Frederick J. Dorey

Risk of Prostate Cancer–Specific Mortality Following Biochemical Recurrence After Radical Prostatectomy

ContextThe natural history of biochemical recurrence after radical prostatectomy can be long but variable. Better risk assessment models are needed to identify men who are at high risk for prostate cancer death early and who may benefit from aggressive salvage treatment and to identify men who are at low risk for prostate cancer death and can be safely observed.ObjectivesTo define risk factors for prostate cancer death following radical prostatectomy and to develop tables to risk stratify for prostate cancer–specific survival.Design, Setting, and PatientsRetrospective cohort study of 379 men who had undergone radical prostatectomy at an urban tertiary care hospital between 1982 and 2000 and who had a biochemical recurrence and after biochemical failure had at least 2 prostate-specific antigen (PSA) values at least 3 months apart in order to calculate PSA doubling time (PSADT). The mean (SD) follow-up after surgery was 10.3 (4.7) years and median follow-up was 10 years (range, 1-20 years).Main Outcome MeasureProstate cancer–specific mortality.ResultsMedian survival had not been reached after 16 years of follow-up after biochemical recurrence. Prostate-specific doubling time (<3.0 vs 3.0-8.9 vs 9.0-14.9 vs ≥15.0 months), pathological Gleason score (≤7 vs 8-10), and time from surgery to biochemical recurrence (≤3 vs >3 years) were all significant risk factors for time to prostate-specific mortality. Using these 3 variables, tables were constructed to estimate the risk of prostate cancer–specific survival at year 15 after biochemical recurrence.ConclusionClinical parameters (PSADT, pathological Gleason score, and time from surgery to biochemical recurrence) can help risk stratify patients for prostate cancer–specific mortality following biochemical recurrence after radical prostatectomy. These preliminary findings may serve as useful guides to patients and their physicians to identify patients at high risk for prostate cancer–specific mortality following biochemical recurrence after radical prostatectomy to enroll them in early aggressive treatment trials. In addition, these preliminary findings highlight that survival in low-risk patients can be quite prolonged.

Nitric Oxide as a Mediator of Relaxation of the Corpus Cavernosum in Response to Nonadrenergic, Noncholinergic Neurotransmission

Abstract Background. Nitric oxide has been identified as an endothelium-derived relaxing factor in blood vessels. We tried to determine whether it is involved in the relaxation of the corpus cavernosum that allows penile erection. The relaxation of this smooth muscle is known to occur in response to stimulation by nonadrenergic, noncholinergic neurons. Methods. We studied strips of corpus cavernosum tissue obtained from 21 men in whom penile prostheses were inserted because of impotence. The mounted smooth-muscle specimens were pretreated with guanethidine and atropine and submaximally contracted with phenylephrine. We then studied the smooth-muscle relaxant responses to stimulation by an electrical field and to nitric oxide. Results. Electrical-field stimulation caused a marked, transient, frequency-dependent relaxation of the corpus cavernosum that was inhibited in the presence of N-nitro-L-arginine and N-amino-L-arginine, which selectively inhibit the biosynthesis of nitric oxide from L-arginine. The a...

Metal-on-Metal Hybrid Surface Arthroplasty: Two to Six-Year Follow-up Study

BACKGROUND Following the reintroduction of metal-on-metal articulating surfaces for total hip arthroplasty in Europe in 1988, we developed a surface arthroplasty prosthetic system using a metal-on-metal articulation. The present study describes the clinical and radiographic results of the first 400 hips treated with metal-on-metal hybrid surface arthroplasties at an average follow-up of three and a half years. METHODS Between November 1996 and November 2000, 400 metal-on-metal hybrid surface arthroplasties were performed in 355 patients. All femoral head components were cemented, but only fifty-nine of the short metaphyseal stems were cemented. The patients had an average age of forty-eight years, 73% were men, and 66% had a diagnosis of osteoarthritis. Clinical and radiographic follow-up were performed at three months postoperatively and yearly thereafter. RESULTS The majority of the patients returned to a high level of activity, including sports, and 54% had activity scores of >7 on the University of California at Los Angeles activity assessment system. Kaplan-Meier survivorship curves demonstrated that the rate of survival of the components at four years was 94.4%. For patients with a surface arthroplasty risk index score of >3, the rate of survival of the components at four years was 89% compared with a rate of 97% for those with a score of </=3. The patients with a higher risk index were 4.2 times more likely to undergo revision to a total hip replacement at four years. Twelve hips (3%) had a revision to a total hip replacement. Seven of the twelve hips were revised because of loosening of the femoral component, and three were revised because of a femoral neck fracture. Substantial radiolucencies were seen around sixteen uncemented metaphyseal femoral stems. No femoral radiolucencies were observed among the hips in which the metaphyseal stem was cemented. The most important risk factors for femoral component loosening and substantial stem radiolucencies were large femoral head cysts (p = 0.029), patient height (p = 0.032), female gender (p = 0.005), and smaller component size in male patients (p = 0.005). CONCLUSIONS The preliminary experience with this hybrid metal-on-metal bearing is encouraging. Optimal femoral bone preparation and component fixation are critical to improving durability. The metal-on-metal hybrid surface arthroplasty is easily revised to a standard femoral component if necessary. LEVEL OF EVIDENCE Therapeutic study, Level IV (case series [no, or historical, control group]). See Instructions to Authors for a complete description of levels of evidence.

