Imaging-based prostate cancer screening among BRCA mutation carriers-results from the first round of screening.

BACKGROUND: Male-carriers of BRCA1/2 gene mutations have an increased risk of prostate cancer (PCa) with a more aggressive phenotype. Current screening-guidelines suggest the use of prostate-specific antigen (PSA) only among BRCA2 carriers. Female carriers have extensive guidelines that include imaging. Our objective was to test the prevalence of PCa among BRCA carriers and examine screening strategies, using PSA and multiparametric magnetic resonance imaging (mpMRI). PATIENTS AND METHODS: We recruited men aged 40-70 years with BRCA1/2 germline mutations and no prior history of prostate biopsy. All men underwent an initial round of screening which included PSA, and prostate mpMRI. PSA was considered elevated using an age-stratified threshold of ≥1 ng/ml for 40-50 years of age, ≥2 ng/ml for 50-60 years of age, and 2.5 ng/ml for 60-70 years of age. Men with elevated PSA and/or suspicious lesion on mpMRI were offered a prostate biopsy. PSA levels, MRI findings, PCa incidence, and tumor characteristics were evaluated. Decision curve analysis was used to compare screening strategies. RESULTS: We recruited 188 men (108 BRCA1, 80 BRCA2), mean age 54 years (9.8). One hundred and ten (57%) had either elevated age-stratified PSA (75; 40%), a suspicious MRI lesion (67; 36%), or both (32; 17%). Of these, 92 (85%) agreed to perform a prostate biopsy. Sixteen (8.5%) were diagnosed with PCa; 44% of the tumors were classified as intermediate- or high-risk disease. mpMRI-based screening missed only one of the cancers (6%), while age-stratified PSA would have missed five (31%). Decision curve analysis showed that mpMRI screening, regardless of PSA, had the highest net benefit for PCa diagnosis, especially among men younger than 55 years of age. We found no difference in the risk of PCa between BRCA1 and BRCA2 (8.3% versus 8.7%, P = 0.91). Ninety percent had a Jewish founder mutation, thus the results cannot be generalized to all ethnic groups. CONCLUSIONS: PCa is prevalent among BRCA carriers. Age may affect screening strategy for PCa in this population. Young carriers could benefit from initial MRI screening. BRCA carriers aged older than 55 years should use PSA and be referred to mpMRI if elevated. TRIAL REGISTRATION: ClinicalTrial.gov ID: NCT02053805.

Oncotype-DX recurrence score distribution in breast cancer patients with BRCA1/2 mutations.

Oncotype-DX assay has never been validated for BRCA mutation carriers. This study compares the recurrence score (RS) distribution in BRCA-positive breast cancer patients with that of a general population (GP) of patients and reports their outcomes. Eligible patients were BRCA carriers who performed the Oncotype-DX assay. Two sets of databases were cross-linked: BRCA carriers at Rabin Medical Center and Sheba Medical Center with Oncotype-DX tests performed through Clalit Health Services HMO, from 2003 to 2015. Fifty-eight BRCA patients were included (20 BRCA1, 38 BRCA2). The GP included 1020 patients. Compared to the GP, BRCA1 patients were younger, had higher rate of grade three tumors, and higher Ki67. BRCA2 patients had lower PR index, higher rate of grade three tumors, and higher Ki67. Among the GP, 52.9, 37.9, and 9.1 % had low, intermediate, and high risk RS, respectively. Corresponding rates were 15, 35, and 50 % in BRCA1 patients, and 18.4, 52.6, and 29 % in BRCA2 patients. Subgroup analysis revealed a similar RS distribution pattern regardless of the nodal status. Median follow-up was 45 months. Four BRCA patients (7 %) developed disease recurrence. RS of these patients were in the intermediate and low range. All recurrences occurred in chemo-naïve patients who had not undergone bilateral oophorectomy. This study revealed significantly different RS distributions between BRCA patients and the GP. RS values shifted toward high and intermediate risk categories. This pattern held regardless of the nodal status and was more pronounced in the BRCA1 group.

Retrograde intrarenal surgery as second-line therapy yields a lower success rate.

