Giancarlo Albo

Alterations of the serum peptidome in renal cell carcinoma discriminating benign and malignant kidney tumors

Renal cell carcinoma (RCC) is typically asymptomatic and surgery usually increases patients life only for early stage tumors. However, some cystic and solid renal lesions cannot be confidently differentiated from clear-cell-RCC. Therefore possible markers for early detection and to distinguish malignant kidney tumors are needed. To this aim, we applied MALDI-TOF and LC-MS/MS analysis to RPC18 MB purified serum of ccRCC, non-ccRCC patients and controls. A cluster of five signals differentiate malignant tumors from benign renal masses and healthy subjects. Moreover, a combination of six ions showed the highest specificity and sensitivity to distinguish ccRCC from controls. Healthy subjects were also differentiated from non-ccRCC by three features. Peptide ratios obtained by MALDI-TOF were compared with those from label-free LC-ESI and no statistical difference was found (p>0.05). ESI-results were linked with MALDI profiles by both TOF/TOF sequencing and MALDI FT-ICR accurate mass measurements. About 200 unique endogenous peptides, originating from 32 proteins, were identified. Among them, SDPR and ZYX were found down-expressed, while SRGN and TMSL3 were up-expressed. In conclusion, our results suggest the possibility to discriminate malignant kidney tumors based on a cluster of serum peptides. Moreover, label-free approach may represent a valid method to verify results obtained by MALDI-TOF. This article is part of a Special Issue entitled: Integrated omics.

Bicalutamide failure in prostate cancer treatment: Involvement of Multi Drug Resistance proteins

Prolonged bicalutamide treatment induced pathology regression although relapses with a more aggressive form of prostate cancer have been observed. This failure could be due to androgen receptor mutation. In the present work we hypothesized an alternative mechanism responsible for bicalutamide failure involving activity of ATP-binding cassette (ABC) pumps such as P-glycoprotein, Breast Cancer Receptor Protein (BCRP), and Multi Resistant Proteins (MRPs) that extrude the androgen antagonist from the cell membrane. As experimental models androgen-dependent (LnCap) and androgen-independent (PC-3) prostate cancer cell lines have been employed. Bicalutamide has been tested in the cell lines mentioned above in the absence and in the presence of MC18, our potent P-glycoprotein/BCRP/MRP1 inhibitor. The results displayed that bicalutamide antiproliferative effect at 72 h was ameliorated in LnCap cells (EC(50) from 51.9+/-6.1 microM to 17.8+/-2.6 microM in the absence and in the presence of MC18, respectively) and restored in PC-3 cells (EC(50) from 150+/-2.4 microM to 60+/-3.5 microM in the absence and in the presence of MC18, respectively). Moreover, we established the contribution of each transporter employing stable transfected cells (MDCK) overexpressing P-glycoprotein or BCRP or MRP1 pump. The results displayed that P-glycoprotein and BCRP were involved in bicalutamide efflux while MRP1 was unable to bind the antiandrogen drug.

A Group of Genome-Based Biomarkers That Add to a Kattan Nomogram for Predicting Progression in Men with High-Risk Prostate Cancer

Purpose: The three main treatment options for primary prostate cancer are surgery, radiation, and active surveillance. Surgical and radiation intervention for prostate cancer can be associated with significant morbidity. Therefore, accurate stratification predictive of outcome for prostate cancer patients is essential for appropriate treatment decisions. Nomograms that use clinical and pathologic variables are often used for risk prediction. Favorable outcomes exist even among men classified by nomograms as being at high risk of recurrence. Experimental Design: Previously, we identified a set of DNA-based biomarkers termed Genomic Evaluators of Metastatic Prostate Cancer (GEMCaP) and have shown that they can predict risk of recurrence with 80% accuracy. Here, we examined the risk prediction ability of GEMCaP in a high-risk cohort and compared it to a Kattan nomogram. Results: We determined that the GEMCaP genotype alone is comparable with the nomogram, and that for a subset of cases with negative lymph nodes improves upon it. Conclusion: Thus, GEMCaP shows promise for predicting unfavorable outcomes for negative lymph node high-risk cases, where the nomogram falls short, and suggests that addition of GEMCaP to nomograms may be warranted. Clin Cancer Res; 16(1); 195–202

