Simon Conti

Pathological Outcomes of Candidates for Active Surveillance of Prostate Cancer

PURPOSE Active surveillance of prostate cancer has emerged as a viable treatment option for men with features of low risk disease. Five prospective studies have enrolled patients for active surveillance with varying inclusion criteria. We evaluated the pathological outcomes of men meeting published criteria for active surveillance who elected immediate radical prostatectomy to assess the risk of under grading and under staging in candidates for active surveillance. MATERIALS AND METHODS Data were extracted from our institutional urological oncology database for all men who underwent radical prostatectomy between 1996 and 2007. The primary outcome was pathological up staging, defined as the occurrence of extracapsular extension or seminal vesicle involvement. Pathological upgrading was identified as a secondary outcome. We determined the proportion of men who would have qualified for each published active surveillance study and the respective rates of upgrading and up staging in each group. RESULTS We identified 1,097 men who underwent radical prostatectomy with a mean age of 59 years. Overall 28% of the men experienced a Gleason upgrade, 21% had extracapsular extension and 11% had seminal vesicle involvement. In men qualifying based on published active surveillance inclusion criteria, rates of upgrading varied between 23% and 35%, the incidence of extracapsular extension ranged from 7% to 19% and seminal vesicle involvement ranged from 2% to 9%. CONCLUSIONS Varying entry criteria for active surveillance show different rates of adverse pathological features at radical prostatectomy. Predictably fewer men met the more stringent criteria but these men had a lower incidence of seminal vesicle involvement and extracapsular extension. Such data can be used to advise men of the risks of active surveillance.

Utilization of cytoreductive nephrectomy and patient survival in the targeted therapy era

We sought to analyze utilization and survival outcomes of cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma (RCC) before and after introduction of targeted therapy. We identified patients with metastatic RCC between 1993 and 2010 in the SEER registry and examined temporal trends in utilization. We performed a joinpoint regression to determine when changes in utilization of CN occurred. We fitted multivariable proportional hazard models in full and propensity score‐matched cohorts. We performed a difference‐in‐difference analysis to compare survival outcomes before and after introduction of targeted therapy. The proportion of patients undergoing CN increased from 1993 to 2004, from 29% to 39%. We identified a primary joinpoint of 2004, just prior to the introduction of targeted therapy. Beginning in 2005, there was a modest decrease in utilization of CN. CN was associated with a lower adjusted relative hazard (0.41, 95% confidence interval 0.34–0.43). Median survival among patients receiving CN increased in the targeted therapy era (19 vs. 13 months), while median survival among patients not receiving CN increased only slightly (4 vs. 3 months). Difference‐in‐difference analysis showed a significant decrease in hazard of death among patients who received CN in the targeted therapy era. Despite decreased utilization in the targeted therapy era, CN remains associated with improved survival. Prospective randomized trials are needed to confirm the benefit of CN among patients with metastatic RCC treated with novel targeted therapies.

Paleolithic Y-haplogroup heritage predominates in a Cretan highland plateau

The island of Crete, credited by some historical scholars as a central crucible of western civilization, has been under continuous archeological investigation since the second half of the nineteenth century. In the present work, the geographic stratification of the contemporary Cretan Y-chromosome gene pool was assessed by high-resolution haplotyping to investigate the potential imprints of past colonization episodes and the population substructure. In addition to analyzing the possible geographic origins of Y-chromosome lineages in relatively accessible areas of the island, this study includes samples from the isolated interior of the Lasithi Plateau – a mountain plain located in eastern Crete. The potential significance of the results from the latter region is underscored by the possibility that this region was used as a Minoan refugium. Comparisons of Y-haplogroup frequencies among three Cretan populations as well as with published data from additional Mediterranean locations revealed significant differences in the frequency distributions of Y-chromosome haplogroups within the island. The most outstanding differences were observed in haplogroups J2 and R1, with the predominance of haplogroup R lineages in the Lasithi Plateau and of haplogroup J lineages in the more accessible regions of the island. Y-STR-based analyses demonstrated the close affinity that R1a1 chromosomes from the Lasithi Plateau shared with those from the Balkans, but not with those from lowland eastern Crete. In contrast, Cretan R1b microsatellite-defined haplotypes displayed more resemblance to those from Northeast Italy than to those from Turkey and the Balkans.

