Changes in radical prostatectomy and radiation therapy rates for African Americans and whites.

There are racial differences in prostate cancer outcomes. One variable influencing end results is treatment for cure: either radical prostatectomy (RP) or radiation therapy (RT). The purpose of this report is to determine changes in diagnosis rates of localized prostate cancer between the years before prostate-specific antigen (PSA) use (1973-1988) and the years after PSA use (1989-1996), to evaluate differences in RP and RT rates between the pre-PSA and post-PSA eras, to assess differences in RP and RT rates between African Americans and whites between these intervals. The Surveillance, Epidemiology, and End Results (SEER) data were used and evaluated. Both African Americans and whites had statistically increased rates of localized prostate cancer diagnosed (70.4 and 49.0 in 1973 through 1988 and 123.1 and 84.9 in 1989 through 1996, respectively [p < 0.05]). The differences between the pre-PSA and post-PSA eras for African Americans and whites for RP (3.6 vs. 44.3 and 5.0 vs. 44.9, respectively) and RT (23.6 vs. 61.6 and 17.0 vs. 38.1, respectively) were all significant (p < 0.05). Both African Americans and whites had increased rates of RP from 3.6 and 5.0 to 44.3 and 44.9, respectively, and RT from 23.6 and 17.0 to 61.6 and 38.1 during the pre- and post-PSA years.

Renal medullary carcinoma in patients with sickle cell trait.

Renal medullary carcinoma has recently been described as an aggressive neoplasm affecting young African Americans with sickle cell disease or sickle cell trait. We report the presentation, treatment, and outcome in 3 patients with renal medullary carcinoma along with a description of the unsuccessful treatment attempts. A brief discussion and review of the literature is included.

Percutaneous cryoablation of the prostate: preliminary results after 95 procedures.

PURPOSE: We examined the role of percutaneous cryoablation of the prostate in the treatment of prostate cancer. MATERIALS AND METHODS: We performed 95 percutaneous cryoablations of the prostate on 87 patients with prostate cancer. Of the patients 6 had positive lymph nodes preoperatively, radiation failed in 9 and 9 began postoperative hormonal therapy because of treatment failure. Mean patient age, prostate specific antigen (PSA) level (ng./ml.) and Gleason score were 65.4, 12.60 and 6.03, respectively. Median followup was 12 months (mean 9.3, range 1 to 24). In 49 of the 87 patients (56%) the lymph nodes were evaluated before cryoablation based on the treatment protocol. RESULTS: Median PSA level at 12 months was 0.55 ng./ml. (mean 1.73) with a 17% positive biopsy rate at 3 months. When the positive lymph node, radiation failure and postoperative hormonal therapy groups were removed from analysis, the median PSA level was 0.80 ng./ml. (mean 1.86) with a 5% positive biopsy rate. Of the patients in the radiation failure group 37% had a positive biopsy at 3 months. Cases were classified according to stage, grade and PSA level, and the biopsy results were presented. The complications of percutaneous cryoablation of the prostate were reviewed. CONCLUSIONS: The low percentage of positive biopsies is encouraging but the significance of the persistent PSA levels remains uncertain.

Transurethral microwave thermotherapy for management of benign prostatic hyperplasia: results of the United States Prostatron Cooperative Study.

