Nicholas A. Romas

Bone Marrow Acid Phosphatase: Prognostic Value in Patients Undergoing Radical Prostatectomy

Preoperative bone marrow acid phosphatase determinations were elevated in 18 of 31 patients who underwent radical prostatectomies. A review of the surgical pathology and clinical followup demonstrated a higher incidence of metastasis in these patients.

Long-term treatment with finasteride in men with symptomatic benign prostatic hyperplasia: 10-year follow-up.

OBJECTIVES To evaluate the safety and efficacy of finasteride 5 mg during a 10-year period in men with enlarged prostates from a single center who participated in the double-blind and extension phases of the multicenter, Phase III, North American benign prostatic hyperplasia (BPH) trial. It is important that the long-term safety and efficacy of drugs intended for chronic administration in men with BPH be well understood. METHODS The Phase III North American BPH trial involved a 1-year, placebo-controlled, double-blind study, followed by a 5-year open extension with finasteride 5 mg/day. The trial enrolled men with symptomatic BPH, an enlarged prostate on digital rectal examination, and no evidence of prostate cancer. Of the 46 patients originally enrolled from our institution, 43 were randomized to receive finasteride or placebo, of whom 41 (95%) completed the double-blind study and entered the 5-year extension. Thirty (73%) of these 41 patients completed the 5-year extension. Patients continued to be followed up by their physicians for an additional 5 years, for a total follow-up of at least 10 years. RESULTS Twenty-four (56%) of the original 43 patients randomized to finasteride or placebo were judged as successfully treated during the 10-year finasteride follow-up (17 patients taking finasteride alone at 10 years and 7 patients who were taking finasteride alone when they discontinued during the 10-year follow-up for reasons not related to finasteride treatment). Altogether, 22 (51%) of the original 43 randomized patients continued finasteride treatment at 10 years (17 taking finasteride alone, 4 taking finasteride plus an alpha-blocker, and 1 taking finasteride for treatment of hematuria). Finasteride was well tolerated, with no new adverse experiences occurring with increasing duration of exposure to the drug. CONCLUSIONS This long-term follow-up study has demonstrated that appropriately selected patients with symptomatic BPH and enlarged prostates are likely to have a long-term response to taking finasteride 5 mg daily.

Carcinoembryonic Antigen and Bladder Carcinoma

The 24-hour urinary carcinoembryonic antigen determinations were performed on 61 patients with different stages of bladder carcinoma. Elevated titers were found in 81 per cent of the patients with active tumors and falsely positive studies were found in 7 per cent. High stage lesions were found to have high carcinoembryonic antigen levels. Plasma carcinoembryonic antigen determinations were elevated in only 45 per cent of the patients with active tumors but further study may be warranted in advanced bladder cancer cases. The 24-hour urinary carcinoembryonic antigen measurements yield the highest percentage elevations in bladder carcinoma and further investigation is required to better define its clinical application.

Acid phosphatase localization in prostatic carcinoma. A comparison of monoclonal antibody to heteroantisera

A series of 39 prostatic carcinomas was characterized in terms of grade, stage, histologic pattern, and serum acid phosphatase values. These cases were studied immunohistochemically with two different heteroantisera, a goat and rabbit antiserum, and with a monoclonal antibody to prostatic acid phosphatase (PAP). Eighty‐three percent of carcinomas had some degree of PAP positivity when stained by the goat anti‐PAP. Seventy percent were positive with the rabbit antiserum, and 59% showed positivity with the monoclonal antibody. Microacinar patterns were consistently the most positive for PAP, followed by cribriform patterns. The least positivity was observed in the undifferentiated, singlefile and sheet‐like patterns. Likewise, there was more PAP positivity in the lower Gleason and Mostofi grades. When the serum PAP positivity (done by counterimmunoelectrophoresis [CIEP]) was compared with tissue positivity (using the same goat antiserum), 37% were positive in both serum and tissue; 48% were negative in serum, but positive in tissue; and in only 9% the tissue sample was negative when the serum was positive. Based on these data, conclusions are drawn about the significance of the serum acid phosphatase elevations and the role of monoclonal antibodies and heteroantisera in clinical–diagnostic and research work.

