Carlo Introini

A Randomized Prospective Trial to Assess the Impact of Transurethral Resection in Narrow Band Imaging Modality on Non–Muscle-Invasive Bladder Cancer Recurrence

BACKGROUND Narrow band imaging (NBI) is an optical enhancement technology that filters white light into two bandwidths of illumination centered on 415nm (blue) and 540nm (green). NBI cystoscopy can increase bladder cancer (BCa) visualization and detection at the time of transurethral resection (TUR). NBI may therefore reduce subsequent relapse following TUR. OBJECTIVE Assess the impact of NBI modality on 1-yr non-muscle-invasive BCa (NMIBC) recurrence risk. DESIGN, SETTING, AND PARTICIPANTS Consecutive patients with overt or suspected BCa were included in a prospective study powered to test a 10% difference in 1-yr recurrence risk in favor of cases submitted to NBI TUR. Excluding patients with muscle-invasive BCa, negative pathologic examination, or without follow-up, the study population was composed of 148 subjects randomized from August 2009 to September 2010 to NBI TUR (76 cases) or white light (WL) TUR (72 cases). INTERVENTION TUR was performed in NBI or standard WL modality. MEASUREMENTS The 1-yr recurrence risks in NBI or WL TUR groups were compared using odds ratio (OR) point and interval estimates derived from logistic regression modeling. RESULTS AND LIMITATIONS The 1-yr recurrence-risk was 25 of 76 patients (32.9%) in the NBI and 37 of 72 patients (51.4%) in the WL group (OR=0.62; p=0.0141). Simple and multiple logistic regression analyses provided similar OR points and interval estimates. CONCLUSIONS TUR performed in the NBI modality reduces the recurrence risk of NMIBC by at least 10% at 1 yr.

Narrow band imaging for detecting residual/ recurrent cancerous tissue during second transurethral resection of newly diagnosed non-muscle-invasive high-grade bladder cancer

Study Type – Diagnostic (case series)
Level of Evidence 4

Predictors of Symptomatic Lymphocele After Lymph Node Excision and Radical Prostatectomy

OBJECTIVES To identify the prognostic factors of symptomatic lymphocele. METHODS From January 2004, 359 patients underwent pelvic lymph node excision during radical prostatectomy at our center, of whom, 347 were followed up for > or = 6 months. RESULTS At a median follow-up of 14.5 months (range 6-54), 44 patients had developed a lymphocele (12.6%). In 26 patients (7.4%), it was symptomatic and required treatment. On univariate analysis, lymphocele was associated with the extension of the lymph node dissection, the number of nodes retrieved, and the presence of nodal metastasis. Patient age, year of surgery, surgeon, anticoagulant or antiplatelet oral therapy before and after the period of low-molecular-weight heparin prophylaxis, American Society of Anesthesiologists score, use of neoadjuvant hormonal therapy, preoperative prostate-specific antigen value, Gleason score, and pathologic stage were not influential. After adjusting for covariates, logistic regression analysis revealed that only the number of nodes was significantly associated with the onset of a symptomatic lymphocele. The risk of lymphocele seemed to increase linearly with the number of nodes retrieved, and the incidence of positive nodes reached a plateau when >10-13 nodes were harvested. CONCLUSIONS The benefit of more extensive nodal excision during radical prostatectomy should be weighed against the increased risk of lymphocele and its sequelae, including reintervention. In our series, no other factor, including previous anticoagulant or antiplatelet therapy, neoadjuvant hormonal therapy, and surgeon experience, influenced the incidence of symptomatic lymphocele.