Posterior musculofascial reconstruction after radical prostatectomy: an updated systematic review and a meta‐analysis

To evaluate the influence of posterior musculofascial plate reconstruction (PR) on early return of continence after radical prostatectomy (RP); an updated systematic review of the literature. A systematic review of the literature was performed in June 2015, following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement and searching Medline, Embase, Scopus and Web of Science databases. We searched the terms posterior reconstruction prostatectomy, double layer anastomosis prostatectomy across the ‘Title’ and ‘Abstract’ fields of the records, with the following limits: humans, gender (male), and language (English). The authors reviewed the records to identify studies comparing cohorts of patients who underwent RP with or without restoration of the posterior aspect of the rhabdosphincter. A meta‐analysis of the risk ratios estimated using data from the selected studies was performed. In all, 21 studies were identified, including three randomised controlled trials. The overall analysis of comparative studies showed that PR improved early continence recovery at 3–7, 30, and 90 days after catheter removal, while the continence rate at 180 days was statistically but not clinically affected. Statistically significantly lower anastomotic leakage rates were described after PR. There were no significant differences for positive surgical margins rates or for complications such as acute urinary retention and bladder neck stricture. The analysis confirms the benefits at 30 days after catheter removal already discussed in the review published in 2012, but also shows a significant advantage in terms of urinary continence recovery in the first 90 days. A multicentre prospective randomised controlled trial is currently being conducted in several institutions around the world to better assess the effectiveness of PR in facilitating an earlier recovery of postoperative urinary continence.

Recent advances in the surgical treatment of benign prostatic hyperplasia

TURP for many years has been considered the gold standard for surgical treatment of BPH. Symptoms relief, improvement in Maximum flow rate and reduction of post void residual urine have been reported in several experiences. Notwithstanding a satisfactory efficacy, concerns have been reported in terms of safety outcomes:intracapsular perforation, TUR syndrome, bleeding with a higher risk of transfusion particularly in larger prostates have been extensivelyreported in the literature. In the recent years the use of new forms of energy and devices suchas bipolar resector, Ho: YAG and potassium-titanyl-phosphate laserare challenging the role of traditional TURP for BPH surgical treatment. In 1999 TURP represented the 81% of surgical treatment for BPHversus 39% of 2005. Is this a marketing driven change or is there areal advantage in new technologies? We analyzed guidelines and higher evidence studies to evaluate therole of the most relevant new surgical approaches compared to TURPfor the treatment of BPH. In case of prostates of very large size the challenge is ongoing, withminimally invasive laparoscopic approach and most recently roboticapproach. We will evaluate the most recent literature on thisemerging field.

Deregulation of MiR-34b/Sox2 Predicts Prostate Cancer Progression.

Most men diagnosed with prostate cancer will have an indolent and curable disease, whereas approximately 15% of these patients will rapidly progress to a castrate-resistant and metastatic stage with high morbidity and mortality. Therefore, the identification of molecular signature(s) that detect men at risk of progressing disease remains a pressing and still unmet need for these patients. Here, we used an integrated discovery platform combining prostate cancer cell lines, a Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model and clinically-annotated human tissue samples to identify loss of expression of microRNA-34b as consistently associated with prostate cancer relapse. Mechanistically, this was associated with epigenetics silencing of the MIR34B/C locus and increased DNA copy number loss, selectively in androgen-dependent prostate cancer. In turn, loss of miR-34b resulted in downstream deregulation and overexpression of the “stemness” marker, Sox2. These findings identify loss of miR-34b as a robust biomarker for prostate cancer progression in androgen-sensitive tumors, and anticipate a potential role of progenitor/stem cell signaling in this stage of disease.

Massive recurring angiomyxoma of the scrotum in a obese man.

