Food to Overcome Outcomes Disparities: A Randomized Controlled Trial of Food Insecurity Interventions to Improve Cancer Outcomes.

PURPOSE: Food insecurity is prevalent among low-income immigrant and minority patients with cancer. To our knowledge, this randomized controlled trial is the first to prospectively examine the impact on cancer outcomes of food insecurity interventions, with the goal of informing evidence-based interventions to address food insecurity in patients with cancer. METHODS: A three-arm randomized controlled trial was conducted among food-insecure (18-item US Department of Agriculture Household Food Security Survey Module score ≥ 3) patients with cancer (N = 117) at four New York City safety net cancer clinics. Arms included a hospital cancer clinic-based food pantry (arm 1), food voucher plus pantry (arm 2), and home grocery delivery plus pantry (arm 3). Treatment completion (primary outcome) and full appointment attendance were assessed at 6 months. Food security status, depression symptoms (Patient Health Questionnaire-9), and quality-of-life scores (Functional Assessment of Cancer Therapy-General) were assessed at baseline and at 6 months. RESULTS: Voucher plus pantry had the highest treatment completion rate (94.6%), followed by grocery delivery plus pantry (82.5%) and pantry (77.5%; P = .046). Food security scores improved significantly in all arms, and Patient Health Questionnaire-9 and Functional Assessment of Cancer Therapy-General scores improved significantly in the pantry and delivery plus pantry arms. CONCLUSION: Our findings in this preliminary study suggest that voucher plus pantry was the most effective intervention at improving treatment completion, and it met our a priori criterion for a promising intervention (≥ 90%). All interventions demonstrated the potential to improve food security among medically underserved, food-insecure patients with cancer at risk of impaired nutrition status, reduced quality of life, and poorer survival. All patients with cancer should be screened for food insecurity, with evidence-based food insecurity interventions made available.

Adrenal Myelolipoma Masquerading as an Adrenal Malignancy.

An adrenal myelolipoma presenting with suspicious features may pose a diagnostic challenge to surgeons and endocrinologists. In this case report of an adult patient with undiagnosed congenital adrenal hyperplasia presenting with bilateral adrenal masses, we review his radiographic and clinical findings which were highly suspicious for adrenal malignancy. Features of adrenal myelolipoma that may resemble malignant lesions are reviewed. This case report highlights important features of adrenal myelolipoma that the surgeon and endocrinologist should be aware of. The importance of avoiding overtreating adrenal myelolipomas presenting as tumors of uncertain malignant potential is crucial.

Phase I Study of Intermittent High-Dose Lapatinib Alternating with Capecitabine for HER2-Positive Breast Cancer Patients with Central Nervous System Metastases.

PURPOSE: Lapatinib and capecitabine cross the blood-tumor barrier in breast cancer brain metastasis but have modest clinical efficacy. Administration of high-dose tyrosine kinase inhibitor has been evaluated in brain metastases and primary brain tumors as a strategy to improve drug exposure in the central nervous system (CNS). We derived a rational drug scheduling of intermittent high-dose lapatinib alternating with capecitabine based on our preclinical data and Norton-Simon mathematical modeling. We tested this intermittent, sequential drug schedule in patients with breast cancer with CNS metastasis. PATIENTS AND METHODS: We conducted a phase I trial using an accelerated dose escalation design in patients with HER2-positive (HER2+) breast cancer with CNS metastasis. Lapatinib was given on day 1-3 and day 15-17 with capecitabine on day 8-14 and day 22-28 on an every 28-day cycle. Lapatinib dose was escalated, and capecitabine given as a flat dose at 1,500 mg BID. Toxicity and efficacy were evaluated. RESULTS: Eleven patients were enrolled: brain only (4 patients, 36%), leptomeningeal (5 patients, 45%), and intramedullary spinal cord (2 patients, 18%). Grade 3 nausea and vomiting were dose-limiting toxicities. The MTD of lapatinib was 1,500 mg BID. Three patients remained on therapy for greater than 6 months. CONCLUSIONS: High-dose lapatinib is tolerable when given intermittently and sequentially with capecitabine. Antitumor activity was noted in both CNS and non-CNS sites of disease. This novel administration regimen is feasible and efficacious in patients with HER2+ breast cancer with CNS metastasis and warrants further investigation.

