John Cashy

Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24

Prostate cancer is the most prevalent noncutaneous cancer in males in developed regions, with African American men having among the highest worldwide incidence and mortality rates. Here we report a second genetic variant in the 8q24 region that, in conjunction with another variant we recently discovered, accounts for about 11%–13% of prostate cancer cases in individuals of European descent and 31% of cases in African Americans. We made the current discovery through a genome-wide association scan of 1,453 affected Icelandic individuals and 3,064 controls using the Illumina HumanHap300 BeadChip followed by four replication studies. A key step in the discovery was the construction of a 14-SNP haplotype that efficiently tags a relatively uncommon (2%–4%) susceptibility variant in individuals of European descent that happens to be very common (∼42%) in African Americans. The newly identified variant shows a stronger association with affected individuals who have an earlier age at diagnosis.

Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes

We performed a genome-wide association scan to search for sequence variants conferring risk of prostate cancer using 1,501 Icelandic men with prostate cancer and 11,290 controls. Follow-up studies involving three additional case-control groups replicated an association of two variants on chromosome 17 with the disease. These two variants, 33 Mb apart, fall within a region previously implicated by family-based linkage studies on prostate cancer. The risks conferred by these variants are moderate individually (allele odds ratio of about 1.20), but because they are common, their joint population attributable risk is substantial. One of the variants is in TCF2 (HNF1β), a gene known to be mutated in individuals with maturity-onset diabetes of the young type 5. Results from eight case-control groups, including one West African and one Chinese, demonstrate that this variant confers protection against type 2 diabetes.

General Population and Cancer Patient Norms for the Functional Assessment of Cancer Therapy-General (FACT-G)

Given the number of new cancer cases diagnosed each year and the increases in survival rates, the importance of having a clinically useful health-related quality of life (HRQOL) instrument has increased. The Functional Assessment of Cancer Therapy-General (FACT-G) is one such instrument that has been used worldwide to assess HRQOL. Previously, the use of the FACT-G had been limited because of a lack of published normative data. Normative data are useful for consumers to place their results in an appropriate context by comparing their scores of individuals or group of individuals to a reference group. Here, we present normative data for the FACT-G for two reference groups: (a) a sample of the general U.S. adult population and (b) a large, heterogeneous sample of adult patients with cancer. In addition, we demonstrate various uses of the normative data.

Targeted antimicrobial prophylaxis using rectal swab cultures in men undergoing transrectal ultrasound guided prostate biopsy is associated with reduced incidence of postoperative infectious complications and cost of care.

PURPOSE We evaluated targeted antimicrobial prophylaxis in men undergoing transrectal ultrasound guided prostate biopsy based on rectal swab culture results. MATERIALS AND METHODS From July 2010 to March 2011 we studied differences in infectious complications in men who received targeted vs standard empirical ciprofloxacin prophylaxis before transrectal ultrasound guided prostate biopsy. Targeted prophylaxis used rectal swab cultures plated on selective media containing ciprofloxacin to identify fluoroquinolone resistant bacteria. Patients with fluoroquinolone susceptible organisms received ciprofloxacin while those with fluoroquinolone resistant organisms received directed antimicrobial prophylaxis. We identified men with infectious complications within 30 days after transrectal ultrasound guided prostate biopsy using the electronic medical record. RESULTS A total of 457 men underwent transrectal ultrasound guided prostate biopsy, and of these men 112 (24.5%) had rectal swab obtained while 345 (75.5%) did not. Among those who received targeted prophylaxis 22 (19.6%) men had fluoroquinolone resistant organisms. There were no infectious complications in the 112 men who received targeted antimicrobial prophylaxis, while there were 9 cases (including 1 of sepsis) among the 345 on empirical therapy (p=0.12). Fluoroquinolone resistant organisms caused 7 of these infections. The total cost of managing infectious complications in patients in the empirical group was

Prevalence of Poor Performance Status in Lung Cancer Patients: Implications for Research

13,219. The calculated cost of targeted vs empirical prophylaxis per 100 men undergoing transrectal ultrasound guided prostate biopsy was

Prospective Analysis of Erectile Dysfunction After Anterior Urethroplasty: Incidence and Recovery of Function

1,346 vs

Improved fertility preservation care for male patients with cancer after establishment of formalized oncofertility program

5,598, respectively. Cost-effectiveness analysis revealed that targeted prophylaxis yielded a cost savings of

A live-attenuated vaccine for the treatment of urinary tract infection by uropathogenic Escherichia coli.

