Richard C. Klugo

Aggressive Versus Conservative Management of Stage IV Renal Cell Carcinoma

Improved modalities to treat metastatic renal cell carcinoma will require an aggressive surgical and chemotherapeutic approach. Nephrectomy with hormonal and non-hormonal chemotherapy does improve median survival and 3-year survival significantly. The use of xenogeneic specific immune ribonucleic acid and Bacillus Calmette-Guerin offers promising immunotherapeutic modalities that may be combined with surgical and chemotherapeutic regimens. Early diagnosis of metastatic disease is important to evaluate properly the results of various modalities of treatment and possibly to improve the efficiency of these modalities. The management of solitary metastatic nodules should involve aggressive resection of the primary and metastatic nodule. Adjuvant hormonal and non-hormonal chemotherapy should be considered in all stages of the disease.

Bilateral orchiectomy for carcinoma of prostate Response of serum testosterone and clinical Response to subsequent estrogen therapy

Forty-five patients with symptomatic Stage D carcinoma of the prostate were treated with bilateral orchiectomy. Serum testosterone levels were obtained before orchiectomy, seven days after and a six-month intervals. With relapse after orchiectomy remission patients were treated with diethylstilbesterol (DES) 1 mg. daily. After bilateral complete orchiectomy 40 patients had serum testosterone levels in the anorchic range (21.5 to 39.7 ng./dl) while 5 had testosterone levels between 117 and 187 ng./dl. The mean remission response after orchiectomy was 9.1 months (three to twenty-four months) in the anorchic group and 9.4 months in the imcomplete anorchic group. Mean relapse response to estrogen therapy in the anorchic group was four months (one to six months). While in the incomplete anorchic group mean relapse response to estrogen therapy was 20.8 months (one to sixty). Serum testosterone levels in the imcomplete group decreased with estrogen therapy while those in the anorchic group were stable with estrogen therapy. Our findings suggest that bilateral complete orchiectomy does not always provide serum testosterone levels in the anorchic range. Subsequently these patients show an improved mean response to oral estrogen therapy.

Response of Micropenis to Topical Testosterone and Gonadotropin

Five patients were treated with gonadotropin and topical testosterone for micropenis associated with hypothalamic hypogonadotropic hypogonadism. All patients received 1,000 units of gonadotropin weekly for 3 weeks, with a 6-week interval followed by 10% topical testosterone cream twice daily for 3 weeks. Serum testosterone levels were measured and remained equivalent for both modes of therapy. Average penile growth response with gonadotropin was 14.3% increase in length and 5.0% increase of girth. Topical testosterone produced an average increase of 60% in penile length and 52.9% in girth. The greatest growth response occurred in prepubertal male subjects with a minimal response in postpubertal male subjects. This study suggests that 10% topical testosterone cream twice daily will produce effective penile growth. The response appears to be greater in younger children, which is consistent with previously published studies of age-related 5 reductase activity.

The Synergistic Effect of Hyperthermia and Chemotherapy on Murine Transitional Cell Carcinoma

The in vivo effect of hyperthermia and chemotherapy was studied in a murine transitional cell carcinoma model. Localized hyperthermia (43.5C) of 60 and 90 minutes duration was combined with systemic doxorubicin hydrochloride, cis-platinum, cyclophosphamide or mitomycin to treat tumors implanted into the hind legs of C3H mice. The data were compared to the results obtained from the application of hyperthermia or chemotherapy alone as well as to the natural growth rate of untreated tumors. Untreated tumors grew with an exponential rate and had a doubling time of 4 +/- 1.5 days. Animals bearing such tumors survived for 25 +/- 7 days. When treated with hyperthermia alone, there was no significant reduction in the growth rate and no improvement was noted in the survival time. Treatment with doxorubicin hydrochloride, cyclophosphamide or mitomycin administered alone was likewise not effective. Cis-platinum alone was able to induce a minimal decrease in the growth rate. When the administration of chemotherapy was accompanied by hyperthermia, significant synergistic effect was noted for doxorubicin hydrochloride, cis-platinum and cyclophosphamide (p less than .01); only the mitomycin and hyperthermia combination failed to improve survival and decrease the growth rate. The duration of the hyperthermia exposure influenced the degree of tumor response. Hyperthermia of 90 minutes duration resulted in consistently greater decrease in tumor growth rate with doxorubicin hydrochloride, cis-platinum or cyclophosphamide than 60 minutes of hyperthermia combined with the same agents. These results indicate that local hyperthermia combined with doxorubicin hydrochloride, cis-platinum or cyclophosphamide can induce tumor regression, increase tumor doubling time and improve the survival of the tumor-bearing animal. Only the hyperthermia-mitomycin combination did not result in significant improvement from the baseline values. Thus, hyperthermia combined with selected chemotherapeutic agents can have an adjuvant effect in the treatment of established, implanted mouse bladder tumors.

Xanthogranulomatous pyelonephritis in children.

Xanthogranulomatous pyelonephritis in children, contrary to adult onset, rarely is associated with non-function or calcification. The lesion is predominantly on the left side in children. There appears to be a normal humoral but temporarily impaired cellular immune response in addition to sustained depression of polymorphonuclear chemotaxis. The etiology of this is uncertain but may be attributed partially to hyperosmolarity of serum and urine, and to leukocyte specific antinuclear antibodies. The presence of leukocyte specific antinuclear antibody or cold agglutining may interfere with normal phagocyte chemotaxis requiring tissue macrophages to produce a xanthogranulomatous reaction to bacterial invasion.

Cytogenic studies of cryptorchid testes

Twenty-nine patients with unilateral or bilateral cryptochism underwent biopsies of the testis at the time of orchiopexy. Karyotype evaluation of fibroblasts obtained from tissue cultures of the biopsy specimen was completed counting a minimum of twenty-five cells. In 1 patient with multiple anomalies a 46,XYDq+ karyotype was identified. All other karyotypes were normal suggesting cryptorchism is not associated with abnormal testicular cytogenetics.

Standard water cystometry and electromyography of the external urethral sphincter.

Water cystometry and external urethral spincter electromyography permit an accurate diagnosis and provide a rational foundation for treatment of both neurogenic and nonneurogenic vesical dysfunction. The techniques are compatible with and have enhanced our understanding of the pathophysiology of micturition. Properly performed and interpreted, water cystometry and urethral sphincter electromyography a) are an integral part of the work-up of any patient with incontinence or urinary tract infection, b) together with urethral pressure profilometry and uroflowmetry, assist in the selection of those patients who will or will not benefit from attempted surgical correction of incontinence, and c) can be employed to monitor preoperative and postoperative sequelae of major spinal or paraspinal surgery.