The relationship of the intensity of posttreatment prostate-specific antigen surveillance and prostate cancer outcomes: results from a population-based cohort.

OBJECTIVE: To determine whether higher intensity of prostate-specific antigen (PSA) surveillance was associated with earlier detection of biochemical recurrence (BCR) or survival. PATIENTS AND METHODS: We identified a population-based cohort of 832 men diagnosed with nonmetastatic prostate cancer between January 1, 1995, and July 31, 2006. These men were treated with radical prostatectomy (RP), brachytherapy or external beam radiation therapy (RT), or primary androgen deprivation therapy or chose watchful waiting. To test the associations of intensity in PSA surveillance with study outcomes, we used a 2-year landmark analysis to assess whether the number of PSA tests during the first 2 years after treatment was associated with earlier detection of BCR, prostate cancer-related mortality, and all-cause mortality. We used landmark analysis to assess the association of PSA intensity, adjusting for clinicopathologic covariate, with outcome. RESULTS: Median follow-up time for the entire cohort was 6.7 years. Higher Gleason score was the only clinicopathologic variable associated with higher PSA frequency in multivariable analysis for both the RP and RT groups (P value of .001 and .05, respectively). After adjustment for other covariates, the frequency of PSA tests during the first 2 years after RP did not increase the ability to detect BCR (hazard ratio, 1.00; 95% confidence interval, 0.84-1.19) or all-cause mortality (hazard ratio, 0.95; 95% confidence interval, 0.70-1.30) in the landmark analysis. CONCLUSION: Higher intensity of PSA surveillance during the 2 years after RP or RT did not improve earlier detection of BCR or survival. Evidence-based guidelines for PSA surveillance after primary treatment are needed.

Three-year outcomes of Uretex Urethral Support System for treatment of stress urinary incontinence.

To assess the medium-term performance of the Uretex Urethral Support System, patients were evaluated by the 1-h pad test, cough stress test (CST), Valsalva leak-point pressure test (VLPP), and validated questionnaires. Seventy-five patients were enrolled; median follow-up was 3.6 years (range, 3.1-4.3 years). All patients had a negative CST, 65 (87%) had no leakage during VLPP, and 62 of 72 patients (86%) had a negative 1-h pad test. Compared with baseline values of 50.0 and 28.6, median Urogenital Distress Inventory and Incontinence Impact Questionnaire-7 scores at 3-year follow-up were 16.7 and 0, respectively (P<0.001). Observed medium-term morbidity included de novo urgency in four (5%), frequency in three (4%), and urge incontinence in one (1%). No patients reported graft erosion. The Uretex Urethral Support System is highly effective (both objectively and subjectively) for treatment of stress urinary incontinence and improves quality of life in women with minimal adverse sequelae.

After radical retropubic prostatectomy 'insignificant' prostate cancer has a risk of progression similar to low-risk 'significant' cancer.

OBJECTIVE: To assess progression and survival among patients with small-volume, well-differentiated, organ-confined prostate cancer found at radical retropubic prostatectomy (RRP), often defined as being 'insignificant', thus testing whether they are indeed 'insignificant'. PATIENTS AND METHODS: We identified 6496 men treated for prostate cancer by RRP between 1990 and 1999, and defined 'insignificant' tumours as those in men having a prostate-specific antigen (PSA) level of < 10 ng/mL before RRP, a cancer volume of < or = 0.5 mL, a specimen Gleason of score < or = 6 and stage < or = pT2. Survival was assessed using the Kaplan-Meier method and compared using the two-sided log-rank test. RESULTS: 'Insignificant' tumours were found in 354 (5.5%) men, of whom only one had metastatic progression and none died from prostate cancer, with a median (range) follow-up of 9.2 (0.8-15.6) years. Biochemical progression-free survival (87% vs 85%, respectively, at 10 years, P = 0.5), systemic progression-free survival (100% vs 99%, P = 0.3), overall survival (91% vs 88%, P = 0.16) and cancer-specific survival (100% in each group, P = 0.32) were each similar among men with 'insignificant' prostate cancer and men with low-risk (defined by Gleason score, preoperative PSA level, seminal vesicle and surgical margin status) 'significant' cancer. Clinical stage, biopsy Gleason score and preoperative PSA doubling time were multivariably predictive of 'insignificant' tumours at RRP. CONCLUSIONS: 'Insignificant' prostate cancer at RRP is associated with a comparable risk of biochemical progression as low-risk 'significant' cancer. Although clinical predictors for 'insignificant' pathology can be identified, it remains to be established whether such patients can be safely managed conservatively.

