, focal uptake of [18F]PSMA-1007 outside its physiological distribution is not a categorical sign of metastasis and can arise from non-specific uptake of the ligand. The interpretation of [18F]PSMA-1007 PET/CT studies should always consider the clinical context, and lesions with SUVmax < 7 are suspicious for FP.

Is there a correlation between meatal stenosis severity, lower urinary tract symptoms and uroflowmetry?

INTRODUCTION: We have recently validated a meatal Stenosis (MS) severity grading system that is based on physical examination. OBJECTIVES: The study objective was to examine the correlation between this grading system, patients' urinary symptoms, uroflowmetry and postvoid residual parameters. STUDY DESIGN: Patients referred for our clinic for urinary and non-urinary complaints, were prospectively enrolled. Urinary symptoms questionnaire, uroflowmetry parameters and post-voiding residuals (PVR) were assessed, and photographs of the urethral meatus were taken for each patient. The photographs were graded blindly according to the previously validated grading system and correlated with urinary symptoms, uroflowmetry parameters and PVR. RESULTS: Overall, 75 patients were assessed (20 grade 0, 23 grade 1 and 32 grade 2). When using grade 0 as a reference, the odds ratio (OR) for reporting narrow stream was 6.4 (95%CI 1.65-24.77) and 4 (95%CI 1.18-14.16) for grade 1 and 2 respectively. OR for prolonged urination was 6 (95% CI 1.47-24.89) for Grade 1 and 2; OR for upward stream deviation was10.08 (95%CI -2.43-41.82) for grade 1 and 15.12 (95%CI - 3.74-61.17) for grade 2. Uroflowmetry results showed lower Qmax from 16.8(SD ± 8.0) ml/sec in grade 0-9.6 ml/s on grade 1 and 2 (p < 0.001) (Figure 1). PVR was not statistically different in the three groups. DISCUSSION: Our main findings were that meatal stenosis severity grade is associated with narrow stream as reported by parent, prolonged urination, and upward deviation of urinary stream, with increasing severity with worsening stenosis. MS grade was also associated with significant worsening of uroflow measures: a lower Qmax, Qmean and a longer time-to-Qmax. Post-void residual volume was not significantly different between the different severity grades. This study showed the clinical significance of the grading system. With subjective and objective measures. The implementation of this grading system in clinics, may aid in decision making regarding surgical intervention in the appropriate patients, and avoid unnecessary procedures. CONCLUSION: The Severity of MS seen on physical examination correlates well with obstructive symptoms and decrease of urine stream seen on uroflowmetry. These findings confirm the importance of the grading system in the evaluation of patients with MS and may be additional measure that assist in consulting parents on the indications to meatotomy.

[NEOADJUVANT CHEMOTHERAPY BEFORE RADICAL CYSTECTOMY - MIGHT IT BE OFFERED SELECTIVELY?]

INTRODUCTION: Neoadjuvant cisplatin-based chemotherapy prior radical cystectomy is the standard of care in patients with a muscle invasive bladder cancer. It is intended to treat micro-metastases. However, most patients do not develop metastases even without chemotherapy and are receiving this treatment in vain. In this study, we looked for pre-operative risk factors for developing metastases that can triage the patients that really need neoadjuvant therapy. METHODS: From 1998 to 2018, 285 patients underwent radical cystectomy without neoadjuvant chemotherapy. During a median follow-up of 42.5 months, 99 patients (34%) developed recurrent disease after a median duration of 12 months. The study compared 10 different preoperative parameters of patients who developed or did not develop recurrence. RESULTS: An increased risk of metastases was found in older patients (39.8% in older than 69 years vs. 33.3% in younger patients, p=0.045), in patients with a high Charlson Comorbidity index (46.2% in 5 and above vs. 28.2% when lower than 4, p=0.003), and in patients with large tumor diameter (p=0.01). No difference was found in the other variables examined including: gender, primary versus secondary tumor, tumor stage, presence of histological variant, hydronephrosis, carcinoma in situ (CIS) or sarcomatoid differentiation. CONCLUSIONS: Older age, comorbidity, and large tumor diameter predict the risk of recurrence after radical cystectomy. However, overlap between the groups precludes the use of these parameters for clinical decisions. Therefore, neoadjuvant chemotherapy treatment should currently be offered to all candidates for radical cystectomy. Hopefully, future molecular markers will be able to predict the risk of metastases.

