Angiogenesis: a prognostic determinant in pancreatic cancer?

Angiogenesis has been associated with disease progression in many solid tumours, however the statement that tumours need angiogenesis to grow, invade and metastasise seems no longer applicable to all tumours or to all tumour subtypes. Prognostic studies in pancreatic cancer are conflicting. In fact, pancreatic cancer has been suggested an example of a tumour in which angiogenesis is less essential for tumour progression. The aim of the present study was therefore to measure angiogenesis in two anatomically closely related however prognostically different types of pancreatic cancer, pancreatic head and periampullary cancer, and investigate its relation with outcome. Vessels were stained by CD31 on original paraffin embedded tissue from 206 patients with microscopic radical resection (R0) of pancreatic head (n=98) or periampullary cancer (n=108). Angiogenesis was quantified by microvessel density (MVD) and measured by computerised image analysis of three randomly selected fields and investigated for associations with recurrence free survival (RFS), cancer specific survival (CSS), overall survival (OS) and conventional prognostic factors. MVD was heterogeneous both between and within tumours. A higher MVD was observed in periampullary cancers compared with pancreatic head cancers (p<.01). Furthermore, MVD was associated with lymph node involvement in pancreatic head (p=.014), but not in periampullary cancer (p=.55). Interestingly, MVD was not associated with RFS, CSS or with OS. In conclusion, angiogenesis is higher in periampullary cancer and although associated with nodal involvement in pancreatic head cancer, pancreatic cancer prognosis seems indeed angiogenesis independent.     

The impact of genomics on the management of myeloma

Myeloma is a complex disease, characterized by a wide heterogeneity in clinical presentation, evolution, and molecular portraits. The successive use of cytogenetics, molecular cytogenetics, expression genomics, copy number genomics, and, more recently, deep sequencing, has shown that this heterogeneity can be used to identify markers usable for not only prognostication but also therapeutic choice and, ultimately, discovery of druggable targets. The use of some of these techniques is now mandatory for the management of patients. Although risk-adapted therapy is not yet a routine practice in myeloma, these molecular changes are essential for the definition of the prognosis.     

The NQO1*2/*2 polymorphism is associated with poor overall survival in patients following resection of stages II and IIIa non-small cell lung cancer

NAD(P)H:quinone oxidoreductase 1 (NQO1), is a cytosolic flavoenzyme that catalyzes the two-electron reduction of quinones into hydroquinones. A polymorphism (NQO1*2) alters enzymatic activity of NQO1 resulting in diminished NQO1 activity. Malignancies with NQO1*2 may be resistant to radiation and chemotherapy with resulting poorer survival. NQO1 allele was evaluated in subjects enrolled in ECOG 3590, a randomized comparison of radiation (RT) vs radiation and chemotherapy with cisplatin/etoposide (RCT) in patients with completely resected stages II and IIIa NSCLC. Overall survival was estimated using the Kaplan-Meier method and compared via the log-rank test. Cox models were used to assess the impact of covariates on outcomes. Among 152 patients with assessable samples, 24 (16%) had NQO1*2. Median follow-up was 139 months. The presence of NQO1*2/*2 was associated with decreased overall survival (OS) (median in the heterozygote/wild-type group 42.3 vs. 33.5 months in the variant group, p=0.04). In a multivariable Cox model, variant NQO1 (HR = 1.58, p = 0.05), age <60 (HR = 0.67, p = 0.04), PS 1 (HR = 1.47, p = 0.05), cardiovascular disease (HR = 1.93, p = 0.003) and alkaline phosphatase <100 mg/ml (HR = 0.59, p = 0.005) were all significant predictors of OS. NQO1*2/*2 may be an independent predictor of poor overall survival in individuals with resected stages II and IIIa NSCLC. Although the basis for the NQO1 association with decreased survival requires additional evaluation, NQO1 may represent a biomarker for guiding individualized therapy.     