The natural history of peyronie's disease

The natural history of Peyronies disease was evaluated in 97 men by means of a questionnaire. Disease duration ranged from 3 months to 8 years. Questions addressed pain, bending, ability for intercourse, over-all effect of the disease, psychological effects, treatments received and degree of disease progression. Approximately 40% of the patients found pain, bending, ability for intercourse and over-all effects to be unchanged during the course of the disease. Bending and ability for relations worsened in 40% of the patients during the same interval, while only 6% had worsening of pain. Of the patients 77% reported psychological effects due to Peyronies disease, which improved in 28%, did not change in 36% and worsened in 36%. Over-all, 13% of the patients believed the disease to be one of gradual resolution, 47% believed there had been little or no change and 40% believed that the disease pattern was one of gradual progression. We found no statistically significant association between disease duration and spontaneous improvement in penile bending. A similar lack of statistical significance was found when improvement in a variety of categories was compared in patients who received no therapy versus those who received a variety of conventional medical therapies.

Wear is a function of use, not time

Polyethylene wear (linear penetration) in 37 hip replacements was assessed from digital images using a validated two-dimensional, edge detection-based computer algorithm. Patient activity was assessed with a pedometer, a step activity monitor and a simple visual analog scale. Joint use was related to wear at the 90% confidence level. Without three recognized outliers, wear was highly correlated to use. The visual analog scale activity rating was significantly related to wear for the 24 hip replacements with standard polyethylene. Univariate regression analysis indicated that male gender, height, weight (which were both highly correlated to male gender) and hip center of rotation were significantly correlated to wear. Multivariate regression analysis indicated that male gender, femoral off-set, and Hylamer® were significantly correlated to wear. Based on the wear and activity data from the 24 hip replacements with standard polyethylene, the average volumetric wear rate per million cycles with a 70 kg patient weight was 30 mm3. This unique in vivo result can be considered a target wear rate for standard polyethylene in hip simulator studies.

Prostate stem cell antigen (PSCA) expression increases with high gleason score, advanced stage and bone metastasis in prostate cancer.

Prostate stem cell antigen (PSCA) is a recently defined homologue of the Thy-1/Ly-6 family of glycosylphosphatidylinositol (GPI)-anchored cell surface antigens. PSCA mRNA is expressed in the basal cells of normal prostate and in more than 80% of prostate cancers. The purpose of the present study was to examine PSCA protein expression in clinical specimens of human prostate cancer. Five monoclonal antibodies were raised against a PSCA-GST fusion protein and screened for their ability to recognize PSCA on the cell surface of human prostate cancer cells. Immunohistochemical analysis of PSCA expression was performed on paraffin-embedded sections from 25 normal tissues, 112 primary prostate cancers and nine prostate cancers metastatic to bone. The level of PSCA expression in prostate tumors was quantified and compared with expression in adjacent normal glands. The antibodies detect PSCA expression on the cell surface of normal and malignant prostate cells and distinguish three extracellular epitopes on PSCA. Prostate and transitional epithelium reacted strongly with PSCA. PSCA staining was also seen in placental trophoblasts, renal collecting ducts and neuroendocrine cells in the stomach and colon. All other normal tissues tested were negative. PSCA protein expression was identified in 105/112 (94%) primary prostate tumors and 9/9 (100%) bone metastases. The level of PSCA expression increased with higher Gleason score (P=0.016), higher tumor stage (P=0.010) and progression to androgen-independence (P=0.021). Intense, homogeneous staining was seen in all nine bone metastases. PSCA is a cell surface protein with limited expression in extraprostatic normal tissues. PSCA expression correlates with tumor stage, grade and androgen independence and may have prognostic utility. Because expression on the surface of prostate cancer cells increases with tumor progression, PSCA may be a useful molecular target in advanced prostate cancer.

Low‐Level, High‐Frequency Mechanical Signals Enhance Musculoskeletal Development of Young Women With Low BMD

The potential for brief periods of low‐magnitude, high‐frequency mechanical signals to enhance the musculoskeletal system was evaluated in young women with low BMD. Twelve months of this noninvasive signal, induced as whole body vibration for at least 2 minutes each day, increased bone and muscle mass in the axial skeleton and lower extremities compared with controls.

