GRADE 2+BLADDER TOXICITY IN PATIENTS RECEIVING SBRT FOR PROSTATE CANCER: INCIDENCE AND DOSIMETRIC CHARACTERIZATION IN A LARGE PATIENT COHORT [Meeting Abstract]
The role of mannitol in alleviating renal injury during extracorporeal shock wave lithotripsy
PURPOSE/OBJECTIVE:We determined the role of mannitol in preventing or alleviating renal injury during extracorporeal shock wave lithotripsy (ESWL, Dornier Medical Systems, Inc., Marietta, Georgia). MATERIALS AND METHODS/METHODS:Patients undergoing ESWL were randomized to receive mannitol or control. Change in the levels of urinary enzymes, beta 2-microglobulin and microalbumin were compared in the groups before and after the procedure. RESULTS:Mannitol treated patients had a statistically significant decrease in beta 2-microglobulin excretion after ESWL compared with the control group. CONCLUSIONS:Mannitol may serve a protective function by decreasing the amount of renal injury caused by ESWL for renal calculous disease.
Cure of undifferentiated small cell carcinoma of the urinary bladder with M-VAC chemotherapy
Small cell carcinoma (SCC) of the urinary bladder is a rare, aggressive malignancy with approximately 135 cases reported in the literature. Treatments have included chemotherapy, radical surgery, radiotherapy, and combinations of these. We present the apparent cure of a 73-year-old man who presented with clinical stage T2 SCC of the urinary bladder. He was treated with three cycles of methotrexate, vinblastine, Adriamycin (doxorubicin), and cisplatin (M-VAC) chemotherapy. Subsequent radical cystoprostatectomy revealed no pathologic evidence of tumor. The patient is alive and well with no evidence of recurrence 3 years post cystectomy. A brief review of the literature is also presented.
A prospective analysis of time to normalization of serum testosterone after withdrawal of androgen deprivation therapy
PURPOSE/OBJECTIVE:Patients with prostate cancer are treated with neoadjuvant, adjuvant and intermittent androgen deprivation therapy. Prostate specific antigen (PSA) is altered during androgen deprivation therapy, and as a result the prognostic significance and accuracy of PSA values measured before serum testosterone has normalized are questionable because the patient is still effectively on androgen deprivation therapy. We determine the time it takes for serum testosterone to return to normal after withdrawal of androgen deprivation therapy. MATERIALS AND METHODS/METHODS:Serial serum testosterone was prospectively measured at 3-month intervals in 68 men after withdrawal of androgen deprivation therapy. The number of months to return to normal serum testosterone 270 ng./dl. or greater, was calculated for each patient. Patients were stratified according to duration of androgen deprivation, age and type of luteinizing hormone releasing hormone agonist used. RESULTS:Median patient age was 71 years (range 46 to 88). Median time to normalization of testosterone was 7 months (range 1 to 58). At 3, 6 and 12 months 28%, 48% and 74% of men had normal serum testosterone, respectively. Serum testosterone took significantly longer to return to normal in patients on androgen deprivation therapy for 24 months or greater compared to those on therapy for less than 24 months (log-rank p = 0.0034). There was no statistical significance based on age or type of luteinizing hormone releasing hormone agonist used. CONCLUSIONS:Androgen deprivation has an effect on serum testosterone that extends beyond the cessation of treatment. Serum testosterone should be measured in all men until normalization. These results should be applied to the interpretation of PSA levels after withdrawal of androgen deprivation therapy. In addition, these data have implications regarding dose scheduling and definition of biochemical (PSA) failure after primary therapy.