Real-world Israeli single institution experience with PET-PSMA for staging of patients with clinically staged localized prostate carcinoma.

BACKGROUND: A recent prospective trial, the proPSMA study, showed superior specificity and sensitivity of Positron emission tomography (PET) - Prostate-specific membrane antigen (PSMA) imaging compared standard Computerized tomography (CT) and bone scan for staging of recently diagnosed high-risk local prostate carcinoma for curative intent treatment. AIM: To share our experience with false-positive PET PSMA scans in newly diagnosed intermediate-risk prostate cancer. METHODS AND RESULTS: Here, we report a series of eight patients who underwent systemic staging using PET-PSMA with false-positive results who were ultimately treated with definitive radiation or surgery. Of the eight patients, two patients were diagnosed with favorable intermediate disease, four with unfavorable intermediate risk, and two with high-risk disease. Seven of eight were shown to have false-positive bone uptake, one patient had uptake in lung nodules. Three patients underwent bone biopsy and proven benign. The rest of the patients were proven as non-metastatic radiologically by repeat PSMA, CT, or Magnetic resonance imaging (MRI). All subsequently preceded to definitive localized treatment and remain disease free as of this study. CONCLUSION: This study emphasizes the importance of prudent clinical judgment when utilizing this highly sensitive imaging technique.

Transurethral Prostatectomy Before or After External Beam Radiotherapy: Complications and Reoperation Rates.

PURPOSE: Patients treated by external beam radiotherapy (EBRT) for localized carcinoma of the prostate (CAP) often suffer from urinary obstruction. While most patients can be treated medically, some require transurethral prostatectomy (TURP) for alleviation of obstruction. The consequences of combing EBRT and TURP are controversial. The objective of this study was to evaluate the success and complication rates of TURP combined with EBRT. PATIENTS AND METHODS: Between 2001 and 2017, 3501 patients underwent TURP. Sixty-six of them were treated with EBRT for CAP. Surgical complications according to the Clavien-Dindo (CD) scale and the need for secondary interventions were compared to 66 randomly selected patients operated on for benign prostatic hyperplasia (BPH). RESULTS: Patients who underwent TURP for BPH were significantly older compared to the patients with CAP with an average of 76.4 (SD 4.3) vs 71 (SD 8.2) years, p<0.0001. Substantial post-operative complications were rare in both groups with only a single case of CD grade 3 in each group. However, patients with CAP required significantly more secondary surgeries (21% vs 6%, p=0.02) and significantly more additional interventions (37.9% vs 13.6%, p=0.0025). There was no difference in complication rate, in the need for additional interventions or in the oncological outcome when comparing patients operated before or after EBRT. CONCLUSION: The complication rate of TURP done before or after EBRT is low and comparable to surgery for BPH. However, the rates of secondary surgeries and additional interventions in these patients are high (40%). TURP before or after EBRT provides similar results.

Trimodal therapy in T2-4aN0M0 bladder cancer--How to select the best candidate?

The reported results of trimodal treatment (TMT) in muscle-invasive bladder cancer vary widely. We attempted to characterize the profile of ideal candidates for this approach. Between 2000 and 2019, 105 patients (median age 78 years) with T2-4aN0M0 bladder cancer were treated with TMT and analyzed retrospectively. Mean radiotherapy dose was 62 Gy (SD 8.4). Ten pretreatment prognostic parameters were evaluated including tumor diameter on pre-TURBT CT. Multivariate analyses was performed and combination of parameters was studied. After a median follow-up of 29 months, 53 patients (50.5%) developed recurrence and 70 patients (67.7%) died. Death was disease-specific in 46 patients (65.7%). Tumor diameter was the most significant prognostic parameter with p < 0.0001 for overall, disease-specific and recurrence-free survivals. For every 1 cm increase in tumor diameter, the risk of disease-specific mortality increased by 1.57. Age, cisplatin eligibility and the Charlson Comorbidity Index were significant predictors of overall survival but not of disease-specific or recurrence-free survival. Patients who were cisplatin-eligible with a tumor diameter ≤3 cm had a 5-year disease-specific survival rate of 79.2% as opposed to 33.9% in patients without one of these features (p < 0.001). When tumor diameter exceeded 5 cm (irrelevant of all other parameters), 5-year disease-specific survival rate was only 28.2%. Patient profiles can accurately predict response to TMT. In cisplatin-eligible patients with a tumor diameter ≤3 cm, TMT provides an excellent disease-specific survival rate. In patients with a tumor diameter >5 cm TMT renders unacceptably poor treatment outcomes.