ORIGINAL RESEARCH—PEYRONIE'S DISEASE: Penile Sonographic and Clinical Characteristics in Men with Peyronie's Disease

INTRODUCTION Ultrasonography of the penis is readily available to the urologist and gives good anatomic detail of soft tissue structures. It has not been widely utilized in the assessment of Peyronies disease (PD). AIMS To describe the sonographic characteristics of the penis in PD and the relationship between clinical and sonographic features. METHODS This cross-sectional study enrolled patients from a single clinical practice. A PD-specific questionnaire was administered and sonographic evaluations were performed. MAIN OUTCOME MEASURES Sonographic characteristics of men with PD. RESULTS Tunical thickening, calcifications, septal fibrosis, and intracavernosal fibrosis, were observed at initial clinical evaluation in 50%, 31%, 20%, and 15% of men, respectively. Men aged 40-49 (OR 2.4, P = 0.02) and men aged 50-59 (OR 2.4, P = 0.004) were more likely to have sub-tunical calcifications relative to men under age 40. Men with septal fibrosis had fewer chronic medical conditions such as diabetes (OR 0.3, P = 0.04), hypertension (OR 0.5, P = 0.03), and coronary artery disease (OR 0.2, P = 0.05), and presented within 1 year of disease onset (OR 2.1, P = 0.001). Men with septal fibrosis were less likely to have lost penile length (OR 0.5, P = 0.04) and more likely to be able to have intercourse (OR 1.9, P = 0.05). Men with intracavernosal fibrosis were less likely to have penile pain (OR 0.5, P = 0.05), but more likely to have penetration difficulty during intercourse (OR 1.9, P = 0.008), an additional penile deformity (OR 1.8, P = 0.02), or rapid onset of disease (OR 1.7, P = 0.04). Tunical thickening was associated with a decreased ability to have intercourse (OR 2.3, P < 0.001). CONCLUSION PD is a clinically and sonographically heterogeneous condition. Sonography is a safe, low-cost, and rapid means of objectively characterizing lesions in this condition. This may help track the evolution of the condition in individual patients and in the future may be useful for tailoring treatment strategies.

Minimally invasive infrapubic inflatable penile prosthesis implant for erectile dysfunction: evaluation of efficacy, satisfaction profile and complications

Erectile dysfunction (ED), the second most common male sexual disorder, has an important impact on man sexuality and quality of life affecting also female partner’s sexual life. ED is usually related to cardiovascular disease or is an iatrogenic cause of pelvic surgery. Many non-surgical treatments have been developed with results that are controversial, while surgical treatment has reached high levels of satisfaction. The aim is to evaluate outcomes and complications related to prosthesis implant in patients suffering from ED not responding to conventional medical therapy or reporting side effects with such a therapy. One hundred eighty Caucasian male suffering from ED were selected. The patient population were divided into two groups: 84 patients with diabetes and metabolic syndrome (group A) and 96 patients with dysfunction following laparoscopic radical prostatectomy for prostate cancer (group B). All subjects underwent primary inflatable penile prosthesis implant with an infrapubic minimally invasive approach. During 12 months of follow-up, we reported 3 (1.67%) explants for infection, 1 (0.56%) urethral erosion, 1 (0.56%) prosthesis extrusion while no intraoperative complications were reported. Mean International Index of Erectile Function-5 (IIEF-5) was 8.2±4.0 and after the surgery (12 months later) was 20.6±2.7. The improvement after the implant is significant in both groups without a statistically significant difference between the two groups (P-value 0.65). Mean Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) score 1 year after the implant is 72.2±20.7, and there was no statistically significant difference between groups A and B (P-value 0.55). Implantation of an inflatable prosthesis, for treatment of ED, is a safe and efficacious approach; and the patient and partner satisfaction is very high. Surgical technique should be minimally invasive and latest technology equipment should be implanted in order to decrease after surgery common complications (infection and mechanical failure).

Prostate size does not predict high grade cancer.

PURPOSE Several radical prostatectomy series have linked small prostates with high grade cancer based on the hypothesis that a small prostate results from a low androgen milieu that selects for less hormone dependent, more aggressive tumors. We previously reported that this association resulted from ascertainment bias from the performance characteristics of prostate specific antigen rather than from tumor biology in our radical prostatectomy cohort. In this study we analyzed this association in a more generalized population of men who underwent prostate needle biopsy. MATERIALS AND METHODS The prostate needle biopsy database at our institution was queried for all initial biopsies. Included patient characteristics were age, race, family history of prostate cancer, prostate specific antigen, abnormal digital rectal examination and prostate volume in ml on transrectal ultrasound. Multivariate logistic regression was used to determine the influence of prostate volume on the odds of high grade cancer. RESULTS The study population included 1,295 patients during 2000 to 2010, of whom 582 (44.9%) had prostate cancer and 398 (30.7%) had high grade cancer. When all patients were pooled, the OR for high grade cancer was 0.85 (95% CI 0.78-0.92) for each 10 ml increase in prostate volume. When patients were divided by clinical T stage, the corresponding ORs for those with T1c disease was 0.83 (95% CI 0.74-0.93) and for those with T2 or greater disease it was 0.99 (0.98-1.00). CONCLUSIONS The association between small prostates and high grade cancer exists only in men with clinical T1c (normal digital rectal examination) prostate cancer. It likely resulted from ascertainment bias due to the performance characteristics of prostate specific antigen rather than tumor biology.

