Biomedical subjects

M S Cookson

Publications and source records attributed to M S Cookson.

30 records · Page 2Linked to original sources

PubMed1997

Pathological staging and biochemical recurrence after neoadjuvant androgen deprivation therapy in combination with radical prostatectomy in clinically localized prostate cancer: results of a phase II study.

OBJECTIVES: To assess the pathological staging and biochemical progression-free survival (assessed using serum prostate-specific antigen level) of patients with clinically localized prostate cancer using neoadjuvant androgen deprivation therapy (ADT) in combination with radical retropubic prostatectomy (RRP). PATIENTS AND METHODS: A prospective study was carried out on 69 patients with localized prostate cancer who were enrolled in a trial of 3 months of ADT followed by RRP (group 1). These patients were compared with 72 patients matched for age and clinical stage who declined ADT therapy and had RRP concurrently (group 2). Assignment to the individual treatment groups was thus determined by the patient's preference and not the physician's selection. Pathological staging and biochemical progression-free recurrence were compared between the groups. RESULTS: The rate of organ-confined (pT2) tumours was 74% in group 1 and 49% in group 2 (P < 0.01), and the rate of margin-negative tumours was 87% in group 1 and 64% in group 2 (P < 0.01). Within a median follow-up of 35 months, there was no significant difference in biochemical failure between the groups (P = 0.37). Patients with pT2 disease, regardless of treatment, had similar biochemical failure rates. In the patients with margin-positive disease, there was a significantly higher biochemical failure rate in group 1 (P = 0.02). CONCLUSIONS: The rates of organ- and specimen-confined disease were higher among the patients treated with ADT. The preliminary follow-up suggested that patients with pT2 disease after ADT have a biochemical progression-free recurrence rate similar to pT2 patients treated with RRP alone. Additionally, high biochemical failure rates in patients with margin-positive disease after ADT may identify a subset of more biologically aggressive tumours in need of early adjuvant treatment.

Aged↗

PubMed1997

The treated natural history of high risk superficial bladder cancer: 15-year outcome.

PURPOSE: The long-term outcome of patients with high risk superficial bladder cancer is unknown. We report the results of 15 years of followup of high risk patients treated initially with aggressive local therapy, including transurethral resection alone or combined with intravesical bacillus Calmette-Guerin. MATERIALS AND METHODS: Between 1978 and 1981, 86 high risk patients enrolled in a randomized study of transurethral resection alone or with intravesical bacillus Calmette-Guerin for superficial bladder cancer. Of these patients 81% had diffuse carcinoma in situ and 44% had stage T1 tumors before entry into the study. Patients were followed until death (61%) or until the present time (median followup 184 months). RESULTS: Disease stage progressed in 46 patients (53%) and 31 (36%) eventually underwent cystectomy for progression (28) or refractory carcinoma in situ (3), while 18 (21%) had upper tract tumors at a median of 7.3 years. The 10 and 15-year disease specific survival rates were 70 and 63%, respectively. At 15 years 34% of patients overall were dead of bladder cancer, 27% were dead of other causes and 37% were alive, including 27% with an intact functioning bladder. CONCLUSIONS: Despite aggressive local therapy patients with high risk superficial bladder cancer are at lifelong risk for development of stage progression and upper tract tumors. A third of patients are at risk for death from bladder cancer, justifying careful and vigilant long-term followup. These results support the use of initial aggressive local therapy in patients with high risk superficial bladder cancer.

Disease Progression↗

PubMed1997

Correlation between Gleason score of needle biopsy and radical prostatectomy specimen: accuracy and clinical implications.

PURPOSE: Despite the reliability of Gleason grading with respect to the same specimen, the correlation between the biopsy and prostatectomy specimen is less well defined. We compared the accuracy of Gleason grading of biopsies in predicting histological grading of radical retropublic prostatectomy specimens. MATERIAL AND METHODS: Gleason scores of 18 gauge needle biopsies were compared to those of radical retropublic prostatectomy specimens in 226 consecutive patients. In addition to comparing numeric discrepancies, differences between biopsy and specimen Gleason scores of 2 or more and a change in group from Gleason scores 2 to 4, 5 to 7 or 8 to 10 were evaluated by kappa testing, as well as any change in group from Gleason scores 2 to 4, 5 and 6, 7 and 8 to 10. RESULTS: The biopsy score was identical to the specimen score in 31% of cases, while 26% were discrepant by 2 or more Gleason scores. Overall, 54% of biopsies were under graded, while 15% were over graded. If only cases in which discrepancies of 2 or more Gleason scores and a change in group were considered, there was good overall agreement (kappa 0.468, accuracy 80%). Among the cases with any change in group, the accuracy was only 46% with poor agreement (kappa 0.153). CONCLUSIONS: Overall, the reliability of Gleason grading of needle biopsies in predicting final pathology was good. However, the limitations of Gleason grading based on biopsy should be considered when discussing treatment options and comparing results based on biopsy data.