The primary objective of the study was to determine the safety and efficacy of transurethral microwave thermotherapy for the treatment of symptomatic benign prostatic hyperplasia. From March to August 1991, 150 patients were entered into a multi-site study and treated with transurethral microwave thermotherapy under a Food and Drug Administration approved protocol. Only patients with symmetrical trilobar or bilobar prostatic hypertrophy, peak flow rate of less than 15 cc per second (on 2 voided volumes of 150 cc or greater) and a total Madsen symptom score of more than 8 were treated. Transurethral microwave thermotherapy was performed with a 20F catheter and 1,296 MHz. microwave antenna for 60 minutes. The mean power achieved for this single session was 32.1 watts, with a mean power at maximum urethral temperature of 41.1 watts. Mean urethral temperature was 44.3C and the mean rectal temperature was 42.2C. The rectal and urethral temperatures were continuously monitored. Mean peak urinary flow rates, Madsen symptom score, post-void residual volume and improvement in motivating symptom to seek treatment were measured at 6 weeks, and 3, 6 and 12 months. Mean peak urinary flow rates improved 33% at 12 months (p < 0.0001). Overall, the mean Madsen symptom score improved 61% (p < 0.0001). The obstructive score and the irritative score improved 67% and 43%, respectively. Of 17 patients 12 (71%) reported improvement in weak stream when that was the motivating symptom to seek treatment. Of 28 men 18 (64%) reported improvement in nocturia, while 11 of 30 (37%) reported improvement in daytime frequency and 12 of 17 (71%) reported improvement in urgency. There was no statistically significant difference in post-void residual volume at 12 months from baseline. The treatment was well tolerated by all patients, and side effects were considered mild and transitory. Our study demonstrates the safety, effectiveness, patient tolerability and durability of transurethral microwave thermotherapy.

Acquired immunodeficiency syndrome presenting as testicular lymphoma.

A case of a rapidly expanding testicular mass in a 38-year-old homosexual whose human immunodeficiency virus status was unknown is presented. The mass proved to be lymphoma and serological testing for human immunodeficiency virus was positive. To our knowledge this is the second reported case of acquired immunodeficiency syndrome presenting as a testicular lymphoma.

Coordinate loss of growth regulatory factors following castration of rats carrying the Dunning R3327 G prostatic tumor.

Hormonal manipulation of prostate cancer is an effective therapy for metastatic disease. Unfortunately, following an initial response tumors reestablish themselves as hormone independent variants and progress. This study was designed to assess the interrelationship of cytokeratin P (Cyto P), vimentin, epidermal growth factor receptor (rEGF) and tissue testosterone following androgen deprivation therapy. Animals bearing the hormone dependent Dunning R3327 G subline prostatic adenocarcinoma were surgically castrated and progressing tumors from both hormone intact and castrated groups were quantitatively assayed for immunohistologic reactivity against the described markers. The results demonstrate a significant (p < 0.05) decrease in cytokeratin (Cyto P), rEGF and testosterone levels following castration. When the expression of both rEGF and Cyto P are related to the tissue testosterone content, it is observed that the ratio between rEGF and testosterone remains essentially unchanged (0.65 +/- 0.21 to 0.65 +/- 0.41), suggesting that in the Dunning R3327 G subline, rEGF expression is coordinately under androgen control. At least some cytokeratin expression also appears to be particularly sensitive to androgen levels, since the ratio between Cyto P and testosterone decreased from 0.92 +/- 0.39 to 0.35 +/- 0.41 following castration. In contrast, following castration, the expression of vimentin was unaffected.

Tumor infiltrating lymphocytes: the effect of bacillus Calmette Guerin on helper/suppressor-T cell ratios of treated and untreated tumors.

Copenhagen X Fischer rats bearing single and bilateral Dunning R3327 AT-3 tumors were either treated or not treated at a single site with bacillus Calmette Guerin (BCG). One week later tumors were removed, tumor infiltrating lymphocytes (TIL's) isolated, and then characterized for total-T, helper-T and suppressor-T cell subsets utilizing monoclonal antibodies. The purpose was to determine the effect of BCG on TIL's in treated as well as untreated tumors. In summary: 1) BCG treatment significantly alters TIL distributions at both injected and noninjected sites; 2) a noninjected contralateral tumor compromises the effectiveness of BCG therapy at the suppressor T cell level; 3) contralateral tumors, whether inoculated or not, have similar TIL distributions.

GM-CSF restoration of a differentiated (growth factor-regulated) phenotype in an anaplastic tumor.

GM-CSF (granulocyte-macrophage-derived colony-stimulating factor) is a differentiation agent that stimulates bone marrow activity in patients receiving chemotherapy. GM-CSF (1 microgram/ml daily for 10 days), administered intralesionally, was evaluated to determine whether it would restore a more differentiated phenotype to an anaplastic, rapidly growing, hormone-independent variant (R3327 MAT-LyLu) of the Dunning prostatic adenocarcinoma. Immunohistology was used to quantitate the expression of epithelial growth factor receptors (rEGF) and the tissue testosterone content. GM-CSF therapy significantly (P less than 0.05) restored rEGF expression and tissue testosterone to levels associated with better differentiated, slower growing, androgen-dependent Dunning variants (R3327 H and G). GM-CSF may have a role in treatment of prostatic cancers by promoting androgen and epithelial growth factor regulation.

