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Biomedical subjects

P Guinan

Publications and source records attributed to P Guinan.

At least 19 recordsLinked to original sources

The impact of transrectal ultrasound on stage migration in a predominantly African-American population.

An important question left unanswered is whether transrectal ultrasound will result in earlier diagnosis in African Americans. Tumor registry data for 1985 and 1990 for a predominantly African-American population were reviewed to determine whether transrectal ultrasound influenced the stage at diagnosis of prostate cancer. Diagnosis by ultrasound increased from 0% to 60% of cases in those 5 years. Curable diseases (stages A and B) increased from 38% to 57% of cases. It is concluded that transrectal ultrasound can increase the diagnostic yield of potentially curable disease in a predominantly African-American population.

Aged

Urethral diverticular carcinoma.

BACKGROUND: Urethral diverticular carcinoma is an unusual finding in a urologic lesion commonly found in female patients. METHODS: This report presents 6 new cases and reviews the other 53 cases in the English literature. RESULTS: Adenocarcinoma occurs more frequently than transitional and squamous cell cancers combined. CONCLUSION: The prognosis of the former is more favorable. In general, radical therapy is recommended. However, in some instances of localized disease, and with careful follow-up, a more conservative approach might be attempted.

Adult

Renal pelvic transitional cell carcinoma. The role of the kidney in tumor-node-metastasis staging.

Renal pelvic carcinoma is a rare tumor. There are several staging systems currently in use based on a bladder cancer staging model. An analysis of the American Cancer Society, Illinois Division, experience with 611 cases of renal pelvic transitional cell carcinoma suggested that the kidney parenchyma may be a determinant in the anatomic spread of disease. A tumor-node-metastasis system for renal pelvic (separate from ureteral) cancer is recommended.

Carcinoma, Transitional Cell

Microsurgical approach to the abdominal thoracic duct in the rat: considerations in the collection of lymphocytes.

In experiments involving the collection of thoracic duct lymphocytes the anatomy of the abdominal thoracic duct in the rat has been further defined. In general, the abdominal thoracic duct lies posterior and to the left of the aorta between the renal arteries and the diaphragm. There are variations in the microsurgical approach to the classically described location of this organ that should be noted by investigators attempting to identify and dissect this structure.

Animal Welfare

Renal pelvic cancer: a review of 611 patients treated in Illinois 1975-1985. Cancer Incidence and End Results Committee.

Renal pelvic transitional cell carcinoma constitutes about 7 percent of all kidney cancer. This report is a summary of 611 Illinois patients with this tumor treated between 1975 and 1985. Overall, the five-year relative survival rate was 62 percent and the observed five-year rate was 48 percent. Stage was a major determinant of survival, as expected, in these cancer patients. The Illinois experience is reviewed and compared with the accumulated literature experience with renal pelvic cancers since 1944.

Age Factors

The effect of BCG on thoracic duct lymphocytes.

Adoptive immunotherapy is becoming increasingly more important in the management of advanced malignancies. This report describes the results of immunomodulation therapy with BCG in the Dunning tumor. In addition it describes new techniques in the harvesting of lymphocytes. Thoracic duct lymphocytes from 34 rats were evaluated for the effect of the presence of the Dunning R-3327 AT-3 tumor as well as for the response to bacillus Calmette Guerin (BCG). Both tumor and BCG resulted in significant changes in the helper/suppressor T cell ratios.

Animals

Bone scan as a stratification variable in advanced prostate cancer.

The serial technetium 99 (99Tc) bone scans of 76 patients with Stage D-2 prostate cancers were reviewed. Sites of metastases in skeletal areas in decreasing order were vertebrae, ribs, pelvis, long bones, and skull. Patients with one or two involved skeletal areas had a significantly longer progression-free interval and survival time than patients with three or more bony areas of uptake. Bone scans might be used as a stratification variable in future prospective clinical trials of Stage D-2 prostate cancer.

Aged

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.

Administration, Intravesical

A comparison of Zoladex and DES in the treatment of advanced prostate cancer: results of a randomized, multicenter trial.

This open, prospective study was conducted to compare ZOLADEX (goserelin acetate implant) and diethylstilbestrol (DES) in the treatment of stage D2 prostate cancer. Sixty-seven patients were allocated to receive 3.6 mg of ZOLADEX every 28 days by subcutaneous injection (n = 48) or 3 mg of DES daily by oral administration (n = 19). Median serum levels of testosterone were reduced to castrate levels (less than 50 ng/dl) within one month of therapy in each group and remained so for up to 120 weeks. According to modified criteria of the National Prostatic Cancer Project, 88% of patients in the ZOLADEX group and 84% in the DES group were objective responders. Time to treatment failure and survival were not significantly different between groups, yet the confidence limits for the hazard ratios were wide. ZOLADEX was better tolerated than DES. We conclude that ZOLADEX is an alternative to DES in patients with stage D2 prostate cancer.

Aged

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.

Adenocarcinoma

Long-term complete remission in bladder carcinoma in situ with intravesical TICE bacillus Calmette Guerin. Overview analysis of six phase II clinical trials.

