Al B. Barqawi

Association of Testosterone Therapy With Mortality, Myocardial Infarction, and Stroke in Men With Low Testosterone Levels

IMPORTANCE Rates of testosterone therapy are increasing and the effects of testosterone therapy on cardiovascular outcomes and mortality are unknown. A recent randomized clinical trial of testosterone therapy in men with a high prevalence of cardiovascular diseases was stopped prematurely due to adverse cardiovascular events raising concerns about testosterone therapy safety. OBJECTIVES To assess the association between testosterone therapy and all-cause mortality, myocardial infarction (MI), or stroke among male veterans and to determine whether this association is modified by underlying coronary artery disease. DESIGN, SETTING, AND PATIENTS A retrospective national cohort study of men with low testosterone levels (<300 ng/dL) who underwent coronary angiography in the Veterans Affairs (VA) system between 2005 and 2011. MAIN OUTCOMES AND MEASURES Primary outcome was a composite of all-cause mortality, MI, and ischemic stroke. RESULTS Of the 8709 men with a total testosterone level lower than 300 ng/dL, 1223 patients started testosterone therapy after a median of 531 days following coronary angiography. Of the 1710 outcome events, 748 men died, 443 had MIs, and 519 had strokes. Of 7486 patients not receiving testosterone therapy, 681 died, 420 had MIs, and 486 had strokes. Among 1223 patients receiving testosterone therapy, 67 died, 23 had MIs, and 33 had strokes. At 3 years after coronary angiography, the Kaplan-Meier estimated cumulative percentages with events were 19.9%in the no testosterone therapy group vs 25.7%in the testosterone therapy group,with an absolute risk difference of 5.8%(95%CI, -1.4%to 13.1%) [corrected].The Kaplan-Meier estimated cumulative percentages with events among the no testosterone therapy group vs testosterone therapy group at 1 year after coronary angiography were 10.1% vs 11.3%; at 2 years, 15.4% vs 18.5%; and at 3 years, 19.9% vs 25.7 [corrected].There was no significant difference in the effect size of testosterone therapy among those with and without coronary artery disease (test for interaction, P = .41). CONCLUSIONS AND RELEVANCE Among a cohort of men in the VA health care system who underwent coronary angiography and had a low serum testosterone level, the use of testosterone therapy was associated with increased risk of adverse outcomes. These findings may inform the discussion about the potential risks of testosterone therapy.

Photodynamic therapy for treatment of solid tumors--potential and technical challenges.

Photodynamic therapy (PDT) involves the administration of photosensitizer followed by local illumination with visible light of specific wavelength(s). In the presence of oxygen molecules, the light illumination of photosensitizer can lead to a series of photochemical reactions and consequently the generation of cytotoxic species. The quantity and location of PDT-induced cytotoxic species determine the nature and consequence of PDT. Much progress has been seen in both basic research and clinical application in recent years. Although the majority of approved PDT clinical protocols have primarily been used for the treatment of superficial lesions of both malignant and non-malignant diseases, interstitial PDT for the ablation of deep-seated solid tumors are now being investigated worldwide. The complexity of the geometry and non-homogeneity of solid tumor pose a great challenge on the implementation of minimally invasive interstitial PDT and the estimation of PDT dosimetry. This review will discuss the recent progress and technical challenges of various forms of interstitial PDT for the treatment of parenchymal and/or stromal tissues of solid tumors.

The Insults of Illicit Drug Use on Male Fertility

One-third of infertile couples may have a male factor present. Illicit drug use can be an important cause of male factor infertility and includes use of anabolic-androgenic steroids, marijuana, opioid narcotics, cocaine, and methamphetamines. The use of these illicit drugs is common in the United States, with a yearly prevalence rate for any drug consistently higher in males compared with females. We aim to provide a review of recent literature on the prevalence and effects of illicit drug use on male fertility and to aid health professionals when counseling infertile men whose social history suggests illicit drug use. Anabolic-androgenic steroids, marijuana, cocaine, methamphetamines, and opioid narcotics all negatively impact male fertility, and adverse effects have been reported on the hypothalamic-pituitary-testicular axis, sperm function, and testicular structure. The use of illicit drugs is prevalent in our society and likely adversely impacting the fertility of men who abuse drugs.

The Role of 3-Dimensional Mapping Biopsy in Decision Making for Treatment of Apparent Early Stage Prostate Cancer