The role of reverse transcriptase-polymerase chain reaction for staging patients with clinically localized prostate cancer
Recent advances in molecular technology have been applied to the detection, staging, and prognosis of prostate cancer. The reverse transcriptase-polymerase chain reaction (RT-PCR) is an exquisitely sensitive tool that allows for the detection of minimal quantities of cells. The assay has been studied clinically to distinguish metastatic prostate cancer patients from controls, and to preoperatively stage prostatic carcinoma; it also has been studied as a marker for postoperative recurrences. We review our experience at Columbia University and reports in the literature from other institutions to date. In addition, we provide our most recent data correlating the "enhanced" RT-PCR for PSA assay of peripheral blood specimens with final pathologic stage in 300 radical prostatectomy patients.
Identification, localization and functional analysis of imidazoline and alpha adrenergic receptors in canine prostate
In nonsurgical management of benign prostatic hyperplasia, drugs which interfere with prostate contraction mediated through the alpha-1 adrenergic receptor are used. Clonidine acts at alpha adrenergic and I1-imidazoline receptors. In the present study, we found the Kd for [3H]clonidine binding to I1 sites in canine prostate to be 4 +/- 1 nM; the Bmax was 18 +/- 2 fmol/mg of protein. Inhibition of binding by imidazolines and by brain extracts containing putative endogenous ligand confirmed the identity of these sites as I1-imidazoline. Autoradiographic studies showed localization of both I1 and alpha-2 sites to the glandular epithelium. We sought to determine whether in vivo activation of the I1-imidazoline sites by clonidine mediates its contractile action in canine prostate. Dose-response curves were generated for para-aminoclonidine in the presence of vehicle alone, yohimbine (alpha-2 antagonist), idazoxan (alpha-2/I1/I2 antagonist) and prazosin (alpha-1 antagonist). Prazosin was the most effective antagonist. Yohimbine was less effective and did not effectively discriminate between para-aminoclonidine and phenylephrine, an alpha-1-selective agonist. Idazoxan antagonized para-aminoclonidine, but by not more than 50% at any dose. These results suggest that clonidine is active primarily at alpha-1 receptors on prostate smooth muscle in vivo. Thus the function of the I1 and alpha-2 receptors in the prostate remains to be determined; however, they may be involved in epithelial cell function.
Independent expression of two pharmacologically distinct supraspinal mu analgesic systems in genetically different mouse strains
Morphine coadministered at the level of the brainstem and the spinal cord in rodents elicits a profound synergism with a combined analgesic potency almost 10-fold greater than that seen with morphine in either region alone. In the present study, we demonstrate that supraspinal mu2 receptors mediate this synergy, whereas morphine given only within the brainstem elicits analgesia through mu1 receptors. In the mu1-deficient CXBK strain of mice, morphine given intracerebroventricularly (i.c.v.) alone at doses up to 10 micrograms fails to produce greater than 20% analgesia in marked contrast to CD-1 mice (ED50 0.51 micrograms i.c.v.). At the spinal level, both the CXBK and CD-1 strains are equally sensitive to morphine (ED50 0.91 and 0.94 micrograms intrathecally, respectively), a mu2 action. Morphine administered i.c.v. potentiates a fixed low dose of intrathecal morphine as effectively in the CXBK mice as the CD-1 mice. Additional studies using selective mu antagonists differentiated these two analgesic responses pharmacologically. The mu1-selective drug naloxonazine (35 mg/kg s.c.) antagonizes the analgesic actions of morphine given only supraspinally without diminishing the potency of i.c.v. morphine in the synergy model. beta-Funaltrexamine, which blocks both mu1 and mu2 receptors, given i.c.v. antagonizes the analgesia after supraspinal morphine alone (ID50 2.5 micrograms i.c.v.) or its potentiation of intrathecal morphine (ID50 2.4 micrograms i.c.v.) equally well, confirming the involvement of mu receptors in both actions. In contrast, naloxonazine reverses the analgesia after supraspinal morphine alone (ID50 2.8 micrograms i.c.v.) almost 6-fold more potently than the synergy between i.c.v. and intrathecal morphine (ID50 18.3 micrograms i.c.v.). Together our results indicate the presence of two genetically and pharmacologically distinct populations of supraspinal mu receptors capable of mediating analgesia.