BACKGROUND AND PURPOSE: Retrograde intrarenal surgery (RIRS) is a recent addition to the treatment options for renal calculi. Therefore, the indications, as well as the predictors of success, are still being studied. Herein, we report a retrospective comparison of RIRS performed as the primary treatment and as second-line therapy, mostly after shockwave lithotripsy (SWL) failure. PATIENTS AND METHODS: Between October 2001 and August 2004, 93 patients underwent RIRS (11% of all ureteroscopies), all by the same surgeon. Patients were divided into two groups: group 1 (n = 42) consisted of patients undergoing RIRS as a first-line modality and group 2 (n = 51) of those having RIRS as secondline therapy. The indications for RIRS in group 1 were renal calculi with prior placement of a double-J stent (30%), renal + ureteral stone (25%), pushback of ureteral stone during ureteroscopy (22%), a radiolucent stone (8%), coagulopathy, and abnormal renal anatomy. In group 2, the patients were initially treated by SWL (92%) or percutaneous nephrolithotomy. The groups did not differ significantly in demographic characteristics, mean stone size (9.5 and 8.7 mm, respectively), or stone location (in both 60% in the lower pole). The variables analyzed were operating time, complications, length of hospitalization, and stone-free rate. RESULTS: The overall stone-free rate was 73%. However, the stone-free rate was significantly higher in group 1 than in group 2: 80% v 67%, respectively. A higher complication rate and longer hospitalization were noted in group 2, although the difference was not statistically significant. CONCLUSIONS: When RIRS is performed after failed SWL, it has a lower success rate and may be associated with a higher morbidity rate than if it is performed as first-line therapy. These results suggest that the success rate of RIRS may be influenced by the same negative factors that reduce SWL success. Therefore, if a patient fails SWL, careful consideration should be given to the best second-line therapy comparing RIRS with percutaneous stone removal.

Hypoxia Marker GLUT-1 (Glucose Transporter 1) is an Independent Prognostic Factor for Survival in Bladder Cancer Patients Treated with Radical Cystectomy.

BACKGROUND: Tumour hypoxia, which is frequent in many cancer types, is associated with treatment resistance and poor prognosis. The role of hypoxia in surgically treated bladder cancer (BC) is not well described. We studied the role of hypoxia in two independent series of urothelial bladder cancers treated with radical cystectomy. METHODS: 279 patients from the University Hospital Network (UHN), Toronto, Canada, and Turku University, Finland were studied. Hypoxia biomarkers (HIF1-α, CAIX, GLUT-1) and proliferation marker Ki-67 were analyzed with immunohistochemistry using defined tissue microarrays. Kaplan-Meier methods and Cox proportional hazards regression models were used to investigate prognostic role of the factors. RESULTS: In univariate analyses, strong GLUT-1 positivity and a high Ki-67 index were associated with poor survival. In multivariate model containing clinical prognostic variables, GLUT-1 was an independent prognostic factor associated with worse disease-specific survival (HR 2.9, 95% CI 0.7-12.6, Wald p = 0.15 in the Toronto cohort and HR 3.2, 95% CI 1.3-7.5, Wald p = 0.0085 in the Turku cohort). CONCLUSION: GLUT-1 is frequently upregulated and is an independent prognostic factor in surgically treated bladder cancer. Further studies are needed to evaluate the potential role of hypoxia-based and targeted therapies in hypoxic bladder tumours.

Predictors of erectile function improvement in obstructive sleep apnea patients with long-term CPAP treatment.

The long-term effect of treatment with continuous positive airway pressure (CPAP) on erectile function was assessed in 60 patients with obstructive sleep apnea syndrome (OSAS). Severity of OSAS was evaluated by respiratory disturbance index (RDI) and minimal oxygen saturation (OxiMin). Severity of erectile dysfunction (ED) was assessed with the five question International Index of Erectile Function (IIEF-5) before and after CPAP treatment. Subjects were categorized into three groups on the basis of the change in IIEF-5 score: Group 1, no change (n=37); Group 2, improvement from 10+/-5.65 to 19.1+/-5.7, P<0.01 (n=12); Group 3, worsening from 19.9+/-4.7 to 9.5+/-7.8, P<0.01 (n=11). Group 2 had significantly higher RDI and lower OxiMin than the other groups, and was also more compliant and satisfied with CPAP. Change in IIEF-5 with CPAP treatment was negatively correlated (Pearson coefficient) with OxiMin (r=-0.374), and positively correlated with adherence to CPAP treatment (r=0.689). In conclusion, in selected patients, CPAP treatment for OSAS may by itself have a positive effect on erectile function by improving respiration during sleep. Predictors of erectile improvement include high RDI, low OxiMin, and CPAP compliance.

Appendicitis in the elderly: what has changed?

BACKGROUND: The course and outcome of appendicitis in the elderly differs from that of the general population. The rates of perforated appendices, error in diagnosis, postoperative complications and mortality may be related to the time lapse between onset of symptoms and admission, and hence delay in surgery. OBJECTIVES: To evaluate if these factors have improved in recent years. METHODS: A retrospective study was carried out of all 61 patients over age 60 who underwent appendectomies in a major metropolitan hospital during 1988-98. RESULTS: We found that most patients had appendectomies within the first 24 hours of admission and within 3 days of symptoms. Rate of perforation was 43%, error 5.6%, morbidity 41%, and mortality 3.2%. CONCLUSIONS: The high rate of appendix perforation in the elderly is not due to delay. The literature reveals little improvement in the statistics of the disease over the last five decades, despite advances in imaging and surgical technique. This may be explained by the increasing inclusion of octogenarian patients.

Early initiation of aspirin after prostate and transurethral bladder surgeries is not associated with increased incidence of postoperative bleeding: a prospective, randomized trial.