Avelumab (anti-PD-L1) as first-line switch-maintenance or second-line therapy in patients with advanced gastric or gastroesophageal junction cancer: phase 1b results from the JAVELIN Solid Tumor trial.

BACKGROUND: We evaluated the antitumor activity and safety of avelumab, a human anti-PD-L1 IgG1 antibody, as first-line switch-maintenance (1 L-mn) or second-line (2 L) treatment in patients with advanced gastric/gastroesophageal cancer (GC/GEJC) previously treated with chemotherapy. METHODS: In a phase 1b expansion cohort, patients without (1 L-mn) or with (2 L) disease progression following first-line chemotherapy for advanced GC/GEJC received avelumab 10 mg/kg intravenously every 2 weeks. Endpoints included best overall response, progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Overall, 150 patients were enrolled (1 L-mn, n = 90; 2 L, n = 60) and median follow-up in the 1 L-mn and 2 L subgroups was 36.0 and 33.7 months, respectively. The confirmed objective response rate was 6.7% in both subgroups (95% CI, 2.5-13.9% and 1.8-16.2%, respectively), including complete responses in 2.2% of the 1 L-mn subgroup (n = 2). In the 1 L-mn and 2 L subgroups, median duration of response was 21.4 months (95% CI, 4.0-not estimable) and 3.5 months (95% CI, 2.8-8.3) and disease control rates were 56.7 and 28.3%, respectively. Median PFS in the 1 L-mn and 2 L subgroups was 2.8 months (95% CI, 2.3-4.1) and 1.4 months (95% CI, 1.3-1.5), with 6-month PFS rates of 23.0% (95% CI, 14.7-32.4%) and 7.9% (95% CI, 2.6-17.2%), and median OS was 11.1 months (95% CI, 8.9-13.7) and 6.6 months (95% CI, 5.4-9.4), respectively. In the 1 L-mn subgroup, median OS measured from start of 1 L chemotherapy was 18.7 months (95% CI, 15.4-20.6). Across both subgroups, 20.7% had an infusion-related reaction of any grade. Other common treatment-related adverse events (TRAEs) of any grade included fatigue (10.0%) and nausea (6.7%). Treatment-related serious adverse events occurred in 4.0% of patients. Overall, 8.7% had a grade ≥3 TRAE, including 1 treatment-related death. CONCLUSION: Avelumab showed clinical activity and an acceptable safety profile in patients with GC/GEJC. TRIAL REGISTRATION: ClinicalTrials.gov NCT01772004 ; registered 21 January 2013.

A preliminary investigation of attachment style and inflammation in African-American young adults.

Individuals' social experiences are associated with their mental health, physical health, and even mortality. Over the last 30 years, researchers have examined the ways in which these social experiences might be associated with chronic inflammation - a component underlying many of the chronic diseases of aging. Little research, however, has examined the role of adults' attachment style as a specific social component that might be associated with inflammation. In the present study, we utilized data from a sample of 59 African-American adults from the Maryland Adolescent Development in Context Study (MADICS) to examine the links between attachment avoidance and attachment anxiety and C-reactive protein (CRP) and interleukin (IL)-6. After controlling for demographic characteristics, body mass index, and depressive symptoms, attachment avoidance and anxiety were associated with IL-6 but not CRP. This study adds to the growing body of research identifying the wide range of social experiences associated with inflammation and further suggests that attachment relationship experiences may have implications for biological processes relevant to many chronic diseases of aging.

Phase 1b Study of Trebananib Plus Paclitaxel and Trastuzumab in Patients With HER2-Positive Locally Recurrent or Metastatic Breast Cancer.

