Publications

PURPOSE

To estimate the effects of a tablet-based, breast cancer risk education intervention for use in primary care settings (BreastCARE) on patients' breast cancer knowledge, risk perception and concern.

METHODS

From June 2011-August 2012, we enrolled women from two clinics, aged 40-74 years with no personal breast cancer history, and randomized them to the BreastCARE intervention group or to the control group. All patients completed a baseline telephone survey and risk assessment (via telephone for controls, via tablet computer in clinic waiting room prior to visit for intervention). All women were categorized as high or average risk based on the Referral Screening Tool, the Gail model or the Breast Cancer Surveillance Consortium model. Intervention patients and their physicians received an individualized risk report to discuss during the visit. All women completed a follow-up telephone survey 1-2 weeks after risk assessment. Post-test comparisons estimated differences at follow-up in breast cancer knowledge, risk perception and concern.

RESULTS

580 intervention and 655 control women completed follow-up interviews. Mean age was 56 years (SD = 9). At follow-up, 73% of controls and 71% of intervention women correctly perceived their breast cancer risk and 22% of controls and 24% of intervention women were very concerned about breast cancer. Intervention patients had greater knowledge (≥75% correct answers) of breast cancer risk factors at follow-up (24% vs. 16%; p = 0.002). In multivariable analysis, there were no differences in correct risk perception or concern, but intervention patients had greater knowledge ([OR] = 1.62; 95% [CI] = 1.19-2.23).

CONCLUSIONS

A simple, practical intervention involving physicians at the point of care can improve knowledge of breast cancer without increasing concern.

TRIAL REGISTRATION

ClinicalTrials.gov identifier NCT01830933.

The management of advanced prostate cancer, specifically metastatic castrate-resistant prostate cancer (mCRPC), remains a therapeutic challenge. Sipuleucel-T (Provenge; APC8015) was approved by the FDA in 2010 for the treatment of asymptomatic or minimally symptomatic mCRPC patients, and it remains the only FDA-approved immunotherapy for prostate cancer of any indication to date. Given the continued need to improve therapeutics in patients with advanced prostate cancer, as well as recent enthusiasm for cancer immunotherapy, there is a wide range of ongoing trials evaluating combinations of sipuleucel-T with other therapeutics. Additional trials are aiming to expand the application of sipuleucel-T to prostate cancer patients beyond the mCRPC setting. Ongoing challenges include understanding the full mechanism of action of sipuleucel-T, optimizing the sequence of sipuleucel-T in relation to other therapies for mCRPC in clinical practice, and the identification of surrogate markers to predict survival benefit in clinical trials.

BACKGROUND & AIMS

As many as 50% of large sessile serrated adenomas/polyps (SSPs) are removed incompletely, which is significant because SSPs have been implicated in the development of interval cancers. It is unclear if endoscopic mucosal resection (EMR) is an optimal method for removal of SSPs. We assessed the efficacy and safety of removal of SSPs 10 mm and larger using a standardized inject-and-cut EMR technique.

METHODS

We performed a retrospective analysis of colonoscopy data, collected over 7 years (2007-2013) at 2 centers, from 199 patients with proximal colon SSPs 10 mm and larger (251 polyps) removed by EMR by 4 endoscopists. The primary outcome measure was local recurrence. The secondary outcome measure was safety.

RESULTS

At the index colonoscopy, patients had a median of 1 serrated lesion (range, 1-12) and 1 nonserrated neoplastic lesion (range, 0-15). The mean SSP size was 15.9 ± 5.3 mm; most were superficially elevated (84.5%) and located in the ascending colon (51%), and 3 SSPs (1.2%) had dysplasia. Surveillance colonoscopies were performed on 138 patients (69.3%) over a mean follow-up period of 25.5 ± 17.4 months. Of these patients, 5 had local recurrences (3.6%; 95% confidence interval, 0.5%-6.7%), detected after 17.8 ± 15.4 months, with a median size of 4 mm. No patients developed postprocedural bleeding, perforation, or advanced colon cancer, or had a death related to the index colorectal lesion during the study period.