PURPOSE: Lower urinary tract operations are being increasingly performed in elderly patients, in whom aspirin intake is common for preventing cardiovascular disease. We determined the safety of early aspirin re-initiation after lower urinary tract surgeries. MATERIALS AND METHODS: A randomized, open label clinical trial was done. The study cohort included patients referred for transurethral prostatectomy, open prostatectomy and transurethral resection of bladder tumor while receiving aspirin prophylaxis. After controlling for surgical modality patients were randomized into 2 arms, including aspirin treatment initiation 24 hours after discontinuing of bladder irrigation (early treatment group) and aspirin treatment initiation 3 weeks after surgery (late treatment group). Primary end points were pre-discharge hematuria necessitating the restoration of bladder irrigation or the cessation of aspirin treatment and late hematuria treated in an urgent care setting, requiring hospital admission or compelling the cessation of aspirin treatment. RESULTS: A total of 120 patients were enrolled, including 60 per treatment group. There were no significant differences between the groups in surgery related factors that could have affected postoperative bleeding. Primary end points were attained by 16 of the 120 patients (13.6%), including 10 of the 60 (16.7%) in the early treatment group and 6 (10%) in the late treatment group (p = 0.28). Time to catheter removal and persistent hematuria duration were similar in the 2 groups. Cardiovascular morbidity was noted in 3 of 120 patients, of whom all were assigned to the early treatment group. CONCLUSIONS: Early aspirin initiation after lower urinary tract surgeries does not appear to carry an increased risk of postoperative bleeding. Thus, it may be considered in patients at high risk for cardiovascular morbidity.

Clinical implication of routine stone culture in percutaneous nephrolithotomy--a prospective study.

OBJECTIVES: To evaluate the correlation between preoperative urine culture (UC) and intraoperative stone culture (SC) and the impact of SC findings on clinical decisions. METHODS: UC and intraoperative fragmented SC were prospectively obtained in all patients undergoing percutaneous nephrolithotomy between January 2004 and March 2005. Patients with a positive UC received a full course of antibiotics before surgery. All postoperative systemic inflammatory response syndrome (SIRS) events were recorded, as was the antibiotic regimen used and any changes in antibiotic treatment secondary to the SC results. RESULTS: The study group consisted of 75 consecutive patients. Of these 75 patients, 33 (49%) had sterile UC and SC results. Both urine and renal stones were colonized in 17 patients (24%); in 6 of them, the UC and SC showed different pathogens. A colonized SC associated with a sterile UC was found in 19 patients (25%). The calculated UC sensitivity, specificity, and positive and negative predictive value for the detection of stone colonization was 30%, 94%, and 84% and 58%, respectively. Seventeen patients (22%) had postoperative SIRS. In 13 of them, a change in antibiotic treatment was made according to the SC findings. On univariate analysis, the incidence of SIRS was not related to the length of the operation, stone-free rate, or supracostal or infracostal access. The relative risk of SIRS when the SC was positive was 3.6. CONCLUSIONS: Renal calculi pathogens are one of the predisposing factors for infectious events; however, preoperative UC often fails to grow stone-colonizing bacteria. Intraoperative SC may be essential in directing the antibiotic regimen postoperatively and should be routinely used.

Transanal endoscopic microsurgery: experience with 75 rectal neoplasms.

PURPOSE: The aim of this study was to describe a single institution's experience with transanal endoscopic microsurgery in patients with benign and malignant rectal tumors. PATIENTS: Between January 1992 and April 1998, 75 patients with a mean follow up of 38 months, underwent transanal endoscopic microsurgery excision of benign (46) or malignant (29) rectal tumors, located 3 to 18 cm from the dentate line. RESULTS: A total of 3 of 46 (6.5 percent) patients with benign tumors underwent conversion to radical surgery owing to tumor size. During the follow-up period, benign tumor recurrence was observed in four (9 percent) patients, three of whom were managed by repeat transanal endoscopic microsurgery, whereas one required radical surgery. Histologic staging of malignant tumors was T1 (10), T2 (10), and T3 (9). Seven patients with either inadequate resection margins or T3 tumors were complimented with radical surgery. Of the remaining 22 patients, 11 received adjuvant radiation therapy whereas 11 had no further treatment. Four (18 percent) had recurrent disease, which was managed by repeat transanal endoscopic microsurgery in two, radical surgery in one, and laser ablation in one. No cancer-related deaths were observed during the follow-up period. There was one operative mortality in a cardiac-crippled patient. Postoperative complications were mainly of a minor character and included fever, urinary retention, and bleeding; none of which required reintervention. Rectourethral fistula developed in one patient who underwent repeat transanal endoscopic microsurgery excision for a T3 malignancy. Fecal soiling was transient in three patients and persisted in two. CONCLUSION: Transanal endoscopic microsurgery excision is a safe and precise technique that is well tolerated even in high operative risk patients. Transanal endoscopic microsurgery may become a procedure of choice for benign rectal tumors and selected early malignant neoplasms.