Initial experience in combined ultra-mini percutaneous nephrolithotomy with the use of 120-W laser and the anti-retropulsion "Moses effect": the future of percutaneous nephrolithotomy?

The purpose is to present our preliminary results where ultra-mini PCNL (UMPCNL) with the new 120-watt laser with the anti-retropulsion (Lumenis® MOSES Pulse™120H Holmium: YAG laser) was used for the first time to our knowledge. Twelve patients underwent ultra-mini PCNL in prone position under general anesthesia using a 12-F nephroscope with a 14-F Access sheath in our tertiary center. The fragmentation was performed with a 500 µm laser fiber using the 120-watt Lumenis® MOSES Pulse™120H Holmium: YAG laser). Efficacy was considered in terms of stone-free rates (SFR), complication rate, duration of the operation, and hospital stay. Our SFR was 91.6% with 11 patients out of 12 being completely free of any residual stone. The duration of the operation was 86.4 ± 36.8 (40-165) min, whereas the mean laser time (real stone fragmentation laser time) was 755.7 ± 954.7(241-3425) sec. The total laser energy used was 39.7 ± 52 KJoules (11.3-182). The fluoroscopy time and radiation doses were 358.5 ± 180.4 (154-750) sec and 64.7 ± 41.2 (14.7-159.0) mGy, respectively. The mean reduction in levels of hemoglobin postoperatively was 0.6 ± 0.3 (0.1-0.9) g/dL, and no complications were observed. The combination of UMPCNL with the new 120-watt laser and the unique anti-retropulsion technology (Lumenis® MOSES Pulse™120H Holmium: YAG laser) delivered very promising results and it could be the future of PCNL.

Factors Predicting Operating Room Time in Ureteroscopy and Ureterorenoscopy.

BACKGROUNDS/AIMS: Operation room (OR) time is of great value affecting surgical outcome, complications and the daily surgical program with financial implications. METHODS: We retrospectively evaluated 570 consecutive patients submitted to ureteroscopy or ureterorenoscopy for the treatment of ureteral or renal stones. Demographic parameters, patient's stones characteristics, type of ureteroscope, surgeon experience and surgical theater characteristics were analyzed. OR time was calculated from the initiation of anesthesia to patient extubation. Multivariate analysis was conducted using a linear regression test with multiple parameters to identify predictors of OR time. RESULTS: Eight factors were identified as significant. These include total stones volume, ureteroscope used, stone number, nurses experience, radio-opacity of the stone on kidney-ureter-bladder X-ray, main surgeon experience, operating room type, and having a nephrostomy tube prior to surgery. CONCLUSIONS: The surgical team experience and familiarity with endourological procedure, and the surgical room characteristics has a crucial impact on OR time and effectiveness.

Door To Detorsion Time Determines Testicular Survival.

OBJECTIVE: To determine the importance of the duration of in-hospital management of patients with testicular torsion for testes survival. The time from onset of symptoms until surgery is a well-known factor determining testicular survival but there is no data regarding the contribution of in-hospital management duration to testicular survival. Unlike the time from onset of symptoms until seeking medical attention, the time from registration to the emergency department (ED) to the time of detorsion-"Door To Detorsion time" (DTD) is dependent on medical providers and should be minimized. MATERIALS AND METHODS: Data was retrieved on all patients who underwent surgery for testicular torsion in 1994-2014 (N = 219). We used multivariable logistic regression analysis to examine independent association between DTD time or duration of symptoms to testicular survival. RESULTS: Median DTD time was 135 minutes (range 23-546). Among patients with a viable testis, median DTD time was 107 minutes (range 35-381) compared to 160 minutes (range 23-546) among patients with a nonviable testis (P <.001). Logistic regression models showed that both DTD time (P = .04) and duration of symptoms (P <.001) are independent factors associated with testicular survival. Adjusted odds ratio was 1.0048 for a nonviable testis for every minute of delayed management in the ED (P = .04). Results suggest that every 10 minutes of delay in the ED increases the chance of having a nonviable testis in exploration by 4.8%. CONCLUSION: DTD is an independent factor predicting testicular survival. Institutional efforts should be made to decrease duration of DTD. DTD should be considered as a measure for quality of care.

