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Biomedical subjects

M C Benson

Publications and source records attributed to M C Benson.

At least 19 recordsLinked to original sources

Arteriovenous malformation of ureter.

Congenital arteriovenous malformations of the genitourinary tract are rare. We report the first case of an arteriovenous malformation of the ureter. The patient presented with recurrent hematuria and left flank pain. Evaluation included an intravenous urogram, cystoscopy, and retrograde pyelography. A pedunculated lesion thought to be a fibroepithelial polyp was seen at the time of ureteroscopy, and the lesion treated by excisional biopsy and fulguration. Pathologic examination demonstrated an arteriovenous malformation. After thirty-month follow-up, the patient remains asymptomatic and free of recurrence.

Adult

The predictive value of flow cytometry and urinary cytology in the followup of patients with transitional cell carcinoma of the bladder.

To determine the predictive value of flow cytometric deoxyribonucleic acid (DNA) ploidy and urine cytology in patients with superficial transitional cell carcinoma of the bladder, a retrospective analysis was performed on 181 patients who presented for evaluation of presumed superficial transitional cell carcinoma of the bladder. Of the patients 91 were confirmed to have superficial transitional cell carcinoma and were systematically followed with cystoscopy, flow cytometry and urine cytology from 1984 until 1989. They underwent 637 evaluations (mean 7 evaluations per patient). At initial evaluation, flow cytometry had 81% sensitivity and 57% specificity, while urine cytology was 75% sensitive and 94% specific. During the followup flow cytometry was 76% sensitive and 36% specific. Urine cytology was less sensitive (40%) but more specific (81%) than flow cytometry in followup evaluation. These results were similar whether intravesical chemotherapy or bacillus Calmette-Guerin was administered. To ascertain whether false positive flow cytometry represented early detection of recurrent transitional cell carcinoma not apparent at cystoscopy, patients with positive flow cytometry and urine cytology were followed longitudinally. False positive flow cytometry and urine cytology were equally predictive of recurrent transitional cell carcinoma progressively with time. However, for any given examination flow cytometry was more likely to detect and predict recurrent transitional cell carcinoma. At 4 years the bladder transitional cell carcinoma incidence for false positive flow cytometry and urine cytology was 87% and 84%, respectively.

Adult

Prostate specific antigen density: a means of distinguishing benign prostatic hypertrophy and prostate cancer.

Isolated prostate specific antigen (PSA) determinations in asymptomatic individuals have not demonstrated sufficient sensitivity and specificity to be useful in the routine evaluation of prostate disease. To enhance the accuracy of serum PSA we have used a quotient of serum PSA and prostate volume, which we refer to as prostate specific antigen density (PSAD). Prostate volume in this study was calculated from magnetic resonance imaging determinations of benign prostatic hypertrophy (BPH) or from the dimensions of the surgical specimen of cancer using the formula, length x width x depth x 0.5 = volume. A total of 61 patients with prostatic disease clinically confined to the prostate glands (41 with prostate cancer undergoing radical prostatectomy and 20 with BPH) was evaluated. The mean PSAD for prostate cancer was 0.581 while that for BPH was 0.044 (p less than 0.002). No patient with BPH had a PSAD of greater than 0.117 and only 1 patient had a density of 0.1 or greater. Of 34 patients with a PSAD of 0.1 or greater 33 had prostate cancer. Only 2 of the 41 prostate cancer patients and 14 of the BPH patients had a PSAD of 0.05 or less. There were 11 patients with a PSAD of greater than 0.05 and less than 0.1, including 6 with prostate cancer (1 with P0 disease) and 5 with BPH. Of the 6 prostate cancer patients 5 had a PSA of 4.0 or less and among the 5 patients with BPH 4 had a serum PSA of greater than 4.0 and 1 had a PSA of greater than 10. These results suggest that PSAD may be useful in distinguishing BPH and prostate cancer.

Antigens, Neoplasm

The use of prostate specific antigen density to enhance the predictive value of intermediate levels of serum prostate specific antigen.

Prostate specific antigen (PSA) is an extremely valuable tumor marker. However, its use in detection is limited by its low positive and negative predictive values. The ability of serum PSA to distinguish between benign and malignant prostatic conditions is particularly poor in the intermediate range of 4.1 and 10 ng./ml. by the Hybritech assay. We used transrectal ultrasound determined prostate volumes in a well characterized population of 533 men to form a serum PSA/prostate volume ratio called prostate specific antigen density (PSAD). The prevalence of cancer in the entire population was 18.4%. Discriminant analysis according to negative or positive outcome allowed for the construction of nomograms, which resulted in a PSAD defined cancer risk ranging from 3 to 100%. Predictive value nomograms created from PSAD may allow for a more individualized approach to evaluation of patients with intermediate levels of Hybritech serum PSA.

