Search

Purpose: Androgen receptors are present in virtually all epithelial cells of the prostate, including benign epithelium, high grade prostatic intraepithelial neoplasia and cancer. However, there have been variable results regarding the clinical significance of cells expressing androgen receptors in prostate cancer. We evaluated the predictive accuracy of androgen receptor expression in prostatic intraepithelial neoplasia and cancer for clinical progression and survival in patients with organ confined prostate cancer treated with radical prostatectomy.Materials and Methods: The study consisted of 172 previously untreated patients who underwent radical prostatectomy at our clinic between 1987 and 1991 with intermediate to high grade (Gleason score 6 to 9), pathological stage T2 cancer and negative surgical margins. Mean followup was 7.4 years (range 1.2 to 10.1). Mouse monoclonal anti-human androgen receptor antibody was used for immunohistochemical studies on select tissue sections from each case. W...

BACKGROUND The biologic behavior of T1a prostate adenocarcinoma is variable. A critical issue in the management of patients with T1a prostate adenocarcinoma is to distinguish those who will develop cancer progression from those who will not. Predictive factors that identify those at high risk of cancer progression are needed to stratify patients for treatment. In the current study the authors attempted to identify such predictors of cancer progression in a large series of untreated patients with lengthy follow-up. METHODS The authors studied 102 patients who were diagnosed with T1a prostate adenocarcinoma (incidental tumor involving ≤ 5% of the resected prostatic tissue) at the time they underwent transurethral resection of the prostate (TURP) at the Mayo Clinic between 1960–1970. None of these patients were treated. Patient ages ranged from 48–91 years (mean ± standard deviation, 69 ± 7 years). The average weight of the resected prostate tissue was 24 ±18 g (range, 3–115 g; median, 18 g). Tumor volume was measured by the grid method. Cox proportional hazards models were used to identify factors associated with cancer progression. Survival curves were estimated using the Kaplan-Meier method. RESULTS Five-year and 10-year progression free survival rates were 93% and 87%, respectively. During the mean follow-up of 9.5 ± 6.8 years (range, 0.3–31 years; median, 9.0 years), 14 patients developed clinical cancer progression, including 5 patients with systemic progression (1 with distant metastases and 4 who died of prostate adenocarcinoma). The interval from diagnosis to clinical cancer progression ranged from 1–23 years (mean, 7.3 years). The amount of resected prostate tissue (TURP weight) was associated with progression (P = 0.04). Patients with a TURP weight ≥ 30 g had 100% progression free survival at 10 years compared with a progression free survival rate of 73% in patients with a TURP weight < 12 g. Gleason score, tumor volume, number of chips involved by tumor, number of tumor foci, and the presence of high grade prostatic intraepithelial neoplasia were not significant in predicting cancer progression. There was a trend toward a worse prognosis with the increasing number of chips involved by cancer (P = 0.16). Patients with < 3 chips involved by cancer had a 88% 10-year progression free survival rate compared with 73% in patients with ≥ 3 chips involved by cancer. CONCLUSIONS The clinical course of T1a prostate adenocarcinoma is variable. If left untreated, a small but significant proportion of patients are at risk for disease progression and death. However, the current study found that patients with a TURP weight ≥ 30 g have an excellent prognosis and can be managed conservatively. Cancer 1999;85:1300–4. © 1999 American Cancer Society.

BACKGROUND The biologic changes in recurrent prostate carcinoma following radiation therapy are not fully understood. The authors sought to determine the level of p53 protein overexpression and its association with cellular proliferation (Ki-67 labeling index), glutathione S-transferase-π (GST-π) expression, and other clinical pathologic findings in patients with locally persistent prostate carcinoma after radiation therapy. METHODS The authors investigated p53 nuclear accumulation, cellular proliferation activity (Ki-67 labeling index by digital image analysis), and GST-π expression in 55 patients with persistent or recurrent prostate carcinoma after radiation therapy. All patients underwent salvage radical prostatectomy and bilateral pelvic lymphadenectomy following irradiation failure. The interval from radiation therapy to cancer recurrence ranged from 6 months to 17 years (mean, 3.8 years). Age at surgery ranged from 51 to 78 years (mean, 65 years). Mean follow-up after surgery was 5.7 years (range, 1–13 years). RESULTS p53 protein overexpression was associated with increased cell proliferation (Spearman rank correlation coefficient = 0.29, P = 0.03). A substantial proportion (62%) of recurrent cancer also showed GST-π immunoreactivity. No apparent correlation was observed between p53 protein overexpression, cellular proliferation (Ki-67 labeling index), or GST-π expression and Gleason score, pathologic stage, DNA ploidy, or patient outcome. There was an inverse correlation between GST-π expression and Gleason score (P = 0.06). The majority of prostate carcinomas (95%) were proliferative (mean Ki-67 labeling index, 7.0; range, 0–20), whereas concurrent prostatic intraepithelial neoplasia (PIN) had a lower Ki-67 labeling index (mean, 3.1; range, 0–11.5). Nineteen of 28 (68%) concurrent PIN demonstrated p53 immunoreactivity. A trend toward adverse clinical outcome was observed in patients with a higher Ki-67 labeling index in recurrent cancer. CONCLUSIONS In this study cohort selected for salvage prostatectomy, recurrent cancers were biologically aggressive following radiation therapy. Whether this represents selective persistence and regrowth of prognostically unfavorable tumor clonogens or stepwise clonogenic progression is uncertain. Further investigation is needed to elucidate the correlation between p53 overexpression and the presence of other biologic changes after radiation therapy. Cancer 1999;85:1293–9. © 1999 American Cancer Society.

Purpose: We describe trends in prostate cancer mortality from 1980 to 1997, before and after the introduction of serum prostate specific antigen (PSA) testing to the community medical practice, and provide an update on trends in incidence since 1992.Materials and Methods: All men with a diagnosis of prostate cancer who died between 1980 and 1997 were identified and parts 1 and 2 of the death certificates were reviewed for a diagnosis of prostate cancer. In addition, all men with biopsy proved prostate cancer diagnosed between 1983 and 1995 were identified. The complete medical records of incident cases of prostate cancer were reviewed for signs and symptoms at diagnosis and for the first treatment received.Results: Age adjusted, community mortality rates from prostate cancer increased from 25.8/100,000 men in 1980 to 1984 to a peak of 34/100,000 in 1989 to 1992, and have since declined to 19.4/100,000 in 1993 to 1997 (22% decline in mortality, 95% confidence interval 49% decline to 17% increase). ...

Recent experiments in cultured cyst epithelial cells from kidneys of patients with autosomal dominant polycystic kidney disease (ADPKD) have shown that the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is present in the apical surface of these cells and mediates chloride (Cl-) and fluid secretion in vitro. To determine whether the presence of CF with the expression of mutated CFTR proteins modifies cyst formation in ADPKD, we studied a large family with both inherited diseases. ADPKD in this family is linked to PKD1. The family is composed of 26 members; 11 members with ADPKD, 4 members with CF, and 2 members with both diseases. Renal volumes measured by computerized tomography (CT), calculated creatinine clearances, and other clinical parameters in the family members with ADPKD and CF were compared with those in the family members with ADPKD alone, as well as to a large population of patients with ADPKD. The patients with CF and ADPKD, but not the CF heterozygote carriers with ADPKD, had less severe polycystic kidney and liver disease, as indicated by normal renal function; smaller renal volume, even when corrected for height and body surface area; and the absence of hypertension and liver cysts. These observations suggest that the coexistence of CF may reduce the severity of ADPKD.

