Hospital-related differences in breast cancer management

A retrospective review is presented of 1353 consecutivepatients with histopathologically confirmed invasive breast carcinoma treatedradically with curative intent during the decade 1980–89.None had received adjuvant systemic therapy with hormonesor prolonged chemotherapy. The distribution of lymph-node negative(N–) and lymph-node positive (N+) patients was 75%and 25%, respectively.The treatment and outcome were analysed as regardsconventional prognostic parameters, in particular considering the axillarylymph-node status and the responsible hospital category (GeneralMunicipal Hospitals (MH)) versus Comprehensive Cancer Center (CC)).The most striking difference was detected as regardsthe number of examined lymph nodes. The mediannumber of nodes described at the MH was7, as compared to 14 at the CC(p < 0.001). In patients with pT1 tumoursthe highest rate of lymph-node positivity was observedwhen 10 or more axillary nodes were removed.Adjuvant radiotherapy reduced the loco-regional recurrence rate inthe N– patients, whereas only the regional recurrenceswere reduced among the N+ patients. The five-and 10-year tumor-related survival rates were 86% and76%, respectively, with no difference between the MHand the CC.As life-prolonging adjuvant hormone therapy and chemotherapy isnow available for patients with axillary lymph nodemetastases, it is important that patients with breastcancer are operated adequately with the aim toremove at least 10 axillary lymph nodes. Athorough examination of the axillary content should beperformed by the pathologist, and the number ofresected lymph nodes and metastases should be reported.The establishment of nation-wide standard criteria for themanagement of breast cancer is recommended.     

Diffuse splenic and visceral hemangiomas complicated by chronic consumption coagulopathy

Abstract The case of a 7-year-old girl with a 2 year history of easy bruising associated with thrombocytopenia is reported. On admission she presented with ecchymoses, abdominal distention and splenomegaly. Hemostasis investigation revealed a consumption coagulopathy. Several radiological studies failed to confirm the diagnosis of diffuse splenic and visceral hemangiomatosis, which was eventually estasblished by an explorative laparotomy. Platelet count and the other coagulation abnormalities progressively returned to normal after splenectomy, although the remaining hemangiomas were extensive.     

Is there a relationship between overweight and obesity and mental health problems in 4- to 5-year-old Australian children?

OBJECTIVE: To investigate the relationship between overweight and obesity, and mental health problems in Australian 4- to 5-year-old children. METHODS: The study used data from wave 1 (2004) of the Longitudinal Study of Australian Children (LSAC). The participants were 4983 4- to 5-year-old children (2537 boys and 2446 girls) with a mean age of 56.9 months (standard deviation 2.6 months; range 51-67 months). Children were classified as nonoverweight, overweight, and obese on the basis of International Obesity Task Force definitions. Mental health problems were assessed by the Strengths and Difficulties Questionnaire (SDQ) completed by parents and teachers. RESULTS: Although obese 4- to 5-year-old boys had more mental health problems than nonoverweight boys, differences between the groups were small and substantially reduced when analyses controlled for children's sociodemographic characteristics. Parents reported that overweight/obese girls had more peer problems, whereas teachers reported they had more conduct problems. Children in all weight groups had mean scores within the normal range of scores on all the SDQ subscales. CONCLUSIONS: Differences in rates of mental health problems experienced by young children of different weight status appear relatively small. Higher rates of mental health problems experienced by more obese boys may reflect differences in their sociodemographic characteristics rather than their weight status per se. Policies that reduce the number of young children living in poverty or experiencing other adverse social circumstances have the potential to reduce rates of mental health problems experienced by older children with overweight/obesity.     

Dissociation between the locomotor and anxiolytic effects of acetaldehyde in the elevated plus-maze: Evidence that acetaldehyde is not involved in the anxiolytic effects of ethanol in mice

Acetaldehyde, the first product of ethanol metabolism, has been suggested to play a major role in many behavioral effects of ethanol. However, very few studies have directly tested the behavioral effects of the acute administration of acetaldehyde. In particular, the role of this metabolite in ethanol-induced anxiolytic effects has never been extensively tested. The aim of the present study was to characterize the anxiolytic effects of acetaldehyde in two strains of mice, C57BL/6J and CD1 mice with the elevated plus-maze procedure. The results show that acute injections of ethanol (1–2 g/kg) induced significant dose-dependent anxiolytic effects in both strains of mice. In contrast, acetaldehyde failed to produce any anxiolytic effect, although it induced a significant hypolocomotor effect at the highest doses. In an independent experiment, cyanamide, an aldehyde dehydrogenase inhibitor, prevented the locomotor stimulant effects of ethanol, although it failed to alter its anxiolytic effects. Together, the results of the present study indicate that acetaldehyde is not involved in ethanol-induced anxiolytic effects, although it may be involved in its sedative/hypolocomotor effects.     