Will Stone Density Stop Being a Key Factor in Endourology? The Impact of Stone Density on Laser Time Using Lumenis Laser p120w and Standard 20 W Laser: A Comparative Study.

Introduction and Objectives: Ureteroscopy is the gold standard for most urinary tract calculi. Our institute recently incorporated a powerful 120 W holmium laser machine integrating innovative technology (Lumenis® MOSES PulseTM120H Holmium:YAG laser; Lumenis Ltd.). In this retrospective comparative study, we evaluated the influence of stone density on laser dusting time in a high-power 120 W laser machine vs a standard 20 W machine (Dornier Medilas® H20 Holmium:YAG laser; Dornier Ltd.) Methods: We conducted a retrospective review of medical records of patients who underwent ureteroscopy during the years 2013-2018 for a solitary stone. Stone and clinical characteristics, among other parameters, have been evaluated, including the total laser time until complete stone dusting. Results: Among 631 eligible patients, 462 were treated with a 20 W standard laser and 169 patients with a p120w laser machine. Overall laser time was less than half with p120w laser vs d20w (195 seconds vs 397.14 seconds, p-value <0.001). Multivariate regression demonstrated 234.91 seconds shorter laser time with a p120w laser while controlling confounders such as stone volume, hydronephrosis, and location (p value <0.0001). This pattern was demonstrated in all stone densities. The association between laser dusting time per stone volume and stone density demonstrated relatively constant laser time when using p120w laser, even for hard stones. When the standard 20 W laser was used, laser time was longer in each stone density. Moreover, a stone density of 1164 HU and more demonstrated an upward shift of laser time to stone density curve in standard d20w laser group only. Conclusions: Time to complete stone dusting using p120w laser is extremely shorter, approximately half, comparing with the standard 20 W laser. This pattern is robust and even exponential when evaluating laser time per stone density, especially in hard stones. A new horizon of powerful innovative laser technology will enable to improve endourology practice and patients' care.

Is emergency percutaneous antegrade drainage of the upper urinary tract useful for future percutaneous nephrolithotomy access?

PURPOSE: To compare percutaneous nephrolithotomy (PCNL) operations between patients with a preoperative nephrostomy tube and patients that the renal access was obtained at the time of the surgery. MATERIALS AND METHODS: We retrospectively evaluated PCNL cases. Patients were divided into two groups. Group 1 - a non-nephrostomy tube (percutaneous nephrostomy, PCN) group and Group 2 - patients with a PCN placed before the procedure. All preoperatively placed PCN's were performed in emergency situations by interventional radiologists (IR). Complications were classified according to the Clavien-Dindo classification. We compared stone characteristics, operation time, complications, efficacy and PCN usability at surgery. RESULTS: Five hundred twenty-seven patients who were submitted to PCNL for renal stones were included in the study. In 73 patients (13.9%) the PCNs were placed before the surgery. Patients and stone characteristics, mean operative time (p=0.830), complications (p=0.859) and stone-free rates (93.0%) were similar between the groups. There was a trend toward higher complication rates in Group 1, but the difference was not statistically significant. Only 21 (29.0%) of preoperatively placed PCNs were used during PCNL for establishing a tract. The reasons for not using PCN tract were: pelvic or infundibular insertion (30.0%) and suboptimal anatomic location (70.0%). CONCLUSIONS: Preoperative emergency inserted PCNs by IR usage rates were low during PCNL. Its placement neither affects the incidence of complications nor affects the operation time and outcomes. As such, when emergency renal drainage is indicated, the need for a future definitive PCNL should not influence the decision about the modality of renal drainage.