INTRODUCTION: Trebananib, a peptide-Fc fusion protein, blocks angiogenesis by inhibiting binding of angiopoietin-1/2 to the receptor tyrosine kinase Tie2. Trebananib plus trastuzumab and paclitaxel was evaluated in human epidermal growth factor receptor 2-positive breast cancer in an open-label phase 1b clinical study. PATIENTS AND METHODS: Women with human epidermal growth factor receptor 2-positive breast cancer received weekly paclitaxel (80 mg/m2), trastuzumab (8 mg/m2 then 6 mg/kg every 3 weeks), and intravenous trebananib (10 mg/kg or 30 mg/kg weekly) beginning week 2. The primary end point was the incidence of dose-limiting toxicities. Secondary end points included incidence of adverse events (AEs), pharmacokinetics, and tumor response (objective response and duration of response). RESULTS: Forty women were enrolled; 2 experienced dose-limiting toxicities (grade 3 ocular transient ischemic attack [10 mg/kg cohort] and grade 3 elevation in γ-glutamyl transferase [30 mg/kg cohort]). The most common treatment-emergent AEs were peripheral edema (n = 28), diarrhea (n = 27), alopecia (n = 26), fatigue (n = 24), and nausea (n = 24). Maximum observed concentration and area under the concentration-time curve increased proportionally with the trebananib dose. Objective response was confirmed in 31 patients. In the 10 mg/kg cohort, 16 patients (80%) experienced partial response, and none experienced complete response. In the 30 mg/kg cohort, 12 patients (71%) experienced partial response and 3 (18%) experienced complete response. Median (95% confidence interval) duration of response in the 10 and 30 mg/kg cohorts was 12.6 (4.3-20.2) and 16.6 (8.2-not estimable) months, respectively. CONCLUSION: This phase 1b study showed that trebananib was tolerated with manageable AEs at a dose up to 30 mg/kg weekly. Trebananib demonstrated anticancer activity, as indicated by objective response and duration of response.

A randomized, controlled trial of mindfulness-based stress reduction in HIV infection.

OBJECTIVE: Evidence links depression and stress to more rapid progression of HIV-1 disease. We conducted a randomized controlled trial to test whether an intervention aimed at improving stress management and emotion regulation, mindfulness-based stress reduction (MBSR), would improve immunological (i.e. CD4+ T-cell counts) and psychological outcomes in persons with HIV-1 infection. METHODS: We randomly assigned participants with HIV-1 infection and CD4 T-cell counts >350 cells/µl who were not on antiretroviral therapy in a 1:1 ratio to either an MBSR group (n = 89) or an HIV disease self-management skills group (n = 88). The study was conducted at the University of California at San Francisco. We assessed immunologic (CD4, c-reactive protein, IL-6, and d-dimer) and psychological measures (Beck Depression Inventory for depression, modified Differential Emotions Scale for positive and negative affect, Perceived stress-scale, and mindfulness) at 3, 6 and 12 months after initiation of the intervention; we used multiple imputation to address missing values. RESULTS: We observed statistically significant improvements from baseline to 3-months within the MBSR group in depression, positive and negative affect, perceived stress, and mindfulness; between group differences in change were significantly greater in the MBSR group only for positive affect (per item difference on DES-positive 0.25, 95% CI 0.049, 0.44, p = .015). By 12 months the between group difference in positive affect was not statistically significant, although both groups had trends toward improvements compared to baseline in several psychological outcomes that were maintained at 12-months; these improvements were only statistically significant for depression and negative affect in the MBSR group and perceived stress for the control group. The groups did not differ significantly on rates of antiretroviral therapy initiation (MBSR = 39%, control = 29%, p = .22). After 12 months, the mean decrease in CD4+ T-cell count was 49.6 cells/µl in participants in the MBSR arm, compared to 54.2 cells/µl in the control group, a difference of 4.6 cells favoring the MBSR group (95% CI, -44.6, 53.7, p = .85). The between group differences in other immunologic-related outcomes (c-reactive protein, IL-6, HIV-1 viral load, and d-dimer) were not statistically significant at any time point. CONCLUSIONS: MBSR improved positive affect more than an active control arm in the 3 months following the start of the intervention. However, this difference was not maintained over the 12-month follow-up and there were no significant differences in immunologic outcomes between intervention groups. These results emphasize the need for further carefully designed research if we are to translate evidence linking psychological states to immunological outcomes into evidence-based clinical practices.