Background: Controversy continues regarding the optimal extent of primary thyroid resection in most patients with papillary thyroid carcinoma (PTC), who are at minimal risk of cause-specific mortality (CSM). This study was designed to compare CSM and recurrence rates after either unilateral lobectomy (UL) or bilateral lobar resection (BLR) in patients with PTC considered low risk by AMES criteria. Methods: Outcome was studied in 1685 patients initially treated during 1940 through 1991 and followed for up to 54 postoperative years (mean, 18 years). One thousand six hundred fifty-six patients (98%) had complete primary tumor resection; 634 (38%) had involvement of regional nodes. One hundred ninety-five patients (12%) had UL; BLR accounted for 1468 (near-total 60%; total thyroidectomy 18%). Results: Thirty-year rates for CSM and distant metastasis were 2% and 3%, respectively. Twenty-year rates for local recurrence and nodal metastasis were 4% and 8%, respectively. There were no significant differences in CSM or distant metastasis rates between UL and BLR ( P > .2). After UL, 20-year rates for local recurrence and nodal metastasis were 14% and 19%, significantly higher ( P = .0001) than the 2% and 6% rates seen after BLR. Conclusions: UL was not associated with higher CSM rates, but it was associated with a significantly higher risk of locoregional recurrence. Thus BLR probably represents a preferable initial surgical approach to patients with low-risk PTC. (Surgery 1998;124:958-66.)

Clinical outcome is variable in prostate cancer patients with regional lymph node metastasis. We studied 269 patients who had regional lymph node metastasis at the time of radical retropubic prostatectomy and bilateral pelvic lymphadenectomy at the Mayo Clinic between January 1987 and December 1992. Two hundred fifty-three (94%) patients received androgen deprivation therapy within 90 days of radical prostatectomy. Patients ranged in age from 47 to 79 years (median, 67 years). Median follow-up was 6.1 years (range, 0.3-10.5 years). Nodal cancer volume (size) was measured by the grid-counting method. Cox proportional hazards models were used to determine the impact of numerous clinical and pathologic findings on systemic progression-free survival. Systemic progression was defined as the presence of distant metastasis documented by biopsies or radiographic examinations (abdominal computerized tomography, plain radiographs, or bone scan). Five-year progression-free survival was 90%. In predicting systemic progression using Cox multivariate analysis, only nodal cancer volume added significantly to the model containing the primary cancer variables (Gleason score, cancer volume, and DNA ploidy). The relative hazard rate for a doubling in nodal cancer volume was 1.6 (95% confidence interval, 1.3 to 2.0; p < 0.0001). Spearman rank analysis showed a correlation between nodal cancer volume and Gleason score of the primary cancer, the number of positive nodes, the aggregate length of metastases, and the largest nodal cancer diameter (correlation efficient = 0.37, 0.63, 0.96, and 0.95, respectively). Our data indicate that nodal cancer volume was the most significant nodal determinant of progression to distant metastasis in lymph node-positive prostate cancer patients. We recommend that the diameter of the largest metastasis be evaluated in patients with metastases, because this is a more powerful predictor of patient outcome than current methods, which recommend mere counting of the number of positive nodes.

BACKGROUND Salvage radical prostatectomy is a treatment option for patients with recurrent cancer following radiation therapy. This study was conducted to identify predictors of survival for patients treated with salvage radical prostatectomy. METHODS The authors studied 86 prostate carcinoma patients who underwent salvage radical prostatectomy for locally persistent or recurrent prostate carcinoma at Mayo Clinic between 1967 and 1996. The mean interval from radiation therapy to biopsy-proven recurrence was 3.7 years (range, 6 months to 17 years). Patient age at surgery ranged from 51 to 78 years (median, 66 years). The mean follow-up after surgery was 5.8 years (range, 1.0-15.2 years). Cox proportional hazards models were used to identify clinical and pathologic factors associated with distant metastasis free survival and cancer specific survival. RESULTS Actuarial distant metastasis free survival, cancer specific survival, and overall survival were 83%, 91%, and 85% at 5 years and 69%, 64%, and 54% at 10 years, respectively. In multivariate analysis, radical prostatectomy Gleason score and DNA ploidy were independent predictors of distant metastasis free survival and cancer specific survival. CONCLUSIONS Postirradiation Gleason score and DNA ploidy were highly predictive of the clinical outcomes of patients treated by salvage radical prostatectomy after radiation therapy. Cancer 1998;83:2164-2171. © 1998 American Cancer Society.

Purpose: We estimated the changes in utilization of radical prostatectomy for treatment of prostate cancer and describe the clinical characteristics of men undergoing radical prostatectomy in a population based setting.Materials and Methods: The Rochester Epidemiology Project was used to identify all Olmsted County residents who underwent radical prostatectomy from 1980 to 1995. The community medical records of these men were reviewed to determine the clinical and pathological stage and grade at biopsy and following surgery.Results: From 1980 to 1995, 311 radical prostatectomies were performed on Olmsted County men. From 1980 to 1987 prostatectomy rates ranged from 6.3 to 31.0/100,000 men but rates increased dramatically to 53.6/100,000 in 1988 and 106.2/100,000 in 1992. The rate after 1992 decreased to 53.0/100,000 and then increased slightly to 80.4/100,000. There was a shift to younger age in more recent times (mean patient age 65.4 years in 1980 to 1986 and 62.4 in 1993 to 1995, p = 0.02), a n...

BACKGROUND A proposed pathologic (pTNM) classification system for prostate carcinoma was analyzed for its impact on survival outcome in the prostate specific antigen (PSA) era. The impact of margin status on the survival outcome of patients with otherwise organ-confined disease (i.e., without extraprostatic extension or seminal vesicle involvement) was assessed. METHODS Among 5467 patients, the original pathologic classification was T2 in 2094 patients; those with evidence of positive margins, extraprostatic extension, or seminal vesicle involvement were initially classified as having pT3 disease (2920 patients) or pT4 residual disease (211 patients). According to the proposed pTNM system, 1512 patients for whom margin status was considered independent of T classification were reclassified. RESULTS After reclassification, 803 specimens had been down-classified to pT2, resulting in 2932 (54%) with pT2N0 organ-confined disease and a margin positivity rate of 27%; originally, only 38% of patients had been classified as pT2N0. When the old and new classifications were compared, 5-year progression free survival to the combined endpoint of clinical and/or PSA progression (≤0.2 ng/mL) was 86% versus 84% and 70% versus 67% for disease classified as pT2N0 and pT3N0, respectively. Multivariate analysis assessed the effect of margin status on 2334 pT2N0 patients (classified according to the proposed pTNM system) who did not receive adjuvant therapy; adjustments were made for Gleason grade, preoperative PSA, and DNA ploidy. In this analysis, the relative risk (with 95% confidence interval) associated with positive margins was 1.65 (1.24-2.18); this was significant for the combined endpoint of clinical/PSA progression. The 5-year survival, free of clinical/PSA progression, was 86% for those without versus 75% for those with positive margins. CONCLUSIONS This analysis supports the adoption of the proposed pTNM system, which will allow for uniform reporting of pathologic data on prostate carcinoma. For patients with organ-confined disease, positive margins are associated with higher rates of PSA progression. Accordingly, patients should be stratified based on margin positivity in addition to pT classification. Cancer 1998;82:902-8. © 1998 American Cancer Society.

