Background:The impact of an inherited BRCA2 mutation on the prognosis of women with breast cancer has not been well documented. We studied the effects of oestrogen receptor (ER) status, other prognostic factors and treatments on survival in a large cohort of BRCA2 mutation carriers.Methods:We identified 285 breast cancer patients with a 999del5 BRCA2 mutation and matched them with 570 non-carrier patients. Clinical information was abstracted from patient charts and pathology records and supplemented by evaluation of tumour grade and ER status using archived tissue specimens. Univariate and multivariate hazard ratios (HR) were estimated for breast cancer-specific survival using Cox regression. The effects of various therapies were studied in patients treated from 1980 to 2012.Results:Among mutation carriers, positive ER status was associated with higher risk of death than negative ER status (HR=1.94; 95% CI=1.22–3.07, P=0.005). The reverse association was seen for non-carriers (HR=0.71; 95% CI: 0.51–0.97; P=0.03).Conclusions:Among BRCA2 carriers, ER-positive status is an adverse prognostic factor. BRCA2 carrier status should be known at the time when treatment decisions are made.

Background/Purpose: In Hirschsprung disease (HD) surgery, confirming ganglionic bowel is essential. A faster diagnostic method than the current frozen biopsy is desirable. This study investigated whether aganglionic and ganglionic intestinal wall can be distinguished from each other by ultra high frequency ultrasound (UHF ultrasound). Methods: In an HD center during 2019, intestinal walls of recto-sigmoid specimens from HD patients were examined ex vivo with a 70 MHz UHF ultrasound transducer. Data from four sites were described. Histopathologic analysis was compared to the ultrasonography outcome at each site. Each patient's specimen served as its own control. Results: 11 resected recto-sigmoid specimens (median 20 cm long [range 6.5-33]) with transition zones of 5 cm (2-11 cm) were taken from children aged 22 days (13-48) weighing 3668 g (3500-5508); 44 key sites were analyzed. There was full concordance for 42/44 (95%) key sites and 10 of 11 (91%) specimens. The specimen with discordance of two key sites contained a segment of aganglionosis (3 cm) and a transition zone (1 cm): the site discordance was limited to the transition zone ends. Conclusions: This first report on UHF ultrasound in recto-sigmoid HD shows promising results in identifying aganglionosis, transition zones and ganglionic bowel. Further in vivo studies are required.

Background In the validation of new imaging technology for children with Hirschsprung’s disease (HSCR), basic anatomical parameters of the bowel wall must be established specifically for this patient group. Aim To explore differences in histoanatomical layers of bowel wall, comparing ganglionic and aganglionic bowel walls, and to examine if the bowel wall thickness is linked to patient weight. Methods This was an observational study of bowel specimens from children weighing 0–10 kg, operated on consecutively during 2018–2020. Ganglionic and aganglionic bowel walls were measured in digitalized microscopy images from 10 sites per trans-sectional specimen and compared regarding the thickness of their histoanatomical layers. Results Bowel walls were measured in 21 children. Full bowel wall thickness did not differ between aganglionic and ganglionic bowel (2.20 vs 2.04; p = 0.802) while weight at surgery correlated positively with both ganglionic and aganglionic bowel wall thickness (r = 0.688 and 0.849, respectively), and age at surgery with ganglionic bowel wall thickness (r = 0.517). In aganglionic segments, the muscularis externa layer was thicker compared to that in ganglionosis (0.45 vs 0.31 mm, p = 0.012) whereas the muscularis interna was thinner (0.45 vs 0.62 mm, p < 0.001). A diagnostic index was identified whereby a lower ratio of muscularis interna/externa thickness followed by a thinner muscularis interna differed between aganglionic and ganglionic bowel in all specimens. Conclusion Thicknesses of the bowel wall’s muscle layers differ between aganglionic and ganglionic bowel walls in children with HSCR. These findings support a diagnostic index that could be validated for transfer to instant diagnostic imaging techniques. Level of evidence Diagnostic: 3