Facilitating online support groups for cancer patients: the learning experience of psycho‐oncology clinicians

Objective: Counsellor familiarity and engagement with technology‐mediated communication represents an important factor in the ability to implement support programs to cancer patients. This study describes the experiences of a cohort of expert psycho‐oncology counsellors who learned to facilitate online support groups (OSGs) and identifies the important elements of their learning experience that led to their engagement. Procedure and method: Six psycho‐oncology counsellors were trained to facilitate OSGs and later facilitated OSGs in their own practice context. They subsequently reflected on and discussed their experiences with OSGs over time: in a panel discussion within 6 months of training, and in two focus groups. A participatory method was used to describe and interpret key elements of the learning process. Results and discussion: Three themes of the counsellors' learning experience emerged: immersion in experiential learning, perceptions of clinical value and benefit, and overcoming challenges with adapted skills. Counsellors described components of their experiential learning: co‐facilitating online cancer support groups with an expert, debriefing online, and participating in an online peer supervision group, as critical to their becoming engaged. Despite initial challenges, the counsellors learned new skills, and adapted known clinical skills, to the text‐only environment. Conclusion: With appropriate training and practice over time, counsellors familiar with delivering face‐to‐face support groups to cancer patients became skilled and engaged in leading OSG's for cancer patients. Learning to facilitate OSGs shifted practice by significantly expanding the scope of services they were able to provide their patients and has implications for expanding access to support services. Copyright © 2010 John Wiley & Sons, Ltd.     

Exercise training improves cardiovascular autonomic modulation in response to glucose ingestion in obese adults with and without type 2 diabetes mellitus

This study examined the effect of aerobic exercise training on vagal and sympathetic influences on the modulations of heart rate and systolic blood pressure in response to an oral glucose load in obese individuals with and without type 2 diabetes mellitus (T2D). Beat-to-beat arterial pressure and continuous electrocardiogram were measured after a 12-hour overnight fast and in response to glucose ingestion (75 g dextrose) in obese subjects with (T2D group, n = 23) and without (OB group, n = 36) T2D before and after 16 weeks of aerobic exercise training at moderate intensity. Autonomic modulation was assessed using spectral analysis of systolic blood pressure variability (BPV), heart rate variability (HRV), and analysis of baroreflex sensitivity (BRS). Glucose ingestion significantly increased low-frequency (LF_SBP), low-frequency HRV (LF_RRI), and the ratio of low- to high-frequency components of HRV (LF_RRI/HF_RRI), and decreased the high-frequency power (HF_RRI) (P < .05). Exercise training increased LF_RRI and LF_RRI/HF_RRI responses, and reduced HF_RRI and LF_SBP to glucose ingestion in both groups (P < .05), but increased fasted BRS in the OB group only (P < .05); glucose intake had no effect on BRS (P > .05). In conclusion, a 16-week exercise training program improved cardiac autonomic modulation in response to an oral glucose load in obese adults, independently of diabetes status, and in the absence of remarkable changes in body weight, body composition, fitness level, and glycemic control.     

Reducing Psychosocial and Behavioral Pregnancy Risk Factors: Results of a Randomized Clinical Trial Among High-Risk Pregnant African American Women