PURPOSE We determined the impact of a grid based, transperineal 3-dimensional mapping biopsy on decision making for primary management of early stage prostate cancer. MATERIALS AND METHODS We prospectively performed 3-dimensional mapping biopsy on 180 consecutive men who presented to our clinic between 2006 and 2009 with early stage, organ confined prostate cancer based on transrectal ultrasound guided 10 to 12-core biopsy, and on 35 with prior negative transrectal ultrasound biopsies. RESULTS At presentation median patient age was 60.5 years (range 43 to 77), median prostate specific antigen was 4.8 ng/ml (range 0.5 to 72.4) and median prostate volume was 35 cc (range 9 to 95). The median number of cores acquired by transrectal ultrasound and 3-dimensional mapping biopsy was 12 and 56, and the median number of positive cores was 1 and 2, respectively. We documented Gleason score upgrade in 49 of 180 cases (27.2%) and up-stage in 82 (45.6%). The incidence of urinary retention catheter requirement of greater than 48 hours was 3.2% and the incidence of transient orthostatic hypotension was 5%. No urinary tract infections were documented. A total of 38 men received radical extirpative therapy, 11 radiation and 45 cryotherapy while 60 enrolled in a targeted focal therapy study, 44 entered active surveillance and 5 underwent other focal investigational treatments. Post-mapping data on 12 men were not available for analysis. CONCLUSIONS Three-dimensional mapping biopsy revealed that a significant portion of men initially diagnosed with apparently low risk disease harbored clinically significant cancers requiring more aggressive therapy. The technique also enabled a number of men with low risk disease to elect surveillance or another less morbid option.

Adaptation of a 3D prostate cancer atlas for transrectal ultrasound guided target-specific biopsy

Due to lack of imaging modalities to identify prostate cancer in vivo, current TRUS guided prostate biopsies are taken randomly. Consequently, many important cancers are missed during initial biopsies. The purpose of this study was to determine the potential clinical utility of a high-speed registration algorithm for a 3D prostate cancer atlas. This 3D prostate cancer atlas provides voxel-level likelihood of cancer and optimized biopsy locations on a template space (Zhan et al 2007). The atlas was constructed from 158 expert annotated, 3D reconstructed radical prostatectomy specimens outlined for cancers (Shen et al 2004). For successful clinical implementation, the prostate atlas needs to be registered to each patients TRUS image with high registration accuracy in a time-efficient manner. This is implemented in a two-step procedure, the segmentation of the prostate gland from a patients TRUS image followed by the registration of the prostate atlas. We have developed a fast registration algorithm suitable for clinical applications of this prostate cancer atlas. The registration algorithm was implemented on a graphical processing unit (GPU) to meet the critical processing speed requirements for atlas guided biopsy. A color overlay of the atlas superposed on the TRUS image was presented to help pick statistically likely regions known to harbor cancer. We validated our fast registration algorithm using computer simulations of two optimized 7- and 12-core biopsy protocols to maximize the overall detection rate. Using a GPU, patients TRUS image segmentation and atlas registration took less than 12 s. The prostate cancer atlas guided 7- and 12-core biopsy protocols had cancer detection rates of 84.81% and 89.87% respectively when validated on the same set of data. Whereas the sextant biopsy approach without the utility of 3D cancer atlas detected only 70.5% of the cancers using the same histology data. We estimate 10-20% increase in prostate cancer detection rates when TRUS guided biopsies are assisted by the 3D prostate cancer atlas compared to the current standard of care. The fast registration algorithm we have developed can easily be adapted for clinical applications for the improved diagnosis of prostate cancer.

The Role of Targeted Focal Therapy in the Management of Low-Risk Prostate Cancer: Update on Current Challenges

Prostate cancer is one of the most prevalent cancers among men in the United States, second only to nonmelanomatous skin cancer. Since prostate-specific antigen (PSA) testing came into widespread use in the late 1980s, there has been a sharp increase in annual prostate cancer incidence. Cancer-specific mortality, though, is relatively low. The majority of these cancers will not progress to mortal disease, yet most men who are diagnosed opt for treatment as opposed to observation or active surveillance (AS). These men are thus burdened with the morbidities associated with aggressive treatments, commonly incontinence and erectile dysfunction, without receiving a mortality benefit. It is therefore necessary to both continue investigating outcomes associated with AS and to develop less invasive techniques for those who desire treatment but without the significant potential for quality-of-life side effects seen with aggressive modalities. The goals of this paper are to discuss the problems of overdiagnosis and overtreatment since the advent of PSA screening as well as the potential for targeted focal therapy (TFT) to bridge the gap between AS and definitive therapies. Furthermore, patient selection criteria for TFT, costs, side effects, and brachytherapy template-guided three-dimensional mapping biopsies (3DMB) for tumor localization will also be explored.

Validation of the Modified American Urological Association Symptom Score

PURPOSE We created a shorter version of the American Urological Association symptom score, called UWIN (urgency, weak stream, incomplete emptying and nocturia). MATERIALS AND METHODS Participants in Prostate Cancer Awareness Week from 2006 and 2007 were administered the regular American Urological Association symptom score and UWIN. A total of 278 participants completed each questionnaire. Total scores of each participant for the American Urological Association symptom score (range 0 to 35) and UWIN (range 0 to 12) were evaluated using Spearmans correlation coefficients and Bland-Altman plots to determine the level of agreement between the 2 questionnaires. RESULTS The correlation between the total American Urological Association symptom score (range 0 to 35) and the total UWIN score (range 0 to 12) was 0.913 (p<0.0001). The correlation between the quality of life question on the American Urological Association symptom score and UWIN was 0.821 using the Spearman correlation coefficient (p<0.0001). A second analysis performed using Bland-Altman plots showed good agreement between the American Urological Association symptom score and UWIN. Overall, respondents tended to have slightly higher UWIN total scores than their American Urological Association symptom scores. CONCLUSIONS This study validates that the UWIN questionnaire can be used in place of the American Urological Association symptom score. The UWIN questionnaire will lessen the burden on the respondent, broaden the applicability of the instrument and make collecting data as efficient and effective as possible.

