Stefano Casellato

Upper Urinary Tract Recurrence Following Radical Cystectomy for Bladder Cancer: A Meta-Analysis on 13,185 Patients

PURPOSE Patients who undergo radical cystectomy for urothelial cancer are at risk for upper urinary tract disease in the remnant transitional tissue. Previous studies have identified several risk factors for upper urinary tract recurrence but the predictive value of each factor remains controversial. Furthermore, the schedule for surveillance of the upper urinary tract with imaging techniques and cytology has not been established. International guidelines do not address these topics and refer only to isolated works with a large case based analysis. We performed this meta-analysis to evaluate the effective incidence of upper urinary tract recurrence after cystectomy for bladder cancer, to analyze the risk factors so we can create subgroups of patients at high risk for recurrence and to investigate the real role of screening in the detection of upper tract lesions at an early stage. MATERIALS AND METHODS A bibliographic search covering the period from January 1970 to July 2010 was conducted using PubMed®, MEDLINE and EMBASE®. This analysis is based on the 27 studies that fulfilled the predefined inclusion criteria. Data were analyzed using a fixed effect logistic regression approach and classic meta-analysis. RESULTS A total of 13,185 participants were included in the analysis. Followup was described in 22 studies and ranged from 0.36 to 349.2 months. The overall prevalence of upper tract transitional cell cancer after cystectomy ranged from 0.75% to 6.4%. Recurrence appeared at a range of 2.4 to 164 months, and in an advanced (64.6%) or metastatic state (35.6%) as reflected in poor survival rates. Patients with low grade vs high grade lesions at cystectomy showed as strong a significant difference in incidence as those with carcinoma in situ and superficial cancer vs invasive cancers and as strong as in those without lymph node involvement, with multifocal disease, with a history of multiple urothelial recurrences, with positive ureteral margins, with positive urethral margins, with urethral involvement and a history of upper urinary tract urothelial cancer. Data do not support a statistically significant difference in recurrence among patients with a history of carcinoma in situ, solitary lesion and among various types of urinary diversion adopted. In 24 studies the followup schedule included periodic radiological assessment of the upper urinary tract and in 20 it included urinary cytology. In 14 studies in 63 of 166 patients (38%) upper urinary tract recurrence was diagnosed by followup investigation whereas in the remaining 62% diagnosis was based on symptoms. When urine cytology was used in surveillance the rate of primary detection was 7% and with upper urinary tract imaging it was 29.6%. Of 5,537 patients who underwent routine cytological examination, recurrence was diagnosed in 1.8/1,000 and of those who underwent upper urinary tract imaging recurrence was diagnosed in 7.6/1,000. CONCLUSIONS The recurrence values could appear low when considering the pan-urothelial field defect theory, but these values reflect, in part, the mortality associated with the initial bladder cancer. Based on anamnesis and pathological examination of cystectomy specimens, a group of patients is at high risk. Extensive regular followup with cytology, urography and loopgraphy yields insufficient benefits. Periodic computerized tomography with urography combines the ability to study the upper urinary tract oncologically and functionally, and the identification of any parenchymal, osseous or lymph node secondary lesion.

Human urine biomarkers of renal cell carcinoma evaluated by ClinProt

Renal cell carcinoma (RCC) is one of the major causes of cancer death and is radio‐ and chemoresistant. Urine of 29 healthy subjects and 39 clear cell RCC patients were analyzed using the ClinProt technique to search for possible biomarkers for early RCC diagnosis. A cluster of three signals (marker A= at m/z 1827 ± 8 Da, marker B = 1914 ± 8 Da and marker C = 1968 ± 8 Da) was able to discriminate patients from controls. A receiver operating characteristic curve analysis showed values of area under the curve (AUC) higher than 0.9 for marker A and B, corresponding to a sensitivity of 85–90% and a specificity of 90%, while marker C gave a lower AUC (0.84) corresponding to sensitivity of 70% and specificity of 100%. The combination of three markers lead to an improvement in diagnostic efficacy, with specificity and sensitivity of 100% and 95%, respectively, in the training test and of 100% and of 85% in the test experiment. The efficacy of this cluster of signals to distinguish RCC patients grouped by tumor stage showed a sensibility of 100% for patients at the primary tumor 1 stage. One of the signals present in the cluster was identified as a fragment of Tamm‐Horsfall protein.