Frequent allelic imbalance of polymorphic markers mapped to regions of the 7q, 8p, 16q, and 18q arms has been reported in prostate cancer. To better define the clinical significance of these genetic alterations, we undertook a retrospective analysis of systemic progression and survival in patients with a single stage of prostate cancer. We ascertained all 227 patients from the Mayo Clinic Radical Prostatectomy Registry who had a histologic high-grade, pathologic stage C (pT3N0M0) tumor surgically removed between 1966 and 1987. The mean follow-up of this population of patients was 7.7 years. DNAs were extracted from cancer lesions identified in 5-micron paraffin-embedded tumor sections. Control DNAs were obtained from surgically removed lymph nodes. Paired DNA samples of 153 patients were available for analysis using 16 polymorphic microsatellite markers mapped to 7q31, 8p22-p21, 16q23-qter, and 18q21-q22. The frequencies of allelic imbalance for at least one marker mapped to 7q31, 8p22-p21, 16q23-qter, and 18q21-q22 were 30, 58, 53, and 45% of all informative cases, respectively. Allelic imbalance at 7q31 strongly correlated with systemic cancer progression and to a slightly lesser extent with cancer-specific death. Eight-year systemic cancer progression-free rates were 58 and 81% for cases with and without 7q31 allelic imbalance, respectively (P < 0.001). Eight-year prostate cancer-specific survival rates were 70 and 85% with and without 7q31 allelic imbalance, respectively (P = 0.019). Multivariate analysis indicated that allelic imbalance at 7q31 is a significant independent predictor of systemic progression (P < 0.001) and possibly prostate cancer death (P = 0.029). In addition, allelic imbalance of the specific loci D7S522 (7q31.1) and D8S258 (8p22-p21.3) was strongly associated with systemic progression (P < 0.001 and P = 0.010, respectively) and with prostate cancer death (P < 0.001 and P = 0.009, respectively). The results suggest that a gene or genes mapped to 7q31.1 and possibly 8p22-p21.3 play an important role in tumor progression, and that allelic imbalances at these regions are markers for poor prognosis in prostate carcinoma.

Objectives. Some patients with palpable intermediate- and high-grade, margin-free, organ-confined prostate cancer experience recurrence following prostatectomy. We studied the ability of microvessel density and other factors to predict recurrence in such patients with pathologic Stage T2 cancer. Methods. Between 1987 and 1991, 307 patients underwent radical prostatectomy for Gleason score 6 to 9, margin-free, organ-confined prostate cancer at Mayo Clinic, Rochester, Minnesota. Specimens from 147 patients with sufficient cancer tissue for immunohistochemical staining with Factor VIII-related antigen were studied by computer-assisted digital image analysis for optimized microvessel density (OMVD). The correlation of deoxyribonucleic acid (DNA) ploidy, Gleason score, OMVD, unilateral disease, bilateral disease, and preoperative prostate-specific antigen (PSA) to cancer recurrence was assessed using the Cox model. Biochemical recurrence was defined as postoperative increase in PSA of greater than 0.2 ng/mL, and clinical recurrence was defined as positive biopsy or metastasis on bone scan. Results. Mean follow-up for all patients was 6.1 years, with 12 deaths (1 due to prostate cancer) and 58 cases of clinical and/or biochemical recurrence. OMVD was not significantly associated with DNA ploidy, Gleason grade, unilateral disease, bilateral disease, or preoperative PSA. Preoperative PSA was the strongest predictor of clinical and/or biochemical recurrence in both univariate and multivariate analysis. OMVD was not a significant univariate or multivariate predictor of clinical and/or biochemical recurrence. The estimated relative risk of clinical and biochemical recurrence associated with a change in OMVD from the 25th percentile (OMVD 45) to the 75th percentile (OMVD 84) was 1.08 (95% confidence interval 0.79 to 1.47). Conclusions. Preoperative PSA was the strongest predictor of clinical and/or biochemical recurrence of prostate cancer in this group of patients. Optimized microvessel density did not predict outcome in a select cohort of patients with palpable intermediate- and high-grade, margin-free, organ-confined prostate cancer (TNM stage T2N0M0).

Immunoglobulin A (IgA) nephropathy, the most common form of glomerulonephritis worldwide, is characterized by a heterogeneous clinical course. In this study, multivariate analysis was performed to identify histopathologic and clinical features that most accurately predict adverse outcome from a dataset of 148 individuals with IgA nephropathy who underwent renal biopsy at our institution between 1973 and 1995. A semiquantitative scoring system was developed for assessment of six glomerular, eight interstitial, and six vascular histopathologic features of IgA nephropathy. Glomerular and interstitial proliferative activity was evaluated by immunostaining archival biopsy specimens with Mib-1, an antibody directed against the Ki-67 antigen. Kaplan-Meier survival analysis was performed, with renal failure being defined as onset of dialysis or transplantation. A number of clinicopathologic factors were univariately associated with adverse outcome, including elevated serum creatinine levels; the presence of hypertension; proteinuria; component and total histopathologic scores; and positive glomerular or interstitial Mib-1 scores. The total glomerular score, consisting of the arithmetic sum of each of the six component scores, was the strongest histopathologic predictor of adverse outcome. Total interstitial and vascular scores also provided more prognostic information than did individual component scores. By multivariate analysis, high total glomerular scores, increased serum creatinine levels at diagnosis, and younger age were significant (P < 0.01) independent predictors of renal failure. Our studies provide a rational basis for the inclusion of composite histopathologic scores in clinical intervention studies of patients with IgA nephropathy and other glomerular disorders.

Due to their varied outcomes, men with biochemical recurrence (BCR) following radical prostatectomy (RP) present a management dilemma. Here, we evaluate Decipher, a genomic classifier (GC), for its ability to predict metastasis following BCR. The study population included 85 clinically high-risk patients who developed BCR after RP. Time-dependent receiver operating characteristic (ROC) curves, weighted Cox proportional hazard models and decision curves were used to compare GC scores to Gleason score (GS), PSA doubling time (PSAdT), time to BCR (ttBCR), the Stephenson nomogram and CAPRA-S for predicting metastatic disease progression. All tests were two-sided with a type I error probability of 5%. GC scores stratified men with BCR into those who would or would not develop metastasis (8% of patients with low versus 40% with high scores developed metastasis, P

Self-reported utilization of health care services is important in epidemiological studies and in health care planning, policy, and research, and the accuracy of such information is essential. This study assessed the validity of self-reported utilization of health care services in a randomly selected cohort of 500 community-dwelling men aged 40 to 79 years in Olmsted County, Minnesota. Men had previously completed a self-administered questionnaire that elicited information on utilization of health care services; questions included total inpatient hospital nights in the previous year, total ambulatory physician visits in the previous year, and physician visits in the previous 2 weeks. The complete community medical records of the men were reviewed, and the accuracy of self-reported information was evaluated by assessing the difference between self-reported utilization and actual medical record utilization as ascertained from the medical records, and the distribution of these differences. Exact agreement was 93% for inpatient hospital nights, 91% for ambulatory physician visits in 2 weeks, and 30% for ambulatory physician visits in the previous year. There was an increase in the variability of the difference between self-reported and medical record utilization with an increasing number of inpatient nights or ambulatory physician visits, and a significant bias toward underreporting with an increasing number of ambulatory physician visits in the previous year. These findings suggest that self-reported inpatient nights in the previous year and ambulatory physician visits in 2 weeks are reasonably accurate, but self-reported ambulatory physician visits in the previous year may be less accurate and likely to be biased toward underreporting at higher numbers of visits. This information should be taken into account by researchers and health planners using self-reported measures of utilization.

