Analgesic use and the risk of kidney cancer: A meta‐analysis of epidemiologic studies

Analgesics are the most commonly used over‐the‐counter drugs worldwide with certain analgesics having cancer prevention effect. The evidence for an increased risk of developing kidney cancer with analgesic use is mixed. Using a meta‐analysis design of available observational epidemiologic studies, we investigated the association between analgesic use and kidney cancer risk. We searched the MEDLINE and EMBASE databases to identify eligible case–control or cohort studies published in English until June 2012 for three categories of analgesics: acetaminophen, aspirin or other non‐steroidal anti‐inflammatory drugs (NSAIDs). Study‐specific effect estimates were pooled to compute an overall relative risk (RR) and its 95% confidence interval (CI) using a random‐effects model for each category of the analgesics. We identified 20 studies (14 with acetaminophen, 13 with aspirin and five with other NSAIDs) that were performed in six countries, including 8,420 cases of kidney cancer. Use of acetaminophen and non‐aspirin NSAIDs were associated with an increased risk of kidney cancer (pooled RR: 1.28; 95% CI: 1.15–1.44 and 1.25; 95% CI: 1.06–1.46, respectively). For aspirin use, we found no overall increased risk (pooled RR: 1.10; 95% CI: 0.95–1.28), except for non‐US studies (five studies, pooled RR: 1.17; 95% CI: 1.04–1.33). Similar increases in risks were seen with higher analgesic intake. In this largest meta‐analysis to date, we found that acetaminophen and non‐aspirin NSAIDs are associated with a significant risk of developing kidney cancer. Further work is needed to elucidate biologic mechanisms behind these findings.     

De novo 16p13.11 microdeletion identified by high-resolution array CGH in a fetus with increased nuchal translucency

Objective  We investigated the application of high-resolution microarray-based comparative genomic hybridisation (array CGH) on a fetus showing increased nuchal translucency (NT).
Design  Case study.
Setting  Tertiary referral obstetrics unit.
Sample  Pregnant woman attended the antenatal clinic.
Methods  Conventional karyotyping and genetic test was carried out for the alpha-globin gene. High-resolution array CGH using the high-density 244K Agilent microarray was performed on fetal blood sample by cordocentesis to investigate the possibility of any genomic imbalance.
Main outcome measures  Detection of chromosomal abnormality.
Results  Karyotyping analysis showed 46,XY. Molecular genetic diagnosis confirms the fetus has Hb-H constant spring disease but cannot explain the increased NT to 3.2 mm. Array CGH analysis discovered a 1.32-Mb microdeletion on chromosome 16p13.11. Deletion at 16p13.11 has been implicated to predispose to autism and/or mental retardation. Baby was delivered at 40 weeks of gestation, and follow up was carried out at 3 months of age without sign of mental retardation/developmental delay.
Conclusions  This case study demonstrated that array CGH can accurately calibrate the size and identify de novo interstitial chromosome imbalances. However, the presence of chromosome copy variants with unknown clinical significance currently limits its wider scale application in prenatal diagnosis and needs further investigations.     

High-definition imaging of trabeculectomy blebs using spectral domain optical coherence tomography adapted for the anterior segment

Background:  The aim of this work was to image trabeculectomy blebs using spectral domain optical coherence tomography (SDOCT).
Methods:  In this prospective cross-sectional study, patients who had undergone trabeculectomy with at least 3 months of follow up were included. Blebs were imaged using an adapted SDOCT system (Cirrus HD-OCT, Carl Zeiss Meditec Inc., Dublin, CA, USA) and time domain anterior segment optical coherence tomography (ASOCT) (Visante OCT, Carl Zeiss Meditec Inc.). An observer masked to clinical data assessed the utility of SDOCT and ASOCT in visualizing structures in successful and failed blebs.
Results:  Fifty-one eyes were imaged, of which 43 (84.3%) were successful. SDOCT showed wall thickening (93.0% vs. 67.4%, P  = 0.006) and discrete hyporeflective spaces in the wall (88.4% vs. 14.0%, P  < 0.0001) in a greater proportion of successful blebs than ASOCT. SDOCT showed the bleb cavity (23.3% vs. 48.8%, P  = 0.02), scleral flap (34.9% vs. 90.7%, P  < 0.0001), subflap space (20.9% vs . 72.1%, P  < 0.0001) and ostium (9.3% vs. 88.4%, P  < 0.0001) in fewer successful blebs than ASOCT. The internal ostium was not visualized in any failed bleb using SDOCT, whereas ASOCT showed the ostium in 87.5% of failed blebs ( P  = 0.001). SDOCT showed cystic spaces in the bleb wall in a greater proportion of successful blebs than failed blebs (88.4% vs. 37.5%, P  = 0.005).
Conclusions:  SDOCT imaging was able to show fine superficial features in the bleb wall. However, SDOCT had limited clinical utility in that it did not provide useful information about deep features such as flap position, bleb cavity formation or patency of the subflap space and internal ostium.     