Aged

Analysis of continent versus standard urinary diversion.

The seemingly high complication and re-operation rates associated with continent urinary diversion have led some to criticize its morbidity and question its role in reconstructive urological surgery. We therefore reviewed our experience with all patients undergoing either continent or standard urinary diversion performed by 3 urological surgeons during a specified 3-year period. In 73 consecutive patients (22 continent urinary diversion, 51 standard urinary diversion), no significant difference was demonstrated with respect to the number of post-operative in-hospital days, complication rate, re-operation rate and operative mortality rate between the 2 groups. While those undergoing continent diversion were on average younger and healthier than their counterparts receiving standard diversion, stratification of patients in each group according to age and a pre-operative "fitness" score showed no significant difference in operative mortality or major morbidity between comparable patients in each group. The mean post-operative length of hospital stay was, however, 3 days shorter for the youngest and fittest patients receiving standard versus continent urinary diversion.

Adult

Detection of cellular proliferation during compensatory renal growth using flow cytometry.

Compensatory renal growth (CRG) consists of cellular enlargement and a small but consistent increase in DNA content. It has been assumed that the increase in total renal DNA content was due to new cell formation, however, the possibility of nuclear polyploidy remained an alternative explanation. To test the hypothesis whether cellular hyperplasia is the cause of the increase in DNA content during compensatory growth after renal deprivation, we performed cell cycle analysis using flow cytometry. Following unilateral nephrectomy, the amount of cortical cells in the S phase increased by 12% at 10 h while the number of cells in the G2M phase increased by 7% at 120 h. Medullary cells entering the S phase increased by 26% at 24 h and those in G2M increased by 12% at 168 h. DNA synthesis and replication occurs during CRG following unilateral nephrectomy as evidenced by an increase in cells entering both the S and G2M phases of the cell cycle. The increase in DNA content during CRG is a result of cellular proliferation and not polyploidy.

Animals

Urinary diversion.

The patient facing cystectomy now has the opportunity to select various forms of urinary diversion. Although not all of the newer techniques have stood the test of time, preliminary results indicate that these continent diversions should be considered safe and effective. These procedures definitely alter the patient's lifestyle, resulting in a significantly better adjustment to the need for bladder removal. With experience, these procedures can be performed with morbidity rates very similar to those encountered with ileal conduit diversion. As with any procedures, however, appropriate patient selection and surgical training are imperative.

Carcinoma, Transitional Cell

Flow cytometric determination of the multidrug resistant phenotype in transitional cell cancer of the bladder: implications and applications.

We detail our experience with a monoclonal antibody to detect the cell surface P-glycoprotein product of the multidrug resistance gene (MDR-1) in the human bladder. A total of 32 patients had 44 different specimens analyzed. The samples consisted of 8 normal bladders, 21 transitional cell carcinomas, 1 mucinous adenocarcinoma, 3 P-0 bladder wall specimens and 10 nonmalignant urothelial samples from cystectomies. P-glycoprotein was not detected in the normal adult or pediatric bladder. Bladder specimens from 3 children with a neurogenic bladder revealed enhanced expression (21%, 14% and 4% positivity). Transitional cell carcinoma usually demonstrates low expression at diagnosis (less than 6%), although 3 patients had enhanced initial expression (11%, 12% and 31%). Three patients treated with chemotherapy demonstrated 56%, 76% and 50% expression of MDR-1. Nonmalignant tissue from cystectomy specimens had low expression of MDR-1. The specificity of this system was confirmed with human bladder cell lines. The ability of flow cytometry to detect and quantify the expression of MDR-1 may allow for the early detection of chemotherapy resistance in patients with transitional cell carcinoma treated with systemic and intravesical therapy.

ATP Binding Cassette Transporter, Subfamily B, Mem

Flow cytometric analysis of localized adenocarcinoma of the prostate: the use of archival DNA analysis in conjunction with pathological grading to predict clinical outcome following radical retropubic prostatectomy.