Paternal aging and increased risk of congenital disease, psychiatric disorders, and cancer

As couples are increasingly delaying parenthood, the effect of the aging men and women on reproductive outcomes has been an area of increased interest. Advanced paternal age has been shown to independently affect the entire spectrum of male fertility as assessed by reductions in sperm quality and fertilization (both assisted and unassisted). Moreover, epidemiological data suggest that paternal age can lead to higher rates of adverse birth outcomes and congenital anomalies. Mounting evidence also suggests increased risk of specific pediatric and adult disease states ranging from cancer to behavioral traits. While disease states associated with advancing paternal age have been well described, consensus recommendations for neonatal screening have not been as widely implemented as have been with advanced maternal age.

Alterations in DNA methylation may be the key to early detection and treatment of schistosomal bladder cancer

Bladder cancers arise from transformed urothelial cells that line the bladder. These cancers are urothelial or squamous cell carcinomas or, more rarely, additional histologic variants such as adenocarcinoma. The most important bladder cancer risk factors worldwide are arguably smoking and urogenital schistosomiasis. The parasitic Schistosoma haematobium worm causes urogenital schistosomiasis in approximately 112 million people, primarily in sub-Saharan Africa and the Middle East [1]. During infection, S. haematobium worms lay highly inflammatory eggs in the bladder wall. This inflammation is thought to promote carcinogenesis through unclear mechanisms. People with chronic urogenital schistosomiasis exhibit increased risk and earlier onset of bladder cancer (up to two decades earlier), with a predominance of squamous cell carcinoma [2]. Consequently, S. haematobium has been categorized as a Group I carcinogen (“carcinogenic to humans”) by the International Agency on Research on Cancer of the World Health Organization [3].

A pilot study to develop a prediction instrument for endocarditis in injection drug users admitted with fever

OBJECTIVE Seeking to evaluate the feasibility of a prediction instrument for endocarditis in febrile injection drug users (IDUs), we determined (1) the frequency percentage of IDUs admitted with fever diagnosed with endocarditis and (2) whether individual or combinations of emergency department (ED) clinical criteria (patient history, physical examination findings, and laboratory tests) are associated with endocarditis in IDUs admitted to rule out endocarditis. METHODS The ED and inpatient charts of all IDUs with a diagnosis of rule out endocarditis admitted at 3 urban hospitals in 2006 were reviewed. Screening performance of individual criteria was determined, and the most sensitive combination of criteria was derived by classification tree analysis. RESULTS Of 236 IDUs admitted with fever, 20 (8.5%) were diagnosed with endocarditis. Lack of skin infection, tachycardia, hyponatremia, pneumonia on chest radiograph, history of endocarditis, thrombocytopenia, and heart murmur had the best screening performance. The classification tree-derived best criteria combination of tachycardia, lack of skin infection, and cardiac murmur had a sensitivity of 100% (95% confidence interval, 84%-100%) and negative predictive value of 100% (95% confidence interval, 88%-100%). CONCLUSIONS Using ED clinical criteria, a multicenter prospective study to develop an instrument for endocarditis prediction in febrile IDUs is feasible, with an estimated target enrollment of 588 patients.

Inflatable Penile Prosthesis Placement, Scratch Technique and Postoperative Vacuum Therapy as a Combined Approach to Definitive Treatment of Peyronie’s Disease

Purpose: Peyronies disease is a devastating condition resulting in penile malformation, erectile dysfunction, pain and emotional distress. In this prospective, 2 institution study we evaluated a multimodal surgical and mechanical combined approach to the definitive treatment of Peyronies disease and concomitant erectile dysfunction. Materials and Methods: A total of 145 select patients underwent endocavernous disruption of Peyronies disease plaques via the scratch technique, followed by inflatable penile prosthesis insertion. Postoperatively patients were assigned to vacuum device therapy for 3 minutes twice daily to continue penile curvature correction. Followup continued for 1 year after surgery. Anatomical and functional results were assessed. Results: Patients with plaques in the proximal third, middle third and subcoronal areas of the penis had a mean ± SD postoperative residual curvature of 21.5 ± 4.5, 17.3 ± 4.8 and 14.1 ± 3.1 degrees, respectively. After 24 weeks of vacuum therapy the mean penile curvature deviation decreased to 8.7 ± 2.5, 9.1 ± 2.9 and 7.7 ± 0.9 degrees, respectively. The mean IIEF‐5 (International Index of Erectile Function) score was 9.8 ± 2.3 preoperatively, 18.9 ± 3.1 at 6 months (p <0.001) and 24.1 ± 3.6 at 1 year (p <0.001). The mean EDITS (Erectile Dysfunction Inventory of Treatment Satisfaction) score at the end of followup was 64.6 ± 11.8. Operative and postoperative complications were minimal. Conclusions: Our novel combination of intraoperative and postoperative therapies in the treatment of patients with Peyronies disease and an inflatable penile prosthesis was safe and efficacious with excellent functional outcomes. Penile curvature corrections were statistically significant and complications were negligible.