Biomedical subjects
Publications and source records attributed to I M Thompson.
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Despite a heightened focus of the medical and research community on prostate cancer, many important questions about this disease remain unanswered. These include questions about the possible prevention of prostate cancer, as well as the optimal treatment approaches for localized, locally advanced, metastatic, and hormone-refractory disease. A whole host of prospective, well-designed clinical trials are currently in progress that should answer many of these questions. This review briefly explores some of these unresolved issues and describes ongoing trials designed to address them.
The changing clinical dynamics of prostate cancer have resulted in a broadening of the research focus of the Genitourinary (GU) Cancer Committee of the Southwest Oncology Group (SWOG). Beginning with an emphasis on hormone-refractory disease in its early years, SWOG prostate cancer trials now cover the entire spectrum of the disease: localized, locally advanced, metastatic and hormone-refractory disease. As the world's largest GU cancer research group, the GU committee of SWOG has pioneered studies in combined androgen therapy for metastatic disease, quality-of-life (QOL) assessments for patients with localized and advanced disease, adjuvant therapy models, and prostate cancer chemoprevention. The committee has also formed the GU Global Group, whose purpose is to convene the chairs of the GU committees of all the major national and international oncology cooperative groups. Meeting semiannually, this group discusses activities within their respective organizations, plans collaborative strategies and protocols, and establishes global strategy in prostate cancer clinical research. The future directions of national and international prostate cancer trials will build on this broad foundation of well-conceived, logically sequenced studies.
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OBJECTIVES: We applied the advances in anatomic techniques as developed for the radical retropubic prostatectomy to the perineal approach to radical prostatectomy. The anatomic radical perineal prostatectomy maximizes cancer control and minimizes postoperative incontinence and impotence. This technique capitalizes on the many advantages associated with the perineal approach to the prostate. METHODS: The anatomic radical perineal prostatectomy addresses the posterior surface and posterior bladder neck regions prior to urethral division at the prostatic apex. Anatomic dissection of the striated urethral sphincter and preservation of the bladder neck, as well as a "watertight" anastomosis, are accomplished with excellent exposure. Cavernosal nerve preservation is possible in appropriately selected patients. Data are accumulated prospectively and reported herein. RESULTS: Prostate-specific antigen detectability is seen in 2% and 4% of pT2 and pT2 to T3b cases, respectively at an average follow-up of 1 year. Immediate full continence is seen in 30% of cases; ultimately, 97.5% achieve full urinary control. Nerve-sparing techniques result in spontaneous erectile activity in 73%. Average length of hospital stay is less than 2 days, with most recent patients discharged on the day after surgery. CONCLUSIONS: The anatomic radical perineal prostatectomy is a safe and effective method of treating men with clinically localized prostate cancer and should be part of every urologist's surgical armamentarium.
The Hospital Infection Society, in association with the Public Health Laboratory Service and the Infection Control Nurses Association, launched the Second National Prevalence Survey of Infection in Hospitals in 1993. On completion of the survey, 157 hospitals throughout the British Isles had taken part with approximately 37 000 patients surveyed. The survey in the Royal Hospitals Trust, Belfast, included all inpatients who were present in the wards on the survey day. Infection control nurses (ICNs) from a selected number of the other participating hospitals were sent questionnaires and asked about their methods of data collection, and their overall impression of the Second National Survey. All respondents received help in performing the survey, but only 10% provided prior training to ward staff before the survey visit. Sixty-five percent of respondents supplied information to the wards prior to the survey visit. In comparison with the questionnaire respondents, it was found that using a 'link' nurse to assist in data collection was much more efficient in relation to the time involved. Many ICNs expressed concern over the amount of time spent on this survey, although in general the value of such a survey was appreciated. Twenty-six percent of respondents indicated that they would not be willing to undertake a future survey.
Asymptomatic progression following definitive therapy for prostate cancer can take the form of a detectable prostate-specific antigen (PSA) or local recurrence following radical prostatectomy or a rising PSA or palpable recurrence following radiotherapy. Options for treatment include hormonal therapy, radiotherapy, salvage surgery, and experimental therapies. Although such forms of treatment have known effects on intermediate endpoints, such as reduction of PSA, the overall effect on survival and quality of life is uncertain.
