M. Falsaperla

Differential role of CD133 and CXCR4 in renal cell carcinoma

The chemokine receptor CXCR4 and CD133, putative stem cell markers, were previously described in renal cancer (RCC). To evaluate the biological and prognostic role of CD133 and CXCR4 in RCC the expression was evaluated through qPCR and immunoblotting in human renal cancer cell lines (786-O, A498, ACHN, CAKI-1, SN12C, TK10, UO31) and patients biopsies. Renal cancer cells and surgical biopsies expressed functional CXCR4 while CD133 was not detectable. CXCR4 and CD133 expression was then evaluated in 240 renal cancer patients through immunohistochemistry. CXCR4 and CD133 were low in 19.1% and 59.6%; intermediate in 20% and 17.9%; high in 60.8% and 22.5% of the cases, respectively. CXCR4 was overexpressed in tumours (p= 0.02), while CD133 was over expressed in healthy tissues (p= 0.04). Disease free survival Kaplan Meier plots suggest that prognosis is unfavourable for patients whose primary tumours express CXCR4 (p= 0.0199) but nor CD133 (p= 0.151) neither the concomitant CXCR4-CD133 (p=0.848) high expression affected prognosis. Analysis of prognostic factors suggests that age, clinical presentation, AJCC stage and CXCR4 had a significant prognostic value at the univariate analysis. The CXCR4 predictive ability was confirmed at the multivariate analysis while no prognostic role was identified for CD133. Thus concomitant CD133 and CXCR4 evaluation is not worth in RCC patient while the CXCR4 prognostic role encourage CXCR4 antagonists as promising therapeutic option.

Analysis of radical cystectomy and urinary diversion complications with the Clavien classification system in an Italian real life cohort

INTRODUCTION Standardized methods of reporting complications after radical cystectomy (RC) and urinary diversions (UD) are necessary to evaluate the morbidity associated with this operation to evaluate the modified Clavien classification system (CCS) in grading perioperative complications of RC and UD in a real life cohort of patients with bladder cancer. MATERIALS AND METHODS A consecutive series of patients treated with RC and UD from April 2011 to March 2012 at 19 centers in Italy was evaluated. Complications were recorded according to the modified CCS. Results were presented as complication rates per grade. Univariate and binary logistic regression analysis were used for statistical analysis. RESULTS RESULTS AND LIMITATIONS 467 patients were enrolled. Median age was 70 years (range 35-89). UD consisted in orthotopic neobladder in 112 patients, ileal conduit in 217 patients and cutaneous ureterostomy in 138 patients. 415 complications were observed in 302 patients and were classified as Clavien type I (109 patients) or II (220 patients); Clavien type IIIa (45 patients), IIIb (22 patients); IV (11 patients) and V (8 patients). Patients with cutaneous ureterostomy presented a lower rate (8%) of CCS type ≥IIIa (p = 0.03). A longer operative time was an independent risk factor of CCS ≥III (OR: 1.005; CI: 1.002-1.007 per minute; p = 0.0001). CONCLUSIONS In our study, RC is associated with a significant morbidity (65%) and a reduced mortality (1.7%) when compared to previous experiences. The modified CCS represents an easily applicable tool to classify the complications of RC and UD in a more objective and detailed way.

A 1-year maintenance after early adjuvant intravesical chemotherapy has a limited efficacy in preventing recurrence of intermediate risk non-muscle-invasive bladder cancer

Study Type – Therapy (RCT)
Level of Evidence 1b

Immunohistochemical and molecular analysis in recurrent urethral stricture

Abstract The authors have analyzed the most recent additions to the literature of immunohistochemical and molecular assessment of acquired urethral strictures and report on their data obtained in a selected clinical series. Innovative immunohistochemical studies in patients presenting with plurirecurrent symptoms suggest that urethral mesenchymal changes caused by tissue de-epithelialization may be the underlying cause of stricture. This condition may be congenital or acquired. It may determine aberrant connective tissue formation induced by abnormal fibroblastic activation with formation of over abundant hyperdense collagen scar tissue.

