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Metastatic pancreatic adenocarcinoma (PDAC) is a rapidly lethal disease, with less than half of patients surviving 12 months, and 5-year survival approximately 3%. These outcomes are in large part due to a lack of effective medical and surgical therapies for metastatic PDAC. Herein, we present the case of a patient with oligometastatic liver recurrence of BRCA2-mutated PDAC following a curative-intent resection. Through a combination of systemic chemotherapy, metastasectomy, radiotherapy, and subsequent targeted therapy with olaparib, the patient is asymptomatic four years following metastatic diagnosis with stable low-volume disease. This patient's excellent outcome is attributable to the multi-disciplinary care received, all aspects of which were informed by new evidence surrounding metastasectomy for metastatic PDAC, the unique biology and medical treatment of BRCA-mutated PDAC, and the role of radiotherapy in controlling locoregional recurrence. We provide a review of this evidence, while highlighting the importance of evaluating disease biology through somatic and germline genetic testing as well as monitoring response to systemic chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Physical activity (PA) is recommended for women with breast cancer (BC); however, data are sparse on the association of PA with quality of life (QOL) and patient-reported symptoms for women on adjuvant endocrine therapy (AET).Methods: Women with hormone receptor-positive BC who were taking AET completed standardized surveys about their health-related QOL, AET-related symptoms, and levels of PA using validated measures. A Wald chi-square test and an analysis of variance were used to assess associations with PA and independent variables. Generalized linear regression analyses assessed associations between PA, QOL, and AET-related symptoms.Results: The analytic cohort included 485 Black and White women. Black race, a high body mass index (BMI), and being on aromatase inhibitors (vs tamoxifen) were associated with lower PA in a bivariate analysis. In a multivariate analysis, lower self-reported PA was associated with a high BMI (P = .02) and chemotherapy uptake (P = .006). Better health-related QOL (P = .01), less severe overall AET-related symptoms (P = .02), and less severe gynecological symptoms (P = .03) were associated with increasing levels of moderate PA.Conclusions: Among women taking AET, moderate levels of PA may be associated with fewer medication-related symptoms and overall better ratings of health-related QOL. Because of the low levels of PA observed in the sample overall and particularly for Black women, identifying successful strategies to promote PA are needed. [ABSTRACT FROM AUTHOR]

Objective  To explore whether the effect of azithromycin (AZI) on postcesarean infections varied by the presence/absence of genital mycoplasmataceae placental colonization. Study Design  This was a single-center substudy of multicenter double-blind C/SOAP (Cesarean Section Optimal Antibiotic Prophylaxis) trial of women randomized to AZI or placebo (+cefazolin) antibiotic prophylaxis at cesarean. Chorioamnion/placenta specimens were tested for genital mycoplasmataceae colonization by polymerase chain reaction. Primary outcome was a composite of endometritis, wound infection, or other infections up to 6 weeks postpartum. Analysis was intent-to-treat; logistic regression was used to evaluate interactions between treatment assignment (AZI/placebo) and the presence/absence of mycoplasmataceae and to quantify effects of AZI in analyses stratified by the presence/absence of these microorganisms. Results  Specimens from 613 women (303 AZI and 310 placebo) were evaluated. Baseline characteristics were similar between groups, and approximately 1/3 (30.3%) had mycoplasmataceae placental/chorioamnion colonization. There was no evidence of effect modification (p interaction  = 0.79) between treatment assignment and the presence/absence of organisms. Stratified analyses showed fewer events in the AZI group in the presence (odds ratio [OR]: 0.42; 95% confidence interval [CI]: 0.17–1.01) and absence (OR: 0.49; 95% CI: 0.24–1) of mycoplasmataceae. Results were similar with endometritis/wound infections and with ureaplasmas/mycoplasmas considered separately. Conclusion  The reduction in postcesarean infection with AZI does not vary based on the presence or absence of genital mycoplasmataceae placental colonization. [ABSTRACT FROM AUTHOR]

