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We report a case of a 74-year-old patient who received 41 courses of maintenance therapy with gemcitabine over a length of 28 months for metastatic transitional cell carcinoma. One year earlier the patient had received three cycles of adjuvant cisplatin-based combination chemotherapy after nephro-ureterectomy for a locally advanced urothelial cancer of the right renal pelvis. This case demonstrates a paradigm shift in the palliative treatment of advanced urothelial cancer, with the implementation of more tolerable agents such as gemcitabine. Even elderly patients with impaired renal function may benefit in terms of tumor reduction and survival from systemic chemotherapy, which may be applied over a prolonged period of time.

Purpose: We retrospectively reviewed the outcome in our patients with prostate cancer and regional positive lymph nodes who underwent prostatectomy., Materials and Methods: Between January 1984 and December 2002, 147 men were found to have local lymph node metastases after surgery, of whom 135 underwent further androgen ablation, including 88% within 6 weeks after prostatectomy. We especially determined overall, cancer specific and progression-free survival rates., Results: Median patient age was 63.2 years (range 46 to 75 years). Postoperative followup was up to 214 months (median 41.9). There was 1 death secondary to surgery. To date 49 patients (33.3%) had disease progression, including 6 with a prostate specific antigen increase later than 100 months after surgery, and 36 (24.5%) died, including 22 of prostate cancer and 14 of other causes. Overall and cause specific survival probabilities at 5, 10 and 15 years were 76.6% and 86.5%, 60.1% and 73.7%, and 47.2% and 57.9%, respectively. Median overall survival was 144 months and median cancer specific survival was greater than 145 months. Overall progression-free probabilities at 5, 10 and 15 years were 72.7%, 49.8% and 31.6%, respectively. Biochemical progression-free survival rates were 77.4% after 5, 53.0% after 10 and 33.7% after 15 years., Conclusions: Since three-quarters of our patients were likely not to die of prostate cancer within the 10 years after surgery despite histological evidence of lymph node metastases, radical prostatectomy with or without hormonal therapy is a viable option for patients with local lymph node involvement, particularly in view of long-term survival.

The increased sympathetic neurotransmission in benign prostatic hyperplasia (BPH) results in a alpha 1C-adrenoceptor-mediated increase in prostatic smooth muscle tone which seems to be responsible for the dynamic infravesical obstruction occurring in BPH. The prostatic smooth muscle contractions evoked by norepinephrine can be efficiently blocked by alpha 1-adrenoceptor blockers. Moreover, an impressive number of clinical trials illustrated the beneficial results of alpha 1-adrenoceptor blockers in the treatment of BPH. However, despite knowledge of alpha 1-adrenergic neurotransmission and the clinical application of its blockade by selective alpha 1-adrenoceptor antagonists, very little is known about the intracellular pathways involved in the regulation of prostatic smooth muscle contractility. To study the intracellular mechanism of the alpha 1C-adrenoceptor-induced prostatic smooth muscle contraction, the patch-clamp technique in the whole-cell configuration mode combined with the Fura-II fluorescence technique was used in human, enzymatically isolated smooth muscle cells obtained from patients undergoing transurethral resection of the prostate because of symptomatic BPH. Furthermore changes in prostatic smooth muscle contractility were registered in organ bath experiments. Application of the selective alpha 1-adrenoceptor agonist phenylephrine (PE) increased the L-type Ca(2+)-channel current (ICa) dose dependently from 8 up to 18.5 microA/cm2, simultaneously elevating the free cytoplasmic Ca2+ concentration ([Ca2+]i) up to 1.9 microM. Pretreating the myocytes with pertussis toxin, an exotoxin of Bordetella pertussis which inactivates GTP-binding proteins (G proteins) of the Gi and G(o) family by ADP ribosylation, reduced the PE-induced ICa stimulation by 71.5 +/- 5.6% (n = 21). Dialysis of the cytosol with the second messenger inositol-1,4,5-trisphosphate (IP3), which releases Ca2+ from intracellular non-mitochondrial, IP3-sensitive Ca2+ pools, imitated the PE-evoked responses. Pretreating the myocytes with the Ca(2+)-release blockers ryanodine (10-100 microM, n = 8), thapsigargin (0.1 microM, n = 11) or low-molecular weight heparin (n = 14) largely attenuated the PE-evoked responses. The experimental results suggest a coupling of alpha 1-adrenoceptors to phospholipase C-converting phosphoinositol-4,5-bisphosphate into diacylglycerol, an endogenous activator of the protein kinase C and IP3 which releases Ca2+ from intracellular stores stimulating ICa via Ca(2+)-calmodulin-dependent protein kinase induced phosphorylation of voltage-dependent Ca2+ channels. This knowledge could be of interest for conservative treatment in symptomatic BPH.