Transuretral resection of the bladder (TURB): Analysis of complications using a modified Clavien system in an Italian real life cohort

INTRODUCTION To evaluate the applicability of a modified Clavien classification system (CCS) in grading postoperative complications of transurethral resection of bladder tumours (TURB). MATERIALS AND METHODS A series of patients undergoing monopolar TURB from April 2011 to March 2012 at five Italian centers were enrolled. All complications occurring within the first 30-day postoperative period were prospectively recorded and graded according to the CCS. RESULTS Overall, 275 patients were included. Median age was 71 (63/78) years; median BMI was 28 (25.4/30.8) Kg/m(2), median tumour size was 2 (1-3) cm; median number of tumour lesions was 1 (1-3). Median operative time was 30 (20/45) min. Fifty-seven complications were recorded in 43 patients. Overall postoperative morbidity rate was 16%. Most of the complications were not serious and classified as Clavien type I (42 cases; 74%) or II (8 cases, 14%). Higher grade complications were scarce: CCS IIIa in 1 case (2%) and CCS IIIb in six cases (10%). No TURB related death was reported. Six patients were re-operated due to significant bleeding or clot retention on postoperative days 2-7. On univariate (73.5 ± 38 versus 36.7 ± 21.6 min) and multivariate analysis longer operative time was an independent predictor of complications (OR: 1.06 per min, 95%CI 1.04-1.08, p = 0.001). CONCLUSIONS A modified CCS can be used as a standardized tool to objectively define the complications of TURB which confirms to be a safe procedure with a low surgical morbidity. This tool can be used to aid in patient counselling and to facilitate scientific assessment.

Use of BCG in Immunotherapy of Superficial Bladder Cancer: Multicentric Investigation on Safety and Compliance

Aim: Instillation-induced toxicity of BCG immunotherapy represent a real drawback. We decided to carry out a multicentric study to evaluate the tolerability of intravesical immunotherapy with BCG and in particular its effect on patient compliance and quality of life (QoL). Methods: A total of 92 patients were enrolled in the study, males and females aged >18 years, undergoing transurethral resection for superficial bladder cancer, Ta–T1, G1–GIII. After TUR, an induction cycle was started consisting of BCG Connaught at the dose of ∼81 mg/week per 6 consecutive weeks. This was followed by the SWOG 8507 maintenance scheme (3×3). Tolerability to the immunotherapy was assessed by determining the main BCG-induced side effects, such as dysuria, macrohematuria, strangury, fever and rarer symptoms (urethral bleeding, diarrhea, nausea, renal pain, penile pain). The percentage of patients who did not stop BCG therapy as a result of side effects was measured. To estimate the influence of the side effects of the intra...

Oral Chemotherapy in Hormone-Refractory Prostate Carcinoma Patients Unwilling to Be Admitted to Hospital

Objectives: To investigate the safety and efficacy in terms of PSA response of a low-dose oral combination of estramustine phosphate (EMP) and etoposide (VP16) in hormone- refractory prostate cancer (HRPC) patients. Well-tolerated outpatient chemotherapy regimens for patients unfit and/or unwilling to be admitted to hospital are needed. Methods: Fifty-six HRPC patients with metastatic disease (median age 75 years) were randomized between arm A (daily oral EMP 10 mg/kg, in 3 doses) and arm B (28-day cycle with low-dose EMP 3 mg/kg once daily plus VP16 25 mg/m2 once daily on days 1 through 14). Baseline characteristics between the two groups were similar. LHRH therapy was maintained. Anti- androgen was stopped 1 month before entry. Results: The low-dose combination was better tolerated, with a significant advantage in terms of time to treatment interruption for any reason (p = 0.01) or toxicity (6 vs. 12 months, p = 0.02). A trend in favour of arm B was evident in terms of PSA reduction (41.4 vs. 15%), performance status and pain improvement. Hospital admission due to toxicity was never required for arm B patients and there were no treatment-related deaths. Conclusions: Low-dose oral combination of EMP and VP16 might represent a treatment option for patients unfit for i.v. chemotherapy. This regimen requires minimal toxicity monitoring when administered at home for prolonged periods.

