Stefano Picozzi

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.

Long-Term Follow-Up Using Testicle-Sparing Surgery for Leydig Cell Tumor

BACKGROUND Our objective was to perform a long-term evaluation of conservative surgical treatment of Leydig cell tumors. PATIENTS AND METHODS A multicenter retrospective clinical study was performed at 6 European centers. Case files of all patients diagnosed with Leydig cell tumor and treated with conservative surgery were examined. Patients underwent physical examination, hormone and tumor marker assays, scrotal and abdominal ultrasonography, chest radiography, and endocrinologic examination. RESULTS From 1987 to 2006, 22 patients with Leydig cell tumor underwent conservative surgery. Mean patient age was 35 years (range, 5-61 years). Mean follow-up was 180 months (range, 77-290 months). No local recurrence or metastasis was observed. Patients presented with a palpable testicular nodule (3 patients [13.7%]), a nodule diagnosed by ultrasonography (15 patients [68.2%]), gynecomastia (2 patients [9.1%]), precocious pseudopuberty (1 patient [4.5%]), or scrotal pain (1 patient [4.5%]). Diagnosis after frozen section examination was Leydig cell tumor in 20 of 22 patients (91%). Mean histologic size of the nodule was 1.11 cm. Follow-up was conducted for all patients every 3 to 6 months, with physical examination, tumor marker assays, scrotal and abdominal ultrasonography, chest radiography, and computed tomography (CT). No local recurrences or metastases were observed. One hundred percent of patients are still alive with a 100% disease-free survival. CONCLUSIONS When diagnosed and treated early, long-term favorable outcomes are seen at follow-up in Leydig cell tumors, even with its potential metastatic behavior. In these patients, testicle-sparing surgery proved to be a feasible and safe choice and could be regarded as the first line of therapy.

Serum biomarkers of Renal Cell Carcinoma assessed using a protein profiling approach based on ClinProt technique

OBJECTIVES To investigate the possibility of using the ClinProt technique to find serum cancer related diagnostic markers that are able to better discriminate healthy subjects from patients affected by renal cell carcinoma (ccRCC). Renal cell carcinoma is the most common malignancy of the kidney. Biomarkers for early detection, prognosis, follow-up, and differential diagnosis of ccRCC from benign renal lesions are needed in daily clinical practice when imaging is not helpful. METHODS Serum of 29 healthy subjects and 33 ccRCC patients was analyzed by the ClinProt/MALDI-ToF technique. RESULTS A cluster of 3 peptides (A = m/z 1083 +/- 8 Da, B = m/z 1445 +/- 8 Da and C = m/z 6879 +/- 8 Da) was able to discriminate patients from control subjects. Cross-validation analysis using the whole casistic showed 88% and 96% of sensitivity and specificity, respectively. Moreover, the cluster showed 100% sensitivity for the identification of patients at pT2 (n = 5) and pT3 (n = 8) and 85% for pT1 patients (n = 20). The intensity of peaks A and C continuously decreased from pT1 to pT3, whereas peak B increased in pT1 and pT2. CONCLUSIONS These results may be useful to set up new diagnostic or prognostic tools.

Transrectal ultrasound-guided prostate biopsies in patients taking aspirin for cardiovascular disease: A meta-analysis

INTRODUCTION The management of anti-platelet therapy in the peri-operative period is a source of great concern. The dilemma is between whether to stop these agents peri-operatively in order to reduce the risk of bleeding complications, or to continue them in order not to compromise the protection they afford against the risk of cardiovascular events. MATERIALS AND METHODS The aim of this systematic review and meta-analysis was to understand whether continued aspirin therapy is a risk factor for bleeding complications after ultrasound-guided biopsy of the prostate. A bibliographic search covering the period from January 1990 to May 2011 was conducted in PubMed, MEDLINE and EMBASE. We also included our own series in the analysis. RESULTS A total of 3218 participants were included. Haematuria was statistically more frequent (P=0.001) among patients taking aspirin than in the control group with an odds ratio estimate of 1.36 [1.13;1.64]. This increased risk was, however, due to minor bleeding. The occurrence of rectal bleeding and haematospermia was not statistically increased (P=0.33 and P=0.24, respectively) in patients taking aspirin compared to in the control group with odds ratios estimate of 1.24 [0.80;1.93] and 1.52 [0.75;3.08], respectively. DISCUSSION There is limited information of the relationship between continued use of aspirin and haemorrhagic complications after transrectal ultrasound-guided biopsy of the prostate. This is the first comprehensive analysis on this topic. CONCLUSION Continued use of aspirin does not increase the risk of overall bleeding or moderate and severe haematuria after prostatic biopsy, and thus stopping aspirin before such biopsies is unnecessary.

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.

A knotted ureteral stent: A case report and review of the literature

The indications for ureteral stent placement have expanded significantly with the progress of surgical procedures and techniques. Although such stents are now an integral part of contemporary urological practice, their use is not free of complications and consequences. There are very rare descriptions of knot formation in a ureteral stent and the consequences of this occurrence, with only 12 cases previously reported. Here, we report an additional case and review all the literature concerning this urological complication with emphasis on its predisposing factors and conservative and surgical management.

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.