Anxiety, Culture, and Expectations: Oncologist-Perceived Factors Associated With Use of Nonrecommended Serum Tumor Marker Tests for Surveillance of Early-Stage Breast Cancer.

PURPOSE: Breast cancer offers several opportunities for reducing use of ineffective practices based on American Society of Clinical Oncology guidelines. We assessed oncologist-perceived factors associated with use of one such practice-serum tumor markers for post-treatment breast cancer surveillance-focusing on medical oncologists with high, medium, or low test use. METHODS: Using a mixed-methods design, we identified patients who had been treated for early-stage breast cancer diagnosed between January 1, 2009, and December 31, 2012, within Kaiser Permanente Southern California and calculated the number of tests ordered from January 1, 2010, to December 31, 2014. We identified oncologists with high, medium, or low use and subsequently performed semistructured interviews. We used patient satisfaction data to assess association between pattern of use and satisfaction score. RESULTS: We identified 7,363 patients, with 40,114 tests ordered. High-use oncologists were defined as those ordering at least one test annually for 35% of patients or more, low-use oncologists as those ordering at least one test for 5% of patients or less; 42% of oncologists were high, 27% low, and 31% medium users. We interviewed 17 oncologists: six high, eight low, and three medium users. Factors associated with high use included: perceived patient anxiety, oncologist anxiety, belief that there was nothing else to offer, concern about satisfaction, patient competition, peer use, and system barriers. Factors associated with low use included: beliefs about consequences (eg, causes harms) and medical center culture (eg, collective decision to follow guidelines). We found no association between satisfaction score and pattern of use. CONCLUSION: Barriers to deimplementation are numerous and complex. Traditional strategies of practice change alone are unlikely to be effective. Multifaceted, multilevel strategies deployed to address patient-, clinician-, and system-related barriers may be required.

Inhibition of the adenosine2A receptor-epoxyeicosatrienoic acid pathway renders Dahl salt-resistant rats hypertensive.

Adenosine-induced renovasodilation in Dahl rats is mediated via activation of adenosine(2A) receptors (A(2A)Rs) and stimulation of epoxyeicosatrienoic acid (EET) synthesis. Unlike Dahl salt-resistant rats, salt-sensitive rats exhibit an inability to upregulate the A(2A)R-EET pathway with salt loading; therefore, we examined the effect of in vivo inhibition of the A(2A)R-EET pathway on blood pressure and the natriuretic response to salt-loading in Dahl salt-resistant rats. N-Methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide (MS-PPOH; 20 mg/kg per day), an epoxygenase inhibitor, or ZM241385 (ZM; 5 mg/kg per day), an A(2A)R antagonist, was given daily as an IV bolus dose for 3 days before and after placing rats on high salt intake (2% saline). After 3 days of high salt, systolic blood pressure per 24 hours increased from 108+/-2 mm Hg to 136+/-5 mm Hg and 140+/-4 mm Hg when treated with MS-PPOH or ZM, respectively (P<0.001). Plasma levels of EETs and dihydroxyeicosatrienoic acids during salt loading and MS-PPOH (29.3+/-1.8 ng/mL) or ZM treatment (9.8+/-0.5 ng/mL) did not increase to the same extent as in vehicle-treated rats (59.4+/-1.7 ng/mL; P<0.001), and renal levels of EETs+dihydroxyeicosatrienoic acids were 2-fold lower with MS-PPOH or ZM treatment. On day 3 of the high salt intake, MS-PPOH- and ZM-treated rats exhibited a positive Na(+) balance, and plasma Na(+) levels were significantly increased (163.3+/-1.2 and 158.1+/-4.5 mEq/L, respectively) compared with vehicle-treated rats (142.1+/-1 mEq/L), reflecting a diminished natriuretic capacity. These data support a role for the A(2A)R-EET pathway in the adaptive natriuretic response to modulate blood pressure during salt loading.

Extracellular matrix protein 1 (ECM1) is over-expressed in malignant epithelial tumors.

The extracellular matrix protein 1 (ECM1) is a secreted protein that has been implicated with cell proliferation, angiogenesis and differentiation. In the present study, we used immunohistochemical staining to examine the expression of ECM1 in a panel of human tumors and found that it was closely correlated with some types of tumors including: invasive breast ductal carcinoma (83%), esophageal squamous carcinoma (73%), gastric cancer (88%) and colorectal cancer (78%). Significantly, ECM1expression was correlated with the metastatic properties of the tumors. Primary breast cancers that had formed metastases were 76% positive while those that had not metastasized were only 33% positive. ECM1 expression was also correlated with PCNA a marker for proliferation, but not with CD34, a marker for endothelial cells. These results indicate that ECM1 tends to be preferentially expressed by metastatic epithelial tumors.