Showing papers by "John T. Wei published in 2007"

Integrative molecular concept modeling of prostate cancer progression

Abstract: Despite efforts to profile prostate cancer, the genetic alterations and biological processes that correlate with the observed histological progression are unclear. Using laser-capture microdissection to isolate 101 cell populations, we have profiled prostate cancer progression from benign epithelium to metastatic disease. By analyzing expression signatures in the context of over 14,000 'molecular concepts', or sets of biologically connected genes, we generated an integrative model of progression. Molecular concepts that demarcate critical transitions in progression include protein biosynthesis, E26 transformation-specific (ETS) family transcriptional targets, androgen signaling and cell proliferation. Of note, relative to low-grade prostate cancer (Gleason pattern 3), high-grade cancer (Gleason pattern 4) shows an attenuated androgen signaling signature, similar to metastatic prostate cancer, which may reflect dedifferentiation and explain the clinical association of grade with prognosis. Taken together, these data show that analyzing gene expression signatures in the context of a compendium of molecular concepts is useful in understanding cancer biology.

Measuring health-related quality of life outcomes in bladder cancer patients using the Bladder Cancer Index (BCI).

Abstract: BACKGROUND. Health-related quality of life (HRQOL) has not been adequately measured in bladder cancer. A recently developed reliable and disease-specific quality of life instrument (Bladder Cancer Index, BCI) was used to measure urinary, sexual, and bowel function and bother domains in patients with bladder cancer managed with several different interventions, including cystectomy and endoscopic-based procedures. METHODS. Patients with bladder cancer were identified from a prospective bladder cancer outcomes database and contacted as part of an Institutional Review Board-approved study to assess treatment impact on HRQOL. HRQOL was measured using the BCI across stratified treatment groups. Bivariate and multivariable analyses adjusted for age, gender, income, education, relationship status, and follow-up time were performed to compare urinary, bowel, and sexual domains between treatment groups. RESULTS. In all, 315 bladder cancer patients treated at the University of Michigan completed the BCI in 2004. Significant differences were seen in mean BCI function and bother scores between cystectomy and native bladder treatment groups. In addition, urinary function scores were significantly lower among cystectomy patients treated with continent neobladder compared with those treated with ileal conduit (all pairwise P <.05). CONCLUSIONS. The BCI is responsive to functional and bother differences in patients with bladder cancer treated with different surgical approaches. Significant differences between therapy groups in each of the urinary, bowel, and sexual domains exist. Among patients treated with orthotopic continent urinary diversion, functional impairments related to urinary incontinence and lack of urinary control account for the low observed urinary function scores. Cancer 2007;109:1756–62. � 2007 American Cancer Society.

The benign prostatic hyperplasia registry and patient survey: study design, methods and patient baseline characteristics.

Abstract: The first paper describes the design and baseline characteristics of patients in the BPH Registry and Patient Survey in the USA. This important study will provide information on management practices and outcomes of men with this condition, as well as examining the effects of demographics, socio-economics, comorbidities and medical therapies. Another important study in the USA is the Boston Area Community Health Survey, and in this issue the authors estimate the future magnitude of urological symptoms in that country. They found that it might reach the current level of cardiovascular disease and suggested that this will have huge affects on health service policy. OBJECTIVE To describe the design and baseline cohort characteristics of the Benign Prostatic Hyperplasia (BPH) Registry and Patient Survey, an ongoing, prospective, observational, disease registry documenting management practices and patient outcomes in men in the USA with lower urinary tract symptoms associated with BPH (LUTS/BPH) in actual clinical practice settings. PATIENTS AND METHODS Men with LUTS/BPH who were either untreated or treated with α1-adrenergic blockers (ABs), 5α-reductase inhibitors (5ARIs), a combination of these medications, or anticholinergics, and who met selection criteria, were enrolled at sites throughout the USA. At each visit, standardized forms and validated questionnaires were completed to assess the physicians’ management practices and patients’ clinical characteristics, sexual function, and health-related quality of life. RESULTS At the close of recruitment (February 2005), 6909 men (mean age 66.0 years) were enrolled at 402 sites by urologists and primary-care physicians. Before enrolment, 49% of the men were managed with watchful waiting (WW), 21% with uroselective AB monotherapy, 11% with non-uroselective AB monotherapy, 6% with 5ARI monotherapy, 11% with AB + 5ARI, and 2% with anticholinergics. After enrolment, 42% were on WW and 26% were on selective AB monotherapy; changes in other management groups were minimal. Overall, 33% of the men had mild, 52% had moderate and 15% had severe LUTS. The most common comorbidities were hypertension (53%), high cholesterol (45%) and sexual dysfunction (36%). CONCLUSION The BPH Registry and Patient Survey will provide information on physician management practices and outcomes of men with LUTS/BPH, while examining the effects of demographics, socio-economics, comorbidities, and medical therapies.