Differential proteomic analysis of nuclear matrix in muscle-invasive bladder cancer: Potential to improve diagnosis and prognosis ∗

Introduction: Although several molecular markers for bladder cancer have been identified, at present little information on prognostic biomarkers is available in the literature. Prognostication of this tumor is largely based on clinicopathological characteristics. Our aim was to identify nuclear matrix (NM) proteins that might serve to better characterize the phenotype of the invasive bladder cancer and to investigate their diagnostic and prognostic roles. Methods: NM proteins expressed in normal (n=3) or non-tumoral (n=9) tissue specimens and muscle-invasive bladder cancer (n=21) specimens were analyzed by two dimensional (2D) gel electrophoresis. PDQuest image analysis software was used to generate a comparative NM proteome analysis. Selected spots were characterized by liquid chromatography coupled to tandem mass spectrometry and Western blot. Results: We detected over 800 protein spots in each 2D map and 43 spots were identified. 30 proteins were differentially expressed by bladder tumor cells; among these, 19 proteins were detected in bladder tumoral tissues but not in normal and non-tumoral tissues and seven proteins correlated with tumor stage. One protein (p54nrb) was strongly correlated with vascular invasions and appeared to be also significantly (P <0.0001) associated with a decreased probability of survival. Conclusion: Important alterations in NM proteins occur in muscle-invasive bladder cancer. The differentially expressed proteins include biomarkers potentially useful for disease diagnosis, progression and prognosis. Our findings beyond improving the understanding of the biology of bladder cancer, could help to stratify patients into different prognostic subgroups and to select those who might be better candidate to multimodal therapeutic approaches.

Potency preserving cystectomy with intrafascial prostatectomy for high risk superficial bladder cancer.

PURPOSE We report the oncological and functional results of potency sparing cystectomy with intrafascial prostatectomy for high risk, superficial bladder cancer. MATERIALS AND METHODS A total of 37 patients underwent potency sparing cystectomy and orthotopic urinary substitution from 2001 to 2005. Inclusion criteria were age younger than 70 years, Charlson comorbidity index less than 2, high risk superficial bladder cancer, prostate specific antigen less than 4 ng/ml, free-to-total PSA ratio greater than 20% and normal digital rectal examination. RESULTS Median patient age was 58 years (range 52 to 66). Median followup was 35 months (range 24 to 71). One patient died of disease progression and 1 died of an unrelated cause. Of the 37 patients 35 (95%) were free of tumor. Daily continence was achieved in 36 patients (97.2%) and nighttime continence was achieved in 35 (95%). Two patients (5%) needed clean intermittent catheterization. A total of 35 patients (95%) stated that they maintained erectile function, including 28 (76%) without oral drugs. A significant decrease in the median International Index of Erectile Function score from baseline was noted 2 years after surgery (25 vs 21). A total of 32 patients (86%) had an International Index of Erectile Function score of greater than 17 at 2 years after cystectomy. Median scores on the International Continence Society male short form questionnaires did not show any significant difference before and after surgery. Prostate specific antigen was lower than 0.2 ng/ml in all cases. CONCLUSIONS The main criticism about so-called sexuality sparing cystectomy has been the presence of consistent prostatic remnants. Performing intrafascial prostatectomy together with supra-ampullar cystectomy seems to warrant good functional results with while better preserving oncological safety.

En bloc transurethral resection of bladder lesions: a trick to retrieve specimens up to 4.5 cm

The present technique maintains the integrity of voluminous lesions during extraction. Pathological analysis is consequently improved and a proper evaluation of the surgical margins is also possible. Papillary lesions of up to 4.5 cm are amenable to en bloc resection and extraction, while solid lesions comply less well with the urethra and sometimes are very difficult to extract. Nevertheless, the main limitation of the technique remains that lesions originating from the bladder neck are not amenable to en bloc resection,while particular attention should be paid during resection of lesions involving the ureteric orifice to avoid ureteric stripping.

