Clear Cell carcinoma of the urinary bladder, A case report: Surgical and oncological management.

INTRODUCTION: Bladder cancer is a condition characterized by a broad spectrum of histological variants and clinical courses. The morphological description of histological variants is becoming increasingly important. The 75% of cases of these cancers are classified as pure urothelial carcinoma, while the remaining 25% is represented by other histological variants. The clear cell carcinoma is part of urothelial group and is a very rare entity. Oncological outcomes of this variant are still uncertain, but seems to be worst than for patiens with pure urothelial carcinoma. Moreover it seems to metastasize more easily to the lymph nodes. CASE REPORT: We present a case of a Caucasian 73 year old woman who, after an episode of gross hematuria, underwent an ultrasound of the urinary system, a cystoscopy and a total body computed tomography (CT) which confirmed the presence of a bladder neoformation. A transurethral resection of the bladder (TURB) was performed: the result of the histological examination was "poorly differentiated clear cell carcinoma". Given the rarity of histological characterization, we required a PET CT scan for more accurate staging, at which a suspected right pelvic lymph node was detected. We proposed a radical cystectomy with hysteroannessiectomy and extended lymphadenectomy. During the pre-hospitalization process, the patient developed anuria, with acute renal failure and bilateral hydronephrosis, which required the placement of bilateral nephrostomies; we performed the planned surgical procedure and the histological exam confirmed: high grade urothelial carcinoma with a high percentage (more than 70%) of clear cell carcinoma, with a strong local aggression and lymphnode metastates. We referred the patient to the oncologist who suggested a treatment plan within an immunotherapy based clinical trial and cisplatin. CONCLUSIONS: The morphological description of histological variants in bladder cancer is gaining increasing importance, especially for infiltrating and aggressive forms. The clear cell carcinoma is a very rare entity part of the urothelial group; they would seem more aggressive forms with an early lymph node involvement. This evidence is confirmed by the clinical case described, in which we have seen a large local aggression with an involvement of the lymph nodes of the right side of the pelvis of the pre-sacral ones. In these cases, the multimodal approach is crucial.

Safety and efficacy of retroperitoneal sutureless zero ischemia laparoscopic partial nephrectomy for low nephrometry score masses.

OBJECTIVES: To evaluate oncological feasibility and oncological and functional results of retroperitoneal sutureless zero ischemia laparoscopic partial nephrectomy (LPN). PATIENTS AND METHODS: Patients with posterior renal masses with low nephrometry score (RENAL ≤ 7) treated who underwent retroperitoneal sutureless zero ischemia.in a single center from January 2016 to November 2017. Clinical, surgical and pathological data were prospectively collected. Complications were reported according to the modified Clavien classification. RESULTS: Retroperitoneal sutureless zero ischemia laparoscopic partial nephrectomy was performed on 15 patients. The indication for nephron-sparing surgery was elective in 11 (73%) patients and imperative in 4 (27%). Median RENAL score was 5 (IQR: 5-7), median tumor diameter 25 mm (IQR: 20-35). In 11 cases, the tumor was located polar (85%), and in 2 cases hilar (15%). There were no intraoperative complications. No cases were converted to radical nephrectomy, and in no case parenchyma suture was necessary. Median operative time was 90 min (IQR:40-150), in no case clamping of the renal artery was necessary, median hospital stay was 4 days, median estimated blood loss (EBL) was 310 (180-500) ml. Pathological analysis showed renal cell carcinoma in 11 patients (85%), 9 (60%) staged T1a and 2 (13%) T1b. In 4 (27%) an oncocytoma was found. There were no positive surgical margins. One patient developed a major postoperative complication (postoperative renal bleeding requiring super-selective embolization). Trifecta rate was 93%. CONCLUSIONS: Sutureless retroperitoneal zero ischemia LPN for the treatment of low-complexity posterior renal masses showed to be safe and feasible. Longer follow-up and higher numbers of patients are, however, warranted to draw definitive conclusions on functional outcomes.

Retropubic, laparoscopic, and robot-assisted radical prostatectomy: surgical, oncological, and functional outcomes: a systematic review.