Management of ureteral calculi and medical expulsive therapy in emergency departments

Introduction: Ureteral stones are a common problem in daily emergency department practice. Patients may be offered medical expulsive therapy (MET1) to facilitate stone expulsion and this should be offered as a treatment for patients with distal ureteral calculi, who are amenable to waiting management. Emergency department clinicians and family practitioners are often in the front line regarding the diagnosis and treatment of symptomatic nephrolithiasis and this commentary is dedicated to them because their decisions directly influence the outcome of the acute stone episode and appropriate referral patterns. Materials and Methods: The aim of this systematic review and meta-analysis was to understand the role of MET in the treatment of obstructing ureteral calculi. A bibliographic search covering the period from January 1980 to March 2010 was conducted in PubMed, MEDLINE and EMBASE. The searches were restricted to publications in English. This analysis is based on the 21 studies that fulfilled the predefined inclusion criteria. Results: A metaregression analysis of expulsion time showed a statistically significant advantage in the experimental group, in which the mean expulsion time was 6.2 days compared to 10.3 days in controls. The treatment effect on expulsion rate (P = 0.53) was partially lost as the size of the stones decreased because of the high spontaneous expulsion rate of small stones and the expulsion time was not influenced by pharmacological treatment (P = 0.76) if the stone size was smaller than 5 mm. Analysis of the tamsulosin database. A total of 1283 participants were included in the 17 studies. These studies showed that compared to standard therapy or placebo, tamsulosin had significant benefits, being associated with both a higher stone expulsion rate (P < 0.001) and reduction of the expulsion time (P = 0.02). Reductions in the need for analgesic therapy, hospitalization and surgery are also shown. Analysis of the nifedipine database. The number of participants in each trial ranged from 25 to 70. Compared to standard therapy, the use of nifedipine significantly improved the spontaneous stone expulsion rate (P < 0.001). The mean expulsion time was slightly, but not statistically significantly, different (P = 0.19) between the treatment and control groups. A possible benefit of nifedipine, in terms of significantly reducing the doses of analgesics required, was reported in three studies. There was no difference between the tamsulosin- and nifedipine-treated groups with regard to expulsion time (P = 0.17) or expulsion rate (P = 0.79). Conclusions: Despite all its advantages, MET is rarely used, representing a failure of the translation of medical science into practice. These data raise concerns not only about the quality of care of patients who could benefit from resolution of stones without anaesthetic and surgical risks but also with regard to potential cost savings. MET should be offered as a treatment for patients with distal ureteral calculi who are amenable to a waiting management.

Extended-spectrum beta-lactamase-positive Escherichia coli causing complicated upper urinary tract infection: Urologist should act in time

Objective: Recently, many articles reported increased incidence of urinary tract infection (UTI) due to Extended-Spectrum Beta-Lactamase (ESBL)-producing E. coli. No data are available to date regarding patients presenting with complicated upper ESBL-positive E. coli UTI and sepsis. We report the clinical presentation, management, and outcomes in seven cases. Materials and Methods: This prospective study was carried out between January 2008 and September 2011. Follow-ups varied in patients according to their disease presentation and clinical outcomes. All strains were cultured and identified by the Clinical Microbiology Laboratory and were recovered from blood and urine cultures. In-vitro presence of ESBL was confirmed with Clinical and Laboratory Standard Institute double disc method. Results: In the study period, 49 patients needed hospitalization for upper UTI. Overall, in 25 patients (51%), cultures were negative. In the remaining, seven patients (14.3%) presented positive blood and urine-culture for ESBL + E. coli. Of these, four were female and three were male. Their median age was 73 years (range 66-84). The median hospital stay of these patients was 23 days (range 13 to 45 days). Conclusions: The current situation of multiple bacterial antibiotic resistance has become a worrisome issue in UTI. Multi-drug-resistant E. coli can be readily encountered in hospital settings during daily clinical practice, and urologist should act timely. The management of such infections is extremely important for the future, with particular reference to prevention of new antibiotic resistance patterns.

Inverted papilloma of the bladder: A review and an analysis of the recent literature of 365 patients

