Bruno Spina

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

Sentinel lymph node mapping in early-stage breast cancer: Technical issues and results with vital blue dye mapping and radioguided surgery

Axillary lymph node status is the most important prognostic factor in patients with operable breast cancer. Recent studies have demonstrated the possibility of identifying the sentinel lymph node (sN) as a reliable predictor of axillary lymph node status in both cutaneous melanoma and breast cancer. Sentinel lymph node identification proved feasible by either peritumoral dye injection (Patent Blue‐V) or radiodetection, with identification rates of 65–97% and 92–98%, respectively. However, some important issues need further definition, namely (a) optimization of the technique for intraoperative detection of the sN, (b) predictive value of the sN with regard to axillary lymph node status, and (c) reliability of intraoperative histology of the sN. We reviewed our experience in sN detection in patients with stage I–II breast cancer to assess the feasibility and accuracy of lymphatic mapping, by vital blue dye or radioguided surgery, and sN histology as a predictor of axillary lymph node status.

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.

Analysis of HLA-G expression in breast cancer tissues.

Among the different mechanisms by which cancer can elude the immune system, alterations in the expression of human leukocyte antigen (HLA) class I molecules on tumor cells may play a crucial role by impairing the HLA molecules interaction with T and natural killer (NK) cells specific receptors. More recently, aberrant expression of HLA-G has been described in different tumor tissues in addition to HLA class I downregulation. The HLA-G molecule is a nonclassical HLA class I antigen selectively expressed by trophoblast and thymic epithelial cells. Several studies reported that the HLA-G function might represent an additional mechanism of tumor immune escape, mainly inhibiting NK and cytotoxic T-cell activity. Here we report the analysis of HLA-G expression both at RNA level by reverse transcriptase-polymerase chain reaction and at protein level by Western blot and immunohistochemistry in 25 breast cancer patient tissues. The aim of this study was to elucidate the HLA-G gene expression pattern in breast tumor tissues and correlate it with HLA class I alterations. Our results demonstrated that HLA-G molecules expression was never found even in a group of patients revealing HLA class I total loss, and that HLA-G is not expressed in breast cancer tissue with a low-tumor grade (G1-G2) and minimal stromal contamination.

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.

Evaluation of Cathepsin D as Prognostic Predictor in Breast Cancer

Cathepsin D is an acidic lysosomal protease expressed in all cells. Some studies have shown correlations between high levels of tissue cathepsin D and poor prognosis. This paper deals with 158 cases of breast cancer in which tissue concentrations in cathepsin D, age, estrogen and progesterone receptor content, and pathological characteristics of the tumor were investigated. Tumors were considered to be cathepsin D+ when a concentration > 40 pmol/mg protein (median value in our samples) was determined. The expression of cathepsin D appears to be related to grading (p = 0.04) and lymph node status (p = 0.05). We found no significant associations among cathepsin D levels, patient age, steroid receptors and histological type. Moreover, the levels of cathepsin D have been evaluated in 9 samples of recurring or metastatic neoplasia and 11 cases of benign breast lesions. We conclude that cathepsin D may be a useful prognostic predictor in breast cancer. Further investigations are required to improve and extend the applications of this assay.

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.