Spirituality has been shown to be important to many individuals dealing with a cancer diagnosis. While African-American breast cancer survivors have been reported to have higher levels of spirituality compared to White women, little is known about how levels of spirituality may vary among African-American breast cancer survivors. The aims of this study were to examine factors associated with spirituality among African-American survivors and test whether spirituality levels were associated with women’s attitudes about treatment or health care. The primary outcome, spirituality, was nine-item scale (Cronbach’s α = .99). Participants completed standardized telephone interviews that captured sociocultural, healthcare process, and treatment attitudes. Medical records were abstracted post-adjuvant therapy for treatment and clinical information. In bivariate analysis, age was not correlated with spirituality (p = .40). Married/living as married women had higher levels of spirituality (m = 32.1) than single women (m = 30.1). Contextual factors that were associated with higher levels spirituality were: collectivism (r = .44; p < 0.0001, Afrocentric worldview (r = .185; p = .01), and self-efficacy scale (r = .17; p = .02). In multivariable analysis, sociodemographic factors were not significant. Collectivism remained a robust predictor (p < 0.0001). Attitudes about the efficacy of cancer treatment were not associated with spirituality. The high levels of spirituality in African-American survivors suggest consideration of integrating spiritual care within the delivery of cancer treatment. Future studies should consider how spirituality may contribute to positive coping and/or behaviors in African-American women with high levels of spirituality. [ABSTRACT FROM AUTHOR]

Administration of sodium pyruvate (SP; 9.08 μmol/kg, i.p.), ethyl pyruvate (EP; 0.34 μmol/kg, i.p.) or glucose (GLC; 11.1 μmol/kg, i.p.) to rats after unilateral controlled cortical impact (CCI) injury has been reported to reduce neuronal loss and improve cerebral metabolism. In the present study these doses of each fuel or 8% saline (SAL; 5.47 nmoles/kg) were administered immediately and at 1, 3, 6 and 23 h post-CCI. At 24 h all CCI groups and non-treated Sham injury controls were infused with [1,2 13 C] glucose for 68 min 13 C nuclear magnetic resonance (NMR) spectra were obtained from cortex + hippocampus tissues from left (injured) and right (contralateral) hemispheres. All three fuels increased lactate labeling to a similar degree in the injured hemisphere. The amount of lactate labeled via the pentose phosphate and pyruvate recycling (PPP + PR) pathway increased in CCI-SAL and was not improved by SP, EP, and GLC treatments. Oxidative metabolism, as assessed by glutamate labeling, was reduced in CCI-SAL animals. The greatest improvement in oxidative metabolism was observed in animals treated with SP and fewer improvements after EP or GLC treatments. Compared to SAL, all three fuels restored glutamate and glutamine labeling via pyruvate carboxylase (PC), suggesting improved astrocyte metabolism following fuel treatment. Only SP treatments restored the amount of [4 13 C] glutamate labeled by the PPP + PR pathway to sham levels. Milder injury effects in the contralateral hemisphere appear normalized by either SP or EP treatments, as increases in the total pool of 13 C lactate and labeling of lactate in glycolysis, or decreases in the ratio of PC/PDH labeling of glutamine, were found only for CCI-SAL and CCI-GLC groups compared to Sham. The doses of SP, EP and GLC examined in this study all enhanced lactate labeling and restored astrocyte-specific PC activity but differentially affected neuronal metabolism after CCI injury. The restoration of astrocyte metabolism by all three fuel treatments may partially underlie their abilities to improve cerebral glucose utilization and to reduce neuronal loss following CCI injury. [ABSTRACT FROM AUTHOR]

Abstract: This study examined whether chronic Δ9-THC during early adulthood would produce the same hormonally-dependent deficits in learning that are produced by chronic Δ9-THC during adolescence. To do this, either sham-operated (intact) or ovariectomized (OVX) female rats received daily saline or 5.6mg/kg of Δ9-THC i.p. for 40days during early adulthood. Following chronic administration, and a drug-free period to train both a learning and performance task, acute dose-effect curves for Δ9-THC (0.56–10mg/kg) were established in each of the four groups (intact/saline, intact/THC, OVX/saline and OVX/THC). The dependent measures of responding under the learning and performance tasks were the overall response rate and the percentage of errors. Although the history of OVX and chronic Δ9-THC in early adulthood did not significantly affect non-drug or baseline behavior under the tasks, acute administration of Δ9-THC produced both rate-decreasing and error-increasing effects on learning and performance behavior, and these effects were dependent on their hormone condition. More specifically, both intact groups were more sensitive to the rate-decreasing and error-increasing effects of Δ9-THC than the OVX groups irrespective of chronic Δ9-THC administration, as there was no significant main effect of chronic treatment and no significant interaction between chronic treatment (saline or Δ9-THC) and the dose of Δ9-THC administered as an adult. Post mortem examination of 10 brain regions also indicated there were significant differences in agonist-stimulated GTPγS binding across brain regions, but no significant effects of chronic treatment and no significant interaction between the chronic treatment and cannabinoid signaling. Thus, acute Δ9-THC produced hormonally-dependent effects on learning and performance behavior, but a period of chronic administration during early adulthood did not alter these effects significantly, which is contrary to what we and others have shown for chronic administration during adolescence. [Copyright &y& Elsevier]