4,499 per post-transrectal ultrasound guided prostate biopsy infectious complication averted. Per estimation, 38 men would need to undergo rectal swab before transrectal ultrasound guided prostate biopsy to prevent 1 infectious complication. CONCLUSIONS Targeted antimicrobial prophylaxis was associated with a notable decrease in the incidence of infectious complications after transrectal ultrasound guided prostate biopsy caused by fluoroquinolone resistant organisms as well as a decrease in the overall cost of care.

Tumor Characteristics of Carriers and Noncarriers of the deCODE 8q24 Prostate Cancer Susceptibility Alleles

Introduction: Performance status (PS) is a standard functional classification in oncology research and practice. However, despite its widespread use, little is known about the prevalence of poor PS in lung cancer patients, in relation to other cancers, based on the assessments of health care providers and patients. Methods: Data from two quality of life studies were pooled for analysis. Analyses were performed on the subset of patients with lung cancer (n = 503) from the entire population of cancer patients (n = 2885). The prevalence of poor PS (defined as PS = 2–4 on a 0–4 scale) was determined for lung cancer patients. Results: Prevalence of poor PS among lung cancer patients was 34% when estimated by providers and 48% when estimated by patients themselves. Agreement between providers and patients was only fair (weighted [kappa] = 0.41). For both advanced and early stage disease, lung cancer patients were at the highest risk for poor PS compared with other common cancers. Conclusions: The prevalence of poor PS is quite high in lung cancer patients. Providers tend to underestimate poor PS. Specific clinical trials and treatment guidelines for this patient population are urgently needed.

Radiofrequency Ablation–Assisted Robotic Laparoscopic Partial Nephrectomy Without Renal Hilar Vessel Clamping Versus Laparoscopic Partial Nephrectomy: A Comparison of Perioperative Outcomes

PURPOSE Anterior urethroplasty has been shown to negatively impact erectile function. Recovery of function is common but the likelihood and extent of recovery have not been fully elucidated. MATERIALS AND METHODS Between October 2006 and May 2008 men undergoing anterior urethroplasty were enrolled in a prospective study to evaluate the effects of urethroplasty on erectile function. The International Index of Erectile Function was completed preoperatively and on all subsequent postoperative visits. Preoperative and postoperative erectile function was compared. RESULTS A total of 52 patients who underwent anterior urethroplasty were included in the study. Repair locations were bulbar (35) and penile (17). Of the patients undergoing bulbar urethroplasty 20 had excision and primary anastomosis, and 15 had augmented anastomotic repair. All penile repairs were ventral onlay repair (11) or inlay repair in 2 stages (6). Postoperative erectile dysfunction was noted in 20 (38%) men, of whom 18 recovered fully at a mean postoperative period of 190 days (range 92 to 398). In patients with normal preoperative erectile function bulbar urethroplasty was more likely than penile urethroplasty to cause erectile dysfunction (76% vs 38%, p = 0.05). Within the bulbar urethra excision and primary anastomosis repairs led to slightly higher erectile dysfunction rates than augmented anastomotic repairs (50% vs 26%, p = 0.16). CONCLUSIONS Anterior urethroplasty caused erectile dysfunction in approximately 40% of patients, although recovery was seen in most by 6 months. Bulbar urethroplasty appears to affect erectile function to a greater extent than penile urethroplasty, which may be explained by the proximity of the bulbar urethra to the nerves responsible for erection.