Caution Ahead: Research Challenges of a Randomized Controlled Trial Implemented to Improve Breast Cancer Treatment at Safety-Net Hospitals.

PURPOSE: To implement and test a Web-based tracking and feedback (T&F) tool to close referral loops and reduce adjuvant breast cancer treatment underuse in safety-net hospitals (SNHs). PATIENT AND METHODS: We randomly assigned 10 SNHs, identified patients with new stage 1 to stage 3 breast cancer, assessed their connection with the oncologist, and relayed this information to surgeons for follow-up. We interviewed key informants about the tool's usefulness. We conducted intention-to-treat and pre- and poststudy analyses to assess the T&F tool and implementation effectiveness, respectively. RESULTS: Between the study start and intervention implementation, several hospitals reorganized care delivery and 49% of patients scheduled to undergo breast cancer surgery were ineligible because they already were in contact with an oncologist. One high-volume hospital closed. Despite randomization of hospitals, intervention (INT) hospitals had fewer white patients (5% v 16%; P = .0005), and more underuse (28% v 15%; P = .002) compared with usual care (UC) hospitals. Over time, INT hospitals with poorer follow-up significantly reduced underuse compared with UC hospitals (INT hospitals, from 33% to 9%, P = .001 v UC hospitals, from 15% to 11%, P = .5). There was no difference in underuse (9% at INT hospitals, 11% at UC hospitals; P = .8). Hospitals with better follow-up (odds ratio, 0.85; 95% CI, 0.73 to 0.98) had less underuse. In settings with poor follow-up and tracking approaches, key informants found the tool useful. The rapidly changing delivery landscape posed significant challenges to this implementation research. CONCLUSION: A T&F tool did not significantly reduce adjuvant underuse but may help reduce underuse in SNHs with poor follow-up capabilities. Inability to discern T&F effectiveness is likely due to encountered challenges that inform lessons for future implementation research.

Reducing Disparities in Cancer Screening and Prevention through Community-Based Participatory Research Partnerships with Local Libraries: A Comprehensive Dynamic Trial.

Reduction of cancer-related disparities requires strategies that link medically underserved communities to preventive care. In this community-based participatory research project, a public library system brought together stakeholders to plan and undertake programs to address cancer screening and risk behavior. This study was implemented over 48 months in 20 large urban neighborhoods, selected to reach diverse communities disconnected from care. In each neighborhood, Cancer Action Councils were organized to conduct a comprehensive dynamic trial, an iterative process of program planning, implementation and evaluation. This process was phased into neighborhoods in random, stepped-wedge sequence. Population-level outcomes included self-reported screening adherence and smoking cessation, based on street intercept interviews. Event-history regressions (n = 9374) demonstrated that adherence outcomes were associated with program implementation, as were mediators such as awareness of screening programs and cancer information seeking. Findings varied by ethnicity, and were strongest among respondents born outside the U.S. or least engaged in care. This intervention impacted health behavior in diverse, underserved and vulnerable neighborhoods. It has been sustained as a routine library system program for several years after conclusion of grant support. In sum, participatory research with the public library system offers a flexible, scalable approach to reduce cancer health disparities.

Perceptions of parental secure base support in African American adolescents and young adults: A preliminary study of predictive links to adult C-reactive protein.

Within the field of relationship science there is increasing interest in the connections between close relationships and physical health. In the present study, we examined whether adolescents' (~12 years old) and young adults' (~20 years old) perceptions of their parents as a secure base prospectively predict C-reactive protein (CRP), a commonly used marker of inflammatory activity, at age 32 in a well-characterized sample of African Americans. We utilized existing data collected as part of the Maryland Adolescent Development in Context Study (MADICS) to construct measures of perceptions of parental secure base support (SBS), general parental support, and peer support in early adolescence and early adulthood. In the present study, SBS was operationalized as the perceived ability to depend on parents in times of need. Fifty-nine African American MADICS participants who reported on perceived support in early adolescence and early adulthood participated in a follow-up home visit at age 32 during which serum CRP was measured via a blood draw. After controlling for inflammation-related confounds (e.g., tobacco use, body mass index), adolescents' perceptions of parental SBS, but not peer support or general parental support, predicted lower CRP values at age 32 (b = -.92, SE = .34, p < .05). None of the support variables in early adulthood predicted CRP at 32 years. This study adds to a growing literature on relationships and health-related outcomes and provides the first evidence for a link between parental SBS in adolescence and a marker of inflammatory activity in adulthood.