Objectives. We evaluated the efficacy of a primary care intervention targeting pregnant African American women and focusing on psychosocial and behavioral risk factors for poor reproductive outcomes (cigarette smoking, secondhand smoke exposure, depression, and intimate partner violence).Methods. Pregnant African American women (N = 1044) were randomized to an intervention or usual care group. Clinic-based, individually tailored counseling sessions were adapted from evidence-based interventions. Follow-up data were obtained for 850 women. Multiple imputation methodology was used to estimate missing data. Outcome measures were number of risks at baseline, first follow-up, and second follow-up and within-person changes in risk from baseline to the second follow-up.Results. Number of risks did not differ between the intervention and usual care groups at baseline, the second trimester, or the third trimester. Women in the intervention group more frequently resolved some or all of their risks than did women in the usual care group (odds ratio = 1.61; 95% confidence interval = 1.08, 2.39; P = .021).Conclusions. In comparison with usual care, a clinic-based behavioral intervention significantly reduced psychosocial and behavioral pregnancy risk factors among high-risk African American women receiving prenatal care.Adverse pregnancy outcomes are particularly common among women who are members of racial/ethnic minority groups.^1–4 African American infants are 3.4 times more likely than are White infants to die in the neonatal period, a disadvantage that persists even when mothers have appropriately early and equal access to prenatal care.⁵ In Washington, DC, death rates among non-Hispanic African American infants remain unacceptably high (17.0 per 1000 live births in 2005) despite an overall decline in infant mortality from 18.6 per 1000 live births in 1992 to 14.0 per 1000 births in 2005.⁶ Psychosocial and behavioral risks are recognized as potential contributors to poor reproductive outcomes.^7–9 Poverty,¹⁰ limited social support,¹¹ smoking,¹² illicit drug use,¹³ depression,¹⁴ anxiety,^14,15 and intimate partner violence (IPV)^16,17 are all associated to varying degrees with pregnancy complications, premature and low-birthweight deliveries, stillbirths, and infant mortality.There is increasing recognition of the role of primary care in screening, diagnosis, and treatment of behavioral, mental health, and psychosocial concerns,^18–27 because of the significant association between medical morbidity and behavioral and mental health problems.²⁸ Although interventions involving primary care providers may have limited success, they can be cost-effective.^18,24 Because access to and use of behavioral and mental health care remain problematic, especially among members of underserved minority groups,^29–32 making such care available through primary care services may avert missed opportunities.Prenatal care may be a venue to address behavioral and mental health issues that can potentially affect the health of pregnant women and their unborn children.³³ The guidelines of the American College of Obstetrics and Gynecology and the American Academy of Pediatrics^34,35 suggest ways primary care providers can screen for behavioral and psychosocial risk factors. Despite these guidelines, many providers still fail to screen pregnant women,^35–38 with screening rates varying according to type of provider,^36,39 risk factors,³⁶ population group,⁴⁰ and provider risk perceptions.⁴¹ Furthermore, when implemented, psychosocial and behavioral interventions have been only moderately successful.^42,43Such inconsistent results may arise from multiple factors, including differences in study design, participant engagement, and intervention content or implementation, including approaches that address only 1 of multiple, co-occurring psychosocial or behavioral risk factors. Behavioral and psychosocial factors associated with poor pregnancy outcomes are related to and serve as risk factors for one another⁴⁴; therefore, an alternative approach would be to provide an intervention simultaneously addressing multiple psychosocial and behavioral risk factors among pregnant women, as has been done in relation to other health risks.^45–47A recent study focusing on 3569 Medicaid-eligible pregnant women examined the effects of the Prenatal Plus Program in Colorado with respect to smoking, inadequate prenatal weight gain, and “psychosocial problems” (defined as “significant or severe stress as a result of personal or family safety needs, lack of support systems, or an inability to meet basic needs”).^48(p1955) Women who had at least 10 Prenatal Plus visits were more likely than were women who did not to reduce these risks; in addition, only 7.0% of women who resolved all of their risks delivered low-birthweight infants, whereas 13.2% of those who resolved none of their risks did so. In spite of these promising results, the nonexperimental nature of the Colorado study may have created unquantifiable biases favoring the intervention.Moreover, only 4% of all births in Colorado, and 7% of Prenatal Plus deliveries, occurred among African American women, the group at greatest risk of adverse pregnancy outcomes. Thus, further experimental investigations in which rigorous randomized trial designs are used to assess vulnerable African American women are needed to better appreciate the potential merits of an integrated intervention focusing on psychosocial and behavioral risk factors during pregnancy.We conducted a randomized clinical trial testing the efficacy of an integrated intervention targeting multiple behavioral and psychosocial risk factors among pregnant African American women in the District of Columbia. The risk factors we chose to address were cigarette smoking, secondhand smoke exposure, depression, and IPV.