Adult↗

PubMed1997

Glutathione S-transferase PI (GST-pi) class expression by immunohistochemistry in benign and malignant prostate tissue.

PURPOSE: Glutathione S-transferase (GST) enzymes may prevent carcinogenesis through inactivation of reactive electrophiles by conjugation to reduced glutathione. Recently, it was reported that most prostate cancers fail to express GST-pi despite an abundant presence in benign prostate tissue, suggesting a common genetic alteration. To define its presence in prostate tissue, we evaluated GST-pi expression in a variety of prostate tissues. MATERIALS AND METHODS: Immunostaining with anti-GST-pi antibody was performed on 69 benign prostates, 44 malignant prostates, 12 incidental prostate carcinomas and 17 prostatic intraepithelial neoplasia (PIN) specimens. Specimens were evaluated for the presence and percent of GST-pi. Within benign tissue, GST-pi immunostaining was distinguished between basal cells and secretory acinar epithelium. RESULTS: In benign epithelium, the basal cells demonstrated intense staining in all cases. The mean percent staining among the basal cells was 67% (R 40-90%). The acinar epithelium stained weakly positive in 94% (65/69) of specimens, however the mean percent staining was only 5% (R 0-25%). GST-pi was detected in only 3.5% (2/56) of the prostate cancers. No incidental prostate cancers and only one (6%) high grade PIN stained positive. CONCLUSIONS: Our study confirms the absence of GST-pi expression in prostate cancer and high grade PIN. Furthermore, GST-pi expression correlates well with the basal cell phenotype, but not with benign epithelial cells. The lack of staining among prostate cancer cells may reflect the absence of a basal cell layer, suggesting that GST-pi is involved more in epithelial differentiation and questioning its role in the malignant transformation of prostatic acinar cells.

Epithelium↗

PubMed1996

Upper tract tumors in patients with primary bladder cancer followed for 15 years.

PURPOSE: We evaluated the long-term incidence of upper tract tumors in patients with primary superficial bladder cancer. MATERIALS AND METHODS: A total of 86 patients with stages Ta, T1 and Tis bladder tumors, who were entered into a prospective trial of bacillus Calmette-Guerin between 1978 and 1981, was followed for 15 years or longer. RESULTS: Of the 86 patients 18 (21%) had upper tract tumors after a median interval of 7.3 years (range 1 to 15). Tumors occurred within 5 years of followup in 6 cases, between 5 and 10 years in 7, and between 10 and 15 years in 5. The majority of cancers were invasive and 7 patients died of upper tract tumors. CONCLUSIONS: Patients with primary bladder tumors are at risk for upper urinary tract disease for up to 15 years, which suggests the need for lifelong regular upper tract monitoring in these cases.

Aged↗

PubMed1995

Can semen analysis predict the presence of antisperm antibodies in patients with primary infertility?

A retrospective study was performed to evaluate the ability to predict sperm-surface antisperm antibodies (ASA) in patients with primary infertility on the basis of semen analysis. In particular, the ability to predict ASA status on the basis of impaired sperm motility was assessed. The clinical and seminal characteristics of 70 consecutive ASA-positive infertility patients detected by routine screening were reviewed. Similar analysis was performed on 128 consecutive patients with infertility who were found on routine screening to be ASA-negative. The association between the presence of ASA and sperm motility, concentration, and clumping was examined using multivariate analysis. Two variables were found to have a significant joint association with the presence of ASAs. Patients with sperm concentrations of > 20 million/ml were significantly more likely to be ASA-positive (P = 0.002). Second, after adjustment for sperm concentration, patients with lower motilities were significantly more likely to be ASA-positive (P = 0.016). Although impaired motility was seen significantly more often in ASA-positive patients, this seminal defect alone should not be used for predictive screening, since 39% of ASA-positive patients had sperm motilities of > 60%. Furthermore, when a normal sperm concentration (> 20 million/ml) was combined with impaired sperm motility (< 60%) as an indication for ASA testing in this population, the result was a sensitivity of only 43%, a specificity of 77%, and positive and negative predictive values of 50% and 77%, respectively. Despite the association between normal sperm concentrations and impaired motility, it appears that the results of semen analysis cannot be used as a sole indication for ASA testing.