Practitioner Review: Unguided and guided self-help interventions for common mental health disorders in children and adolescents: a systematic review and meta-analysis

Mental health problems are common in children and adolescents, yet evidence-based treatments are hard to access. Self-help interventions can increase such access. The aim of this paper was to conduct a systematic review and meta-analysis of the use of guided and unguided self-help for children and young people with symptoms of common mental health disorders. In contrast to previous reviews of self-help in children, all types of self-help and multiple mental health disorders were investigated in order to increase power to investigate potential moderators of efficacy. Importantly, studies with control arms as well as those comparing against traditional face-to-face treatments were included. Fifty studies (n = 3396 participants in self-help/guided self-help conditions) met the inclusion criteria. Results demonstrated a moderate positive effect size for guided and unguided self-help interventions when compared against a control group (n = 44; g = 0.49; 95% CI: 0.37 to 0.61, p < .01) and a small but significant negative effect size when compared to other therapies (n = 15; g = −0.17; 95% CI: –0.27 to –0.07, p < .01). Few potential moderators had a significant effect on outcome. Most comparisons resulted in significant heterogeneity and therefore results are interpreted with caution.     

IRIS study: a phase II study of the steroid sulfatase inhibitor Irosustat when added to an aromatase inhibitor in ER-positive breast cancer patients

Purpose

High mammographic breast density (BD) is a strong risk factor of breast cancer; however, little is known in women under 40 years of age. Recently, dual-energy X-ray Absorptiometry (DXA) has been developed as a low-dose method to measure BD in young populations. Thus, our aims were to describe BD in relation to risk factors in Chilean women under 40 years old and to explore the equivalence of DXA to mammography for the measurement of BD.

Methods

We selected 192 premenopausal Chilean female participants of the DERCAM study for whom we have anthropometric, sociodemographic, and gyneco-obstetric data. The subjects received both digital mammograms (Hologic) and breast DXA scans (GE iDXA). Mammographic BD was estimated using a fully automated commercial method (VOLPARA^®) and BI-RADS. Breast DXA scans were performed using a standardized protocol and the % fibroglandular volume (%FGV) was estimated considering a two-compartment model of adipose and fibroglandular tissue.

Results

The mean age was 37 years (SD = 6.5) and 31.6% of the subjects were obese. The median %FGV and absolute FGV (AFGV) measured by DXA were 9% and 198.1 cm³ and for VOLPARA^®, 8.6% and 58.0 cm³, respectively. The precision for %FGV after reposition was 2.8%. The correlation coefficients for %FGV, AFGV, and breast volume between DXA and mammography were over 0.7. Age and body mass index (BMI) were inversely associated with %FGV, and BMI was positively related to AFGV as estimated with DXA or mammography. We did not observe an association with gyneco-obstetric characteristics, education, and %FGV and AFGV; smoking was only associated with AFGV as measured by VOLPARA^®.

Conclusions

DXA is an alternative method to measure volumetric BD; thus, it could be used to continuously monitor BD in adult women in follow-up studies or to assess BD in young women.

     

Prognostic value of residual node involvement in operable breast cancer after induction chemotherapy