CONCLUSIONS

Inject-and-cut EMR is a safe and effective technique for the resection of SSPs. Less than 5% of patients have a local recurrence, which is usually small and can be treated endoscopically.

Tryptic serine proteases of bronchial epithelium regulate ion flux, barrier integrity, and allergic inflammation. Inhibition of some of these proteases is a strategy to improve mucociliary function in cystic fibrosis and asthmatic inflammation. Several inhibitors have been tested in pre-clinical animal models and humans. We hypothesized that these inhibitors inactivate a variety of airway protease targets, potentially with bystander effects. To establish relative potencies and modes of action, we compared inactivation of human prostasin, matriptase, airway trypsin-like protease (HAT), and β-tryptase by nafamostat, camostat, bis(5-amidino-2-benzimidazolyl)methane (BABIM), aprotinin, and benzamidine. Nafamostat achieved complete, nearly stoichiometric and very slowly reversible inhibition of matriptase and tryptase, but inhibited prostasin less potently and was weakest versus HAT. The IC50 of nafamostat's leaving group, 6-amidino-2-naphthol, was >104-fold higher than that of nafamostat itself, consistent with suicide rather than product inhibition as mechanisms of prolonged inactivation. Stoichiometric release of 6-amidino-2-naphthol allowed highly sensitive fluorometric estimation of active-site concentration in preparations of matriptase and tryptase. Camostat inactivated all enzymes but was less potent overall and weakest towards matriptase, which, however was strongly inhibited by BABIM. Aprotinin exhibited nearly stoichiometric inhibition of prostasin and matriptase, but was much weaker towards HAT and was completely ineffective versus tryptase. Benzamidine was universally weak. Thus, each inhibitor profile was distinct. Nafamostat, camostat and aprotinin markedly reduced tryptic activity on the apical surface of cystic fibrosis airway epithelial monolayers, suggesting prostasin as the major source of such activity and supporting strategies targeting prostasin for inactivation.

The analysis of human population variation is an area of considerable interest in the forensic, medical genetics and anthropological fields. Several forensic single nucleotide polymorphism (SNP) assays provide ancestry-informative genotypes in sensitive tests designed to work with limited DNA samples, including a 34-SNP multiplex differentiating African, European and East Asian ancestries. Although assays capable of differentiating Oceanian ancestry at a global scale have become available, this study describes markers compiled specifically for differentiation of Oceanian populations. A sensitive multiplex assay, termed Pacifiplex, was developed and optimized in a small-scale test applicable to forensic analyses. The Pacifiplex assay comprises 29 ancestry-informative marker SNPs (AIM-SNPs) selected to complement the 34-plex test, that in a combined set distinguish Africans, Europeans, East Asians and Oceanians. Nine Pacific region study populations were genotyped with both SNP assays, then compared to four reference population groups from the HGDP-CEPH human diversity panel. STRUCTURE analyses estimated population cluster membership proportions that aligned with the patterns of variation suggested for each study population's currently inferred demographic histories. Aboriginal Taiwanese and Philippine samples indicated high East Asian ancestry components, Papua New Guinean and Aboriginal Australians samples were predominantly Oceanian, while other populations displayed cluster patterns explained by the distribution of divergence amongst Melanesians, Polynesians and Micronesians. Genotype data from Pacifiplex and 34-plex tests is particularly well suited to analysis of Australian Aboriginal populations and when combined with Y and mitochondrial DNA variation will provide a powerful set of markers for ancestry inference applied to modern Australian demographic profiles. On a broader geographic scale, Pacifiplex adds highly informative data for inferring the ancestry of individuals from Oceanian populations. The sensitivity of Pacifiplex enabled successful genotyping of population samples from 50-year-old serum samples obtained from several Oceanian regions that would otherwise be unlikely to produce useful population data. This indicates tests primarily developed for forensic ancestry analysis also provide an important contribution to studies of populations where useful samples are in limited supply.