Observations on the early detection of prostate cancer from the American Cancer Society National Prostate Cancer Detection Project.

BACKGROUND: The American Cancer Society National Prostate Cancer Detection Project (ACS-NPCDP) was established in 1987. The experience of the ACS-NPCDP demonstrates the yield and impact of periodic examinations for the early detection of prostate cancer. METHODS: A cohort of 2999 well men ages 55-70 years was tested annually at 10 clinical centers by prostate specific antigen (PSA), transrectal ultrasound (TRUS), and digital rectal examination (DRE). Biopsies were performed on men with suspicious findings. Pathologic findings were reviewed. The initial study outcomes were the detection yield of multimodality testing and the comparative sensitivity and specificity of the different tests employed. Longer term outcomes included patient quality of life and survival. RESULTS: The cancer detection rate declined significantly across the years of intervention. DRE had lower sensitivity than TRUS or PSA, particularly in later years of follow-up. The specificity of TRUS was lower than that of DRE. Fewer than 9% of the cancers detected in this study were clinically advanced at the time of diagnosis. Ninety-four percent of patients in whom cancer was detected are alive after an average follow-up of 54 months. In one case, death occurred after surgery. Two deaths were attributed to prostate cancer, and eleven other deaths were unrelated to prostate cancer or its treatment. CONCLUSIONS: Results of the ACS-NPCDP indicate that a combined-modality approach to prostate cancer detection yields high levels of early detection with infrequent adverse outcomes. Continued follow-up is required to evaluate long term morbidity and mortality.

Gossypol arrests human benign prostatic hyperplastic cell growth at G0/G1 phase of the cell cycle.

Recently we demonstrated that gossypol (GP), a male antifertility agent, is a potent inhibitor of malignant human prostate cancer cell growth that acts by arresting cells in G0/G1 phase and that this inhibitory effect may be mediated by transforming growth factor-beta 1 (TGF-beta 1). In this study we examined the effect of GP on the growth of prostatic cells from human benign prostatic hyperplasia (BPH) patients in vitro. Consistent with its inhibitory effect on the growth of malignant human prostate cancer cells, GP also acts as a potent inhibitor of cultured human BPH cell growth as assessed by thymidine incorporation assay. These results were confirmed by flow cytometric analysis which revealed that treatment of human BPH cells with increasing concentrations of GP resulted in a dose-dependent accumulation of cells in the G0/G1 phase with a concomitant decrease in cells progressing to the S and G2/M phases. Since inhibition of prostate cancer cells by GP appears to be mediated by TGF-beta 1, we also investigated the effect of GP on TGF-beta 1 gene expression in BPH cells. The results show that GP treatment resulted in a marked elevation of TGF-beta 1 gene expression indicating that TGF-beta 1 might be involved at least in part in the inhibitory pathway that is initiated by GP.

Inhibition of human prostate cancer cells growth by gossypol is associated with stimulation of transforming growth factor-beta.

Gossypol (GP), an antifertility agent in males, is also capable of inhibiting the proliferation of a wide range of cancer cells in vivo and in vitro. Thus, in this study we investigated the effect of GP on the growth of human androgen-independent prostate cancer cell line (PC3). The results showed that GP acts as a potent inhibitor of PC3 cells as determined by thymidine incorporation assay and flow cytometric analysis. Flow cytometry revealed that treatment of PC3 cells with GP resulted in a dose- and time-dependent accumulation of cells in the GO/GI phase with a concomitant decrease in cells progressing to the S and G2/M phase. These data support our thymidine incorporation results which indicated that GP is a potent inhibitor of PC3 cells. By ribonuclease protection assay, we also investigated the effect of GP on transforming growth factor-beta 1 (TGF-beta 1) gene expression in PC3 cells. Interestingly, the stimulatory effect of GP on TGF-beta 1 gene expression correlates well with its inhibitory effect on PC3 cell DNA synthesis and its ability to arrest cells in GO/G1 phase. Based on these data, it can be concluded that GP is a potent inhibitor of prostate cancer cell growth that acts by arresting cells in GO/G1 phase and that this inhibitory effect may be mediated by TGF-beta 1.

Management of forgotten or retained indwelling ureteral stents.

Five patients presented with forgotten or retained stents, and a plan of management for this complication is described. Stents were in place from 1 to 7 years. We developed an algorithm for evaluating and treating these complications. All patients should have intravenous urogram to determine function and to identify any obstruction. If there is no stent encrustation, a simple extraction under fluoroscopic control can be attempted. If significant stent calcification is present, extracorporeal shock-wave lithotripsy may be tried first. Open procedures are reserved for those patients with more than 3 mm of stent encrustation extending throughout the length of the stent, or with large volume upper tract calcification. For minimally calcified stents or for those stents with upper curls that will not straighten out on gentle traction, percutaneous extraction can be attempted in the radiology suite. If this is unsuccessful, then percutaneous nephrostolithotomy is the next step.

Detection of keratinocyte growth factor (KGF) transcripts from normal human and archival canine benign prostatic hyperplastic tissues.