A study of prostate volumes in patients with spinal cord injury.

AIMS: To evaluate the development of benign prostatic hyperplasia (BPH) in patients with spinal cord injury (SCI) and to deduce the role of the nervous system in this process. METHODS: Prostate volumes (PVs) of 65 men older than 30 years of age who sustained SCI were determined from CT scans. Correlations of PVs with SCI level, age, age during SCI and duration of paralysis were calculated. RESULTS: Average patient's age during SCI was 37.7 (±19) years and during measurement of PV 54.8 (±15.3) years. PVs of patients with SCI were similar to expected age-adjusted volumes (29.7 ± 24 mL vs 29.9 ± 5.7 mL, P = 0.95). We dichotomized the cohort into two groups: High SCI (T5 and above) and low SCI (T6 and below) with almost identical: number of patients, age of SCI and duration of paralysis. Patients with lower injuries, had significantly smaller PVs when compared both to patients with higher injuries (19.4 ± 6.3 and 39.8 ± 30, P = 0.0006) and to age-adjusted normal PVs (19.4 ± 6.3 and 29.2 ± 5.8, P = 0.0005). Correlation of PV with age was found in patients higher injuries (R2 = 0.26, p = 0.003) but not in patients with lower (R2 = 0.08, P = 0.11). Moreover, patients with lower SCI had significantly smaller prostate even compared to expected PVs during SCI (18.7 ± 4.6 cc vs 27.8 ± 6.9 cc, P = 0.00006). CONCLUSIONS: Low SCI stops and reverses age related increase in PV. This phenomenon does not occur in high SCIs. This suggests that continuous support of the nervous system is essential for sustaining BPH and raises the possibility of finding a non-hormonal pharmacological intervention for reversing BPH.

[ACTIVE SURVEILLANCE IN RECURRENT LOW-RISK BLADDER TUMORS].

OBJECTIVES: To report our experience with the active surveillance policy in patients with recurrent low-risk bladder tumors. METHODS: The files of 52 patients who underwent active surveillance instead of immediate surgical resection were reviewed. Different variables concerning tumor growth rate were evaluated. RESULTS: A total of 75 surveillance periods were documented in 52 patients (mean age 75.6 years S.D. 10.45 years, 37 males and 14 females), Mean surveillance period length was 16.5 months (S.D. 16.1). All tumors resected after surveillance were found in stage Ta and in low-grade except one tumor which was high-grade; 70 active surveillance periods ended with tumor resection, and 5 patients were still under surveillance when the research ended; 27 surveillance periods (37.7%) ended because of the growth of additional tumors. Active surveillance therefore spared 27 surgeries. The rate of tumor growth during surveillance depended on the tumor's largest diameter at the beginning of surveillance. If initial tumor diameter was smaller than 5 mm (68 cases), the median tumor growth rate was 1.12 mm3/month (IRQ: 0-6.55). If the initial tumor diameter was ≥5 mm (7 cases), the median tumor growth rate was 137.14 mm3/month (IRQ: 2.21-1787.5, p < 0.05). CONCLUSIONS: Small, recurrent papillary bladder tumors pose minimal risk to the patient. An active surveillance policy, without immediate resection of the tumor is safe, can spare surgeries and can be considered in patients presenting with small papillary recurrence.

Abbreviated CT protocol for postoperative surveillance of renal cancer.