Perineural invasion is a marker for pathologically advanced disease in localized prostate cancer.

Abstract: Purpose: To determine if perineural invasion (PNI) should be included in addition to prostate-specific antigen (PSA), biopsy Gleason score, and clinical T-stage for risk-stratification of patients with localized prostate cancer. Methods and Materials: We analyzed prostatectomy findings for 1550 patients, from a prospectively collected institutional database, to determine whether PNI was a significant predictor for upgrading of Gleason score or pathologic T3 disease after patients were stratified into low-, intermediate-, and high-risk groups (on the basis of PSA, biopsy Gleason score, and clinical T-stage). Results: For the overall population, PNI was associated with a significantly increased frequency of upgrading and of pathologic T3 disease. After stratification, PNI was still associated with significantly increased odds of pathologic T3 disease within each risk group. In particular, for low-risk patients, there was a markedly increased risk of extraprostatic extension (23% vs. 7%), comparable to that of intermediate-risk patients. Among high-risk patients, PNI was associated with an increased risk of seminal vesicle invasion and lymph node involvement. Furthermore, over 80% of high-risk patients with PNI were noted to have an indication for postoperative radiation. Conclusions: Perineural invasion may be useful for risk-stratification of prostate cancer. Our data suggest that low-risk patients with PNI on biopsy may benefit from treatment typically reserved for those with intermediate-risk disease. In addition, men with high-risk disease and PNI, who are contemplating surgery, should be informed of the high likelihood of having an indication for postoperative radiation therapy.

Positional Stability of Electromagnetic Transponders Used for Prostate Localization and Continuous, Real-Time Tracking

Abstract: Purpose: To determine the relative positional stability of implanted glass-encapsulated circuits (transponders) used in continuous electromagnetic localization and tracking of target volumes during radiation therapy. Ideally, the distances between transponders remains constant over the course of treament. In this work, we evaluate the accuracy of these conditions. Methods and Materials: Three transponders were implanted in each of 20 patients. Images (CT scan or X-ray pair) were acquired at 13 time points. These images occurred from the day of implant (2 weeks before simulation) to 4 weeks posttreatment. The distance between transponders was determined from each dataset. The average and standard deviation of each distance were determined, and changes were evaluated over several time periods, including pretreatment and during therapy. Results: Of 60 transponders implanted, 58 showed no significant migration from their intended positions. Of the two transponders that did migrate, one appears to have been implanted in the venous plexus, and the other in the urethra, with no clinical consequences to the patients. An analysis that included the planning CT scan and all subsequent distance measurements showed that the standard deviation of intertransponder distances was ≤1.2 mm for up to 1 month after the completion of therapy. Conclusions: Implanted transponders demonstrate the same long-term stability characteristics as implanted gold markers, within statistical uncertainties. As with gold markers, and using the same implant procedure, basic guidelines for the placement of transponders within the prostate help ensure minimal migration.

Non-surgical management of stress urinary incontinence: ambulatory treatments for leakage associated with stress (ATLAS) trial:

Abstract: Background Non-surgical treatment for stress urinary incontinence (SUI) is recommended as first-line therapy, yet few prospective studies and no randomized trials compare the most common non-surgical treatments for SUI.Purpose To present the design and methodology of the ambulatory treatments for leakage associated with stress (ATLAS) trial, a randomized clinical trial comparing three interventions for predominant SUI in women: intravaginal continence pessary; behavioral therapy (including pelvic floor muscle training and exercise and bladder control strategies); and a combination of the two treatments.Methods Treatment outcome measures, collected at 12 weeks and six and 12 months post randomization, include the Patient Global Impression of Improvement (PGI-I), the Stress Incontinence Scale of the Pelvic Floor Distress Inventory (PFDI), seven-day bladder diaries, Pelvic Floor Impact Questionnaire (PFIQ), Pelvic Organ Prolapse-Urinary Incontinence Sexual Function Questionnaire (PISQ-12), Patient Satisfacti...

Treatment choice and quality of care for men with localized prostate cancer.