The accuracy of prostate cancer localization diagnosed on transrectal ultrasound-guided biopsy compared to 3-dimensional transperineal approach.

Background. Prostate cancer is often understaged following 12-core transrectal ultrasound- (TRUS-) guided biopsies. Our goal is to understand where cancers are typically missed by this method. Methods. Transperineal 3-dimensional mapping biopsy (3DMB) provides a more accurate depiction of disease status than transrectal ultrasound- (TRUS-) guided biopsy. We compared 3DMB findings in men with prior TRUS-guided biopsies to determine grade and location of missed cancer. Results were evaluated for 161 men with low-risk organ confined prostate cancer. Results. The number of cancer-positive biopsy zones per patient with TRUS was 1.38 ± 1.21 compared to 3.33 ± 4.06 with 3DMB, with most newly discovered cancers originating from the middle lobe and apex. Approximately half of all newly discovered cancerous zones resulted from anterior 3DMB sampling. Gleason upgrade was recognized in 56 patients using 3DMB. When both biopsy methods found positive cores in a given zone, Gleason upgrades occurred most frequently in the middle left and right zones. TRUS cancer-positive zones not confirmed by 3DMB were most often the basal zones. Conclusion. Most cancer upgrades and cancers missed from TRUS biopsy originated in the middle left zone of the prostate, specifically in anterior regions. Anterior sampling may lead to more accurate diagnosis and appropriate followup.

Methods of developing UWIN, the modified American Urological Association symptom score

PURPOSE The American Urological Association symptom score instrument is widely used to assess lower urinary tract symptom severity in men. We describe the methods used to develop a shorter form of the American Urological Association symptom score that may provide symptom score assessment with minimal compromise in accuracy. MATERIALS AND METHODS Complete American Urological Association symptom score data were collected on 8,731 men who attended Prostate Cancer Awareness Week in 2003 or 2004. Correlation analysis and area under the ROCs were used to determine the best reduced index and cutoff points in scores for the severity categories of mild, moderate and severe. RESULTS The number of responses in the original 7 American Urological Association symptom score items was lowered from 6 to 4 and for the bothersome index it was lowered from 7 to 3. Four of the original 7 items were retained. Cronbachs α was 0.851 for the symptom score items in our data. The combination of items with the best joint correlation to the American Urological Association symptom score and bothersome score was UWIN (urgency, weak stream, incomplete emptying and nocturia). The correlation of UWIN with the American Urological Association symptom score was 0.938. The correlation of UWIN bother to the American Urological Association bothersome score was 0.638. The ROC for the mild, moderate and severe UWIN categories compared to the categorized American Urological Association symptom score was 0.96, 0.97 and 0.99, respectively. CONCLUSIONS The UWIN instrument may potentially be a valuable tool to assess American Urological Association symptom score severity and bother. Clinical validation of this instrument is indicated in a prospective comparative study.

Prospective Outcome Analysis of the Safety and Efficacy of Partial and Complete Cryoablation in Organ-confined Prostate Cancer

OBJECTIVE To determine the rate of complications and change in International Prostate Symptom Score and Sexual Health Inventory for Men scores following cryotherapy treatment of low- and intermediate-risk prostate cancer. The secondary end points were the change in prostate-specific antigen post cryotherapy and biopsy-proven recurrence. MATERIALS AND METHODS Enrollment occurred from 2007 to 2015 to assess long-term complications of cryotherapy. A prostate biopsy was performed at 1 year or in the event of biochemical failure. Subjects were staged and graded by standard 12- to 14-core transrectal ultrasound (TRUS) biopsy. A subset of subjects underwent additional 3-dimensional mapping biopsy if the cancer was suspected to be downgraded. Analyses of functional outcomes were stratified into focal and nonfocal treatments. RESULTS The study consisted of 393 men with low- and intermediate-risk prostate cancer, aged 44-89 years. Patient IPSS scores improved significantly in the nonfocal treatment strata at all time points and after 1 year in the focal strata with a median drop at 1 year of 4 points (P <.001). No significant difference was detected for a change in preprocedural SHIM score in either treatment strata after 2 years (P >.7). Eighty-two patients (20.9%) had a rise in prostate-specific antigen resulting in biochemical failure. Seventy patients had detected recurrence for an overall recurrence rate of 20.4% in 343 patients. A total of 109 patients (27.7%) reported urinary retention and urgency post cryotherapy, with 15.3% requiring catheterization for up to 3 weeks. Thirty-seven patients (9.4%) experienced urethral meatal stricture, and 36 patients (9.2%) reported unresolved new-onset erectile dysfunction. CONCLUSION Complication rates, most significantly erectile dysfunction, are decreased in this study compared with those previously reported in the literature for cryotherapy for prostate cancer.