INTRODUCTION: Postoperative surveillance protocols after nephrectomy for kidney cancer include periodic computed tomography (CT) scans of the chest and abdomen. A single study exposes the patient to 21 mSv (equivalent to 7-year exposure to natural background radiation). The objective of this study was to evaluate the hypothesis that an abbreviated CT protocol restricted to the chest and upper abdomen (i.e., to the level of the intervertebral disk L3-L4) is sufficient for routine postnephrectomy follow-up as it detects most tumor recurrence with lower radiation exposure. METHODS: We identified 493 patients treated with radical or partial nephrectomy for localized kidney cancer and followed with periodic CT scans of the chest and abdomen for prolonged periods. The frequency and location of cancer recurrence were documented. The ratio of infield recurrence for the complete chest, and abdomen and for the abbreviated protocol was recorded. The decrease in radiation exposure was calculated. RESULTS: At a median follow up of 96 months, 82 patients (16.6%) developed recurrence. The frequent sites of recurrence were the lungs (53), the bones (9), and local recurrence (22). Complete chest and abdominal CT identified 78 of the recurrences (95%) and the abbreviated protocol identifying all but one of these (94%). The abbreviated protocol exposed the patient to 48% (standard deviation 4.3%) less radiation compared to the full protocol. CONCLUSIONS: Using an abbreviated CT protocol that includes the chest and upper abdomen for surveillance after surgery of localized kidney cancer decreases radiation exposure by half with only a minor decrease in the sensitivity of the examination.

"Stoneless" or Negative Ureteroscopy: A Reality in the Endourologic Routine or Avoidable Source of Frustration? Estimating the Risk Factors for a Negative Ureteroscopy.

INTRODUCTION: A "Negative" ureteroscopy (URS) is defined as a URS in which no stone is found during the procedure. It may occur when the stone has already been passed spontaneously or when it is located outside the collecting system. The aim of the study was to outline risk factors for Negative-URS. MATERIALS AND METHODS: We retrospectively analyzed the possible risk factors for Negative-URS from a database of 341 URS cases. In every case where presumptive ureteral stone was not found, a formal nephroscopy as well as a whole collecting system revision was completed. The Negative-URS group was compared with the non-Negative-URS group, in terms of patient and stone characteristics. RESULTS: The database of 341 URS cases included 448 different stone instances, of which 17 (3.8%) were negative and 431 (96.2%) were therapeutic. There was no statistical significant difference between the two groups concerning age, body mass index, stone location in the ureter, stone laterality, and whether the patient was prestented. The stepwise multiple logistic regression revealed three important risk factors, namely CT stone surface area (p < 0.0001), radiopacity of the stone at kidney, ureter, and bladder radiograph (KUB; p = 0.0004), and gender (p = 0.0011) with an area under the curve of 0.91. Women were found to have more possibilities to have a negative procedure by four- to sevenfold than men depending on the model. A nonradio-opaque stone at KUB is more likely to be correlated with a Negative-URS by 9.5- to 11-fold more than a radiopaque stone at KUB. For each increase of 1 U in CT stone surface area, there is an increase of 10%-12% to be non-negative. CONCLUSIONS: Female gender, a nonradio-opaque stone at KUB, and a smaller stone surface were statistically significantly different in the Negative-URS population.

High frequency of bladder cancer after nephroureterectomy: justification for adjuvant intravesical treatment?

BACKGROUND: Bladder recurrence after nephroureterectomy (NU) is common. However, there is no acceptable policy of adjuvant intravesical treatment after NU. OBJECTIVE: To assess the rate of bladder recurrence following NU and to identify the high-risk subgroups that may become candidates for adjuvant intravesical therapy after NU. PATIENTS AND METHODS: Ninety-one patients (mean age 66.4 years) underwent NU. High-grade (HG) tumors were found in 63 patients and low-grade (LG) tumors in 28. Median follow-up was 72 months. The risk of bladder recurrence was assessed by uni- and multivariate analyses of patient and tumor characteristics. RESULTS: Bladder recurrence developed in 38 patients (41.8%) after a median period of 11 months. Among these, 25 patients with HG upper tract urothelial carcinoma (39.7%) and 13 patients with LG upper tract urothelial carcinoma (46.4%) developed recurrence. HG bladder recurrence developed in 24 patients (63.2%) and LG recurrence developed in 14 patients (36.8%). Stages pTa, pT1, pT2, or higher bladder recurrence developed in 26 (68.4%), 7 (18.4%), and 4 patients (10.5%), respectively, and pure pTis developed in 1 patient. On uni- and multivariate analyses, the risk of bladder recurrence was independent of any clinicopathologic characteristics. CONCLUSION: High rate and short time interval of bladder recurrence after NU were found, with no specific subgroup of patients with increased risk. These findings support prescribing adjuvant intravesical therapy to all patients after NU.