Abstract: Background Variations in patterns of care and treatment outcomes suggest differences in the quality of care for men treated for localized prostate cancer. Objective We sought to compare adherence with quality indicators for prostate cancer care among men treated with radical prostatectomy or external beam radiation therapy. Research design and subjects We sampled 5230 men diagnosed in 2000 or 2001 with early-stage prostate cancer from 984 facilities reporting to the National Cancer Data Base. Our analytic cohort includes 2604 men (from 770 facilities) treated with radical prostatectomy or external beam radiation. Main outcome measure Subject-level compliance with the RAND quality indicators for localized prostate cancer care, stratified by treatment. We applied sampling weights to obtain national estimates of quality indicator adherence. Results The weighted samples represent 24,547 and 27,125 men treated with radical prostatectomy or external beam radiation therapy, respectively. Compliance with several quality indicators approached 100% in both treatment groups; however treatment-specific variations were noted. Men receiving radiation were less likely than those undergoing surgery to be treated in facilities with a board-certified urologist (odds ratio [OR] = 0.4, 95% confidence interval [95% CI] = 0.2-0.8). Adherence with process of care indicators was appreciably higher among radiation subjects, including documentation of clinical stage (OR = 7.5, 95% CI = 4.8-11.9), pretherapy assessment of urinary (OR = 2.8, 95% CI = 1.9-4.2) and sexual (OR = 1.6, 95% CI = 1.2-2.2) function, and discussion of treatment options (OR = 1.8, 95% CI = 1.1-2.9). Conclusions Documented compliance with process of care quality indicators among men with localized prostate cancer appears superior for those treated with external beam radiation compared with those treated surgically.

Clinical research methods for surgeons

Abstract: clinical research methods for surgeons springer clinical research methods for surgeons hilfsweise clinical research methods for surgeons maryroos clinical research methods for surgeons clinical research methods for surgeons reprint clinical research methods for surgeons velavita download pdf clinical research methods for surgeons clinical research methods for surgeons gerrymarshall research methods for surgeons: an overview why should surgeons care about clinical research methodology? free download clinical research methods for surgeons book guidelines for the reporting of clinical research data in clinical practice guideline on the treatment of carpal principles and practice of clinical research course for basic principles for conducting human research in southeastern society of plastic and reconstructive surgeons the science of surgery: clinical research springer clinical research for surgeons paperback december 17 2008 basic research american academy of orthopaedic surgeons career development resource clinical research womensurgeons clinical research for surgeons in palliative care critical analysis of clinical research reporting in clinical research methods: from idea to publication current and future orthopedic research level of evidence of clinical orthopedic surgery research chapter 15: clinical research in surgery federal jack strategies to improve clinical research in surgery through writing for clinical orthopaedics and related research aaos clinical practice guideline summary prevention of stem cell therapy in surgery racs | royal australasian contributions from surgeons to clinical trials and clinical research methods for surgeons reprint is less clinical research being published by surgeons in general surgery resident research initiation grant ascrs american society of colon & rectal surgeons ascrs news compensating and measuring surgeons: motivation & methods stereotactic techniques in clinical neurosurgery fakyu evaluation of the society of thoracic surgeons online risk a decade of change—risk pro?les and outcomes for isolated surgical evaluation and knowledge transfer methods of joint replacement surgeons of indiana foundation a psychological profile of surgeons and surgical residents maxillofacial surgeons foundation maxface rcvs ethics review panel for practice-based clinical research consensus guideline on breast surgeon quality measurement a new standard for reporting clinical research in the current concepts review clinical epidemiology and

Does urethral competence affect urodynamic voiding parameters in women with prolapse