Characterization of cellular infiltrates in the rat urinary bladder following BCG and thiotepa intravesical therapy.

We examined rat urinary bladders following intravesical administration of BCG and thiotepa. BCG administration resulted in a relatively greater increase in the mucosal infiltration of mononuclear cells relative to polymorphonuclear cells (P less than 0.01) compared to the thiotepa treated bladders. This finding suggests that the mode of action of the therapeutic effects of these agents may be different. These results may also suggest that the mechanism of action of BCG might be immunologic in nature.

Application of immunohistologic staining to develop a malignant index to aid in distinguishing benign from malignant prostatic tissue.

The development of antisera with reactivities against intermediate filaments, differentiation antigens, and secretory products has aided in identification and characterization of tissue specimens. Such evaluations may assist pathologists in distinguishing between benign (BPH) and malignant (CAP) tissue of prostatic origin. However, attempts to employ this technique are thwarted by 1) the use of frequently incompletely characterized antisera, 2) the use of both paraffin- and frozen-sectioned materials, and 3) a lack of quantitation in the degree of antisera immunoreactivity. To overcome these shortcomings, a mathematical approach was evaluated using eight BPH and 23 CAP specimens. These were sectioned and stained using commercially prepared antisera against cytokeratin (Cyto P, Cyto M), epithelial membrane antigen (EMA), NK cells (Leu-7), prostatic acid phosphatase (PAP), and prostate specific antigen (PSA). Reactivity was quantitated on a scale of 0-5. Mean values for markers elevated in CAP (relative to BPH) were placed in the numerator; those elevated in BPH (relative to CAP) were placed in the denominator: Malignant index = PSA + EMA + Leu-7 + Cyto M/PAP + Cyto P. This malignant index was significantly greater (P less than .001) in CAP tissues than in BPH regardless of Gleason grade (3.2 +/- 0.9 vs 1.6 +/- 0.9). It was also significantly elevated (3.0 +/- 0.8; P less than .01) in nine specimens representing prostatic atypical hyperplasia. These data suggest that immunohistologic staining may be applied as an aid in distinguishing between BPH and CAP.

New transurethral system for interstitial radiation of prostate cancer.

Direct endoscopic implantation of radioactive materials for carcinoma of the prostate without an open operation was accomplished by the use of modified existing transurethral instrumentation and techniques. The closed approach seems applicable particularly to the geriatric population, which is afflicted more commonly but is frequently not treated because of concurrent diseases or because the patient had transurethral resection of the prostate as a diagnostic procedure. Eleven patients were implanted using the transurethral route. Implantations were accomplished successfully with extremely low morbidity. Along with more conventional dosimetry studies, computer tomography was used to assess the placement of seeds. The direct visualization of the method suggests a potential for greater precision of seed placement as illustrated by computer tomography. In addition, this new instrumentation and method offers a low-risk procedure for carcinoma of the prostate that can be performed on an outpatient basis for selected patients.

Effect of BCG upon functional and phenotypic immune markers in rats bearing the Dunning R3327 MAT-LyLu prostatic adenocarcinoma.

Rats bearing (or not bearing) the Dunning R3327 MAT-LyLu prostatic adenocarcinoma were treated with Bacillus Calmette-Guérin (BCG) and evaluated for immune competence using functional and phenotypic markers. Tumor presence significantly depressed total T and helper T cell representation along with the helper/suppressor T cell ratio. Functional immunity, measured by phytohemmagglutinin (PHA) induced blastogenesis, was also significantly depressed. When BCG was administered to non-tumor bearing animals, it had no effect upon T cell subset distributions but significantly reduced PHA induced blastogenesis. BCG similarly administered to tumor bearing animals did not alter the depressed helper/suppressor T cell ratio found in tumor bearing rats, but did significantly elevate PHA induced blastogenesis. However, these elevated levels of functional immunity in BCG treated tumor-bearing rats remained significantly below normal. These data demonstrate a poor correlation between functional and phenotypic assessments of immune capability.