Organizational Factors Affect Safety-Net Hospitals' Breast Cancer Treatment Rates.

OBJECTIVE: To identify key organizational approaches associated with underuse of breast cancer care. SETTING: Nine New York City area safety-net hospitals. STUDY DESIGN: Mixed qualitative-quantitative, cross-sectional cohort. METHODS: We used qualitative comparative analysis (QCA) of key stakeholder interviews, defined organizational "conditions," calibrated conditions, and identified solution pathways. We defined underuse as no radiation after lumpectomy in women <75 years or mastectomy in women with ≥4 positive nodes, or no systemic therapy in women with tumors ≥1 cm. We used hierarchical models to assess organizational and patient factors' impact on underuse. PRINCIPAL FINDINGS: Underuse varied by hospital (8-29 percent). QCA found lower underuse sites designated individuals to track and follow-up no-shows; shared clinical information during handoffs; had fully integrated electronic medical records enabling transfer of responsibility across specialties; had strong system support; allocated resources to cancer clinics; had a patient-centered culture paying close organizational attention to clinic patients. High underuse sites lacked these characteristics. Multivariate modeling found that hospitals with strong approaches to follow-up had low underuse rates (RR = 0.28; 0.08-0.95); individual patient characteristics were not significant. CONCLUSIONS: At safety-net hospitals, underuse of needed cancer therapies is associated with organizational approaches to track and follow-up treatment. Findings provide varying approaches to safety nets to improve cancer care delivery.

Phase II Trial of Abiraterone Acetate Plus Prednisone in Black Men With Metastatic Prostate Cancer.

LESSONS LEARNED: The safety and activity findings of abiraterone acetate plus prednisone treatment in black men with mCRPC were similar to results from previously conducted studies with largely white populations.Poor trial accrual continues to be a challenge in black men with mCRPC and further efforts are needed to address such underrepresentation. BACKGROUND: Self-identified black men have higher incidence and mortality from prostate cancer in the United States compared with white men but are dramatically underrepresented in clinical trials exploring novel therapies for metastatic castration-resistant prostate cancer (mCRPC). METHODS: Black men with mCRPC were treated with abiraterone acetate (AA), 1,000 mg daily, and prednisone (P), 5 mg twice daily. The primary objective was to determine antitumor activity (defined by a ≥30% decline in prostate-specific antigen [PSA] level) and to correlate germline polymorphisms in androgen metabolism genes with antitumor activity. Secondary objectives included determining safety, post-treatment changes in measurable disease, and time to disease progression. RESULTS: From April 2013 to March 2016, a total of 11 black men were enrolled and received AA plus P (AA+P); 7 of 10 evaluable patients were docetaxel naive. Post-treatment declines in PSA level of ≥30% were achieved in 90% of patients. The side effect profile was consistent with prior clinical trials exploring AA+P in mCRPC. Due to poor accrual, the study was closed prematurely with insufficient sample size for the planned pharmacogenetic analyses. CONCLUSION: In this small prospective study terminated for poor accrual, the safety and activity of AA+P in black men with mCRPC was similar to that reported in prior studies exploring AA in largely white populations. Further efforts are needed to address underrepresentation of black men in mCRPC trials.

Cancer beliefs and patient activation in a diverse, multilingual primary care sample.