Abstract: Aims: To (1) compare voiding parameters and (2) correlate symptoms and urodynamic findings in women with pelvic organ prolapse (POP) and varying degrees of urethral competence. Methods: We compared three groups of women with stages II – IV POP. Groups 1 and 2 were symptomatically stress continent women participating in the Colpopexy and Urinary Reduction Efforts (CARE) trial; during prolapse reduction before sacrocolpopexy, Group 1 (n ¼ 67) did not have and Group 2 (n ¼ 84) had urodynamic stress incontinence (USI) during prolapse reduction. Group 3 participants (n ¼ 74), recruited specifically for this study, had stress urinary incontinence (SUI) symptoms and planned sacrocolpopexy. Participants completed standardized uroflowmetry, pressure voiding studies, and validated symptom questionnaires. Results: Subjects’ median age was 61 years, median parity 3 and 87% had stage III or IV POP. Fourteen percent of women in Group 3 demonstrated USI without, and 70% with, prolapse reduction. Women in Groups 2 and 3 had more detrusor overactivity (DO) than Group 1 (17 and 24% vs. 6%, P ¼ 0.02) and detrusor overactivity incontinence (DOI) (15 and 8% vs. 0%, P ¼ 0.004). Based on the Blaivis– Groutz nomogram, 60% of all women were obstructed. Post-void residual volume (PVR), peak flow rate, detrusor pressure at peak flow, voiding mechanisms, voiding patterns, obstruction and urinary retention did not differ among groups. Women in Group 3 had higher irritative and obstructive symptom scores than Group 1 or 2; neither score differed by presence of DO nor obstruction, respectively. Conclusion: Women with POP have significant rates of urodynamic obstruction and retention, independent of their continence status. Symptoms of obstruction and retention correlate poorly with urodynamic findings. Neurourol. Urodynam. 26:1030–1035, 2007. 2007 Wiley-Liss, Inc.

The quality of surgical pathology care for men undergoing radical prostatectomy in the U.S.

Abstract: ging system) to 97% (95% CI, 96–99%) for Gleason score. In composite, RP pathology reports contained 83% (95% CI, 81–84%), 85% (95% CI, 84–87%), and 79% (95% CI, 78–80%) of the recommended data elements measured by the strict CAP category I subset, the broad CAP category I subset, and the full set of 7 indicators, respectively. In contrast to the generally higher composite scores, only 52% (95% CI, 48–56%) and 41% (95% CI, 37–45%) of men who underwent RP had complete documentation in their pathology reports for the strict and broad CAP category I subsets, respectively. CONCLUSIONS. RP surgical pathology reports contained most of the recommended data elements; however, the frequent absence of pathologic stage provides an opportunity for quality improvement. Cancer 2007;109:2445–53. � 2007 American Cancer Society.

Physical activity in women planning sacrocolpopexy.

Abstract: This study describes preoperative physical activity in 314 stress-continent women with prolapse planning sacrocolpopexy. Seventy-six percent reported that they engaged in mild, 60% in moderate, and 26% in strenuous exercise (counts are not mutually exclusive). Activity frequencies did not generally differ by prolapse stage. Prolapse substantially interfered with exercise or recreation in 27% of women, household work or yard work in 19%, and work outside the home in 8%. Compared to women with less symptom distress, more women with greater symptom distress reported that prolapse interfered with household/yard work (43 vs 5%, p<0.0001), working outside the home (29 vs 8%, p<0.005), and recreation/exercise (51 vs 10%, p<0.0001). Prolapse stage was not associated with interference with household/yard work (p=0.28) or work outside home (p=0.89). Although prolapse stage is associated with interference with recreation (p=0.02), this association is not consistently positive : stage II, 42%; stage III, 22%; and stage IV, 32%.

Development of the Measure of Adaptations for Pelvic Symptoms (MAPS): the Importance of Incorporating the Female Patient’s Voice

Abstract: Women with pelvic floor disorders use many adaptations in an attempt to minimize symptoms and enhance the quality of their lives. Existing condition-specific measures fail to capture the extent or impact of these adaptive behaviors. The present paper seeks to extend the women’s health literature and expand the registry of available measures to assess pelvic floor disorders by: 1) documenting the steps taken in the development and initial validation of the Measure of Adaptations for Pelvic Symptoms (MAPS); and 2) describing the added value of incorporating the patient’s voice in the instrument development process through in-depth focus groups. The rigorous process used to develop the measure (i.e., literature review, clinical experts, anecdotal patient reports, telephone-administered pilot study, and focus groups with female patients) is described. Analysis of the focus group data yielded eight important adaptation themes used to further refine the MAPS: disclosure, seclusion, being prepared, planning, clothing considerations, sexuality, order and intensity, and outlook. Specifically, focus group participants confirmed the use of sanitary pads and limiting food and beverage consumption. Women did not endorse keeping a jar or commode nearby. Discussions yielded important modifications to items about restroom use, clothing preferences, “survival kits” and “informal” pessary use. Participants described social isolation and preparations for sexual relations that led to new items. This study confirmed the value of incorporating women’s voices in the questionnaire development process through in-depth focus groups. The process revealed important patient experiences and led to significant refinements of the final measure.