Review of acid phosphatase in the diagnosis and prognosis of prostatic cancers.

Acid phosphatase is a secretory product frequently utilized as a tumor marker for disseminated, late stage (D2) prostatic cancer. In the 40 years since this association has been recognized, this enzyme has been subjected to extensive biochemical and immunological characterizations. These techniques have also been adapted for rapid and specific determinations of the prostatic isoenzyme levels using a variety of techniques. Since acid phosphatase levels do not become significantly elevated until late stage cancer, newer markers such as prostate-specific antigen have been sought which appear earlier and may be more useful for the screening and monitoring of high risk populations. At this time it is appropriate to review the current and future status of acid phosphatase as a diagnostic aid.

Immunoregulatory markers in rats carrying Dunning R3327 H, G, or MAT-LyLu prostatic adenocarcinoma variants.

The Dunning R3327 tumor represents a system for studying prostate cancer in Copenhagen X Fischer rats. Animals bearing variant sublines (H, G, and MAT-LyLu) differing in growth rate, differentiation, hormone responsiveness, and metastatic ability were assayed for three immunological markers. Spleens were passed through a tissue sieve, and mononuclear cells were obtained by Ficoll-Hypaque centrifugation. These were assayed for leukocytic subsets using monoclonal antibodies. An adherent population was isolated and evaluated using thin-layer chromatography for conversion of radiolabeled arachidonic acid to E series prostaglandins. Finally, sera from these animals were assayed for levels of circulating immune complexes using polyethylene glycol precipitation. Data from 52 rats bearing the various tumors were obtained, correlated with subline aggressiveness, and compared to 15 controls. Each tumor group demonstrated significantly lower helper/suppressor T-cell ratios than controls, probably due to general tumor presence. In addition, the most aggressive R3327 MAT-LyLu variant had significantly increased prostaglandin E synthesis by adherent spleen cells compared to the H or G sublines and significantly increased levels of circulating immune complexes relative to the H subline. G subline values for both prostaglandin E and circulating immune complexes levels were intermediate, suggesting that these markers correlate better with tumor aggressiveness than helper/suppressor T-cell ratios.

Effect of cyclophosphamide on leukocytic subset distributions in rats carrying the Dunning R3327-MAT-LyLu prostatic adenocarcinoma.

The Dunning R3327 adenocarcinoma represents a model for studying prostate cancer in rats; early studies have indicated its utility for studying relationships between tumor growth, immunologic markers, and chemotherapy. Normal animals and those bearing the metastatic Dunning R3327 MAT-LyLu tumor were treated with 10, 30, and 100 mg/kg doses of cyclophosphamide (CTX) and their spleens assayed for leukocytic subset distributions using monoclonal antibodies. Tumor-bearing animals had significant reductions in helper T cell content as well as reduced helper/suppressor T cell ratios, compared to controls. These effects occurred rapidly following implantation and were not reversed by chemotherapy. When administered to both tumor- and non-tumor-bearing animals, CTX also depleted T cell populations. Despite reductions produced in all subsets, two administrations of CTX (30 mg/kg) were capable of retaining (in non-tumor-bearing animals) or restoring (in tumor-bearing) normal helper/suppressor T cell ratios. Such studies aid in identifying therapeutically effective dosages of cytotoxic drugs that minimize their deleterious effects on the immune system.

Combination therapy using polyamine synthesis inhibitor alpha-difluoromethylornithine and adriamycin in treatment of rats carrying the Dunning R3327 MAT-LyLu prostatic adenocarcinoma.