OBJECTIVES: Greater patient activation, defined as having the knowledge, skills, and confidence to manage one's health, is associated with cancer control behaviors. Cancer risk beliefs may be associated with patient activation, and delineating this relationship could inform cancer control interventions across diverse patient subgroups. This study examines associations between cancer risk beliefs, language preference, and patient activation within a multilingual urban primary care setting. DESIGN: Patients 18 years and older within a New York City public hospital serving a large proportion of non-native-born Americans were surveyed regarding their cancer risk beliefs and patient activation in Haitian Creole, Spanish, or English based on language preference during a health care visit. RESULTS: The sample (N = 460) included 150 Haitian Creole speakers, 159 Spanish speakers, and 151 English speakers and was primarily non-White (92%). Most participants (84%) had not been born in the United States. Cancer risk beliefs differed across language preference. Beliefs that cancer could be avoided by minimizing thoughts about cancer risk were significantly higher in Haitian Creole speakers than in others; reported negative emotion when thinking about cancer risk was higher in Spanish and English than in Haitian Creole speakers. These cancer risk beliefs were positively related to patient activation, even when controlling for language preference. CONCLUSION: Cancer risk beliefs differ across language preference and are related to patient activation, making them potentially important in cancer control. Consideration of language represents important demographic stratification for understanding the frequency and relevance of different beliefs about cancer and patient activation.

Effects of a mindfulness-based weight loss intervention in adults with obesity: A randomized clinical trial.

OBJECTIVE: To determine whether adding mindfulness-based eating and stress management practices to a diet-exercise program improves weight loss and metabolic syndrome components. METHODS: In this study 194 adults with obesity were randomized to a 5.5-month program with or without mindfulness training and identical diet-exercise guidelines. Intention-to-treat analyses with multiple imputation were used for missing data. The primary outcome was 18-month weight change. RESULTS: Estimated effects comparing the mindfulness to control arm favored the mindfulness arm in (a) weight loss at 12 months, -1.9 kg (95% CI: -4.5, 0.8; P = 0.17), and 18 months, -1.7 kg (95% CI: -4.7, 1.2; P = 0.24), though not statistically significant; (b) changes in fasting glucose at 12 months, -3.1 mg/dl (95% CI: -6.3, 0.1; P = 0.06), and 18 months, -4.1 mg/dl (95% CI: -7.3, -0.9; P = 0.01); and (c) changes in triglyceride/HDL ratio at 12 months, -0.57 (95% CI: -0.95, -0.18; P = 0.004), and 18 months, -0.36 (95% CI: -0.74, 0.03; P = 0.07). Estimates for other metabolic risk factors were not statistically significant, including waist circumference, blood pressure, and C-reactive protein. CONCLUSIONS: Mindfulness enhancements to a diet-exercise program did not show substantial weight loss benefit but may promote long-term improvement in some aspects of metabolic health in obesity that requires further study.

Randomized Multicenter Phase II Study of Modified Docetaxel, Cisplatin, and Fluorouracil (DCF) Versus DCF Plus Growth Factor Support in Patients With Metastatic Gastric Adenocarcinoma: A Study of the US Gastric Cancer Consortium.

PURPOSE: Docetaxel, cisplatin, and fluorouracil (DCF) is a standard first-line three-drug chemotherapy regimen for advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma and is associated with significant toxicity. We examined the safety and efficacy of a modified DCF (mDCF) regimen in a randomized multicenter phase II study. PATIENTS AND METHODS: Previously untreated patients with metastatic gastric or GEJ adenocarcinoma were randomly assigned to receive either mDCF (fluorouracil 2,000 mg/m2 intravenously [IV] over 48 hours, docetaxel 40 mg/m2 IV on day 1, cisplatin 40 mg/m2 IV on day 3, every 2 weeks) or parent DCF (docetaxel 75 mg/m2, cisplatin 75 mg/m2, and fluorouracil 750 mg/m2 IV over 5 days with granulocyte colony-stimulating factor, every 3 weeks). The study had 90% power to differentiate between 6-month progression-free survival of 26% and 43%, with type I and II error rates of 10% each. An early stopping rule for toxicity was included, defined as grade 3 to 4 adverse event rate > 70% in the first 3 months. RESULTS: From November 2006 to June 2010, 85 evaluable patients were enrolled (male, n = 61; female, n = 24; median age, 58 years; Karnofsky performance status, 90%; GEJ, n = 28; gastric, 57). mDCF (n = 54) toxicity rates included 54% grade 3 to 4 toxicity (22% hospitalized) within the first 3 months and 76% grade 3 to 4 toxicity over the course of treatment. The DCF arm (n = 31) closed early because of toxicity, with rates of 71% grade 3 to 4 toxicity (52% hospitalized) within 3 months and 90% grade 3 to 4 toxicity over the course of treatment. Six-month PFS was 63% (95% CI, 48% to 75%) for mDCF and 53% (95% CI, 34% to 69%) for DCF. Median overall survival was improved for mDCF (18.8 v 12.6 months; P = .007). CONCLUSION: mDCF is less toxic than parent DCF, even when supported with growth factors, and is associated with improved efficacy. mDCF should be considered a standard first-line option for patients with metastatic gastric or GEJ adenocarcinoma.