RECURRENCE PATTERNS AFTER RADICAL RETROPUBIC PROSTATECTOMY: CLINICAL USEFULNESS OF PROSTATE SPECIFIC ANTIGEN DOUBLING TIMES AND LOG SLOPE PROSTATE SPECIFIC ANTIGEN

PURPOSE We studied the correlation between prostate specific antigen (PSA) doubling time or, equivalently, log slope PSA and clinical recurrence in patients with detectable PSA after radical retropubic prostatectomy who were followed expectantly. MATERIALS AND METHODS In patients with PSA recurrence after radical retropubic prostatectomy log slope PSA was determined from the difference in the 2 log PSA values divided by the time between readings in months. For a given slope the corresponding PSA doubling time was calculated as log x 2 divided by the slope of the log PSA line. When the initial PSA value was considerably greater than 0.4 ng./ml., the log slope PSA plot was extrapolated to determine the time point at which PSA would have become detectable (0.4 ng./ml.). The relationship between these values, and the time and pattern of clinical recurrence were studied. RESULTS In this series of 77 patients 80% with PSA doubling time of 6 months or greater remained clinically disease-free compared to 64% with PSA doubling time less than 6 months. PSA doubling time had better correlation with time to clinical recurrence after PSA became detectable (p <0.001 Cox proportional hazards model) than Gleason sum, pathological stage or margin status. Biochemical recurrence within 3 months was associated with early clinical recurrence (p <0.002). In addition, short PSA doubling time, that is a high log slope, regardless of the time at which PSA became positive was strongly associated with clinical recurrence (p <0.001). Distant recurrence was invariably associated with short PSA doubling time. Conversely, local recurrence reliably correlated with long PSA doubling time, that is a low log slope. CONCLUSIONS After PSA became detectable PSA doubling time or, equivalently, log slope PSA, was a better indicator of the risk and time to clinical recurrence after radical retropubic prostatectomy than preoperative PSA, specimen Gleason sum or pathological stage. Hormone treatment may be targeted to patients at high risk for early metastatic clinical recurrence, appropriately timed radiation can be offered for proved local recurrence in those with long PSA doubling time and expectant treatment may be proposed for those with long PSA doubling time who remain clinically disease-free. Frequent and expensive imaging does not appear to be cost-effective in this latter group.

Use of the University of California Los Angeles integrated staging system to predict survival in renal cell carcinoma: an international multicenter study.

PURPOSE To evaluate ability of the University of California Los Angeles Integrated Staging System (UISS) to stratify patients with localized and metastatic renal cell carcinoma (RCC) into risk groups in an international multicenter study. PATIENTS AND METHODS 4,202 patients from eight international academic centers were classified according to the UISS, which combines TNM stage, Fuhrman grade, and Eastern Cooperative Oncology Group performance status. Distribution of the UISS categories was assessed in the overall population and in each center. RESULTS The UISS stratified both localized and metastatic RCC into three different risk groups (P <.001). For localized RCC, the 5-year survival rates were 92%, 67%, and 44% for low-, intermediate-, and high-risk groups, respectively. A trend toward a higher risk of death was observed in all centers for increasing UISS risk category. For metastatic RCC, the 3-year survival rates were 37%, 23%, and 12% for low-, intermediate-, and high-risk groups, respectively; in 6 of 8 centers, a trend toward a higher risk of death was observed for increasing UISS risk category. A greater variability in survival rates among centers was observed for high-risk patients. CONCLUSION This study defines the general applicability of the UISS for predicting survival in patients with RCC. The UISS is an accurate predictor of survival for patients with localized RCC applicable to external databases. Although the UISS may be useful for patients with metastatic RCC, it may be less accurate in this subset of patients due to the heterogeneity of patients and treatments.

Turnover intention in new graduate nurses: a multivariate analysis

Title Turnover intention in new graduate nurses: a multivariate analysis Aim This paper is a report of a study to determine the relationship of new nurse turnover intent with individual characteristics, work environment variables and organizational factors and to compare new nurse turnover with actual turnover in the 18 months of employment following completion of a residency. Background Because of their influence on patient safety and health outcomes nurse turnover and turnover intent have received considerable attention worldwide. When nurse staffing is inadequate, especially during nursing shortages, unfavourable clinical outcomes have been documented. Method Prospective data collection took place from 1999 to 2006 with 889 new paediatric nurses who completed the same residency. Scores on study instruments were related to likelihood of turnover intent using logistic regression analysis models. Relationships between turnover intent and actual turnover were compared using Kaplan–Meier survivorship. Results The final model demonstrated that older respondents were more likely to have turnover intent if they did not get their ward choice. Also higher scores on work environment and organizational characteristics contributed to likelihood that the new nurse would not be in the turnover intent group. These factors distinguish a new nurse with turnover intent from one without 79% of the time. Increased seeking of social support was related to turnover intent and older new graduates were more likely to be in the turnover intent group if they did not get their ward choice. Conclusion When new graduate nurses are satisfied with their jobs and pay and feel committed to the organization, the odds against turnover intent decrease. What is already known about this topic There is concern in many countries about nurse turnover and the resulting effects on patient safety and quality of care. Decreasing ability to recruit experienced nurses has increased the emphasis on recruitment of new graduate nurses, particularly in the United States of America. Historically, new graduate nurses have a high turnover rate within the first year of employment. What this paper adds When new graduate nurses are satisfied with their jobs and pay and feel committed to the organization, the odds of turnover intent decrease. Increased seeking social support to cope with the transition from student to competent Registered Nurse is related to turnover intent. Older graduates (>30) are 4·5 times more likely to have turnover intent if they do not get their ward of choice.