OBJECTIVES: Despite the wide diffusion of minimally invasive approaches, such as laparoscopic (LRP) and robot-assisted radical prostatectomy (RALP), few studies compare the results of these techniques with the retropubic radical prostatectomy (RRP) approach. The aim of this study is to compare the surgical, functional, and oncological outcomes and cost-effectiveness of RRP, LRP, and RALP. METHODS: A systematic review of the literature was performed in the PubMed and Embase databases in December 2013. A 'free-text' protocol using the term 'radical prostatectomy' was applied. A total of 16,085 records were found. The authors reviewed the records to identify comparative studies to include in the review. RESULTS: 44 comparative studies were identified. With regard to the perioperative outcome, LRP and RALP were more time-consuming than RRP, but blood loss, transfusion rates, catheterisation time, hospitalisation duration, and complication rates were the most optimal in the laparoscopic approaches. With regard to the functional and oncological results, RALP was found to have the best outcomes. CONCLUSION: Our study confirmed the well-known perioperative advantage of minimally invasive techniques; however, available data were not sufficient to prove the superiority of any surgical approach in terms of functional and oncologic outcomes. On the contrary, cost comparison clearly supports RRP.

[Intravesical therapy with mitomycin through electromotive drug administration]. / Mitomicina intravescicale con Electromotive Drug Administration (EMDA®).

In the management of non-muscle invasive bladder cancer (NMIBC), high-level evidence supports the widespread practice of intravesical therapy with mitomycin-C (MMC). Randomized trials showed a significant reduction in short-term recurrence compared with transurethral resection of bladder tumor (TURBT) alone, but little effect on long-term and no impact at all in preventing progression. Electromotive drug administration (EMDA®) offers a means of controlling and enhancing the tissue transport of certain drugs, in order to increase their efficacy. In both laboratory and clinical studies, intravesical electromotive drug administration (EMDA) increases MMC bladder uptake, resulting in an improved clinical efficacy in NMIBC without systemic side effects. New frameworks for treatment of NMIBC - e.g., sequential intravesical BCG and EMDA/MMC, as well as intravesical EMDA/MMC immediately before TURBT - have provided promising preliminary results with higher remission rates and longer remission times, and they are a priority to minimise the costs of disease management. These findings suggest EMDA-enhanced MMC efficacy against urothelial cancer could be a major therapeutic breakthrough in the treatment of NMIBC.

Electromotive instillation of mitomycin immediately before transurethral resection for patients with primary urothelial non-muscle invasive bladder cancer: a randomised controlled trial.

BACKGROUND: The clinical effect of intravesical instillation of chemotherapy immediately after transurethral resection of bladder tumours (TURBT) has recently been questioned, despite its recommendation in guidelines. Our aim was to compare TURBT alone with immediate post-TURBT intravesical passive diffusion (PD) of mitomycin and immediate pre-TURBT intravesical electromotive drug administration (EMDA) of mitomycin in non-muscle invasive bladder cancer. METHODS: We did a multicentre, randomised, parallel-group study in patients with primary non-muscle invasive bladder cancer in three centres in Italy between Jan 1, 1994, and Dec 31, 2003. Patients were randomly assigned to receive treatment by means of stratified blocked randomisation across six strata. Patients and physicians giving the interventions were aware of assignment, but it was masked from outcome assessors and data analysts. Patients were randomly assigned to receive TURBT alone, immediate post-TURBT instillation of 40 mg PD mitomycin dissolved in 50 mL sterile water infused over 60 min, or immediate pre-TURBT instillation of 40 mg EMDA mitomycin dissolved in 100 mL sterile water with intravesical 20 mA pulsed electric current for 30 min. Our primary endpoints were recurrence rate and disease-free interval. Analyses were done by intention to treat. Follow-up for our trial is complete. This study is registered with ClinicalTrials.gov, number NCT01149174. FINDINGS: 124 patients were randomly assigned to receive TURBT alone, 126 to receive immediate post-TURBT PD mitomycin, and 124 to receive immediate pre-TURBT EMDA mitomycin. 22 patients were excluded from our analyses because they did meet our eligibility criteria after TURBT: 11 had stage pT2 disease and 11 had carcinoma in situ. Median follow-up was 86 months (IQR 57-125). Patients assigned to receive EMDA mitomycin before TURBT had a lower rate of recurrence (44 [38%] of 117) than those assigned to receive PD mitomycin after TURBT (70 [59%] of 119) and TURBT alone (74 [64%] of 116; log-rank p<0·0001). Patients assigned to receive EMDA mitomycin before TURBT also had a higher disease-free interval (52 months, IQR 32-184) than those assigned to receive PD mitomycin after TURBT (16 months, 12-168) and TURBT alone (12 months, 12-37; log-rank p<0·0001). We recorded persistent bladder symptoms after TURBT in 18 (16%) of 116 patients in the TURBT-alone group (duration 3-7 days), 37 (31%) of 119 in the PD mitomycin post-TURBT group (duration 20-30 days), and 24 (21%) of 117 in the EMDA mitomycin pre-TURBT group (duration 7-12 days); haematuria after TURBT in eight (7%) of 116 patients in the TURBT-alone group, 16 (13%) of 119 in the PD mitomycin post-TURBT group, and 11 (9%) of 117 in the EMDA mitomycin pre-TURBT group; and bladder perforation after TURBT in five (4%) of 116 patients in the TURBT-alone group, nine (8%) of 119 in the PD mitomycin post-TURBT group, and seven (6%) of 117 in the EMDA mitomycin pre-TURBT group. INTERPRETATION: Intravesical EMDA mitomycin before TURBT is feasible and safe; moreover, it reduces recurrence rates and enhances the disease-free interval compared with intravesical PD mitomycin after TURBT and TURBT alone. FUNDING: None.

Significance of focal proliferative atrophy lesions in prostate biopsy cores that test negative for prostate carcinoma.

OBJECTIVES: To evaluate the prevalence and short-term follow-up of focal proliferative atrophy lesions, either with or without the presence of inflammation (PIA/PA), and its correlation with the PSA levels, focusing on the prostate biopsy cores that test negative for prostate adenocarcinoma (PCa). METHODS: Five hundred fifty consecutive patients who had undergone a transrectal ultrasound-guided transperineal prostate biopsy were evaluated retrospectively for the presence and follow-up of focal proliferative atrophy lesions. PIA/PA were defined according to De Marzo. The prevalence of atrophy in PCa and negative biopsy cores was compared by means of χ(2). After logarithmic transformations of the PSA values, t-test and ANOVA were applied for the comparison of the means. Incidence of newly diagnosed PCa during follow-up (mean 33.7 months) in patients with or without focal proliferative atrophy was compared by means of χ(2). RESULTS: A focal atrophic lesion resulted in 161/339 negative biopsies. PIA was observed in 93/161 patients (57.8%), while PA was observed in the remaining 68/161 (42.2%). Among the negative biopsy cases, the difference in PSA values were not statistically significant according to the presence or absence of atrophy (P = 0.120). The group of negative biopsies with PIA was similar in terms of PSA characteristics with the benign (PA P = 0.738; non-atrophy P = 0.342), and cancer subgroups (P = 0.094); 245/339 (72.3%) patients were successfully followed-up. Biopsy was repeated in 24/71 (33.8%) patients with PIA, in 14/50 (28%) with PA and in 27/124 (21.7%) with no atrophy lesions at initial biopsy. The incidence of newly diagnosed PCa in the 3 groups was not statistically different (χ(2), P = 0.81). CONCLUSIONS: Focal proliferative atrophy lesions are a common finding in biopsy specimens negative for PCa. Patients with negative biopsy associated with PIA presented similar PSA characteristics as patients with biopsy-proven PCa. However, the incidence of PCa at short-term follow-up did not differ significantly between patients with PIA, PA, or no atrophic lesions at initial biopsy. Based on our findings, early repeat biopsy does not seem to be necessary after an initial diagnosis of PIA/PA, although a longer follow-up is mandatory for definitive conclusions.

Intravesical electromotive drug administration of mitomycin-C for non-muscle invasive bladder cancer.

This article reviews intravesical application of electromotive drug administration (EMDA) for the treatment of bladder cancer and the evidence in support of intravesical passive diffusion chemotherapy in the management of non-muscle invasive bladder cancer. Two recently published randomised trials adopting protocols that use EMDA to enhance urothelial transport of intravesical mitomycin-C showed it provided a therapeutical advantage and suggested that intravesical passive diffusion administration of chemotherapeutic drugs may be suboptimal. Further studies are required to demonstrate feasibility and advantage of intravesical EMDA of mitomycin-C in the wider uro-oncological community.