Developmental histories of perceived racial discrimination and diurnal cortisol profiles in adulthood: A 20-year prospective study.

Perceived racial discrimination (PRD) has been associated with altered diurnal cortisol rhythms in past cross-sectional research. We investigate whether developmental histories of PRD, assessed prospectively, are associated with adult diurnal cortisol profiles. One-hundred and twelve (N=50 Black, N=62 White) adults from the Maryland Adolescent Development in Context Study provided saliva samples in adulthood (at approximately age 32 years) at waking, 30min after waking, and at bedtime for 7 days. Diurnal cortisol measures were calculated, including waking cortisol levels, diurnal cortisol slopes, the cortisol awakening response (CAR), and average daily cortisol (AUC). These cortisol outcomes were predicted from measures of PRD obtained over a 20-year period beginning when individuals were in 7th grade (approximately age 12). Greater average PRD measured across the 20-year period predicted flatter adult diurnal cortisol slopes for both Black and White adults, and a lower CAR. Greater average PRD also predicted lower waking cortisol for Black, but not White adults. PRD experiences in adolescence accounted for many of these effects. When adolescent and young adult PRD are entered together predicting cortisol outcomes, PRD experiences in adolescence (but not young adulthood) significantly predicted flatter diurnal cortisol slopes for both Black and White adults. Adolescent, but not young adult PRD, also significantly predicted lower waking and lower average cortisol for Black adults. Young adult PRD was, however, a stronger predictor of the CAR, predicting a marginally lower CAR for Whites, and a significantly larger CAR for Blacks. Effects were robust to controlling for covariates including health behaviors, depression, income and parent education levels. PRD experiences interacted with parent education and income to predict aspects of the diurnal cortisol rhythm. Although these results suggest PRD influences on cortisol for both Blacks and Whites, the key findings suggest that the effects are more pervasive for Blacks, affecting multiple aspects of the cortisol diurnal rhythm. In addition, adolescence is a more sensitive developmental period than adulthood for the impacts of PRD on adult stress biology.

Breast Metastasis of Extraskeletal Myxoid Chondrosarcoma: A Case Report.

BACKGROUND: Extraskeletal myxoid chondrosarcoma is a unique and distinct clinicopathological entity in terms of its origin, morphology, and biologic behavior. Despite being a slow-growing tumor, it has a high rate of local recurrences and history of metastases to uncommon sites like the mandible, liver, retroperitoneum, right ventricle, pancreas, and central nervous system. Here, we report a very unique case of extraskeletal myxoid chondrosarcoma that metastasized to the breast, which itself is a very rare site for metastases. CASE REPORT: A 58-year-old woman presented with a large, firm, and tender soft-tissue mass (6.0×7.0 cm) underneath the sole of the left foot. A computerized tomography (CT) scan showed a heterogeneous lobulated mass in the plantar aspect of the forefoot, measuring 8.6×8.0×7.1 cm. Punch biopsies revealed histology consistent with extraskeletal myxoid chondrosarcoma. Metastatic work-up was negative. The mass was fully resected with left below-knee amputation. The histology of the resected mass was consistent with extraskeletal myxoid chondrosarcoma. A follow-up CT showed a new right breast nodule along with metastases to lung and bones. The results of the core needle biopsies of the right breast masses seen on mammogram were morphologically identical to extraskeletal myxoid chondrosarcoma. CONCLUSIONS: Although rare, metastases to the breast should be considered in the differential diagnosis of a breast mass. A close long-term follow-up is needed due to the unpredictable behavior of extraskeletal myxoid chondrosarcoma and the high frequency of local recurrences, metastases, and death due to disease.