Carcinoma in situ is a form of superficial transitional cell carcinoma, which is characterized by a lateral spread along the bladder epithelium, with high-grade malignancy and poor prognosis. Early radical cystectomy is considered the definitive treatment even in the absence of associated invasive cancer. In six prospective phase II studies, 123 carcinoma in situ patients were administered intravesical TICE bacillus Calmette-Guerin (BCG). Treatment consisted of at least six weekly instillations (induction) followed by twelve monthly instillations (maintenance) of BCG (50 mg: 1 to 8 x 10(8) colony-forming units). Of 119 evaluable patients, 90 (76%) achieved complete remission including 45 of 63 (71%) patients who received prior intravesical chemotherapy. Forty-five responders (50%) remain in complete remission with negative urine cytology with a median duration of response projected to be greater than or equal to forty-eight months. There is no difference in survival between BCG responders and nonresponders, but there is a significant difference in cystectomy rates: 10 of 90 (11%) responders vs. 16 of 29 (55%) nonresponders (P less than 0.0001, Fisher's exact test) and time to cystectomy (31 vs. 74 mos.) (P less than 0.001, log-rank test). Delaying cystectomy does not seem to affect survival and improves quality of life. Treatment was well tolerated with some major adverse effects. Intravesical TICE BCG is an effective treatment for bladder carcinoma in situ patients with or without prior chemotherapy.

Administration, Intravesical

Prostate cancer: the stage disadvantage in the black male.

In an effort to determine the impact of race on the stage of prostate cancer at presentation, the records of 2102 patients diagnosed in Chicago between 1985 and 1987 were reviewed. For each of three age groups (less than 65, 65 to 75, and greater than 75 years), blacks had a significantly (P less than .05) lower percentage of localized stage disease than whites. Inasmuch as stage at diagnosis is inversely related to survival, these data may explain in part why prostate cancer mortality in every age category is higher for blacks than whites nationally.

Adult

An immunohistologic characterization of human prostatic atypical hyperplasia.

In an effort to better distinguish the morphologic relationship of atypical hyperplasia of the prostate to benign prostatic hypertrophy and prostatic cancer, 43 prostate specimens were analyzed with ten immunohistologic markers. Two cytokeratin antibodies appeared useful (Cyto M and Cyto P, with the latter slightly more discriminatory). In summary, it appears that atypical hyperplasia is immunohistopathologically related to both benign prostatic hypertrophy and prostatic cancer, having characteristics of both.

Aged

Efficacy of immunopriming prior to isolation of tumor infiltrating lymphocytes for use in adoptive immunotherapy.

Adoptive immunotherapy is dependent upon the leukocytic subsets isolated as tumor infiltrating lymphocytes (TIL) prior to in vitro expansion with interleukin-2. To favorably influence T-cell subset representation in TIL the efficacy of bacillus Calmette Guerin (BCG) and cyclophosphamide (CTX) priming was evaluated in rats bearing Dunning R3327-AT prostatic tumors. When assessed by immunohistochemistry, both agents significantly (p less than 0.001) increased helper-T representation and decreased that by suppressor-T cells. As a result helper/suppressor (H/S) T cell ratios of TIL from untreated tumors (0.73 +/- 0.11) were significantly (p less than 0.001) elevated by both BCG (1.93 +/- 0.39) and CTX (1.40 +/- 0.25). Immunopriming might enhance adoptive immunotherapy by increasing the H/S ratio of TIL prior to their culture.

Animals

Effect of early and delayed difluoromethylornithine pretreatment upon cyclophosphamide chemotherapy.

The Dunning R3327 MAT-LyLu prostatic adenocarcinoma was utilized to study the effectiveness of an early versus delayed difluoromethylornithine (DFMO)-induced polyamine-depleted environment on cyclophosphamide (CTX) chemotherapy. DFMO (2%) was administered either at the time of tumor inoculation (early) or 36 h after tumor implantation (delayed). CTX (50 mg/kg) was administered to both DFMO groups in two doses; the first 36 h after initiation of DFMO therapy, and the second 1 week later. Each protocol (early and delayed) for combined DFMO/CTX chemotherapy significantly reduced tumor sizes with the earlier DFMO protocol appearing slightly more effective (p less than 0.001 and 0.02, respectively). DFMO administered alone was not significantly effective with either protocol.

Adenocarcinoma

Evaluation of cytokeratin markers to differentiate between benign and malignant prostatic tissue.

Cytokeratins are intermediate filaments found within basal and secretory epithelial cells. Antisera raised against cytokeratins are available but frequently differ in specificity. Many are incompletely characterized for their reactivity against epithelial components. Cytokeratin (Cyto) P is a polyclonal antisera specific for 56 and 64 kd cytokeratins. Cyto M is a pool of monoclonals reacting against 40, 46, 50, 52, 58, and 65-67 kd cytokeratins. Initially, utilizing immunohistologic techniques, we evaluated these two antisera for their ability to distinguish between prostatic tissues of benign (benign prostatic hypertrophy [BPH]) or malignant (carcinoma of the prostate [CAP]) origin in the 34 cases evaluated. Specimens were analyzed for both Cyto P and Cyto M reactivity, as well as for the degree of reactivity. Lastly, in an effort to determine the morphologic relationship of atypical hyperplasia (AH) with either BPH or CAP, nine additional prostate specimens were analyzed. Cyto P was reactive in 8 of 8 (100%) BPH specimens and in 2 of 26 (8%) CAP specimens. Mean Cyto P degree of reactivity in the positive specimens was greater in BPH than in CAP (2.6 vs. 1.0). Cyto M reactivity was present in 8 of 8 (100%) BPH specimens and in 23 of 25 (92%) CAP specimens. Mean Cyto M degree of reactivity in the positive specimens was greater in CAP than in BPH (3.6 vs. 2.8). Cyto P was reactive in 3 of 9 (33%) AH specimens, with a mean degree of reactivity of 2.7. Cyto M was reactive in 9 of 9 (100%) AH specimens, with a mean degree of reactivity of 3.9. Cyto P reacted with only the basal cells, whereas Cyto M reacted with basal as well as secretory cells. These differences appeared to be the result of the differential reactivity of basal cells, which are present in BPH but absent in CAP. In summary, Cyto P and Cyto M are potentially useful markers in differentiating BPH from CAP, and it appears that AH is immunohistopathologically related to both.

Aged

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.

Diagnosis, Differential