The purpose of this retrospective study was to evaluate the influence of axillary disease on patients' survival after neoadjuvant chemotherapy and to assess patient and tumor characteristics associated with post-chemotherapy axillary involvement.After six induction cycles, 277 patients with operable breast cancer (stage II–III) underwent surgery with axillary dissection, followed by radiotherapy (n = 267) or additional chemotherapy (n = 63) and adjuvant tamoxifen therapy (n = 138). At a median follow-up of 8.5 years, overall survival (OS) and disease-free survival (DFS) were analyzed as a function of node involvement.The differences in OS and DFS according to the number of positive nodes were highly statistically significant with a decreased survival associated with the increasing number of nodes (p = 5 × 10^–6 and 9 × 10^–7, respectively). Upon multivariate analysis, the node number after chemotherapy appeared as the most significant prognostic factor (p = 7 × 10^–4 for OS and p = 3 × 10^–5 for DFS). All the other classical prognostic factors were insignificant, except post-chemotherapy Scarff–Bloom–Richardson (SBR) grading for OS (p = 8 × 10^–4) and adjuvant hormonotherapy for DFS (p = 1 × 10^–2).Although constituting a different parameter from primary surgery data, the number of positive nodes after chemotherapy could still remain a valuable prognostic factor at secondary surgery, raising the question for high risk patients of a second non-cross-resistant adjuvant regimen, or high dose chemotherapy with peripheral blood stem cells support.     

Diagnostic accuracy of p16INK4a immunohistochemistry in oropharyngeal squamous cell carcinomas: A systematic review and meta‐analysis

The accurate diagnosis of human papillomavirus (HPV) causality in oropharyngeal squamous cell carcinomas (OPSCC) is likely to influence therapeutic decisions in affected patients in the near future. We conducted a systematic review and meta‐analysis to determine the diagnostic accuracy of p16^INK4a immunohistochemistry (IHC) to identify HPV‐induced OPSCC. We identified all studies that performed p16^INK4a IHC (index test) and HPV E6/E7 mRNA detection using an amplification‐based method (gold standard to indicate a transforming relevance of HPV) in OPSCC. Testing with one or more comparator tests (HPV DNA PCR, HPV DNA in situ hybridization (ISH) and p16^INK4a IHC/HPV DNA PCR combined testing) was an optional criterion for inclusion. Among 1,636 retrieved studies 24 fulfilled the inclusion criteria. The pooled sensitivity of p16^INK4a IHC, HPV DNA PCR, HPV DNA ISH and p16^INK4a IHC/HPV DNA PCR combined testing was 94% (95%‐confidence interval (CI) 91–97%), 98% (CI 94–100%), 85% (CI 76–92%) and 93% (CI 87–97%), respectively. The pooled specificity was 83% (CI 78–88%), 84% (CI 74–92%), 88% (CI 78–96%) and 96% (CI 89–100%), respectively. p16^INK4a IHC/HPV DNA PCR combined testing was as sensitive as either p16^INK4a IHC or HPV DNA PCR alone but significantly more specific than either separate test. In conclusion, p16^INK4a IHC is highly sensitive but moderately specific to diagnose HPV‐transformed OPSCC when used as a single test. Combined p16^INK4a IHC and HPV DNA PCR testing significantly enhances specificity while maintaining high sensitivity. This diagnostic test combination thus represents an attractive testing strategy for the reliable diagnosis of HPV‐induced OPSCC in the clinical setting and may constitute an inclusion criterion for future therapeutic trials.     

IL‐7 is expressed in malignant mesothelioma and has a prognostic value

Malignant pleural mesothelioma (MPM) is an aggressive cancer mainly related to asbestos exposure. Despite recent therapeutic advances, notably immunotherapies, the benefit remains limited and restricted to a small percentage of patients. Thus, a better understanding of the disease is needed to identify new therapeutic strategies. Recently, interleukin 7 receptor (IL‐7R) has been described as being expressed by MPM cells and associated with poorer patient survival. Thus, the aim of this work was to study the IL‐7R/IL‐7 pathway in MPM using patient samples. We found that, although more than 40% of MPM cells expressed IL‐7R, IL‐7 had no effect on their intracellular signaling. Accordingly, the addition of IL‐7 to the culture medium did not affect MPM cell growth. Using The Cancer Genome Atlas (TCGA) database, we showed that high IL7 gene expression in MPM tumors was associated with a higher overall patient survival and an induction of genes involved in the immune response. In pleural effusions (PEs), we found that IL‐7 concentration was not a good diagnostic biomarker. However, we observed that high IL‐7 levels in PEs were associated with shorter survival of MPM patients, but not of lung cancer patients. The prognostic value of IL‐7 was also conserved when only patients with epithelioid mesothelioma, the most common histological type of MPM, were analyzed. Taken together, our study suggests that, although the IL‐7R/IL‐7 signaling pathway is not functional in MPM cells, IL‐7 expression in PEs may have prognostic value in MPM patients.