Role of Clinical and Surgical Factors for the Prediction of Immediate, Early and Late Functional Results, and its Relationship with Cardiovascular Outcome after Partial Nephrectomy: Results from the Prospective Multicenter RECORd 1 Project

Purpose: We sought to determine the predictors of short‐term and long‐term renal function impairment after partial nephrectomy. Materials and Methods: Clinical data on 769 consecutive patients who underwent partial nephrectomy were prospectively recorded at a total of 19 urological Italian centers from 2009 to 2012 in the RECORd 1 (Italian Registry of Conservative Renal Surgery) Project. We extracted clinical data on 708 of these patients who were alive, free of recurrent disease and with a minimum 2‐year functional followup. Results: Of the patients 47.3% underwent open, 36.6% underwent laparoscopic and 16.1% underwent robot‐assisted partial nephrectomy. The median baseline estimated glomerular filtration rate was 84.5 ml/minute/1.73 m2 (IQR 69.9–99.1). Immediate (day 3 postoperatively), early (month 1) and late (month 24) renal function impairment greater than 25% from baseline was identified in 25.3%, 21.6% and 14.8% of cases, respectively. Female gender and the baseline estimated glomerular filtration rate were independent predictors of immediate, early and late renal function impairment. Age at diagnosis was an independent predictor of immediate and late impairment. Uncontrolled diabetes was an independent predictor of late impairment only. Open and laparoscopic approaches, and pedicle clamping were independent predictors of immediate and early renal function impairment. Overall 58 of 529 patients (11%) experienced postoperative cardiovascular events. Body mass index and late renal function impairment were independent predictors of those events. Conclusions: Surgically modifiable factors were significantly associated with worse immediate and early functional outcomes after partial nephrectomy while clinically unmodifiable factors affected renal function during the entire followup. Late renal function impairment is an independent predictor of postoperative cardiovascular events.

Percutaneous Nephrolithotomy with Multiple Tracts in Complex Renal Stones

Abstract Introduction and Objectives: Percutaneous nephrolithotomy (PCNL) using a single access is the treatment of choice for patients affected by large stones. However, complex and staghorn calculi with multiple caliceal involvement may require a multiple tract treatment. Nowadays, multiple-tract percutaneous access procedures are less performed because there is a widespread use of flexible instruments during a single-access percutaneous nephrolithotripsy (PNL). Our video shows our experience on multiple-access PNL treatments in patients affected by complex renal stones. Materials and Methods: Two patients underwent multiple-access PCNL: a 22-year-old woman who was affected by bilateral complex stones, and a 54-year-old man affected by complex pielocaliceal lithiasis with upper hidrocalix. In both cases we performed ultrasound-fluoroscopy-guided access. The first was treated using a single access in the right kidney in two sessions because of the presence of residual stones after the first treatment. On...

Editorial Comment on: Laparoscopic Radical Nephroureterectomy: A Multicenter Analysis in Japan

Open radical nephroureterectomy has been the gold standard for the treatment of upper urinary tract urothelial carcinoma (UUT-UC) for decades. With advances in minimally invasive surgery, this concept has been increasingly challenged. Since its first description by Clayman et al from Washington University in 1991 [1], the benefits of laparoscopic nephroureterectomy (LNU) have been well established in terms of decreased perioperative morbidity and shortened convalescence and in comparison with open surgery [2]. But despite these benefits, data concerning long-term oncologic efficacy of LNU remain sparse [3,4]. Kamihira and coauthors present data from a survey promoted by the Japanese Society of Endourology and ESWL among almost 50 institutions in Japan [5]. This study represents the largest LNU series, with 5 yr of follow-up, ever reported to date. Most of the procedures have been performed retroperitoneally. Reported oncologic outcomes compare well with those in large open-surgery and previous laparoscopy series. Thus, given the recognized perioperative and morbidity advantages of LNU, it seems that the authors provide an additional rationale for LNU to become the preferred treatment for UUT-UC. Nevertheless, instead of findings from a prospective controlled trial, real-life practice data are provided. These data are of interest but they undoubtedly translate into significant drawbacks. Thus, some issues, strictly related to the retrospective nature of the analysis by Kamihira and coauthors, need to be addressed: