Giuseppe Fasolis

Selective Inhibition of Carbonic Anhydrase IX Decreases Cell Proliferation and Induces Ceramide-Mediated Apoptosis in Human Cancer Cells

Recently, carbonic anhydrase (CA) inhibitors have been proposed as a potential new class of antitumor agents. The aim of this study was to evaluate the antitumor activity of three CA inhibitors, namely acetazolamide (AZ) and two newly synthesized aromatic sulfonamides with high affinity for CA IX, 2-(4-sulfamoylphenyl-amino)-4,6-dichloro-1,3,5-triazine (TR1) and 4-[3-(N,N-dimethylaminopropyl)thioreidophenylsulfonylaminoethyl]benzenesulfonamide (GA15), against human tumor cells. The effects of AZ, TR1, and GA15 on cell proliferation and apoptosis were evaluated in CA IX-positive HeLa and 786-O cells and CA IX-negative 786-O/von Hippel-Lindau (VHL) cells. We also investigated whether the potential antitumor activity of these molecules might be mediated by an increase in ceramide production. AZ, TR1, and GA15 could significantly reduce cell proliferation and induce apoptosis in HeLa and 786-O cells. Moreover, all three inhibitors could decrease intracellular pH (pHi) and increase ceramide production in the same cells. Treatment with the ceramide synthase inhibitor fumonisin B1 prevented the apoptotic effects of the three CA inhibitors. In all experiments, the effects of aromatic sulfonamides were more pronounced than those of AZ. The three inhibitors did not show any antitumor activity in CA IX-negative 786-O/VHL cells and failed to lower pHi or increase intracellular ceramide levels in the same cells. In conclusion, CA inhibition can decrease cell proliferation and induce apoptosis in human tumor cells. The ability of CA inhibitors to decrease pHi might trigger cell apoptosis through mediation of ceramide synthesis. Activation of this apoptotic cascade probably is mediated by inhibition of the CA IX isoform.

Use of Frozen Sections to assess surgical margins during radical prostatectomy

Introduction At present there is no consensus on the use of frozen sections (FS) during radical prostatectomy. Several groups have proposed the benefit of FS although the studies differ widely in sampling methods and sites where FS were taken. This study aims to evaluate the usefulness and reliability of standard assessment of FS in multiple sites during radical prostatectomy. Methods During open radical prostatectomy in all patients we sampled tissue from the urethral stump, the neurovascular bundles, the Denonvillier fascia and the bladder neck after removing the prostate. Where FS showed positive margins, further periprostatic tissue was resected from the prostatic bed until negative margins were achieved. The results of FS were compared with margin status of final pathology. Results From 1998 to 2004 we performed FS during 250 consecutive open radical prostatectomies (104 nerve sparing procedures). 66 patients had positive FS (26.4%) and 53 patients had positive surgical margins at final pathology (21.2%). All patients with positive FS had negative margins when further tissue was resected in the prostatic bed. During nerve sparing procedures positive FS were found in 14 patients. In these cases the procedure was converted into standard prostatectomy by resecting the neurovascular bundles. Sensibility and specificity were both 90%. Positive and negative predictive values were respectively 72% and 97%. Conclusions Standard assessment of FS in multiple sites during radical prostatectomy achieved sensibility and specificity as high as 90%. Although the resection of urethral stump and tissue close to the neurovascular bundles could compromise functional results, standard assessment of FS in multiple sites could help the surgeon to reduce the positive surgical margins, to monitor the oncological safety of a nerve sparing procedure and to improve the pathological staging.INTRODUCTION At present there is no consensus on the use of frozen sections (FS) during radical prostatectomy. Several groups have proposed the benefit of FS although the studies differ widely in sampling methods and sites where FS were taken. This study aims to evaluate the usefulness and reliability of standard assessment of FS in multiple sites during radical prostatectomy. METHODS During open radical prostatectomy in all patients we sampled tissue from the urethral stump, the neurovascular bundles, the Denonvillier fascia and the bladder neck after removing the prostate. Where FS showed positive margins, further periprostatic tissue was resected from the prostatic bed until negative margins were achieved. The results of FS were compared with margin status of final pathology. RESULTS From 1998 to 2004 we performed FS during 250 consecutive open radical prostatectomies (104 nerve sparing procedures). 66 patients had positive FS (26.4%) and 53 patients had positive surgical margins at final pathology (21.2%). All patients with positive FS had negative margins when further tissue was resected in the prostatic bed. During nerve sparing procedures positive FS were found in 14 patients. In these cases the procedure was converted into standard prostatectomy by resecting the neurovascular bundles. Sensibility and specificity were both 90%. Positive and negative predictive values were respectively 72% and 97%. CONCLUSIONS Standard assessment of FS in multiple sites during radical prostatectomy achieved sensibility and specificity as high as 90%. Although the resection of urethral stump and tissue close to the neurovascular bundles could compromise functional results, standard assessment of FS in multiple sites could help the surgeon to reduce the positive surgical margins, to monitor the oncological safety of a nerve sparing procedure and to improve the pathological staging.

Allium stent for the treatment of a malignant ureteral stenosis: A paradigmatic case

Objective: The aim of this study was to present a paradigmatic case where the new-generation Allium URS stent was the optimal choice to treat a malignant ureteral stenosis. Methods: We describe in detail all the steps of our surgery, performed on a 69-year-old patient with left hydronephrosis caused by lumbo-aortic nodal metastases compressing the ureter. The patient was intolerant to double-J stent due to strong irritative urinary symptoms. Allium URS stent was positioned under fluoroscopy in replacement of pre-existing double-J stent. Results: Our approach was successful and irritative urinary symptoms disappeared. At 6 months, the Allium URS was correctly positioned and no hydronephrosis was detected on ultrasound. The stent can be left in place for a maximum of 3 years. Conclusions: In complicated scenarios of chronic ureteral stenosis, the new-generation Allium URS can be an interesting option to treat the obstruction while sparing the patient the irritative urinary symptoms and periodic replacements typical of a double-J stent.

Accuracy of elastic fusion biopsy in daily practice: Results of a multicenter study of 2115 patients

To assess the accuracy of Koelis fusion biopsy for the detection of prostate cancer and clinically significant prostate cancer in the everyday practice.

Therapeutic Ureteral Occlusion with Ifabond Cyanoacrylate Glue: An Interesting Solution

Objective The aim of this study was to present a novel approach for complete and permanent ureteral occlusion using a percutaneous injection of Ifabond cyanoacrylate glue. Methods We describe in detail all the steps of our surgery, performed on a 79-year-old patient with urinary leakage from ureteral stump following radical cystectomy. N-hexyl-cyanoacrylate glue (Ifabond) was used to occlude the distal ureter and solve the leakage. Results Our approach was successful, sparing our already frail patient further surgical procedures. Six months pyelography confirmed the complete ureteral blockage with absence of extravasation. Conclusions In complicated scenarios with urinary leakages and frail patients, synthetic glues such as Ifabond might represent an interesting therapeutic option to solve the fistulas, leading to durable success with a minimally invasive approach.