F. Dal Moro

Pharmacokinetic study of intravesical gemcitabine in carcinoma in situ of the bladder refractory to Bacillus Calmette-Guérin therapy

Introduction: Gemcitabine, a chemotherapeutic agent, has been shown to be active against transitional cell cancer of the bladder. The aim of the study was to determine the pharmacokinetic profile of gemcitabine, administered intravesically in patients with carcinoma in situ(CIS). Material and Methods: Nine patients with CIS refractory to intravesical bacillus Calmette-Guérin (BCG) therapy were enrolled. Gemcitabine was given in 50 ml 0.9% NaCl by catheterization and held in the bladder for 1 h, once weekly for 6 consecutive weeks. The pharmacokinetics for gemcitabine metabolites were performed in plasma and serum. Dose levels were: 1,000, 1,250, and 1,500 mg. Clinical evaluation was repeated 4 weeks after therapy and thereafter every 6 months. Results: Grade-1 neutropenia was observed only in 1 patient. Grade-1 urinary frequency and hematuria were observed in 1 and 3 patients, respectively. No grade 2–4 toxicity or clinically relevant myelosuppression were observed. Gemcitabine was detectable in serum, but with an irrelevant pharmacological effect, in only 1 patient treated with 1,500 mg of gemcitabine. With regard to activity, after 6 instillations of this drug, 4 complete responses were observed. Conclusion: Intravesical gemcitabine is well tolerated and safe. No systemic absorption with a clinical or pharmacological effect was detected and only slightly irritative bladder symptoms were observed. These results warrant further investigation in phase-II trials.

Transvaginal ultrasound and ureteral stones

We would like to congratulate Pateman et al.1 on their work on the possibility of visualizing pelvic segments of ureters directly by means of transvaginal sonography (TVS). In their elegant paper, these authors evaluated results from a large series of TVS examinations and demonstrated the ease with which this technique can visualize the pelvic portions of ureters and detect congenital abnormalities. To confirm these findings and encourage the use of TVS as a routine diagnostic tool, we would like to share our experience of evaluating women with ureteral stones. In the diagnostic work-up for renal colic in women, after standard transabdominal ultrasonography, whenever a stone in the distal portion of the ureter is suspected, we routinely perform TVS (except in patients who have never been sexually active or who are unable to tolerate the procedure). TVS is a simple, fast and well-tolerated examination which can easily identify stones in the terminal portion of the ureter (Figure 1), and has the additional possibility of the Doppler function to show any ‘ureteral jet’, demonstrating whether ureteral obstruction is complete. Not only does TVS seem to be more accurate in identifying intramural stones than is standard pelvic ultrasonography in patients with body mass index > 30 kg/m2, it also avoids the use of non-contrast-enhanced computed tomography (NCCT) to demonstrate the presence and precise site of stones; although recommended (Grade A, level of evidence 1a) in the Guidelines of the European Association of Urology2, to confirm stone diagnosis in patients with acute flank pain, NCCT in fact involves an exposure to radiation of 4.5–5.0 mSv, comparable to 50 chest X-rays! Although, low-dose (1.0–1.9 mSv) NCCT can be performed in patients with BMI < 303, the possibility of accurately defining the site, dimension and presence or absence of a ureteral obstruction, without exposure to radiation, would seem not only to be mandatory during pregnancy, but also preferable in young or obese patients4. For these reasons, in our opinion TVS should become a standard step in the diagnostic work-up of women with Figure 1 Transvaginal ultrasound image showing a 5-mm distal ureteral stone.

The dark knight of syncope: the urologist!

I would like to congratulate Juul-M€ oller et al. [1] on their contributions to the SYNCOPE Symposium, reported in your Journal. The above authors stress the different aspects of this variegated syndrome and the various approaches according to specific causes. In particular, they state that the main aetiology of syncope consists of neurocardiogenic reflexes, autonomic disorders (such as orthostatic hypotension), primary cardiovascular diseases or a combination of these, identifying within the healthcare system various specialists not only involved in the management process, but also in some cases directly responsible for the onset of symptoms: from general practitioners to cardiologists to internists, there are several physicians guilty of having prescribed drugs causing syncope, a time-limited circulatory disorder resulting in loss of consciousness and spontaneous recovery.

The Role of an Extended 24 Cores Biopsy in Patients with Clinically Suspected Prostate Cancer and Prior Negative Biopsy

The aim of this study is to evaluate the role of an extensive “saturation biopsy” in patients at increased risk for prostate cancer with previously negative biopsies, HGPIN or ASAP diagnosis. Materials and Methods We performed an extensive 24 cores biopsy with spinal anaesthesia in 168 patients with at least 1 prior negative biopsy and persistently high PSA and/or abnormal digital rectal examination or with a ASAP or HGPIN diagnosis at previous biopsy. Results A total of 55 patients were diagnosed having prostate cancer for an overall diagnostic yeld of 33 %. Specifically, cancer was detected in 79% of ASAP, 32% of HGPIN and 28% of prior negative biopsies. 31 patients underwent radical retropubic prostatectomy. There was no correlation between number of positive biopsy cores and pathological stage or pathological Gleason score. A high concordance was found between clinical and pathological Gleason score. Conclusions Extensive biopsy can be considered a safe and effective diagnostic tool in men at risk for prostate cancer with previous negative biopsies. This procedure comes out to be particularly useful also in patients with a prior ASAP or HGPIN.

Simultaneous Surgical Treatment of Abdominal Aortic Aneurysm (AAA) and Invasive Transitional Cell Carcinoma

A prospective case-control study on simultaneously occurring abdominal aortic aneurysm (AAA) and invasive transitional cell carcinoma of the bladder (TCCB) was carried out to evaluate short- and long-term mortality and morbidity of the one-stage surgical treatment. Methods From January 1995 to December 2000 16 patients presented a concomitant AAA and TCCB. A standard operative protocol included AAA graft replacement before bladder resection and urinary reconstruction. Control patients (16 AAA and 16 TCCB alone) matched according to time of intervention, type of vascular and urinary procedure and pathologic staging. Results No vascular complications and graft infections were observed. Systemic and urologic complications were similar in study and control groups. One patient simultaneously treated for AAA and TCCB died of MI 32 days after surgery after an uncomplicated postoperative period. Estimated 6–year survival rate was 68% in AAA and TCCB patients simultaneously treated, 93% and 54% in matched control patients undergoing AAA and TCCB treatment alone respectively. Conclusions The present study shows that the one-stage is a safe approach to simultaneous occurring AAA and TCCB. Long-term survival of treated patients is dependent upon cancer progression. Whenever endovascular treatment is not advisable, the simultaneous surgical treatment of coexisting AAA and TCCB is recommended in highly specialized centers.