Follicular Variant of Papillary Thyroid Cancer with Bilateral Renal Metastases Discovered Incidentally During Work-Up of Primary Endometrial Cancer: A Rare Occurrence.

BACKGROUND: Follicular variant of papillary thyroid cancer (FV-PTC) is the second most common subtype of papillary thyroid cancer (PTC) after classic PTC. FV-PTC is characterized by nuclear features consistent with classic PTC but has a follicular architecture that lacks classic papillary morphology. Thyroid cancer rarely metastasizes to the kidney. Only 6 cases of FV-PTC metastasizing to the kidney have been reported in the English literature. We are reporting a case of FV-PTC with bilateral renal metastases discovered incidentally during work-up of primary endometrial cancer. CASE REPORT: A 70-year-old woman presented with post-menopausal bleeding secondary to endometrial cancer. Staging work-up showed multiple bilateral lung nodules, bilateral soft tissue kidney masses, and multinodular goiter. The pathological and immnohistochemical profile of the lung biopsy was consistent with primary well-differentiated lung adenocarcinoma. Follow-up computerized tomography scan showed stable lung nodules and enlarging renal masses, which was suggestive of bilateral renal cancer. While the histologic features of the renal biopsy were not typical, the immunohistochemical staining of renal biopsy was positive for Paired box 8, thyroid transcription factor-1, thyroglobulin, and cytokeratin 7, suggesting the thyroid as the primary cancer site. The final histopathology on surgical specimen of total thyroidectomy revealed follicular variant of papillary thyroid cancer. CONCLUSIONS: The presence of pulmonary nodules and kidney masses does not always suggest the lung or the kidney as primary tumor sites. The clinician should be aware of the possibility of metastasis and look for the primary source, which in the present case was FV-PTC. Immunohistochemistry plays an important role in determining the primary site of origin. In case of multiple-organ metastases, each metastatic lesion should be biopsied as soon as possible for definitive diagnosis and appropriate treatment.

Anticipatory sensitization to repeated stressors: the role of initial cortisol reactivity and meditation/emotion skills training.

Anticipation may play a role in shaping biological reactions to repeated stressors-a common feature of modern life. We aimed to demonstrate that: (a) individuals who display a larger cortisol response to an initial stressor exhibit progressive anticipatory sensitization, showing progressively higher cortisol levels before subsequent exposures, and (b) attention/emotional skills training can reduce the magnitude of this effect on progressive anticipatory sensitization. Female school teachers (N=76) were randomly assigned to attention/emotion skills and meditation training or to a control group. Participants completed 3 separate Trier Social Stress Tests (TSST): at baseline (Session 1), post-training (Session 2), and five months post (Session 3). Each TSST session included preparing and delivering a speech and performing an arithmetic task in front of critical evaluators. In each session participants' salivary cortisol levels were determined before and after the stressor. Control participants with larger cortisol reactivity to the first stressor showed increasing anticipatory (pre-stressor) cortisol levels with each successive stressor exposure (TSST session)-suggesting progressive anticipatory sensitization. Yet this association was absent in the training group. Supplementary analyses indicated that these findings occurred in the absence of group differences in cortisol reactivity. Findings suggest that the stress response can undergo progressive anticipatory sensitization, which may be modulated by attention/emotion-related processes. An important implication of the construct of progressive anticipatory sensitization is a possible self-perpetuating effect of stress reactions, providing a candidate mechanism for the translation of short-to-long-term stress reactions.