P. Bassi

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.

FISH Assay for THE Detection of Bladder Cancer

We evaluated the sensitivity and specificity of fluorescence in situ hybridization (FISH) performed on the urine specimens of patients under follow-up for superficial bladder cancer. Thirty-seven patients were enrolled and underwent cystoscopy, urinary cytology or biopsy and FISH examination. Urinary cytology and FISH were evaluated in exfoliated urothelial cells from bladder washings. A mixture of fluorescent labeled probes to the centromere of chromosomes 3, 7 and 17, and locus 9p21 was used to assess urinary cells for chromosomal abnormalities indicative of malignancy. Nine patients (24.3%) showed an abnormal cystoscopy, but only five patients showed transitional cell carcinoma at histology. Eighteen patients (48.6%) showed an abnormal FISH: one patient (2.7%) had a positive cytology, and three patients (8.1%) showed an atypical cytology. Patients with both positive cystoscopy and histological examination had a positive FISH, while only one patient had a positive cytology. Patients with positive cystoscopy and negative histological examination had a negative FISH. Three patients with negative cystoscopy and suspicious cytology had a positive FISH. Ten patients (27%) with both negative cystoscopy and cytology had a positive FISH. The sensitivity of the FISH assay was 100%, 50% for the cytology and 62% for the cystoscopy. The specificity of the FISH assay, cytology and cystoscopy were 66%, 100% and 86%, respectively. The sensitivity of the FISH assay in detecting non-invasive urothelial tumors is worth further studies.

Nodal Involvement in Bladder Cancer

There are many controversies about the actual meaning of nodal involvement in bladder cancer and, subsequently, about the real benefit of pelvic lymph node dissection (PLND) in patients with positive nodes at the time of cystectomy. In this article we reviewed the literature about the role of nodal involvement and the impact of positive nodes on the prognosis. The finding of positive nodes after radical cystectomy and PLND makes generally consider bladder cancer as a systemic disease and it is associated with poor prognosis. Therefore many urologists dont perform radical surgery in patients with positive nodes at time of cystectomy. P category, N category, and distant metastases are the most important factors in determining the outcome of patients with bladder cancer with nodal involvment. PLND is necessary for accurate staging in bladder cancer and appears to benefit patients with limited nodal involvement. PLND should be considered as a standard procedure that should be performed in every patient with indication of surgical treatment for TCC of the bladder.

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.