Purpose: The National Comprehensive Cancer Network recommends computerized tomography (CT) for monitoring patients with epithelial ovarian cancer (EOC) as clinically indicated. We sought to evaluate the impact of the initial post-treatment CT scan on subsequent therapy in patients with EOC. Patients and Methods: We retrospectively identified patients diagnosed with EOC between January 2000 and December 2007. Eligible patients underwent debulking or staging and received postoperative chemotherapy. Following chemotherapy, disease status was assessed using physical examination, measurement of carcinoma antigen (CA)-125 levels, and CT scan of the abdomen and pelvis. The Student t test and χ2 test were used to determine statistical significance. Results: A total of 187 patients had a complete clinical response to primary chemotherapy as determined by normal physical exam and CA-125 levels. Of this cohort, 127 patients (68%) had a normal CT, 51 patients (27%) had an equivocal CT, and 9 patients (5%) had an abnormal CT. Of the 51 patients with an equivocal CT, 11 had a positron emission tomography scan or repeat CT scan performed; however, no patient received immediate surgery or chemotherapy. Fifty-seven percent of the patients with a normal post-treatment CT compared with 72% of the patients with an equivocal CT experienced a recurrence (P = .07). Patients with normal and equivocal CT scans had similar median times to recurrence, 12.2 months versus 12.6 months, respectively. Conclusion: Immediately following completion of primary chemotherapy, few patients with a complete clinical response will have an abnormal CT scan. Although a significant number of patients will have an equivocal CT scan, it is rare that this finding alters the clinical management of patients with EOC. Although CT scans are useful as a baseline for future imaging studies, they seldom change management in this patient population. [ABSTRACT FROM AUTHOR]

Placebo medication regimens may help educate students about adherence issues. In this randomized trial, 23 third-year medical students took a 2-week placebo regimen mimicking highly active antiretroviral therapy (HAART) during their medicine clerkship; 15 students served as controls. Although no effect was demonstrated from this intervention on an evaluation instrument examining attitudes and beliefs about medication nonadherence, all 23 student-subjects agreed in postintervention interviews that the experience was useful and had learning value. Representative comments from the 19 subjects who expanded their interview responses portray this intervention as an eye-opening and unique method for teaching students about medication adherence issues. [ABSTRACT FROM AUTHOR]

Abnormal calcium transport may be implicated in the membrane defect in myotonic dystrophy. A single blind crossover trial of placebo (t.i.d.), nifedipine 10 mg (t.i.d.) and nifedipine 20 mg (t.i.d.), was performed in 10 patients with myotonic dystrophy. The severity of myotonia was assessed by measuring finger extension time after maximum voluntary finger flexion. A significant improvement in myotonia, after nifedipine, was recorded by this technique and supported by a subjective improvement in 50% of patients and clinical improvement of greater than 20% in five patients. Initial grip strength and muscle fatiguability measured by grip strength ergometry were not significantly altered. [ABSTRACT FROM AUTHOR]