Fifty-four specimens from patients undergoing radical prostatectomy for clinically confined prostate cancer between 1983 and 1987 were reviewed to determine the potential for flow cytometric (FCM) analysis of DNA ploidy and replication rate to predict disease recurrence. Each specimen was deparaffinized for FCM analysis and the pathology slides were reviewed by a single pathologist. FCM characteristics were correlated with pathological grade and stage, and both were correlated with disease status. In this series of patients, routine FCM analysis of DNA ploidy and replication rate failed to significantly enhance the ability of standard histopathological grading to predict disease recurrence in patients having clinically localized prostate cancer. Aneuploid tumors pathologically confined to the prostate did not appear to negatively affect prognosis.

Adenocarcinoma

The flow cytometric analysis of undescended testes in children.

Flow cytometric analysis was performed on the testicular aspirates of 45 consecutive children with unilateral cryptorchidism undergoing elective orchiopexy or orchiectomy. Concomitant histological analysis was performed on the testicular tissue obtained from either biopsy or orchiectomy specimens. In all cases deoxyribonucleic acid histograms appeared to correspond with microscopic appearance. Histograms from prepubescent patients demonstrated 85 to 95% of cells in the diploid (2c) peak and less than 10% of cells in the tetraploid peak (4c), representing prepubertal testes without active spermatogenesis. Three distinct patterns of ploidy were identified in postpubertal children corresponding to the histological appearances of normal spermatogenesis, maturation arrest and the Sertoli-cell-only syndrome, respectively. In addition, we identified an aneuploid cell population in the specimen from 1 patient, suggesting that this testis may be at risk for future malignant degeneration. We conclude that flow cytometry of testicular aspirates is an easy and effective means of testicular evaluation, which may permit predictions regarding the fertility and malignant potential of undescended testes in postpubertal children.

Adolescent

Ureteral reconstruction and bypass: experience with ileal interposition, the Boari flap-psoas hitch and renal autotransplantation.

A total of 18 patients underwent an operation for extensive ureteral loss from 1980 to 1986. The indications included recurrent calculi, retroperitoneal fibrosis, surgical trauma and tumor. Of the patients 10 had construction of an ileal ureter (4 had bilateral reconstruction), 6 had creation of a psoas hitch with a Boari bladder tube and 2 were treated by autotransplantation. Mean duration of followup was 4.8 years. The procedure was successful in 17 patients. There were no apparent differences among the groups. Selection criteria and potential complications are discussed with regard to each technique. These procedures provide an excellent means for reconstruction of the urinary tract in patients who have failed other treatments.

Adult

Enhanced detection of bladder cancer using the epithelial surface marker epithelial membrane antigen: a preliminary report.

The flow cytometry (FCM) technique allows for the rapid quantitative analysis of the DNA content of individual cells. In a variety of genitourinary tumors, DNA ploidy has a significant impact upon prognosis and ultimate patient survival. In patients having transitional cell cancer (TCC) of the bladder, FCM of voided urine and bladder barbotage specimens is highly correlated with cytologic analysis in the detection of malignant cells. One problem with this technique has been decreased sensitivity in samples containing large numbers of inflammatory cells. To improve FCM detection of TCC in bladder wash specimens, we developed a technique using a monoclonal antibody (Mab) specific to human, epithelial membrane antigen (EMA). The EMA cell-surface marker enabled us to differentiate bladder epithelial cells from lymphocytes and cellular debris. In combination with DNA analysis using propidium iodide, the EMA Mab increased the sensitivity and specificity of FCM compared to conventional analysis using propidium iodide alone. We conclude that epithelial cell-surface antigen staining using both EMA Mab and DNA staining can increase the FCM detection of TCC in bladder wash specimens.

Aged

Flow cytometry in carcinoma of the prostate.

Flow cytometry is a quantitative cytologic technique with demonstrated utility in the assessment of prostate cancer as well as other tumors. The authors summarize current data on its use in disease detection and diagnosis, prognostic evaluation, and monitoring of response to therapy. They also project future developments.

Cell Separation

Gene activity during the early phase of androgen-stimulated rat prostate regrowth.

Androgenic steroids regulate the proliferation rate of normal and malignant prostate cells. In order to investigate the molecular basis of this control, we utilized Northern and Western blot techniques to measure changes in the expression of individual genes during the early phase of prostate regrowth. Vestigial ventral prostate glands of 7-day castrated rats showed increased numbers of replicating cells within 12 h of continuous pharmacological testosterone replacement as demonstrated by flow cytometric procedures. The period prior to the onset of proliferative enhancement was accompanied by the sequential induction of a variety of transcripts encoding gene products often associated with cell growth. Within 1 h of treatment, mature mRNA transcripts for c-fos were induced 6-fold, returning to control levels by 2 h. Other genes showed transiently elevated transcript levels after 2 h (c-Ha-ras, c-Ki-ras) or after 8 h (c-myc,c-myb, beta-actin, and Mr 70,000 heat shock protein) of testosterone replacement. Expression of the polypeptide encoded by c-Ha-ras was coordinately enhanced (2-fold) during this period, but not to the levels of the transcript (20-fold induction). Transcripts encoding basic fibroblast growth factor were increased 16 h and later, subsequent to the earlier enhancement in the proliferation rate. By placing these genes in a defined temporal order with regard to their expression in response to testosterone, we have constructed a map of gene activity during early prostate regrowth. This map shows a number of genes, the products of which might participate in the mechanism by which androgens induce mitogenesis of prostate cells.