Adult↗

PubMed1995

The lack of predictive value of prostate specific antigen density in the detection of prostate cancer in patients with normal rectal examinations and intermediate prostate specific antigen levels.

PURPOSE: The management of patients with a normal digital rectal examination and a prostate specific antigen (PSA) level of 4.0 to 10.0 ng./ml. remains controversial. To improve the specificity of cancer detection in this group, PSA density has been recommended with biopsies based on a PSA density of 0.15 or more. To evaluate PSA density as a discriminator of prostate cancer we enrolled patients in a prospective study. MATERIALS AND METHODS: A prospective evaluation was done of 44 consecutive patients with a palpably normal digital rectal examination and a serum PSA level of 4.0 to 10.0 ng./ml. enrolled during a 13-month period. All patients underwent transrectal ultrasound with sextant biopsies regardless of calculated PSA density. RESULTS: Overall, 8 of 44 men (18%) had prostate cancer. There was no significant difference in the mean PSA density between the patients with positive and negative biopsies (mean 0.12 and 0.15, respectively, p = 0.258). Also, there was no significant association between PSA or PSA density and a positive biopsy in multivariate analysis (p = 0.863). Receiver operating characteristic curves for PSA and PSA density failed to demonstrate any superior benefit for PSA density in this patient population. A PSA density of 0.15 was an unreliable indicator of cancer (sensitivity 12.5%, specificity 61.1% and positive predictive value 6.7%). CONCLUSIONS: In our study, PSA density did not discriminate between patients with positive and negative biopsies, and in fact most cancers would not have been detected if a PSA density of 0.15 or more had been used as the sole indication for biopsy. Therefore, we recommend systematic biopsies in these patients independent of calculated PSA density.

Aged↗

PubMed1994

A prospective evaluation of leak point pressure, bladder compliance and clinical status in myelodysplasia patients with tethered spinal cords.

We evaluated prospectively 26 patients with myelodysplasia and a tethered spinal cord to determine whether surgical release of the tethered cord positively influenced leak point pressure, bladder compliance, upper tract status and/or clinical management. Urodynamics were performed immediately before and after the neurosurgical procedure, and at 3 and 6 months postoperatively. Mean patient age was 7.8 years (range 2 days to 34 years) and median interval from onset of symptoms to surgery was 60 days (range 2 days to 4 years). Patient presentation included a combination of orthopedic, neurological and urological symptoms. Of 26 patients 9 (35%) had new hydronephrosis, urinary tract infections or urinary incontinence. Leak point pressure and bladder compliance did not change significantly by 6 months postoperatively. Of the 4 patients who presented with hydronephrosis 1 worsened in status, 2 stabilized and 1 improved. Clinical status was unchanged in 16 patients, improved in 4 and worsened in 6. There was no significant relationship between patient age and urodynamic or clinical outcome. Among patients followed for at least 6 months radiographic and clinical improvement occurred in 25% and 15%, respectively. Urodynamic improvements were transient. Surgical release of a tethered cord improved the urological status in less than a quarter of the patients in this series.

Adolescent↗

PubMed1994

Hormonal therapy for metastatic prostate cancer: issues of timing and total androgen ablation.

This review summarize results of hormonal management in patients with metastatic prostate cancer in terms of both timing and amount of androgen blockade. The standard of delayed hormonal therapy resulted from data of the Veterans Administration Cooperative Urologic Research Group showing high toxicity in patients treated with estrogen therapy. Reanalysis of those data using cancer-specific deaths showed improved cancer-specific survival with early hormonal therapy. A large and growing body of clinical data also suggests a superior benefit to early hormonal therapy. The concept of total androgen (adrenal and testicular) ablation was supported by reports that show a survival advantage using a combined blockade over luteinizing hormone-releasing hormone agonist alone. A National Cancer Institute study showed particularly impressive disease-free and overall survival in a subset of patients with low volume disease and good performance status. However, caution should be exercise in view of differing Canadian and European data. This review provides guidelines for treatment, but ultimately the timing and amount of androgen deprivation must be tailored to the individual patient. Ongoing and future prospective studies hold the promise of answers to these difficult and unresolved questions.