Prostate cells of human and rat origin produce polyamines in high content, whose apparent functions relate to cellular proliferation and secretory activities. Formation is dependent on the enzyme ornithine decarboxylase (ODC) which is irreversibly inhibited by alpha-difluoromethylornithine (DFMO). It has been postulated that pretreatment with DFMO may render cells more susceptible to subsequent chemotherapy. Copenhagen X Fischer F1 rats bearing the Dunning R3327 MAT-LyLu prostatic adenocarcinoma were given DFMO or adriamycin (ADR), alone or in combination. Those receiving DFMO were continuously provided the drug ad libitum, in water (2.5%), for the duration of the experiment, beginning 2 days prior to ADR administration. At intervals, tumor sizes were measured, animal survivals noted and comparisons made to nontreated, tumor-bearing controls. The results indicate that ADR alone or in combination with DFMO significantly reduced tumor progression, but that only combination therapy significantly prolonged survivals. Decreased tumor progression produced by DFMO alone was not statistically significant. Differences produced with combined use were additive and suggest that DFMO may augment ADR chemotherapy.

Administration of recombinant tumor necrosis factor to rats bearing the Dunning R3327 MAT-LyLu prostatic adenocarcinoma.

Copenhagen X Fischer F1 rats bearing palpable Dunning R3327 MAT-LyLu prostatic adenocarcinomas were treated by intraperitoneal (i.p.) or intratumor (i.t.) injection with either human serum albumin alone or in combination with recombinant tumor necrosis factor (rTNF). At intervals tumors were measured and survivals noted. A maximum tolerable dose and least toxic route of administration was then determined. Those treated i.t. with rTNF survived significantly longer and ultimately developed significantly smaller tumors than untreated controls. Those administered rTNF by the i.p. route had less significant increases in survival with intermediate final tumor sizes.

Leukocytic subset distributions of spleen cells obtained from rats bearing variants of the Dunning prostatic adenocarcinoma.

Employing monoclonal antibodies, the relative frequencies of mononuclear cell types found in spleen cell populations were compared between rats bearing variants of the Dunning prostate adenocarcinoma and a series of non-tumor bearing control animals. The identification and quantitation of such subsets greatly expands our knowledge of immune status and function. The results indicate that the spleen cell populations from animals bearing either the Dunning R3327-H, G or MAT-LyLu sublines have significant decreases in their helper T cell/suppressor T cell ratios when comparisons are made to cells obtained from non-tumor bearing animals. In addition decreases in total T cell content and increases in splenic monocytes were noted. It appears that most of these deviations are the result of general Dunning tumor presence, rather than due to any particular subline characteristic. These changes may be analogous to similar alterations reported in the peripheral blood of humans bearing Stage D prostatic cancer, suggesting that the Dunning tumor may provide an appropriate model for evaluating interactions between the immune response, the tumor and therapy.

Immunobiology of the Dunning R-3327 rat prostate adenocarcinoma sublines: plasma and tumor effusion prostaglandins.

Enhanced production of prostaglandins (PGs) by experimentally-induced and naturally occurring tumors and their effect on tumor growth and immunosurveillance have been noted. Directed toward further evaluation of the relationship between prostatic tumor growth and its milieu, i.e., microenvironment, we investigated the possible correlation between levels of PGs, tumor size, and metastatic potential. For this purpose, the levels of PGE2 and PGF2 alpha in plasma and tumor effusions of three tumor sublines of the Dunning R-3327 rat prostate adenocarcinoma were measured: R-3327H, well-differentiated, slow-growing, and poorly metastatic; R-3327G, poorly differentiated, fast-growing, and poorly metastatic; and R-3327 Mat LyLu, anaplastic, fast-growing, and highly metastatic. The level of PGF2 alpha was highly variable with no significant differences being noted between the tumor sublines. The mean values of PGF2 alpha were, however, higher, although not significantly so, in the smaller tumors within each of the sublines. The levels of PGE2 were significantly higher in Mat LyLu effusions than those from the nonmetastasizing R-3327G and H sublines. Evaluation and comparison of the relationship between tumor burden, i.e., size versus levels of PGE2 and PGF2 alpha showed no significant differences. A vasodilator and regulator of immunological responsiveness, PGE2, may function as a modulator of tumor metastases. In consonance with studies by others elevated levels of PGE2 may possibly serve as a prognostic marker for the high metastatic potential of neoplastic cells.