The objectives of this study were to evaluate (1) the effect of spinal muscle strengthening by loading exercises on the bone mineral density (BMD) of the spine, and (2) the effect of upper extremity loading exercises on the BMD of the midradius and femur in healthy, premenopausal women. The study design was a randomized, controlled trial of 3 years' duration. Ninety-six healthy, premenopausal, white women aged 30-40 years participated; 67 completed the study. All subjects were in good health (normal menses) and were active, but not athletic (that is, not involved in a regular sport activity). Subjects were randomized to an exercise or control group. The exercise group performed a supervised, non-strenuous, weight-lifting exercise program. Exercise performance was supervised once a week at the medical facility. In addition, the subjects performed the exercises twice a week on their own. Dietary calcium intake was to be maintained at 1,500 mg/day in both groups. Bone density was measured at the lumbar spine and hip with dual-energy X-ray absorptiometry at 0, 1, and 3 years. BMD of the midradius was measured with single photon absorptiometry. Measurements of muscle strength were obtained at baseline and every 3 months for 3 years. Maximal oxygen uptake was measured, and the level of physical activity was recorded. Compliance with the exercise program was excellent during the first year of the study, but decreased thereafter. At the end of 3 years, subject withdrawal was about 34% from the exercise group and about 22% from the control group (total subject withdrawal was about 30%). Muscle strength in the exercise group increased significantly at all involved skeletal sites (p values all < 0.001). There was a modest positive correlation between the BMD of Ward's triangle with spinal flexor strength (r = 0.32, p = 0.008) and with grip strength (r = 0.38, p = 0.001). Comparing study groups, we found no significant effect of the loading and nonstrenuous strengthening exercises in the exercise group or free physical activity group (our control group) on BMD at the spine, hip, or midradius measurement sites. In active, but not athletic premenopausal women, additional moderate weight-lifting exercises showed no significant effect on BMD.

Aging and osteoporosis have been associated with skeletal changes. Back extensor strengthening exercises are highly recommended for management of back pain, especially back pain related to osteoporosis. To our knowledge, the correlation of thoracic kyphosis, lumbar lordosis, and sacral inclination with back extensor strength, physical activity, and bone mineral density has not been critically studied in healthy, active, estrogen-deficient women. In a study of 65 such women (ages 48-65 yr), back extensor strength, bone mineral density, and physical activity score were evaluated and measured. These factors were then correlated with radiographic factors: (1) vertebral body ratios (anterior/posterior height) calculated for each vertebra from T-4 through L-5; (2) kyphosis index determined by adding the anterior heights of each vertebral body, T-4 through T-12, and then dividing the total by the corresponding sum of the posterior heights of each vertebral body; (3) thoracic kyphosis; (4) lumbar lordosis; and (5) sacral inclination. Back extensor strength had a significant negative correlation with thoracic kyphosis (r = -0.30, P = 0.019) and a positive correlation with lumbar lordosis (r = 0.26, P = 0.048) and sacral inclination (r = 0.34, P = 0.009). However, bone mineral density and physical activity score did not show any significant correlations with the radiographic factors. The results indicate that the stronger the back extensor, the smaller the thoracic kyphosis and the larger the lumbar lordosis and sacral inclination. We conclude that back extensor strength is an important determinant of posture in healthy women. However, prescribing back extensor strengthening exercises alone may also increase lumbar lordosis, which is not desirable.

Objectives Nearly half of men with clinically localized prostate cancer are understaged. We evaluated whether knowledge of preoperative free prostate-specific antigen (f-PSA), complexed (c-PSA) and total (t-PSA) concentrations or the ratios thereof (f-PSA/t-PSA, c-PSA/t-PSA and f-PSA/c-PSA) could improve upon the staging of prostate cancer when compared with standard PSA testing (t-PSA). In addition, we examined their associations with tumor grade and deoxyribonucleic acid (DNA) ploidy. Methods Two hundred ninety patients with prostate cancer, 178 (61 %) of whom were treated with radical prostatectomy, formed the study group. Results Although there were significant differences in the f-PSA concentrations with respect to clinical stage, considerable overlap in PSA levels among the clinical substages was observed. Statistically significant differences but weak correlations were observed between the individual f-PSA, c-PSA and t-PSA concentrations with regard to pathologic stage (organ-confined versus extraprostatic) and grade. No significant relationship, however, was observed with the three ratios. Higher PSA values were not always associated with a pathologic stage of pT3 or greater and lower levels did not ensure that a tumor was organ-confined. Only a slight association was observed between c-PSA and t-PSA levels and DNA ploidy. No significant relationship was observed between the f-PSA levels as well as the three ratios with regard to DNA ploidy. A statistically significant improvement in predicting pathologic stage was observed when combining knowledge of preoperative t-PSA concentration with the c-PSA/t-PSA ratio. However, the area under the receiver operator characteristic curves was only slightly increased; as such this combination was of limited clinical utility. Conclusions Statistically significant but weak correlations were observed between the molecular forms of PSA and stage, grade and DNA ploidy. The significant overlap in f-PSA and c-PSA values among all stages, grades and ploidy values precluded any useful predictive information for the individual patient. As such, preoperative knowledge of f-PSA and c-PSA values and the three ratios provided no additional diagnostic information over standard PSA (t-PSA) values alone.

Purpose: Up to 26 percent of patients with pathologically organ confined prostate cancer will experience clinical progression after radical prostatectomy. We attempted to identify patients at greatest risk for future clinical failure despite a favorable pathological outcome.Materials and Methods: The study group included 904 patients treated with bilateral pelvic lymphadenectomy and radical retropubic prostatectomy for disease confined to the prostate gland. Preoperative serum prostate specific antigen (PSA), clinical stage, pathological grade and stage, and deoxyribonucleic acid (DNA) ploidy were evaluated by multivariate analysis to determine relative value in predicting treatment failure. A prognostic scoring system was created using the regression coefficients from the Cox multivariate model to classify patients further according to risk of progression.Results: Preoperative PSA concentration, clinical stage, grade and DNA ploidy were significant univariate predictors of progression (p less tha...

Purpose: The majority of impalpable prostate cancers (stage T1c) are biologically significant. We report the interim results in 257 patients with stage T1c prostate cancer treated with radical prostatectomy.Materials and Methods: Prostate specific antigen progression-free survival was assessed by the Kaplan-Meier method. Multivariate analyses were performed to determine which clinical and pathological variables independently correlated with progression. Comparisons among the various clinical substages (T1a to T2b/c) were calculated.Results: Of the patients with stage T1c cancers 51 percent had stage pT2c or less and 91 percent had clinically significant tumors on the basis of pathological grade, deoxyribonucleic acid ploidy and tumor volume. High preoperative prostate specific antigen, poorly differentiated tumors and nondiploid status were strong independent predictors of progression. The 5-year survival rate free of progression was 84 percent. Patients with clinical stage T1c cancers had a signi...