OBJECTIVE: To determine whether early removal of the indwelling Foley catheter after transurethral resection of the prostate (TURP) significantly shortens the hospital stay without causing additional morbidity and thus saves costs. PATIENTS AND METHODS: For the year commencing 1 July 1991, 119 patients who had undergone TURP had their indwelling catheter removed on the first day after surgery. The results and morbidity of this group of patients were compared with those in 152 patients undergoing TURP during the previous year. The economic consequences of this protocol were calculated using both Medicare and CHAMPUS data. RESULTS: The demographics of the patients in both groups were similar. Post-operative complications occurred in 5% of the study patients and in 6.6% of controls; a transfusion was required in 2.5% and 1.3%, clot retention developed in 1.7% and 3.3% and the hospital stay was reduced from 3.1 to 1.28 days in the study and control patients, respectively. Using Medicare data, the mean cost saving of early catheter removal would be $829 and $1406 for patients aged < 70 and > 70 years, respectively. For CHAMPUS patients, the cost saving would be $1983. CONCLUSION: Early removal of the catheter after TURP did not increase morbidity and maintained the efficacy of the procedure. If this practice was adopted nationally, the savings resulting from the reduction in hospital stay would be considerable.
The New York Products of Ambulatory Surgery (PAS) patient classification system was implemented by the state of New York for reimbursement of Medicaid ambulatory surgery claims. Using a national claims based database, the PAS system was evaluated for use with emergency department-generated surgical episodes. The PAS system performed well, but would benefit from the inclusion of age, comorbidity, and presence of multiple surgical procedures. Further, model power increased significantly when focused on total episode versus surgical charges alone. The study indicated the high degree to which emergency department-generated charges are closely tied to other charges in any overall care delivery system.
Recent epidemiologic studies have suggested that a risk factor for the development of carcinoma of the prostate may be previous vasectomy. As a majority of prostate cancer cases diagnosed in the U.S. are detected by an elevation in prostate-specific antigen (PSA), an elevation in PSA due to vasectomy may underpin this association. There have been no published reports on the relationship between PSA before and after vasectomy. To study this relationship, this study was undertaken to determine the effects of vasectomy on PSA. Twenty-five men undergoing vasectomy were studied with serial PSA determinations prior to and following vasectomy. Analysis of data suggests that PSA is not affected by previous vasectomy and that other causes for an increased detection in this cohort may be operational.
Although early detection and treatment of prostate cancer is widely advocated, this so-called secondary prevention approach has a number of drawbacks. First, it is not yet certain that active treatment of localized prostate cancer offers any advantage over surveillance. Second, screening may detect indolent tumors while missing some virulent ones. Third, treatment is not uniformly successful, even in patients with early disease. Fourth, radical prostatectomy and radiotherapy are associated with considerable side effects. And finally, the economic and psychological costs of large-scale screening cannot be overlooked. Although attention has been focused on the possibility of primary prevention, neither large-scale dietary manipulation nor long-term prophylactic use of retinoids is considered feasible. With the recent approval of the 5-alpha-reductase inhibitor finasteride for the treatment of benign prostatic hyperplasia, the opportunity for primary chemoprevention has moved closer to reality. The Prostate Cancer Prevention Trial (PCPT), a randomized, placebo-controlled study expected to enroll 18,000 healthy men over the age of 55, is currently addressing the question of whether finasteride prophylaxis can reduce the incidence of prostate cancer over a 7-year period. This is a US government work. There are no restrictions on its use.
The use of bacillus Calmette-Guérin (BCG) for the treatment of bladder cancer has been followed by reports documenting adverse reactions. Eruptions of the skin have been included (although not well described) in the list of side effects. We report a pityriasis rosea-like rash secondary to BCG therapy for bladder cancer. Although the treatment was interrupted because of this reaction, the medication was restarted later with only a mild transient recurrence of the eruption.