Increased optical magnification from 2.5x to 4.3x with technical modification lowers the positive margin rate in open radical retropubic prostatectomy.

PURPOSE: We compared the positive surgical margin rate of 2.5x and 4.3x optical loupe magnification with associated technical improvement during open radical retropubic prostatectomy. MATERIALS AND METHODS: From January 2, 2004 to September 16, 2005, 511 consecutive patients underwent open radical retropubic prostatectomy, as performed by 1 surgeon. Because 10 patients refused authorization for a retrospective chart review, 501 were evaluable. For the first 265 patients 2.5x power loupes were used and for the subsequent 236 we used 4.3x power loupes. We used the chi-square test for univariate analysis, followed by multivariate logistic regression analysis adjusted for commonly recognized predictors of positive surgical margins in the 2 successive cohorts. Focusing on the apex, which was the most commonly reported site of positive surgical margins, we include operative video segments mimicking 4.3x magnification to demonstrate the surgical precision possible at 4.3x for managing the periurethral fascial bands of Walsh and urethral transection at the prostato-urethral junction. RESULTS: Positive surgical margins were identified in 39 of 265 patients (14.7%) at 2.5x and in 12 of 236 (5.1%) at 4.3x. Apical positive surgical margins were identified in 25 of 265 patients (9.4%) at 2.5x and in 5 of 236 (2.1%) at 4.3x. On multivariate analysis 4.3x magnification was independently associated with a 75% decrease in the odds of a positive surgical margin overall and in the apex alone (p <0.001 and 0.003, respectively). CONCLUSIONS: This exploratory retrospective study suggests that, compared with 2.5x magnification, the use of 4.3x magnification with technical refinements that are not possible or deemed safe at 2.5x resulted in a substantial decrease in the positive surgical margin rate.

Severity of childhood asthma and human leukocyte antigens type.

We sought to learn if Class II HLA genes are associated with the severity of asthma in children. We examined a previously recruited cohort of 340 healthy children who had Class II HLA allele data available. We conducted a comprehensive review of their medical records to determine asthma status and, when present, its severity. We found that Class II HLA alleles, which were previously reported to have an association with asthma incidence, appear to have an association as well with asthma severity. These data support our hypothesis that both the incidence and severity of asthma are heritable and that HLA may play an important role in both development and severity of asthma. Because of limited statistical power, our study findings are subject to further investigation.

The epidemiology of tuberculosis among primary refugee arrivals in Minnesota between 1997 and 2001.

BACKGROUND: Minnesota (MN) is home to one of the highest number of refugees in the United States. The primary objective of this study was to evaluate the prevalence of latent and active tuberculosis (TB) infection in primary refugee arrivals to MN. Secondary objectives were to determine the association of TB infection with gender, age, and ethnicity of the refugees. METHODS: A retrospective study of primary refugee arrivals to MN between January 1, 1997, and December 31, 2001, was conducted. Chi-square tests and logistic regression analyses were used to assess the association of TB infection with gender, age, and ethnicity. RESULTS: Of the 9,842 refugees who had Mantoux test results, 4,990 (50.7%) had a positive test. A positive test was more common in men [odds ratio (OR) = 1.6; p < 0.0001], in Africans (OR = 1.6, p = <0.0001), and increased with 10-year age intervals (OR = 1.4; p < 0.0001). A total of 116 (0.8%) refugees received treatment for active TB. Active TB was more common in men (OR = 1.7; p = 0.006), African ethnicity (OR = 4.3; p < 0.0001), and increased with 10-year age intervals (OR = 1.1; p = 0.05). CONCLUSIONS: Screening and treatment for latent and active TB should be actively managed among refugees resettling in the United States, as this is common and can have significant public health implications.

Childhood asthma and measles vaccine response.