The prognosis for patients with primary hyperoxaluria has been ominous, with the expectation of renal failure, poor results with transplantation, and early death.We studied the long-term effects of orthophosphate and pyridoxine therapy in 25 patients with primary hyperoxaluria who were treated for an average of 10 years (range, 0.3 to 26). Their mean age at the start of treatment was 12 years (median, 6; range, 0.5 to 32). We also studied the effect of orthophosphate and pyridoxine on urinary supersaturation with calcium oxalate, crystal inhibition using a seeded growth system, and crystal formation using scanning electron microscopy in 12 patients during three-day stays in the clinical research center.The mean (+/- SD) glomerular filtration rate at the start of treatment was 91 +/- 26 ml per minute per 1.73 m2. The median decline in glomerular filtration rates was 1.4 ml per minute per 1.73 m2 of body-surface area per year. The actuarial survival free of end-stage renal disease was 96, 89, 74, and 74 percent of 5, 10, 15, and 20 years, respectively. Treatment with orthophosphate and pyridoxine reduced urinary supersaturation with calcium oxalate from 8.3 +/- 3.0 to 2.1 +/- 1.7 kJ per mole at 38 degrees C (P0.001), increased the inhibition of calcium oxalate formation from 63 +/- 11 to 108 +/- 10 inhibitor units per 24 hours (P0.001), and improved the crystalluria score from 2.6 +/- 0.3 to 0.6 +/- 0.1 (P0.001).Treatment of patients with primary hyperoxaluria with orthophosphate and pyridoxine decreases urinary calcium oxalate crystallization and appears to preserve renal function.

Background The n-3 fatty acids in fish oil affect eicosanoid and cytokine production and therefore have the potential to alter renal hemodynamics and inflammation. The effects of fish oil could prevent immunologic renal injury in patients with IgA nephropathy. Methods In a multicenter, placebo-controlled, randomized trial we tested the efficacy of fish oil in patients with IgA nephropathy who had persistent proteinuria. The daily dose of fish oil was 12 g; the placebo was a similar dose of olive oil. Serum creatinine concentrations, elevated in 68 percent of the patients at base line, and creatinine clearance were measured for two years. The primary end point was an increase of 50 percent or more in the serum creatinine concentration at the end of the study. Results Fifty-five patients were assigned to receive fish oil, and 51 to receive placebo. According to Kaplan-Meier estimation, 3 patients (6 percent) in the fish-oil group and 14 (33 percent) in the placebo group had increases of 50 percent or more i...

To provide information about long-term outcome after radical prostatectomy for clinically localized prostatic cancer (stage T2c or lower), we undertook a retrospective analysis of 3,170 consecutive patients (mean age 65.3 ± 6.4 years, range 31 to 81) with a mean followup of 5 years. Complication rates for patients who underwent prostatectomy before 1988 were compared with those who underwent radical prostatectomy more recently. Of the patients 49 (1.5%), 178 (5.6%), 897 (28%) and 2,047 (65%) had clinical stages T1a, T1b, T2a and T2b,c disease, respectively. The Gleason score was 3 or less in 292 patients (9%) and 7 or greater in 782 (25%). Overall, 438 patients (14%) died, 159 (5%) of cancer. The crude 10 and 15-year survival rates for all patients were 75% and 60%, respectively, which is comparable to the expected survival of a control group (67% and 46%). The cause specific survival rates were 90% and 82%, respectively, metastasis-free survival rates 82% and 76%, local recurrence-free survival r...

Objective. To determine the effect of perioperative blood transfusions in patients with prostate cancer who underwent radical prostatectomy, we analyzed 1,785 patients with a follow-up of five years or more who were treated during a twenty-one-year period (1966 to 1987). Methods. Patients were divided into three groups according to the number of units transfused during the perioperative period: group 1, 0 units (n = 440), group 2, 1 to 2 units (n = 746), and group 3, 3 or more units (n = 599). Results. With univariate analysis, no statistically significant differences were found among the three groups in overall survival rate (71%, 75%, and 71% at ten years; p = 0.48), cause-specific survival rate (89%, 88%, and 86% at ten years; p = 0.36), or progression-free survival rate (61%, 68%, and 68% at ten years; p = 0.83). Adjusting for tumor grade, pathologic stage, and hormonal therapy using the Cox statistical model, we found no significant association between the blood-use group and overall survival rate (p = 0.45), cause-specific survival rate (p = 0.17), or progression-free survival rate (p = 0.34). The estimated relative risk and 95 percent confidence interval associated with blood transfusion (three or more units versus none) were as follows: 1.03 and 0.76 to 1.38 for total mortality, 1.56 and 0.95 to 2.56 for cause-specific death, and 1.20 and 0.91 to 1.57 for disease progression, respectively. Conclusions. According to these findings, withholding homologous blood transfusion, except for infectious precautions, should not be based on the suspicion that it can accelerate death from cancer in patients who undergo radical prostatectomy for prostate cancer.

To determine if the preoperative variables of serum prostate specific antigen (PSA), primary Gleason grade from the biopsy specimen and local clinical stage as determined from digital rectal examination can accurately predict the pelvic lymph node status in patients with clinically localized prostate cancer, we reviewed the medical records of 1,632 patients who underwent bilateral pelvic lymphadenectomy at our institution between January 1988 and December 1991. Using logistic regression analysis, serum PSA was found to be the best predictor of pelvic lymph node metastases (p0.0001). The predictive power of serum PSA could be enhanced considerably by taking into account the Gleason grade (p0.001) and local clinical stage (p0.001). A statistical model using all 3 variables was developed that allows the practicing urologist to estimate on an individual basis the probability of pelvic lymph node involvement. Using a conservative cutoff point of less than 3% as an acceptable false-negative rate, 61% of the patients with clinical stages T1a to T2b (A1 to B1) disease and 29% of those with clinical stages T1a to T2c (A1 to B2) prostate cancer may be spared an open or laparoscopic staging bilateral pelvic lymphadenectomy. As a result, patient morbidity can be decreased and a significant economic savings to the health care system can be realized. This observation has particular importance for prostate cancer patients being managed with radical perineal prostatectomy or definitive radiation therapy.

Well-differentiated thyroid carcinoma infrequently invades the upper aerodigestive tract. However, when invasion occurs, it is the source of significant morbidity. The most common structures invaded by thyroid carcinoma are the recurrent laryngeal nerves, larynx, pharynx, and esophagus. Invasion of these structures produces symptoms of airway insufficiency, dysphagia, and hemoptysis. This study was designed to define more clearly the significance of invasion of papillary thyroid carcinoma on survival. At the Mayo Clinic, 262 patients treated for invasive papillary thyroid carcinoma between 1940 and 1990 were retrospectively evaluated. In this group the sites of invasion were muscle 53%, trachea 37%, laryngeal nerve 47%, esophagus 21%, larynx 12%, and other sites 30%. Complete tumor removal was accomplished in 56% of cases. Kaplan-Meier survival curves were calculated for the population. The overall survival was 79% at 5 years, 63% at 10 years, and 54% at 15 years. When the Cox proportional hazard model was applied to the survival data, the factors that had significant influence on survival were invasion of the trachea and the esophagus. Completeness of resection approached statistical significance. Muscle invasion, laryngeal invasion, and recurrent laryngeal nerve invasion had no significant independent influence on survival. These data suggest that when papillary thyroid carcinoma extends beyond the thyroid capsule and invades adjacent structures, the site invaded will influence survival. Survival may be improved in those cases in which complete surgical excision of the tumor is performed.