OBJECTIVES: The prevalence of pelvic lymph node metastases in men with clinically localized prostate cancer has decreased dramatically over the past decade, possibly due to efforts at early detection. With a significantly lower incidence of pelvic node involvement, it may be possible to identify a segment of patients for whom pelvic lymph node dissection (PLND) may be omitted. This study was conducted to develop a method to select patients for whom PLND could be omitted. METHODS: We analyzed serum prostate-specific antigen (PSA), clinical stage, biopsy Gleason score, and final pathologic stage in 481 men with clinically localized prostate cancer. These variables were compared to the risk of positive pelvic lymph nodes. RESULTS: Logistic regression analysis determined that combining all three variables provided the best determination of final pathologic stage. A series of probability curves have been created to estimate the risk of positive lymph nodes in a given patient. Based on the distribution of patients in this study and using these probability functions, PLND could be avoided in up to 50% of patients with localized prostate cancer diagnosed by contemporary methods. CONCLUSIONS: In properly selected patients, pelvic lymphadenectomy can be omitted in the staging and treatment of localized prostate cancer.
Recent evidence from an analysis of Medicare patients undergoing radical prostatectomy has suggested that perioperative mortality may be substantially greater than that reported in institutional series. To estimate the perioperative mortality and survival of patients of a younger and potentially more representative population of the United States, Civilian Health and Medical Program of the Uniformed Services institutional claims data from October 1, 1987 to January 1, 1993 were analyzed. A total of 1,059 subjects was examined of an average of 60.0 years and all were younger than 65 years. Using Kaplan-Meier estimates, mortality rates following surgery were calculated to be 0.28% at 30 days, 0.28% at 90 days, 1.02% at 1 year, 1.95% at 2 years, 3.14% at 3 years and 4.64% at 4 years. Observed 1 to 5 mortality rates in this series ranged from 0.362 to 0.487 of the expected mortality when compared to the general population and they were statistically significant. At 30 and 90 days postoperatively 3.1% and 4.6% of the patients were rehospitalized. Data demonstrated that mortality and morbidity from radical prostatectomy were low and that conclusions drawn on outcomes of treatment for carcinoma of the prostate should focus on the entire age range of patients who undergo this procedure in the United States.
OBJECTIVES: The protection of spermatogenesis during chemotherapy using an antiandrogen and a luteinizing hormone-releasing hormone (LHRH) agonist was examined in the rat. Previous studies using LHRH agonists alone have been inconclusive, as both protective and deleterious effects on the germinal epithelium have been reported. Flutamide has not previously been used in this manner but theoretically should protect the germinal epithelium, since flutamide rapidly blocks testosterone at the cellular level and also minimizes the testosterone "flare" when LHRH agonist therapy is initiated. METHODS: Mature Sprague-Dawley rats were pretreated with flutamide, sustained-release goserelin acetate (Zoladex), or a combination of flutamide and sustained-release goserelin acetate for 14 days before 4 weekly doses of procarbazine were initiated. The seminiferous tubules were evaluated histologically after a 90-day regeneration period using the stem cell assay test. RESULTS: After treatment with procarbazine alone, only 43% of the seminiferous tubules were active; however, 80% were active if protected with flutamide, 91% if protected with sustained-release goserelin acetate, and 95% if protected with both flutamide and goserelin acetate. CONCLUSION: Flutamide, sustained-release goserelin acetate, and a combination of these agents were effective in protecting the germinal epithelium of the rat during chemotherapy. A combination of flutamide and goserelin acetate provided the best protection. This study demonstrates for the first time the protective effect of flutamide and flutamide with goserelin acetate on the germinal epithelium during chemotherapy.
Alpha-interferon (IFN) has been shown to produce antitumor responses among patients with advanced renal cell carcinoma. While responses have been observed over a range of IFN doses and schedules, significant toxicities can be experienced from relatively high doses given three to five times weekly. Based upon the report of a pilot study indicating that low dose daily IFN could produce antitumor responses with minimal toxicity, the Southwest Oncology Group investigated this schema in a phase II trial. Patients with bidimensionally measurable disease were treated with Roferon-A 1 million units subcutaneously daily and tumor assessments were conducted on a monthly basis. There were no dose escalations and no dose reductions for toxicity. The treatment was well tolerated with only two patients withdrawing from treatment because of side effects. Among 56 eligible patients treated, there were five partial responses and one complete response for an overall response rate of 11% (95% confidence interval, 4 - 22%). However, objective antitumor responses could not be determined for 16 of the 56 patients. Among the 40 fully evaluable patients the 6 objective responses yields a response rate of 15% (95% confidence interval, 5.7-30%). It is concluded that this dose and schedule of IFN has activity against advanced renal cell carcinoma. A randomized trial would be required to determine if this low dose regimen is as effective as the higher doses which have been used traditionally.