BACKGROUND: Asthmatic patients have a TH2-predominant milieu that is associated with humoral immunity. However, little is known about whether humoral immune responses to viral antigens differ between asthmatic and nonasthmatic children. OBJECTIVE: To determine whether humoral immune response differs in asthmatic patients vs nonasthmatic patients. METHODS: Measles virus specific IgG antibody levels were determined for the Rochester Family Measles Study cohort (n = 876), a convenience sample of healthy children 5 to 12 years of age in Rochester, MN. We conducted comprehensive medical record reviews of 838 children who were eligible for this study. We determined the child's asthma status at the time of determination of antibody levels by applying predetermined criteria for asthma. Comparisons were made using the 2-sample t test or chi2 test. RESULTS: Of the 838 children, 156 (18.6%) had asthma at the time of the determination of antibody levels and were not taking systemic steroids within 14 days of specimen collection. Among those with a nonequivocal antibody reading, the seropositive response rates were similar in asthmatic patients and nonasthmatic patients (89.7% vs 90.3%, respectively; P = .83). However, the equivocal response rates were slightly higher among asthmatic patients than nonasthmatic patients (6.4% vs 4.7%, respectively). CONCLUSION: Asthmatic children seem to have similar humoral immune responses to measles vaccine as those without asthma. Although the findings reassure health care practitioners, whether this finding is generalizable to other vaccines and whether asthmatic patients with low antibody levels have normal cell-mediated immunity need to be elucidated in future studies.

Surgical pathology of the ascending aorta: a clinicopathologic study of 513 cases.

Only 2 comprehensive surgical series, published in 1977 and 1983, have evaluated clinicopathologic features of the ascending aorta. Retrospective review of medical records and microscopic slides was performed on 513 consecutive patients with surgical resection of ascending aortic tissue (1985 to 1999). Patients were 2 to 89 years old (mean 59 y), and 303 (59%) were men. Aneurysm or dissection was the indication for surgery in 479. Aortic valves were also excised in 360. Systemic hypertension was present in 279, inherited connective tissue disease (ICTD) in 67, arteritis in 33, and acquired connective tissue disease in 16. Microscopy showed cystic medial degeneration (CMD) in 209, aortic dissection (AD) in 109 (with CMD in 56), normal media in 90, aortitis in 57 (with CMD in 14), and other findings in 48. The most significant, independent risk factor of CMD and AD was ICTD (confidence interval=7.61 and 2.26, respectively). Systemic hypertension was more common in patients with AD than without (P=0.0202). Normal media was the most common histologic finding associated with bicuspid aortic valve (P<0.0001). Among 57 patients with aortitis (giant cell in 39), ages ranged from 16 to 85 years (mean 64 y), and 42 (74%) were women; only 8 had Takayasu arteritis, and 11 had temporal or systemic arteritis. In surgically resected ascending aorta, the 3 most common histologic findings were CMD, AD, and normal media. ICTD, systemic hypertension, and bicuspid aortic valve were common comorbid findings. Giant cell aortitis occured predominantly in women, usually without systemic disease.

Increasing prostate specific antigen following radical prostatectomy and adjuvant hormonal therapy: doubling time predicts survival.

PURPOSE: Adjuvant hormonal therapy may be beneficial in patients who are treated with RRP and found to have adverse pathological findings. We assessed the natural history of detectable PSA in such patients with particular emphasis on the prognostic usefulness of PSADT. MATERIALS AND METHODS: We identified 903 patients treated with RRP and adjuvant hormonal therapy (started less than 90 days postoperatively) for prostate cancer at our institution between 1990 and 1999. PSADT was calculated by log linear regression in men with 2 or more PSA measurements available at least 90 days apart. CSS and sRFS were estimated by the Kaplan-Meier method and analyzed using Cox proportional hazard models. RESULTS: At a median followup of 9.1 years PSA had become detectable in 369 of 771 patients (47.9%) who achieved an undetectable nadir. PSADT evaluable in 463 patients was less than 12 months in 68 (14.6%) and more than 10 years in 283 (61.1%). N stage and Gleason score were significantly associated with sRFS and CSS. PSADT was a significant predictor of sRFS and CSS in N+ and N0 cases with a cancer death HR of 0.55 (95% CI 0.43 to 0.71) and 0.50 (95% CI 0.31 to 0.79), respectively. The association between PSADT and survival persisted after multivariate adjustment for preoperative PSA, specimen Gleason score and seminal vesicle invasion. CONCLUSIONS: This study demonstrates that many patients have slow progression despite increasing PSA following RRP and adjuvant hormonal therapy. Nodal status, cancer grade and PSADT are predictive of sRFS and CSS, and may be a useful means of selecting patients for future adjuvant therapy trials.