We reviewed records from 428 consecutive patients with severe Graves' ophthalmopathy to determine early and late results after transantral orbital decompression. Optic neuropathy was present in 217 (50.7%) patients. Post-operatively, 402 (89%) of 453 eyes with preoperative visual acuity worse than 20/20 improved or remained the same. Visual field scotomas improved or resolved in 245 (91%) of 269 eyes tested pre- and postoperatively. Preoperative papilledema resolved or improved in 99 (94%) of 105 eyes, and preoperative exposure keratitis improved or resolved in 178 (92%) of 195 eyes. Average proptosis reduction was 4.7 mm. Postoperatively, new diplopia developed in 74 (64%) of 116 patients who had no diplopia before orbital decompression, although 300 patients ultimately had strabismus surgery. At late follow-up (N = 293 patients), 226 (77%) had single vision and 44 (15%) had correction with prism. Complications included sinusitis (18 patients), lower eyelid entropion (38 patients), numb lip (23 patients), cerebrospinal fluid leaks (15 patients), and one frontal lobe hematoma (one patient). The average duration of follow-up was 8.7 years. Transantral orbital decompression effectively reduces proptosis and usually corrects optic neuropathy. In other circumstances, the benefits achieved and the side effects incurred must be carefully balanced for each patient before transantral orbital decompression is considered.

A retrospective analysis was performed on 1,035 patients with pathologic Stage C prostate cancer treated with bilateral pelvic lymphadenectomy and radical retropubic prostatectomy. Of these patients, 661 received no immediate adjuvant treatment, 131 adjuvant radiotherapy only, and 103 postoperative adjuvant orchiectomy only. Overall crude survival at five, ten, and fifteen years was 91 percent, 68 percent, and 46 46 percent, respectively. Cause-specific survival was 96 percent, 81 percent, and 66 percent and overall nonprogression survival was 78 percent, 56 percent, and 48 percent at five, ten, and fifteen years, respectively. Patients with margin-positive and residual disease, high-grade tumors, large tumor bulk, and seminal vesicle involvement were more likely to receive adjuvant treatment. However, both univariately and multivariately, only tumor grade and increasing tumor volume correlated significantly with cause-specific survival and local and systemic progression. Adjuvant treatment significantly decreased local, systemic, and overall progression but did not improve cause-specific or crude survival. Orchiectomy and radiation appeared to demonstrate similar efficacy in controlling local recurrences: five-year local recurrence-free survival in this retrospective analysis was > 95 percent for both treatments compared with 84 percent for those without adjuvant treatment.

The correlation of muscle strength at various sites of the axial and appendicular skeleton with physical activity and aerobic capacity was assessed in women 29 to 40 years old. Muscle strength of the spine and upper extremities was determined with strain gauges in 96 healthy white women, and power grip was used as an indicator of upper extremity strength. The physical activity score, which reflected the level of daily weight-bearing activity and was based on a standardized scale, ranged from 3 to 15. Maximal oxygen uptake (aerobic capacity) was measured in 69 of the 96 subjects. The mean values for maximal oxygen uptake were 1.9 liters/min and 27.9 ml/kg per minute when normalized for weight. In general, muscle strength was significantly correlated between axial and appendicular sites; thus, the axial musculature usually represents overall muscle strength. Maximal oxygen uptake in milliliters per kilogram per minute was not correlated with back extensor strength or upper extremity strength. Physical activity score was significantly correlated with back extensor strength but not with maximal oxygen uptake (aerobic capacity) either in liters per minute or in milliliters per kilogram per minute. Thus, maximal oxygen uptake is an invalid marker for level of daily weight-bearing physical activity.

Pretibial myxedema (thyroid dermopathy), an uncommon autoimmune manifestation of Graves' disease, is almost always associated with significant ophthalmopathy and may be a marker for an unusually prolonged or different course for the ophthalmopathy. However, it is not known if the response to therapy for eye disease is different in patients with pretibial myxedema. We compared the results of orbital decompression in 385 patients without and 52 patients with pretibial myxedema operated on between 1969 and 1989. Preoperative and postoperative characteristics of severe Graves' ophthalmopathy did not differ in patients with or without pretibial myxedema except for slightly, but not significantly, more proptosis and diplopia in the pretibial myxedema group. In response to a 1989-1990 questionnaire (83% response rate, n = 364), 89.1% without (n = 319) and 88.9% with (n = 45) pretibial myxedema reported satisfactory or acceptable appearance of the eyes. Self-assessment of visual acuity, eye comfort, diplopia, and overall rate of satisfaction with the status of the eyes did not differ between the groups. The presence of pretibial myxedema does not herald an unsatisfactory response to transantral orbital decompression.

Background. Untreated Stage D1 prostate cancer is associated with a high progression rate. Various treatment modalities involving monotherapy alone have been associated with dismal results. In this retrospective study, the impact of combination therapy, local (surgery or radiation) and systemic (hormonal), compared with that of monotherapy on disease outcome was evaluated. Methods. The authors reviewed 631 patients who underwent pelvic lymphadenectomy for Stage D1 prostate cancer: 251 had radical prostatectomies and orchiectomies, 78 had radical prostatectomies alone, 97 received local irradiation and underwent orchiectomies, and 60 had orchiectomies alone

We retrospectively reviewed the medical records of 65 consecutive patients with medullary thyroid carcinoma, who had had their primary surgical treatment at the Mayo Clinic during the years 1946 through 1970. Of these patients, 58 had sporadic and 7 had familial medullary thyroid carcinoma. Thyroid nodules were the most common initial manifestation. Near-total thyroidectomy was the most frequent initial operation. Survival was affected by the following factors: male sex, familial inheritance, size of the tumor, stage of the tumor (American Joint Committee on Cancer), and completeness of initial resection of the tumor. The mean duration of follow-up was 23.5 years, and the maximal follow-up was 36 years. Among 52 patients without initial distant metastatic involvement and with complete resection of the tumor, 20-year survival free of distant metastatic lesions was 81%. Overall 10- and 20-year survival rates were 63% and 44%, respectively. Because of the substantial morbidity and mortality associated with medullary thyroid carcinoma, early diagnosis and thorough initial resection of the tumor are important.

The clinical course of 138 children who underwent unilateral nephrectomy and had a normal contralateral kidney at the time of nephrectomy was reviewed. The diagnosis leading to nephrectomy included obstructive uropathy in 46% of the cases, reflux or pyelonephritis in 30%, Wilms tumor in 15%, hypertension in 4%, dysplastic kidney in 2% and trauma in 2%. Mean age at nephrectomy was 7.3 years and median followup was 24.7 years. Of the 138 patients 121 (88%) are well and 17 died, including 14 secondary to metastatic Wilms tumor and 1 of renal failure. Survival of nonWilms tumor patients was similar to that of an age-matched control group. In 30 patients 24-hour creatinine clearance and 24-hour urinary protein excretion were measured. Proteinuria (greater than 150 mg./24 hours) was found in 8 of the 30 patients (27%) (p less than 0.001), renal insufficiency developed in 9 (30%) (p less than 0.0001) and hypertension occurred in 10% (p greater than 0.10). Children with an acquired solitary kidney are at increased risk for proteinuria and renal insufficiency.