Adrenalectomy↗

PubMed1993

Long-term results with vacuum constriction device.

From November 1985 to April 1990, 216 consecutive patients were treated with the vacuum constriction device. Patients were mailed an initial questionnaire (group 1) and a long-term questionnaire (group 2) at a median followup of 3 and 29 months, respectively. Of 202 available patients 161 in group 1 (75%) and 115 in group 2 (57%) responded. Regular use of the vacuum constriction device was reported by 69% group 1 and 70% group 2 patients. patient and partner satisfaction was 82% and 87% in group 1, and 84% and 89% in group 2, respectively. There were no significant differences between the groups with respect to regular use and patient or partner satisfaction (p < 0.05). Quality of erection was evaluated for hardness, length and circumference, and with satisfaction greater than 90% in both groups. Median times per month of successful intercourse were 1, 4 and 4 for the year before, during and after obtaining the vacuum constriction device in group 2. Also, 79% of the patients in group 2 reported a statistically significant increase in the frequency of intercourse per month in the first year, which was sustained beyond the first year in 77% (p < 0.01). Our results support the efficacy of the vacuum constriction device for the treatment of impotence. Overall regular use rates as well as patient and partner satisfaction appear to be high. Furthermore, excellent initial results appear durable in most patients.

Adult↗

PubMed1993

Analysis of microsurgical penile revascularization results by etiology of impotence.

We reviewed the results of microsurgical penile revascularization, with or without a combined procedure to correct cavernosal venous leakage, in 50 consecutive patients with vasculogenic impotence. All patients underwent an extensive preoperative evaluation, including dynamic infusion cavernosography and cavernosometry, and selective penile arteriography. Overall 48% (24 patients) had an excellent postoperative result, 40% (20 patients) were improved and 12% (6 patients) failed, with a median followup of 24 months (range 19 to 56). Furthermore, these results appear durable with no significant difference in length of followup between groups irrespective of surgical outcome (p > 0.05). Analysis of surgical outcomes by preoperative etiology of impotence (pure arterial versus arterial combined with corporeal venous dysfunction) revealed a statistically significant advantage of an excellent surgical outcome in patients with pure arterial impotence compared to those with mixed etiology with results of 67% and 42%, respectively (p < 0.01). There was no significant difference in outcome when patients were analyzed with respect to age or duration of impotence (p > 0.05). We conclude that in patients with arteriogenic impotence identification of concomitant corporeal veno-occlusive dysfunction diagnosed by preoperative dynamic infusion cavernosography and cavernosometry may be helpful, not only in planning a more physiological surgical procedure but also in predicting long-term postoperative success.

Adult↗

PubMed1992

Management of stage T1 superficial bladder cancer with intravesical bacillus Calmette-Guerin therapy.

We reviewed our results with 86 patients who had a pretreatment history of a stage T1 tumor. All patients were treated with transurethral resection of all visible tumor followed by intravesical bacillus Calmette-Guerin (BCG) and many patients received additional maintenance therapy. Local recurrences were treated with repeat transurethral resection followed by additional BCG. Median followup was 59 months, with a range of 9 to 149 months. Overall, 78 of 86 patients (91%) were free of tumor recurrence with BCG therapy. This result includes 69% of the patients who responded to the initial transurethral resection and intravesical BCG, and 22% who ceased having tumors after additional treatments for local recurrences. Only 7% of the patients had progression to stage T2 tumors after BCG therapy. Grade of the stage T1 tumor, concurrent carcinoma in situ and tumor multiplicity before BCG did not predict tumor recurrence or progression. Of patients with recurrences after BCG therapy, those with stage T1 tumors had a higher rate of progression compared to those with stage Ta tumors but the difference was not statistically significant (p = 0.086). These data clearly support the efficacy of transurethral resection plus intravesical BCG immunotherapy in the treatment of stage T1 tumors as well as in the prevention of disease progression.

Administration, Intravesical↗