OBJECTIVES Until the 1970s, inverted urothelial papilloma (IUP) of the bladder was generally regarded as a benign neoplasm. However, in the 1980s, several reported cases suggested the malignant potential of these papillomas, including cases with features indicative of malignancy, recurrent cases, and cases of IUP synchronous or metachronous with transitional cell carcinoma. The aim of this systematic review and analysis of the literature since 1990 to date is to contribute to unresolved issues regarding the biological behavior and prognosis of these neoplasms to establish some key points in the clinical and surgical management of IUP. MATERIALS AND METHODS Database searches yielded 109 references. Exclusion of irrelevant references left 10 references describing studies that fulfilled the predefined inclusion criteria. RESULTS One problem regarding these neoplasms is the difficulty of obtaining a correct histopathologic diagnosis. The main differential diagnosis is endophytic urothelial neoplasia, including papillary urothelial neoplasia of low malignant potential or urothelial carcinoma of low or high grade, while other considerably rare differential diagnoses include nephrogenic adenoma, paraganglioma, carcinoid tumor, cystitis cystica, cystitis glandularis, and Brunns cell nests. The size of the lesions ranged from 1 to 50 mm (mean 12.8 mm). Most cases occurred in the fifth and sixth decade of life. The mean age of affected patients was 59.3 years (range 20-88 years). Analysis of the literature revealed a strong male predominance with a male/female ratio of 5.8:1. The most commonly reported sites of IUP were the bladder neck region and trigone. Of 285 cases included in 8 studies, 12 cases (4.2%) were multiple. Out of the total of 348 patients, 6 patients (1.72%) had a previous history of transitional cell carcinoma of the urinary bladder, 5 patients (1.43%) had synchronous transitional cell carcinoma of the urinary bladder, and 4 patients (1.15%) had subsequent transitional cell carcinoma of the urinary tract. The time before recurrence was <45 months (range 5-45 months, mean 27.7 months) after surgery. CONCLUSIONS Inverted papilloma could be considered a risk factor for transitional cell carcinoma, and it is clinically prudent to exclude transitional cell cancer when it is diagnosed. Follow-up is needed if the histologic diagnosis is definitive or doubtful. We recommend 4-monthly flexible cystoscopy for the first year and then every 6 months for the subsequent 3 years. Routine surveillance of the upper urinary tract in cases of inverted papilloma of the lower part of the urinary tract is not deemed necessary.

Sexual outcome of patients undergoing thulium laser enucleation of the prostate for benign prostatic hyperplasia

Treatment of patients with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) may affect the quality of sexual function and ejaculation. The effect of new surgical procedures, which are currently available to treat BPH, on erection and ejaculation, has been poorly studied. This study aimed to assess the effect of thulium laser enucleation of the prostate (ThuLEP) on sexual function and retrograde ejaculation in patients with LUTS secondary to BPH. We performed a prospective study in 110 consecutive patients who had undergone ThuLEP to analyze changes in sexual function and urinary symptoms. To evaluate changes in erection and ejaculation, and the effect of urinary symptoms on the quality of life (QoL), five validated questionnaires were used: the ICIQ-MLUTSsex, MSHQ-EjD, International Index of Erectile Function 5, International Prognostic Scoring System (IPSS) questionnaire, and QoL index of the intraclass correlation coefficients. Patients also underwent IPSS and flowmetry to assess the outcome of flow. Patients were evaluated before surgery and 3-6 months after ThuLEP, whereas those with previous abdominal surgery were excluded. The patients′ mean age was 67.83 years. Postoperative urinary symptoms improved after surgery. No significant differences in erectile function before and after surgery were observed. As compared with other techniques described in the literature, the percentage of patients with conserved ejaculation increased by 52.7% after ThuLEP. ThuLEP positively affects urinary symptoms and their effect on the QoL of patients as assessed by questionnaire scores. While endoscopic management of BPH (e.g. transurethral resection of the prostate) causes retrograde ejaculation in most patients, those who undergo ThuLEP have conserved ejaculation and erectile function.

A Proposed New Technique in Prostate Cancer Tissue Bio-Banking: Our Experience with a New Protocol

The aim of our study, beyond validating a method of collecting and storing biological samples from patients with prostate cancer, was to validate an innovative biopsy method for the creation of a biobank of prostatic frozen tissues. Patients referred to our hospital between November 2008 and March 2010 to undergo radical prostatectomy were invited to participate in the study. Each patient’s data were stored in two databases (personal information and clinical database) while samples of urine, blood and its derivatives, fresh material and formalin-processed tissue were stored in a correlated biobank. The proposed method for collecting fresh material was to take samples of the neoplastic tissue by carrying out targeted biopsies in the area indicated by the biopsy mapping as the site of the malignancy, under manual palpation to identify the neoplastic nodule. The site of sampling was marked by an injection of India ink. 55 patients agreed to participate in the study. In 43 cases biopsies were correct, with a mean of 48% of core involved by tumour (range, 10–90%). Overall the tumour detection rate was 78.2%. The protocol for collecting biological material and the new method for collecting fresh tissue reduce internal steps and staff involved, thereby reducing all those variables that cause heterogeneity of material and changes in its quality. This process provides high quality, low cost material for research on prostate cancer. The features of the collection protocol mean that the protocol can also be used in non-academic centres with only limited research funds.