BACKGROUND Stage D1 disease is found in at least every sixth patient undergoing bilateral pelvic lymphadenectomy and radical retropubic prostatectomy (RRP) for clinically localized prostate cancer (PC). Previous recommendations for monotherapy using surgery, radiation, or systemic therapy alone for Stage D1 disease have usually been associated with a poor outcome in regard to progression and survival. Unlike other pathologic stages, D1 disease treated with RRP is mainly related to DNA ploidy pattern in regard to all end points (progression and survival) and immediate adjuvant hormonal treatment (AHT) rather than to the usual pathologic variables, including the number of positive nodes. METHODS Complete DNA ploidy information was available in 370 patients with Stage D1 disease (age range, 40-77 years; mean, 64 years) undergoing RRP with or without AHT with a follow-up of up to 22 years (mean, 5 years). RESULTS Overall, 80% of all DNA ploidy classes (diploid, 37%; tetraploid, 46%; and aneuploid, 17%) had AHT that highly significantly delayed progression for diploid (P less than 0.0001) more than tetraploid (P less than 0.0001) and more than aneuploid (P less than 0.0001) tumors. Significant prolongation of the disease-free interval might have improved the quality of life for tetraploid and aneuploid patients. Survival (crude and cause-specific) was significantly (P = 0.02) improved only for diploid patients who received AHT but not for tetraploid and aneuploid patients. This was due to the significantly accelerated death rate after progression in those patients with early AHT for tetraploid and aneuploid (but not diploid) tumors. Delayed (on progression only) AHT resulted in high progression rates for all DNA ploidy classes (aneuploid greater than tetraploid greater than diploid); e.g., 21 of 30 diploid patients progressed and 6 patients died from disease at a median of 31.5 months in spite of immediate hormone treatment on progression. RRP and AHT for patients with Stage D1 disease resulted in a highly significant delay in overall progression (76% at 10 years) and excellent local control, depending on DNA ploidy pattern (diploid greater than tetraploid greater than aneuploid) compared with a treatment regimen without AHT (24% overall nonprogression); only 20% of all patients with AHT are projected to die of disease at 10 years. Disease in diploid patients (37%) treated with AHT rarely progressed and those patients are unlikely to die of disease in 10 years or less; delayed (on progression) hormone treatment for diploid patients seemed ineffective. Inclusion of values for prostate specific antigen led to a higher failure rate on progression, and this is dependent on DNA ploidy class (diploid greater than tetraploid greater than aneuploid). CONCLUSION Only patients with nondiploid tumors should be entered into prospective studies using innovative adjuvant treatment protocols to improve survival.

To evaluate the influence of the pathological Gleason score on the predictive value of the prostate-specific antigen (PSA) doubling time (DT), as this variable predicts a patient's risk of disease progression both before and after definitive therapy for prostate cancer, and there is an inverse correlation between the Gleason score and PSA production.We evaluated all men treated with radical prostatectomy (RP) between 1990 and 1999 who did not receive neoadjuvant or adjuvant therapy. We identified 2296 patients who had multiple PSA values available before RP, and 1323 who had biochemical recurrence after RP and had at least two PSA values available before starting secondary therapy. Systemic progression and cancer-specific survival (CSS) rates were estimated using the Kaplan-Meier method and Cox proportional hazard regression models.A PSA DT of18 vs18 months predicted a lower 10-year systemic progression-free survival for patients with tumours having a pathological Gleason score of7 (98% vs 99%, P = 0.005), 7 (82% vs 91%, P = 0.003) and 8-10 (57% vs 73%, P = 0.042). A PSA DT after RP of12 months was significantly associated with a lower 10-year systemic progression-free survival for patients with tumours having a Gleason score of7 (77% vs 94%, P0.001) and 7 (61% vs 86%, P0.001), but not 8-10 (61% vs 75%, P = 0.11). The ability of PSA DT before and after RP to predict systemic progression and CSS decreased with increasing Gleason score.The PSA DT remains associated with outcome both before and after RP across increasing pathological Gleason scores, although the predictive ability of PSA DT is diminished in Gleason 8-10 cancers.

Over the 38-year period from 1950 through 1987, 1,434 Olmsted County, Minnesota women had a first unilateral oophorectomy, while 1,828 underwent bilateral oophorectomy (including 113 with a second unilateral oophorectomy). Most procedures (61% of unilateral and 87% of bilateral oophorectomies) were

The National Cancer Institute of the United States recently sponsored three large-scale, randomized controlled trials of screening for early lung cancer. The trials were conducted at the Johns Hopkins Medical Institutions, the Memorial Sloan-Kettering Cancer Center, and the Mayo Clinic. Participants were middle-aged and older men who were chronic heavy cigarette smokers and thus at high risk of developing lung cancer. Screening procedures were chest radiography and sputum cytology, the only screening tests of established value for detecting early stage, asymptomatic lung cancer. In the Hopkins and Memorial trials the study population was offered yearly chest radiography plus sputum cytology every 4 months. The control population was offered yearly chest radiography only. In these trials the addition of sputum cytology appeared to confer no lung cancer mortality rate advantage. The Mayo Clinic trial compared offering chest radiography and sputum cytology every 4 months to offering advice that the two tests be obtained once a year. This trial demonstrated significantly increased lung cancer detection, resectability, and survivorship in the group offered screening every 4 months compared with the control group. However, there was no significant difference in lung cancer mortality rate between the two groups. The statistical power of these trials was somewhat limited. Nevertheless, results do not justify recommending large-scale radiologic or cytologic screening for early lung cancer at this time.

Presently, the standard staging evaluation of prostate cancer includes digital rectal examination, measurement of serum tumor markers and a radionuclide bone scan. To evaluate the ability of local clinical stage, tumor grade, serum acid phosphatase, serum prostatic acid phosphatase (PAP) and serum prostate specific antigen (PSA) to predict bone scan findings, a retrospective review of 521 randomly chosen patients (mean age 70 years, range 44 to 92 years) with newly diagnosed, untreated prostate cancer was performed. Local clinical stage, tumor grade, acid phosphatase, PAP and PSA all correlated positively with bone scan findings (p less than 0.0001). Using receiver operating characteristic curves, however, PSA had the best over-all correlation with bone scan results. The median serum PSA concentration in patients with a positive bone scan was 158.0 ng./ml., whereas men with a negative bone scan had a median serum PSA level of 11.3 ng./ml. (p less than 0.0001). Using multivariate logistic regression analysis, local clinical stage, tumor grade, acid phosphatase and PAP were evaluated in combination with PSA to assess whether these parameters increased the ability of PSA alone to predict bone scan findings. None of these clinical parameters, irrespective of the combination used, contributed appreciably to the predictive power of PSA alone. A probability plot with 95% confidence intervals was constructed that allows the practicing urologist to estimate on an individual basis the probability of a positive bone scan for any given serum PSA value. The most significant finding of this study, however, was the negative predictive value of a low serum PSA concentration for bone scan findings. In 306 men with a serum PSA level of 20 ng./ml. or less only 1 (PSA 18.2 ng./ml.) had a positive bone scan (negative predictive value 99.7%). This finding would suggest that a staging radionuclide bone scan in a previously untreated prostate cancer patient with a low serum PSA concentration may not be necessary.