Aggressive angiomyxoma (AAM) is a rare mesenchymal benign myxoid tumor, characterized by locally infiltrative nature and high recurrence rate. AAM occurs almost exclusively in adult females, arising from the soft tissue of the pelvic region: to our knowledge, only 43 cases occurring in men have been reported. We report a case of massive recurrence of scrotal AAM in a 46-year-old obese man, who already underwent surgery for the same disease in 2004 and 2005. The mass had a circumference of 106 cm and weighted 30 kg. It was impossible to appreciate the testes and to find the penis. The patient underwent scrotal resection, bilateral orchidopexia and transposition of the penis, by means of a preputial flap. Residual scrotal skin was modeled in order to create a neoscrotum, where the testes were placed and secured with interrupted sutures. Histologic examination showed diffuse angiomyxoma-like lipomatosis. After three months, the patient presented with local relapse which also involved the external urethral orifice.

Robotic prostatectomy: an update on functional and oncologic outcomes

Since the first procedure performed in 2000, robotic-assisted radical prostatectomy (RARP) has been rapidly gaining increasing acceptance from both urologists and patients. Today, RARP is the dominant treatment option for localised prostate cancer (PCa) in the United States, despite the absence of any prospective randomised trial comparing RARP with other procedures. Robotic systems have been introduced in an attempt to reduce the difficulty involved in performing complex laparoscopic procedures and the related steep learning curve. The recognised advantages of this kind of minimally invasive surgery are three-dimensional (3D) vision, ten-fold magnification, Endowrist technology with seven degrees of freedom, and tremor filtration. In this article, we examine this technique and report its functional (in terms of urinary continence and potency) and oncologic results. We also evaluate the potential advantages of RARP in comparison with open and laparoscopic procedures.

Live surgery: highly educational or harmful?

PurposeLive surgery (LS) is considered a useful teaching opportunity. The benefits must be balanced with patient safety concerns. To evaluate the rate of complications of a series of urologic LS performed by experts during the Congress Challenge in Laparoscopy and Robotics (CILR).MethodsWe present a large, multi-institution, multi-surgeon database that derives from 12 CILR events, from 2004 to 2015 with a total of 224 cases. Radical prostatectomy (RP) was the most common procedure and a selection of complex cases was noted. The primary measure was postoperative complications and use of a Postoperative Morbidity Index (PMI) to allow quantitative weighing of postoperative complications.ResultsFrom 12 events, the number of cases increased from 11 in 2004 to 27 in 2015 and a total of 27 surgeons. Of 224 cases (164 laparoscopic and 60 robotic), there were 26 (11.6%) complications: 5 grade I, 5 grade II, 3 grade IIIa, 12 grade IIIb and 1 grade V, the latter from laparoscopic cystectomy. Analysis of PMI was 23 times higher from cystectomy compared to RP.ConclusionsIn the setting of live surgery, the overall rate of complications is low considering the complexity of surgeries. The PMI is not higher in more complex procedures, whereas RP seems very safe.

Ralp & Rocco Stitch: Original Technique:

Incontinence and impotence are the two chief drawbacks of radical prostatectomy (RP). Incontinence is the most relevant for most of the patients, even if there is high variability in terms of prevalence and definition of continence. Incontinence seems the result of several factors, the most important being the surgical injury of some structures and the biomechanical instability associated with vesicourethral anastomosis. In the posterior urethra, which guarantees the continence mechanism, two functionally independent regions can be recognized: the proximal and the distal. The proximal region can be identified with the bladder neck, while the distal region is the rhabdosphincter urethrae. Concerning the distal functional region, two kinds of strategy can be applied: the preservation of puboprostatic ligaments and urethral attachments, or the reconstruction of the urethral rhabdosphincter, which can be anterior, posterior or total. We describe our technique of choice for posterior reconstruction, first described by Rocco and then modified by Patel et al.L’incontinenza urinaria e l’impotenza sono le due principali complicanze postoperatorie della prostatectomia radicale (RP) (1).L’incontinenza sembra essere il problema che assilla mag -giormente i pazienti, anche se la sua incidenza e inferiore a quella dell’impotenza.A seconda delle varie statistiche, dei metodi usati per il ri-levamento e della definizione che gli autori ne danno, della lunghezza del follow-up e dell’esperienza del chirurgo, l’in -continenza e riportata in percentuali che variano in modo molto considerevole.Considerando per semplicita le linee guida delle due prin-cipali associazioni di Urologia,la percentuale di incontinen -