Agreement between patient reports of cardiovascular disease and patient medical records.

OBJECTIVE: To determine how well patient-reported cardiovascular disease (CVD) and CVD risk factor information agrees with medical record information. METHODS: Information from Patient/Family History (PFH) questionnaires completed between 1996 and 1999 by residents of Olmsted County, Minnesota, aged 20 years and older was compared with information available through the Mayo Clinic medical diagnostic index. Positive and negative agreement values were calculated by comparing agreement between the 2 data sources. Also, with the Mayo Medical Index serving as the criterion standard, sensitivity, specificity, and positive and negative predictive values of questionnaire information were calculated overall and by subgroups of sex, age, and years of education. RESULTS: Questionnaire responses were retrieved for 26,162 patients. Positive agreement values ranged from 31% for report of a medical problem or surgery related to arteries to the head, arms, or legs or the aorta to 78% for high blood pressure. Negative agreement values ranged from 90% for high cholesterol to 98% for medical problem or surgery related to arteries to the head, arms, or legs or the aorta. Sensitivity of questionnaire information ranged from 37% to 73%, whereas positive predictive values ranged from 27% to 86%. Positive agreement, sensitivity, and positive predictive values tended to increase with increasing age of the patient. Specificity and negative predictive values were 87% or greater, and negative agreement, specificity, and negative predictive values decreased with increasing age. CONCLUSION: Positive patient reports of CVD conditions and risk factors are relatively inaccurate. However, negative self-reports of these conditions are unlikely to be noted in the medical record. Further development of the PFH questionnaire is necessary to ensure accurate patient reporting of CVD data.

Adenocarcinoma of the nose and paranasal sinuses: a retrospective study of diagnosis, histologic characteristics, and outcomes in 24 patients.

BACKGROUND: Adenocarcinomas of the sinonasal cavity are unusual tumors with variable clinical courses. METHODS: We conducted a retrospective chart review between 1980 and 2001. RESULTS: Twenty-four patients (17 men) with sinonasal adenocarcinoma were identified. Nasal obstruction was the most common presenting symptom (75%), and the nose was the most common site of involvement (83%). Eleven tumors (46%) were high grade (grade 3 or 4). Twenty-three patients (95%) underwent an attempt at surgical excision with tumor recurrence or residual disease in seven. Age and tumor grade were associated with overall survival, and tumor grade and intracranial extension were associated with death from disease. CONCLUSIONS: Presentation and treatment for nasal adenocarcinoma varies widely. Some low-grade variants of nasal adenocarcinomas seem to be associated with a more favorable prognosis and, depending on the extent of the tumor, can be treated with less-aggressive therapy.

Incidence of tuberculosis in Olmsted County, Minnesota, 1990-2001.

OBJECTIVE: To describe and compare the incidence and clinical characteristics of tuberculosis in Olmsted County, Minnesota, among US-born and foreign-born persons. PATIENTS AND METHODS: We performed a retrospective cohort study at the Mayo Clinic in Rochester, Minn, of all residents of Olmsted County (2000 population: 124,277) diagnosed as having tuberculosis between January 1, 1990, and December 31, 2001. Potential cases were identified with use of a computerized diagnostic coding database and microbiological laboratory data; all identified medical records were abstracted. Definite cases were those in which Mycobacterium tuberculosis was recovered in culture. Probable cases were those that met predefined clinical or radiographic evidence of tuberculosis and other criteria. Age-specific, sex-specific, and country of origin-specific incidence rates were calculated with use of Olmsted County census data. Variables were compared among risk groups using the Fisher exact test. RESULTS: During a 12-year period, 71 cases of tuberculosis (53 definite, 18 probable) were identified, for an incidence of 5.3 per 100,000 person-years. Of these cases, 54 (76%) occurred during the second half of the study (incidence: 7.7 per 100,000 person-years). The incidence among US-born persons was similar throughout the study period; however, the Incidence among foreign-born persons increased more than 3-fold during the second half of the study period. Twenty-five patients (35%) were former refugees. All isoniazid-resistant infections (12% of isolates) and multidrug-resistant infections (6% of isolates) occurred among foreign-born persons. CONCLUSION: The incidence of tuberculosis increased substantially in Olmsted County between 1990 and 2001, primarily because of an increase in the number of cases among foreign-born persons.