The rate of bone loss with age and the incidence of osteoporosis are greater in women than men, which led us to question whether subtle sex differences may occur in the circadian variation of serum ionized calcium (iCa) and PTH. We measured iCa hourly and intact PTH every 2 h for 26 h in 25 women (21-69 yr) and 24 men (20-67 yr) consuming self-selected diets. Urine was collected at 0800-1600, 1600-2400, and 2400-0800 h. Serum iCa levels followed a circadian rhythm in both sexes (P less than or equal to 0.01), and the patterns differed between sexes, notably during early morning, when serum iCa levels were lower in women (P = 0.02). Urinary calcium excretion and fractional excretion of calcium declined in both sexes at night (2400-0800 h), but the decline in men was significantly greater (P = 0.02). Similarly, the percent reduction in urinary calcium excretion at night was greater in men than in women (34% vs. 17%; P less than or equal to 0.05). In women, 26-h mean serum iCa values correlated significantly with total daily calcium intake (r = 0.44; P = 0.03). Serum intact PTH levels showed a significant circadian pattern in both sexes (P less than or equal to 0.001). The patterns of serum intact PTH differed between the sexes (P = 0.05), with an earlier and greater increase at night in men. This blunted nocturnal rise in PTH in women may explain the poor nocturnal adaptation to fasting found in women who, despite lower calcium intake, did not reduce urinary calcium loss at night as effectively as men.

Previous reports have claimed that transurethral resection of the prostate (TURP) preceding definitive radiation therapy for patients with Stage C prostate cancer promotes the risk of distant metastasis and increases the mortality rate. A total of 490 patients with pathologic Stage C adenocarcinoma of the prostate treated by radical prostatectomy were studied. Median time to follow-up was 4.6 years. Comparison was made between patients who had TURP within the six months preceding prostatectomy (n = 54) and those who had needle biopsy (n = 437) prior to operation. No significant differences were noted in local recurrence of disease, systemic progression of disease, disease-free interval, and overall and cause-specific survival, even after adjustment for clinical (adjuvant treatment) and pathologic prognostic variables. Our data suggest that for patients with pathologic Stage C prostate cancer treated by radical surgery, preoperative TURP is not associated with unfavorable outcome.

A comparison of epidemiological and clinical features of trigeminal neuralgia (TN) and glossopharyngeal neuralgia (GN) in Rochester, Minn., reveals several differences. The overall age- and sex-adjusted annual incidence rates were significantly higher for TN than for GN (4.7 vs. 0.8 per 100,000 population). The TN:GN ratio was increased for both men and women and was 5.9:1 for both sexes combined. This ratio is greater than reported in previous non-population-based studies. GN is a milder disease than TN, as indicated by the number of episodes, treatment, and characterization of pain. The right side is affected more often with TN than with GN. Bilaterality was noted less often in TN than in GN cases.

The annual crude incidence rate of glossopharyngeal neuralgia per 100,000 population in Rochester, Minn., for 1945 through 1984, was 0.7 for both sexes combined, suggesting that glossopharyngeal neuralgia is a rare disease. There were no significant differences between the sexes (p greater than 0.10) in the overall age-adjusted (to the total 1980 US population) rates: 1.1 for men and 0.5 for women. Overall age-specific crude rates increased slightly with age. Our results and conclusions, achieved by comparing our data with a large referral study at Mayo Clinic, suggest that glossopharyngeal neuralgia is generally a mild disease, since mild attacks are not uncommon, the average annual recurrence rate for a second episode is low (3.6%), and only one fourth of the cases had to have surgery for relief of symptoms. Bilaterality is not uncommon; it was observed in one fourth of the patients, all of whom had mild disease.

Seasonal variation in physical activity, back extensor muscle strength (BES), and bone mineral density (BMD) of the lumbar spine was studied in 65 healthy postmenopausal women. Physical activity score (PAS) was assessed with an ordinal scale (0-18); this score and the BES were obtained monthly for 2 years (25 readings). BMD values were obtained semiannually (5 readings). A periodic (cosine) regression model was fit to each subject's PAS and BES data to obtain individual estimates of the annual peak day d and the average annual range due to seasonality. There was a strong (P < 0.001) seasonal pattern in physical activity; August 3 was the average peak day, and the seasonal range was 2.0 PAS units. There was modest (P = 0.047) seasonality in BES; June 6 was the estimated peak day, and the seasonal range was 8.22 pounds (about 7% of the mean). BMD averaged 0.015 g/cm2 higher in August through November than February through May (P = 0.002), and the highest monthly average BMD was in August. This seasonal range of 1.4% is larger than the average annual decline with age in BMD observed in longitudinal studies of postmenopausal women. The results of this study have important implications for the planning of longitudinal studies involving changes in physical activity or bone mass in geographic areas with diverse seasons.

We defined age- and sex-specific reference intervals for 19 biologic variables in serum samples from healthy children, 1 to 22 years of age, using common laboratory equipment. Upper and lower reference intervals were defined as the estimated 2.5 and 97.5 percentiles of the distribution. For variables (y) that varied with age, the relationship of y to age was modeled with polynomial regression. Parametric percentile estimates specific to each age were then calculated as the predicted y value +/- 1.96 . SD, in which SD = the standard deviation of the residuals. For variables not associated with age, the nonparametric 2.5 and 97.5 sample percentiles were used to define the reference intervals. No significant age or sex differences were found for serum sodium, total protein, glucose, direct bilirubin, or albumin. Potassium, chloride, and urea showed constant values in children that were higher than adult values in the case of potassium and chloride and lower than adult values in the case of urea. No sex-related differences were seen for these analytes. Creatinine, uric acid, and bicarbonate showed an upward trend in values with increasing age, whereas aspartate aminotransferase, phosphorus, and total and ionized calcium showed a downward trend with increasing age. Sex-related differences were noted for these analytes. The immunoglobulins (IgG, IgA, and IgM) showed an upward trend with increasing age, with no sex-related differences except for IgM in children.

The overall crude incidence rate of trigeminal neuralgia per 100,000 population in Rochester, Minnesota, for 1945 through 1984 was 4.3 for both sexes combined. The age-adjusted (to total 1980 US population) rate for women (5.9) was significantly higher than that for men (3.4). Annual incidence rates increased significantly with age in both women and men. Data based on evidence in the medical records suggest that trigeminal neuralgia is a rather rare and unpredictable disease: The number of episodes varies from 1 to 11, and length of episode from 1 day to 4 years. This study indicates an elevated relative risk associated with hypertension (both overall and among women in the cohort). Also, prevalence of multiple sclerosis was significantly greater among the group of 75 patients who had trigeminal neuralgia. Since the data on treatment in this study do not correspond to a randomized clinical trial, they are presented as empirical results only and show no single treatment of choice for trigeminal neuralgia.

Age- and sex-specific incidence rates of operation for suspected lumbar disc prolapse were determined for residents of Olmsted County, Minnesota, for the 30-year period 1950 through 1979. The incidence rate (adjusted to the age and sex distribution of the United States white population in 1980) was 52.3 per 100,000 person-years for all such operations and 46.3 per 100,000 person-years for initial operations. These rates remained fairly constant over the study period. A distinction was made between surgically proven and unproven cases of lumbar disc prolapse. Patients with a surgically proven lumbar disc prolapse had about 10 times the risk of another operation for disc prolapse within 10 years after the first operation compared with the general population.