Chemotherapy for muscle-invasive bladder cancer treated with definitive radiotherapy: persisting uncertainties

Radical cystectomy for invasive bladder cancer remains the standard of care in many parts of the world, including North America and many parts of Europe; however, a large body of international experience from single institutions and cooperative groups indicates satisfactory results with bladder-sparing approaches in appropriately selected patients. Overall, selective bladder preservation with trimodality therapy, consisting of transurethral resection of the bladder tumor, radiation, and chemotherapy, can achieve complete response rates of 70%, long-term survival rates of 40-50%, and survival rates with an intact bladder of 30-45%. Neoadjuvant chemotherapy followed by radiotherapy might provide up to 5% additional long-term absolute survival benefit compared with radiotherapy alone, although the studies to support this are not appropriately powered. Concomitant chemoradiation provides high response rates and disease control, although the level of evidence for this approach and the follow-up data are even less robust than those for neoadjuvant chemotherapy. Although direct comparison of surgically based and radiotherapy-based approaches would be very useful, it is highly unlikely that such a trial could ever be completed among the patients treated by the clinicians who routinely deal with invasive bladder cancer.     

Factors associated with outcome in patients with advanced renal cell carcinoma in the era of antiangiogenic agents

Known clinical factors associated with outcome in advanced renal cell carcinoma (RCC) include performance status, disease-free interval, number of metastatic sites, and several laboratory variables such as hemoglobin, calcium, and lactate dehydrogenase. These factors were pertinent to the era of immunotherapy. Recent analysis from trials with anti-VEGF agents shows these factors continue to be of major importance. Additionally, several serum and molecular markers, many of which relate to certain alterations of the von Hippel-Lindau (VHL) pathway, are currently being investigated. Responses to VEGF-targeted agents seem to be related to a greater modulation of serum VEGF and soluble VEGF receptors levels. The impact of VHL gene status on clinical objective response to VEGF-targeted therapy was tested in a large study but was not found to predict a higher response rate to these agents. However, subsets of VHL mutations that predict a truncation of the VHL protein seem to have the best responses to these agents. Future prognostic models will incorporate molecular markers with clinical variables to refine prognosis and prediction in patients with metastatic clear-cell RCC treated with novel antiangiogenic agents. These models, if externally and prospectively validated, will rationally select patients for specific VEGF-directed therapeutic agents.     

Health care spending in prostate cancer: An assessment of characteristics and health care utilization of high resource-patients

BackgroundProstate cancer ranks among the top 5 cancers in contribution to national expenditures. Previous reports have identified that 5% of the population accounts for 50% of the nation's annual health care spending. To date, the assessment of the top 5% resource-patients among men diagnosed with prostate cancer (PCa) has never been performed. We investigate the determinants and health care utilization of high resource-patients diagnosed with PCa using a population-based cohort using the Surveillance, Epidemiology, and End Results Medicare-linked database.MethodsMen aged ≥66-year-old with a primary diagnosis of PCa in 2009 were identified. High resource spenders were defined as the top 5% of the sum of the total cost incurred for all services rendered per beneficiary. The spending in each group and predictors of being a high resource-patient were assessed.ResultsThe top 5% resource-patients consisted of 646 men who spent a total of $62,474,504, comprising 26% of the total cost incurred for all 12,875 men who were diagnosed with PCa in 2009. Of the top 5% resource-patients, the average amount spent per patient was $96,710 vs. $14,664 among the bottom 95% resource-patients. In adjusted analyses, older (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.00–1.03), Charlson Comorbidity Index ≥2 (OR: 3.78, 95% CI: 3.10–4.60) men, and advanced disease (metastasis OR: 2.29, 95% CI: 1.68–3.11) were predictors of being a top 5% resource-patient. Of these patients, 210 men died within 1 year of PCa diagnosis (32.5%) vs. 606 men of the bottom 95% resource-patients (5.0%, P < 0.001).ConclusionFive percent of men diagnosed with PCa bore 26% of the total cost incurred for all men diagnosed with the disease in 2009. Multimorbidity and advanced disease stage represent the primary drivers of being a high-resource PCa patient. Multidisciplinary care and shared decision-making is encouraged for such patients to better manage cost and quality of care.