The pectoralis major muscle flap in reconstruction of secondary breast cancer

The use of a new technique for harvesting of the pectoralis major muscle in the reconstruction of locally recurrent breast cancer is presented and illustrated in two cases. This technique provides the versatility of the myocutaneous flap but avoids the significant donor site morbidity and unreliability of the skin paddle.     

p14ARF expression in invasive breast cancers and ductal carcinoma in situ – relationships to p53 and Hdm2

Introduction  

p14^ARF stabilises nuclear p53, with a variable expression of p14^ARF mRNA in breast cancers. In vitro, nuclear p14^ARF binds Hdm2 to block Hdm2-dependent nucleocytoplasmic shuttling of p53, which is required before cytoplasmic degradation of p53. p14^ARF is negatively regulated by p53 and through p53-independent pathways. No studies have yet examined levels of p14^ARF protein expression in breast cancer and their relationship to Hdm2/p53 immunoreactivity or subcellular localisation. Previously, immunohistochemical expression of cytoplasmic p14^ARF, p53 and Hdm2 has been described. HER-2 (c-erbB2/neu) predicts prognosis and interacts with the p14^ARF/Hdm2 pathway to inactivate p14^ARF and to influence Hdm2 activity and localisation. This study examined p14^ARF and p53/Hdm2 expression and subcellular localisation by using immunohistochemistry in a series of invasive ductal breast cancers (IDCs) with concomitant ductal carcinoma in situ (DCIS), to evaluate whether findings in vitro were related to clinicopathological parameters such as HER-2 and their effect on patient outcome.     

TUB is a candidate gene for late-onset obesity in women

Aims/hypotheses We recently reported significant associations between BMI and three TUB single nucleotide polymorphisms (SNPs) in two Dutch cohorts enriched for type 2 diabetes. Here, we attempted a replication of these associations in a large population-based cohort of female twins comprehensively phenotyped for measures of general and central obesity. Methods Two TUB SNPs (rs2272382, rs2272383) and a third (rs1528133), 22 kb distal to RIC3, were genotyped in 2694 Europid women from the St Thomas’ UK Adult Twin Registry (Twins UK) (mean age ± SD: 47.6 ± 12.7 years; 42.8% postmenopausal). We explored the hypothesis that TUB is a candidate gene for late-onset obesity in humans through testing the interaction of the SNPs by menopausal status. Results In the whole cohort, none of the three SNPs showed a significant main effect on measures of general or central obesity. However, for central obesity the rs2272382 SNP showed a significant interaction with menopausal status (p = 0.036). Postmenopausal women homozygous for the minor allele of rs2272382 showed significantly more general obesity (p = 0.022) and central obesity (p = 0.009) than carriers of the major allele. Differences (beta [95% CI]) between the two genotype groups were 0.92 kg/m² (0.03–1.81) for BMI (p = 0.036), 2.73 cm (0.62–4.84) for waist circumference (p = 0.013) and 2.43% (0.27–4.60) for per cent central fat (p = 0.027). These associations were confirmed by a sibling transmission disequilibrium test for central obesity, waist circumference and per cent central fat. Conclusions/interpretation We have replicated associations of TUB SNP rs2272382 with measures of general and central obesity in normal postmenopausal women. These findings confirm TUB as a candidate gene for late-onset obesity in humans.     

Genome-wide search for nevus density shows linkage to two melanoma loci on chromosome 9 and identifies a new QTL on 5q31 in an adult twin cohort

The density of acquired melanocytic nevi represents an important risk factor for malignant melanoma. Total body nevus counts were collected in a cross-sectional study of 1730 healthy females from the UK Adult twin registry comprising 709 dizygous and 156 monozygous pairs. Nevus density (ND) increased up to the age of 35 years and then gradually declined. Quantitative genetic analysis showed a smaller genetic influence (36%) on ND up to 35 years, compared with after 35 years where it rose to 59%. Using a sub-sample of 1238 genotyped individuals, we performed distinct genome-wide scans for individuals above and below 35 separately. In the younger sub-sample, we confirmed a quantitative trait locus (QTL) for ND on chromosomes 9p21 (LOD=2.54), a region already linked to both familial melanoma and ND. We also observed a linkage signal on 9q21 (LOD=2.55) overlapping a recently reported susceptibility locus for ocular and cutaneous melanoma in Danish families. The strongest evidence of linkage identified a novel QTL on chromosome 5q31-32 (LOD=3.47). None of these linkages was observed in the group aged 35 years and over, which showed suggestive linkage on chromosome 2p24 (LOD=2.75). To the best of our knowledge, this is the first genome-wide search for ND in a large sample of healthy adults. The results suggest that different sets of genes are likely to influence the processes leading to the appearance of nevi and their involution. They provide both novel and replicated QTLs for nevus development, some of which might overlap with those for melanoma and warrant detailed investigation.     

The option of Linac-based radiosurgery in a Gamma Knife radiosurgery center

Objective

Due to the fundamental differences in treatment delivery, linear-accelerator-based radiosurgery can be complementary to Gamma Knife (GK) for intracranial lesions. We reviewed the effect of adding GK to an existing linear accelerator (Linac)-based radiosurgery practice and analyzed case selections for the two modalities.

Patients and methods

UC Davis Medical Center installed a Leksell Gamma Knife Model C in October 2003 to supplement an established Linac-based radiosurgery program. Radiosurgery indications for the 15 months before and after installation were compared.

Results

Radiosurgery cases expanded by twofold from 68 patients before GK installation to 139 after, with 106 treated by GK and 33 by Linac. Besides a major increase for trigeminal neuralgia and a general growth for acoustic neuroma, meningioma and brain metastases, case numbers for glioma and arteriovenous malformation (AVM) remained stable. Considering case selections for Linac, glioma decreased from 28 to 18%, while meningioma and metastases increased from 9 to 21% and 38–46%, respectively. The Linac patients receiving fractionated treatment also increased from 37 to 61%.

Conclusions

While the majority of patients were treated with GK, a significant proportion was judged to be suited for Linac treatment. This latter group included particularly patients who benefit from fractionated therapy.     

Alterations in growth and body composition during puberty. IV. Energy intake estimated by the youth-adolescent food-frequency questionnaire: validation by the doubly labeled water method

BACKGROUND: Estimates of energy intake are required for an understanding of growth and disease; however, few methods of energy intake in children have been validated. OBJECTIVE: Our objective was to validate energy intake estimated by the Youth-Adolescent Food-Frequency Questionnaire (YAQ) against the criterion total energy expenditure (TEE) by doubly labeled water (DLW). DESIGN: Twenty-three boys and 27 girls (8.6-16.2 y of age) completed the YAQ and TEE measurements in 1 y. RESULTS: Energy intake by the YAQ (10. 03 +/- 3.12 MJ) and energy expenditure by DLW (9.84 +/- 1.79 MJ) were similar (P: = 0.91) with large lower (-6.30 MJ) and upper (6.67 MJ) +/-2 SD limits of agreement. When within-subject CVs of repeated measures of the DLW and YAQ methods were used, 25 of the 50 subjects were deemed to have misreported their energy intake. The discrepancy in energy intake (YAQ - TEE) was related to body weight (r = -0.25, P: = 0.077) and percentage body fat (r = -0.24, P: = 0.09) but not to age (r = -0.07, P: = 0.63) or the time between measures. From logistic regression, fatter boys were more likely to underreport energy intake than were fatter girls. CONCLUSION: The YAQ provides an accurate estimation of mean energy intake for a group but not for an individual.