Persistent inflammation, mediated in part by increases in cytokines, is a hallmark of traumatlc brain injury (TBI). Minocycline has been shown to inhibit post-TBI neuroinflammation in male rats and mice, but has not been tested in females. Here, we studied sex differences in thermal, stress, and inflammatory responses to TBI and minocycline. Female rats were ovariectomized under isoflurane anesthesia at 33-36 days of age. At 45-55 days of age, male and female rats were implanted intraperitoneally (i.p.) with calibrated transmitters for monitoring body temperature. Moderate cortical contusion injury (CCI) or sham surgery was performed when the rats attained 60-70 days of age. One hour after surgery, rats were injected i.p. with minocycline (50 mg/kg) or saline (0.3 mL); injections were repeated once daily for the next 3 days. At 28 days after CCI or sham surgery, 30 min restraint stress was initiated and blood samples were obtained by tail venipuncture before the onset of restraint and at 30, 60, and 90 min after stress onset. At 35 days after CCI or sham surgery, rats were decapitated and blood was collected for corticosterone (CORT) and cytokine analysis. The brains were removed and ipsilateral cortical tissue and hippocampus were dissected and subsequently assayed for interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. Hyperthermia occurred during days 1-6 post-CCI in male rats, but only on the day of CCI in female rats, and minocycline prevented its occurrence in both sexes. Minocycline facilitated suppression of the CORT response to restraint stress in both sexes. In females, but not males, hippocampal IL-6 content increased post-CCI compared with sham-injured controls, whereas IL-1β content was augmented by minocycline. Hippocampal TNF-α was unaffected by CCI and minocycline. These results demonstrate sex differences in immediate thermal and long-lasting stress and cytokine responses to CCI, and only short-term protective effects of minocycline on hyperthermia. [ABSTRACT FROM AUTHOR]

Experimental traumatic brain injury (TBI) is known to produce an acute increase in cerebral glucose utilization, followed rapidly by a generalized cerebral metabolic depression. The current studies determined effects of single or multiple treatments with sodium pyruvate (SP; 1000 mg/kg, i.p.) or ethyl pyruvate (EP; 40 mg/kg, i.p.) on cerebral glucose metabolism and neuronal injury in rats with unilateral controlled cortical impact (CCI) injury. In Experiment 1 a single treatment was given immediately after CCI. SP significantly improved glucose metabolism in 3 of 13 brain regions while EP improved metabolism in 7 regions compared to saline-treated controls at 24 h post-injury. Both SP and EP produced equivalent and significant reductions in dead/dying neurons in cortex and hippocampus at 24 h post-CCI. In Experiment 2 SP or EP were administered immediately (time 0) and at 1, 3 and 6 h post-CCI. Multiple SP treatments also significantly attenuated TBI-induced reductions in cerebral glucose metabolism (in 4 brain regions) 24 h post-CCI, as did multiple injections of EP (in 4 regions). The four pyruvate treatments produced significant neuroprotection in cortex and hippocampus 1 day after CCI, similar to that found with a single SP or EP treatment. Thus, early administration of pyruvate compounds enhanced cerebral glucose metabolism and neuronal survival, with 40 mg/kg of EP being as effective as 1000 mg/kg of SP, and multiple treatments within 6 h of injury did not improve upon outcomes seen following a single treatment. [ABSTRACT FROM AUTHOR]

Abstract: Clinical studies have indicated an association between acute hyperglycemia and poor outcomes in patients with traumatic brain injury (TBI), although optimal blood glucose levels needed to maximize outcomes for these patients' remain under investigation. Previous results from experimental animal models suggest that post-TBI hyperglycemia may be harmful, neutral, or beneficial. The current studies determined the effects of single or multiple episodes of acute hyperglycemia on cerebral glucose metabolism and neuronal injury in a rodent model of unilateral controlled cortical impact (CCI) injury. In Experiment 1, a single episode of hyperglycemia (50% glucose at 2g/kg, i.p.) initiated immediately after CCI was found to significantly attenuate a TBI-induced depression of glucose metabolism in cerebral cortex (4 of 6 regions) and subcortical regions (2 of 7) as well as to significantly reduce the number of dead/dying neurons in cortex and hippocampus at 24h post-CCI. Experiment 2 examined effects of more prolonged and intermittent hyperglycemia induced by glucose administrations (2g/kg, i.p.) at 0, 1, 3 and 6h post-CCI. The latter study also found significantly improved cerebral metabolism (in 3 of 6 cortical and 3 of 7 subcortical regions) and significant neuroprotection in cortex and hippocampus 1 day after CCI and glucose administration. These results indicate that acute episodes of post-TBI hyperglycemia can be beneficial and are consistent with other recent studies showing benefits of providing exogenous energy substrates during periods of increased cerebral metabolic demand. [Copyright &y& Elsevier]