This study examined the expression of keratinocyte growth factor (KGF) gene in human and canine prostatic tissues. KGF transcript was detected in normal human prostatic tissues by reverse transcription and polymerase chain reactions (RT-PCR). PCR-generated human KGF complementary DNA (cDNA) clone was confirmed by restriction enzyme digestion analysis and partial DNA sequencing. Expression of KGF in archival canine benign prostatic hyperplastic tissues was also examined. In a pilot experiment, RNAs isolated from formalin-fixed (FF) and formalin-fixed and paraffin-embedded (FFPE) canine prostatic tissues were shown to be of sufficient quality to permit amplification of KGF mRNA by RT-PCR. The transcript of a housekeeping gene, glucose-6-phosphate dehydrogenase (G6PD), was detected by RT-PCR indicating the quality of RNAs to be more than adequate for RNA expression analysis. Later, total RNA from two archival canine FF prostate tissue types, benign prostatic hyperplasis and mild glandular hyperplasia, were used to amplify canine KGF transcripts. Southern hybridization analysis using rat and human KGF cDNAs as probes confirmed the fidelity of the amplified PCR product and it was indeed canine KGF.

Laser welding of pedicled flap skin tubes.

The efficacy of the carbon dioxide laser used at high power levels for tissue destruction is well established. This laser at lower power levels has been used to incise and anastomose blood vessels, tendons, nerves, dura, bowel, fallopian tube, vasa deferentia, ureters and skin. Laser welding is faster, reduces surgical manipulation and introduces less foreign material into the wound than conventional suturing techniques. We tested the feasibility of laser welding of pedicled flap skin tubes to determine if there is a potential application in reconstruction, particularly for hypospadias repair.

An in vivo evaluation of alpha adrenergic receptors in canine prostate.

The role of alpha 2 adrenergic receptors in the prostate in vivo is unknown. A model was developed to measure canine prostatic urethral pressure in vivo, and to assess the ability of various alpha adrenergic blocking agents to affect prostatic pressure. In this model, an esophogeal pressure catheter is inserted into the prostatic urethra to record prostatic urethral pressure. We investigated the effects of alpha adrenergic agonists and antagonists on prostatic pressure using this model. Dose-response curves were generated for epinephrine, and were then repeated in the presence of either prazosin (alpha 1 antagonist), yohimbine (alpha 2 antagonist) or SK&F-86466 (alpha 2 antagonist). Prazosin was the most potent of the three drugs in competitively blocking epinephrine-induced contraction of the prostate, with an inhibition constant of 0.24 micrograms./kg. calculated from the double reciprocal plot. Clonidine, an alpha 2 adrenergic agonist, caused contraction of the prostate, which was also blocked by prazosin. Furthermore, the specific alpha 2 agonist BHT-920 was totally inactive in our system. These results demonstrate that the increase in urethral pressure caused by alpha-adrenergic agonists can be blocked by alpha adrenergic antagonists. However, the specific alpha 1 antagonist, prazosin, is more potent than alpha 2 antagonists, and is also effective against an alpha 2 agonist, clonidine. This suggests that blockade of alpha 1 receptors may be a more useful strategy for causing relaxation of the prostate than blockade of alpha 2 receptors.

Renal parenchymal neurilemoma: a rare and unusual kidney tumor.

We report a case of a neurilemoma arising from the renal parenchyma. Renal neurilemoma is an extremely rare tumor, with only 5 cases previously reported. Because so little is known of its natural history and potential for malignancy we recommend radical nephrectomy as the treatment of choice.

The use of ketoconazole in the emergency management of disseminated intravascular coagulation due to metastatic prostatic cancer.

The disseminated intravascular coagulation syndrome is an untoward side effect of metastatic adenocarcinoma of the prostate. In addition to appropriate replacement of blood, platelets and clotting factors, prompt treatment of the prostatic carcinoma is required to correct the underlying pathophysiological defect. Ketoconazole is the ideal method for hormonal manipulation for patients with life-threatening complications of prostatic carcinoma (disseminated intravascular coagulation and acute paraparesis/paraplegia) because of its prompt onset of action in decreasing circulating concentrations of androgens to castrate levels. Serum testosterone levels are castrate within 48 hours of the initiation of therapy with ketoconazole as opposed to a minimum of 10 to 14 days with estrogens. A patient with spontaneous bleeding from disseminated intravascular coagulation was treated with 400 mg. ketoconazole every 8 hours and bleeding stopped within 48 hours. Ketoconazole is particularly valuable when a prompt therapeutic response is needed and orchiectomy is contraindicated because of bleeding diathesis (as in disseminated intravascular coagulation), delay in histological confirmation (as in acute paraparesis/paraplegia) or patient reluctance to undergo castration.

Localized gangrene of the scrotum and penis: a complication of heroin injection into the femoral vessels.

Long-term intravenous heroin abusers have problems of vascular access. After the accessible sites are sclerosed, the neck, axillae and groins are then used frequently. We report on 3 heroin abusers who presented with localized gangrene of the genitalia after injection into the femoral vessels. We postulate that the pathophysiology of this entity is related to arterial embolization of particulate matter into the microcirculation of the genitalia, which causes arterial thrombosis leading to localized gangrene. Of the 3 patients 2 were treated with local excision, débridement and primary closure. A fourth addict who injected heroin directly into the scrotum and perineum, presented with Fournier's gangrene, a completely different, more lethal entity.