One day surgery in the treatment of benign prostatic enlargement with thulium laser: A single institution experience

Purpose Various articles have previously addressed the introduction of new surgical laser therapies for an enlarged prostate gland causing obstructive symptoms. The objective of this study was to report the feasibility of performing the thulium laser vapo-enucleation of the prostate (ThuVEP) procedure for benign prostatic obstruction in a 1-day surgery. Materials and Methods From September 2011 to September 2013, we conducted a prospective study on patients who underwent ThuVEP in a 1-day surgery. The primary outcomes measured perioperatively included operative time, resected tissue weight, hemoglobin decrease, transfusion rate, postoperative irrigation and catheterization time, and postoperative hospital stay. Also, the preoperative and postoperative International Prostate Symptom Score (IPSS) and results of uroflowmetry performed on the 7th and 30th postoperative days were recorded. All perioperative and postoperative complications were monitored. Results A total of 53 patients underwent the surgical treatment in a 1-day surgery. Seven patients continued antiaggregant therapy with aspirin. Mean preoperative prostatic adenoma volume was 56.6 mL. Mean operative time was 71 minutes. The average catheter time was 14.8 hours. The peak urinary flow rate on day 7 improved from 9.3 to 17.42 mL/s (p<0.001) and the IPSS improved from 18 to 10.2 (p<0.01). Patients were routinely discharged on the day of catheter removal. No complications were recorded. Conclusions ThuVEP can be safely conducted as a 1-day surgical procedure. This strategy results in cost savings. ThuVEP shows good standardized outcomes with respect to improvement in flow parameters and length of bladder catheterization.

Sclerotherapy of the Pampiniform Plexus with Modified Marmar Technique in Children and Adolescents

Aims: Treatment of varicocele in children is a debated problem for which no validated guidelines exist. Several techniques have been proposed to solve this problem. The aim of this study was to evaluate the effectiveness and applicability of a modified Marmar technique in the treatment of varicocele in children and adolescents. Methods:From April 2004 to September 2005, we evaluated 25 patients between the ages of 9 and 18 (mean 14.4) years, who suffered from left-sided varicocele with concomitant testicular hypotrophy. The diagnosis was ascertained clinically and with scrotal color Doppler ultrasound using the Dubin and Amelar classification. In 2 cases phimosis was also present. The operation was performed according to a modified Marmar technique, using embolization of the pampiniform plexus with 2 ml of 3% polidocanol. Patients underwent clinical evaluation and scrotal color Doppler ultrasound at 1 week and 3 and 6 months. Results: The mean duration of the operation was 42 min. At 1 week after surgery no persistence of varicocele was found. In 1 patient, edema of the spermatic cord occurred for about 2 months with spontaneous regression, in 1 patient homolateral hydrocele was observed. At 6 months no other complications were reported. No case of testicular atrophy was observed. Conclusions: The technique described has already been validated in the adult population, and although we present only a small number of cases, the operation proved easy to perform, safe, of low cost and can be considered a valid alternative to the microsurgical technique in children and adolescents.

Predicting female ureteral length: a mathematical model:

Aim: Ureteral double J stent placement is a common urological procedure. A stent placement is performed for multiple conditions but some of them are contraindicated, mainly in pregnant female patients, because of X-rays. This work aims to suggest a mathematical model to predict female ureteral length by finding a link among different physical data. Materials and methods: Between June 2007 and July 2009, 100 female patients who had undergone ureteral stent placement were enrolled in the present study with the exception of those with septic conditions, history or evidence of TCC, congenital and acquired kidney or ureteral malformations, and previous ureteral surgery. The physical data of each patient were collected (mean age 55.8 years, range 18–89 SD 15.27, mean height 173 cm, range 160–182 SD 6.31, mean weight 75.33 kg, range 62–94 SD 8.81). A previous ureteral retrograde pyelography was performed during the procedure to individualise the pyeloureteral junction. Ureteral length was estimated through a graduated ureteral catheter with a final result between 24 and 27 cm. The length was read in cystoscopy examining the ureteral orifice while the catheter tip reached the pyeloureteral junction. The collected data were then analysed. Results: A link between the female patients’ ureteral length and height was observed. The following mathematical model can predict female ureteral length starting from the patient’s height: Result: y = 0.151712487 (height expressed in cm) ± 0.12; correlation coefficient: r = 0,973, residual sum of squares: rss = 5.285. No link was found between ureteral length and patients’ age and weight. Conclusions: A good estimation of the length of the ureter to be cannulated enables us to choose in advance the proper one to use. Female patient height correlates with ureteral length. A cost reduction can also be obtained, avoiding an intra-operative X-ray control. An X-ray-free ureteral stenting procedure can be described simply through an ultrasound control mainly in pregnant women. Further studies are needed to obtain a similar mathematical model for male patients.