Chemotherapy for bladder cancer

Abstract Systemic therapy for bladder neoplasms has thus far been ineffective and toxicity has outweighed benefits. Topical therapy by bladder instillations of Thiotepa and Epodyl has been effective for treatment of multiple superficial bladder tumors and appears to be helpful as a prophylactive measure to reduce recurrences of such tumors. Topical therapy is not recommended for invasive tumors. Careful attention to dosage regimens and adjustment of doses as indicated by white blood cell and platelet counts minimizes toxic effects from treatment.

Human sex hormone-binding globulin gene expression- multiple promoters and complex alternative splicing

BackgroundHuman sex hormone-binding globulin (SHBG) regulates free sex steroid concentrations in plasma and modulates rapid, membrane based steroid signaling. SHBG is encoded by an eight exon-long transcript whose expression is regulated by a downstream promoter (PL). The SHBG gene was previously shown to express a second major transcript of unknown function, derived from an upstream promoter (PT), and two minor transcripts.ResultsWe report that transcriptional expression of the human SHBG gene is far more complex than previously described. PL and PT direct the expression of at least six independent transcripts each, resulting from alternative splicing of exons 4, 5, 6, and/or 7. We mapped two transcriptional start sites downstream of PL and PT, and present evidence for a third SHBG gene promoter (PN) within the neighboring FXR2 gene; PN regulates the expression of at least seven independent SHBG gene transcripts, each possessing a novel, 164-nt first exon (1N). Transcriptional expression patterns were generated for human prostate, breast, testis, liver, and brain, and the LNCaP, MCF-7, and HepG2 cell lines. Each expresses the SHBG transcript, albeit in varying abundance. Alternative splicing was more pronounced in the cancer cell lines. PL- PT- and PN-derived transcripts were most abundant in liver, testis, and prostate, respectively. Initial findings reveal the existence of a smaller immunoreactive SHBG species in LNCaP, MCF-7, and HepG2 cells.ConclusionThese results extend our understanding of human SHBG gene transcription, and raise new and important questions regarding the role of novel alternatively spliced transcripts, their function in hormonally responsive tissues including the breast and prostate, and the role that aberrant SHBG gene expression may play in cancer.

Epididymal metastasis from prostatic adenocarcinoma mimicking adenomatoid tumor

A case of epididymal metastasis from prostatic carcinoma is presented. The initial histologic findings were suggestive of adenomatoid tumor, but a diagnosis of metastatic adenocarcinoma of prostatic origin has been established by prostatic acid phosphatase and prostate-specific antigen immunoperoxidase staining.

Bone Marrow Acid Phosphatase in Prostate Cancer: An Assessment by Immunoassay and Biochemical Methods

Comparisons of the bone marrow and serum acid phosphatase values obtained by counterimmunoelectrophoresis and the Roy biochemical test were made in 72 patients with and in 13 patients without prostatic cancer. The counter-immunoelectrophoresis test, when positive at more than 1 international unit per liter, showed only 4.4% falsely positive results. The Roy biochemical test, which uses sodium thymolphthalein monophosphate as the substrate, had 65% falsely positive bone marrow acid phosphatase levels. Conflicting reports regarding the value of bone marrow acid phosphatase determinations in patients with prostatic cancer result from the use of non-specific substrates in biochemical methods for measurement and from the trauma incidental to bone marrow aspiration, which releases many non-prostatic acid phosphatase enzymes. The use of immunoassay such as counter-immunoelectrophoresis minimizes this source of error.

Clinically significant metastaticmelanoma to prostate

Abstract Malignant melanoma metastatic to the lower genitourinary tract is an unusual causeof urinary obstruction. It is usually a diagnosis made at autopsy. Occasionally malignant melanoma may cause significant obstructive symptoms that require intervention, although the prognosis for these patients is uniformly poor due to widespread disseminated disease.

A new method for determination of urinary tryptophan metabolites in bladder carcinoma.

Abnormal tryptophan metabolism in patients with bladder carcinoma has been reported to have an extremely high correlation with future tumor recurrences. The methods for determination of these urinary metabolites have not been applicable for routine clinical use in the past. A new method is described using thin layer chromatography followed by fluorescent scanning with the SD 3000 spectrodensitometer. The range of recovery for the 6 tryptophan metabolites was from 96.9 to 106.7 per cent. In our study 31 per cent of the male and 50 per cent of the female bladder cancer patients had 2 or more abnormal tryptophan metabolites.