Animals

Long-term follow-up in patients treated with methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) for transitional cell carcinoma of urinary bladder: cause for concern.

Twenty-one patients with high-stage transitional cell carcinoma (TCC) of the bladder were treated with a combination of methotrexate, vinblastine, doxorubicin (Adriamycin), and cisplatin (M-VAC). There was a minimum follow-up of thirty-six months (range 36-45) in all patients. Patients were divided into three groups: 10 patients with recurrent TCC post radical cystectomy, 6 patients staged as T3/T4 or N1 treated in a neo-adjuvant setting, and 5 patients who received adjuvant M-VAC four weeks post radical cystectomy. The overall initial response rate in patients with measurable disease was 68 percent (11 of 14), complete response rate 31 percent, and partial response rate 37 percent. There was no response in 31 percent. The durability of response in this series was very disappointing with all complete responders having recurrence of disease, with duration of responses ranging from eight to twenty-one months. Of the 5 patients who received M-VAC as adjunctive therapy, only 1 remains disease-free; the other 4 patients experienced disease progression four to seventeen months postoperative, and all have died. There was one drug-associated death due to nadir sepsis, and myelosuppression occurred in 12 patients. While M-VAC seems to be the best protocol currently available, the real durability of response is most disappointing.

Aged

Calcium channel antagonists delay regression of androgen-dependent tissues and suppress gene activity associated with cell death.

Androgen deprivation subsequent to castration of an adult male rat results in the regression of sexual accessory tissues. Regression of these tissues involves the massive death of androgen-dependent cells. Using the rat ventral prostate gland as a model to study androgen-programed cell death, we have characterized a series of molecular events that accompany its regression. This analysis has shown that there was a sequential induction of specific gene transcripts in the ventral prostate gland following castration. The first event in this cascade was an abrupt induction of transcripts encoding c-fos. Since c-fos expression has been linked to perturbations in intracellular Ca2+ levels, we investigated whether membrane-mediated Ca2+ flux might be an early physiological step involved in the death of prostatic cells. To test this, rats were treated simultaneously upon castration with either verapamil or nifedipine, two different calcium channel antagonist drugs. Compared to the ventral prostate glands of untreated castrated rats, the glands of the calcium channel antagonist-treated rats showed a significant delay in all parameters associated with regression (loss of wet weight and DNA content and delay in histological changes associated with prostatic regression). The seminal vesicle glands of treated rats also showed signs of delayed regression. Furthermore, calcium channel antagonists suppressed the induction of transcripts encoding both c-fos and testosterone-repressed prostate message-2 (TRPM-2), a gene expressed exclusively by dying cells, during the first 62 hr following castration. These findings further support a role for calcium ion influx in the pathway leading to hormonally programed prostate cell death, and suggest the intriguing possibility that modulation of this activity can alter the process by which cells die.

Androgens

A report of cytomegalovirus cystitis and a review of other genitourinary manifestations of the acquired immune deficiency syndrome.

We report a case of symptomatic cytomegalovirus cystitis associated with the acquired immune deficiency syndrome related complex. The diagnosis of the acquired immune deficiency syndrome was established by bladder biopsy. The hematuria resolved after systemic acyclovir therapy. The other known urological manifestations of the acquired immune deficiency syndrome are discussed.

Acquired Immunodeficiency Syndrome

Fine-needle aspiration of the prostate.

Fine-needle aspiration biopsy of the prostate has been used for over 20 years as the prostate biopsy technique of choice throughout much of Europe. However, this technique has only recently gained acceptance in the United States. There is now an enlarging body of data confirming that fine-needle aspiration can be viewed as a safe, accurate, and reliable means for detection and diagnosis of prostate cancer. This review summarizes the European and United States experience with fine-needle aspiration and supports the utility of this biopsy technique as an important addition to the urologist's diagnostic armamentarium.

Biopsy, Needle