Feasibility of Transurethral Resection of Bladder Lesion Performed Entirely by Means of Narrow-Band Imaging

PURPOSE To assess the feasibility of transurethral resection (TUR) of bladder lesions performed entirely by means of a narrowband imaging (NBI) modality. PATIENTS AND METHODS Data from an ongoing prospective randomized trial (NCT01004211) were extracted. Quality outcomes of standard TUR and NBI TUR were compared. Complications were graded according to the Clavien-Dindo system. RESULTS To date, 33 and 29 subjects were randomized to standard and NBI TUR. No significant differences regarding age, sex, American Society of Anesthesiologists score, rate of multiple lesions, or lesions larger than 3 cm in the two groups were found, whereas rate of TUR for recurrent bladder cancer was greater in the NBI group. All procedures ended with complete clearance of the suspected or overt bladder tumor in the modality assigned. No death or major surgical or medical complications were registered. Overall grade I to II complications rate in the NBI and standard groups was, respectively, 8/29 (27%) and 11/33 (33%) (P = 0.831). Median surgery time was, respectively, 20 and 30 minutes in the NBI and standard group (P = 0.381). Median time to catheter removal was, respectively, 2 and 3 days in the NBI and standard groups (P = 0.288). Median time to discharge was 2 and 3 days (P = 0.173). No patient was readmitted after discharge. Muscle tissue was absent in the specimen of one patient who underwent standard TUR. CONCLUSION NBI TUR appears to be feasible. The results of the ongoing randomized trial will show whether NBI TUR is able to reduce significantly the 1-year recurrence rate of bladder tumors.

Prognostic factors of persistently detectable PSA after radical prostatectomy

Objectives:  To determine predictive factors of detectable prostate‐specific antigen (PSA) in patients submitted to radical prostatectomy (RP) and to define the prognostic role of this event.

Surgery insight: advantages and disadvantages of laparoscopic radical cystectomy to treat invasive bladder cancer.

Laparoscopic radical cystectomy (LRC) is a challenging technique, but it has been proposed as an alternative to open radical cystectomy (ORC), which is currently the gold standard treatment for muscle-invasive or high-risk superficial bladder cancer. So far, approximately 200 cases treated with LRC have been reported in the peer-reviewed literature, but follow-up has generally been short (all <48 months). A shorter hospital stay and a quicker recovery of the patient seem to be the main advantages of LRC over ORC. Functional outcomes, cancer control obtained, and safety of the technique need to be confirmed by studies with larger cohorts of patients and longer follow-up than those previously reported, but an initial analysis suggests that LRC is not equivalent to ORC. Given that the majority of patients selected for LRC had lower American Society of Anesthesiologists scores and lower pathological stages than those in ORC studies, the proportion of patients with orthotopic neobladders (47%) and the proportion of disease-free patients (80%) seem to be suboptimal and, actually, those might represent the major disadvantages of LRC.

Prostate cancer: Prognostic significance of the association of heterogeneous nuclear ribonucleoprotein K and androgen receptor expression

The management of prostate cancer (PCa) remains challenging because to date, there has been no way to distinguish between indolent and aggressive tumors. Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is implicated in the network of mechanisms that control androgen receptor (AR) expression. We studied the expression of the two proteins in PCa to evaluate their prognostic potential and elucidate the hnRNP K function in PCa progression. HnRNP K and AR expression were analyzed immunohistochemically in 105 patients who had undergone radical prostatectomy. The association between the expression of hnRNP K and/or AR and PSA progression or death was evaluated by univariate and multivariate analyses. The expression of hnRNP K was also investigated in vitro using the BPH-1 cell line and two different LNCaP populations that recapitulate the progression of PCa towards a more aggressive disease. AR and hnRNP K were differentially expressed between cancer and normal prostate tissues. A strong association with a good prognosis was evident in PCa exhibiting high percentage of AR-positive cells (>75%) (p≤0.005) and more interestingly, the combination of high AR and low cytoplasmic hnRNP K expression emerged as the most significant independent prognostic marker for PSA failure-free survival, in a multivariate analysis (p≤0.001). In vitro, a higher expression of hnRNP K and pERK was associated with higher PSA levels, suggesting a relationship between hnRNP K phosphorylation and AR-regulated genes. These results indicate that the interaction between the AR and hnRNP K has an important role in the progression of PCa. Changes of the expression of the two proteins are strongly associated with the clinical outcome and may be a potential prognostic marker.