Mucoepidermoid carcinoma of the parotid gland: the Mayo clinic experience.

OBJECTIVE: To determine clinical and histopathologic features of mucoepidermoid carcinoma of the parotid gland, specifically, the relation of tumor stage and grade and treatment type with clinical outcome. DESIGN: Retrospective clinical and histopathologic review. SETTING: Tertiary care medical center. PATIENTS: From 1940 to 1994, 128 patients were treated at our institution for parotid mucoepidermoid carcinoma. Eighty-nine of these patients had their first treatment at our institution; these cases were chosen for retrospective clinical and histopathologic review. INTERVENTION: A head and neck pathologist independently reviewed the pathology specimens. MAIN OUTCOME MEASURES: Age, symptoms, stage, treatment type, tumor grade, pathological features, disease progression, and survival. RESULTS: Results of clinical staging were: T1 in 56 patients, T2 in 13, T3 in 1, T4 in 15, N0 in 85, N1 in 2, and N2 in 2. No patient had N3 or M1 disease. All patients underwent parotidectomy with or without neck dissection. Seven patients received postoperative radiotherapy. Tumor grade was low in 43 patients (48%), intermediate in 40 (45%), and high in 6 (7%). Only 5 patients had disease progression (local recurrence in 4, regional recurrence in 4, and distant recurrence in 2). At latest follow-up (mean follow-up, 14.7 years), 64 patients were alive without disease, 1 was alive with disease, 2 had died of mucoepidermoid carcinoma, and 22 had died of other causes. The Kaplan-Meier estimated cancer-specific survival rates at 5, 15, and 25 years were 98.8%, 97.4%, and 97.4%, respectively. CONCLUSIONS: In our study, tumor grade and stage appeared to be less important than previously described. With adequate parotidectomy and appropriate neck dissection, patients with mucoepidermoid carcinoma of the parotid gland appear to do well, with few recurrences.

Acute rapamycin nephrotoxicity in native kidneys of patients with chronic glomerulopathies.

BACKGROUND: Based on its success as a transplant immunosuppressor, there is intense interest in using rapamycin in the treatment of progressive glomerulopathies involving native kidneys. However, we call attention to the potential toxicity associated with the use of rapamycin in this setting. METHODS: We conducted a study to examine the efficacy and safety of rapamycin in patients with progressive chronic renal failure. Eleven patients with either focal segmental glomerulosclerosis, immunoglobulin A nephropathy, membranous nephropathy or membrano-proliferative glomerulonephritis and progressive renal failure (defined as an increase in >25% of baseline serum creatinine over the last year or loss of glomerular filtration rate > or =5 ml/min/year as determined by the Cockcroft-Gault formula), proteinuria > or =1.0 g/24 h and with a creatinine clearance of > or 20 ml/min/1.73 m(2) were entered into a 12 month study. Patients were treated with rapamycin, starting at 5 mg/day, orally, aiming for target blood levels of 7-10 ng/dl. All patients were on treatment with an angiotensin-converting enzyme inhibitor and/or an angiotensin receptor blocker, aiming to control blood pressure < or =145/90 mmHg. RESULTS: Six patients developed acute renal failure, defined as an increase in serum creatinine > or =0.5 mg/dl (baseline: 3.2+/-0.9 mg/dl; peak: 5.6+/-1.6 mg/dl; P<0.01, paired t-test). In four patients, discontinuation of the drug resulted in improvement of renal function close to baseline levels. One patient required haemodialysis and had no subsequent recovery of renal function. In another patient, renal function recovered after discontinuation of the drug and then rapamycin was resumed at a lower dose when creatinine returned to baseline. This resulted in a second acute increase in serum creatinine that failed to return to baseline when the medication was discontinued. Four other patients had the following adverse events: skin rash, severe hypertriglyceridaemia, diarrhoea and hyperkalaemia. In none of the subjects were rapamycin levels >15 ng/dl. CONCLUSIONS: Rapamycin can cause nephrotoxicity in some patients with chronic glomerulopathies. Whether the toxicity is solely related to rapamycin, due to the combination of proteinuria and rapamycin, or other unknown factor use is presently undetermined.