Non-histopathological parameters associated with upgrade of breast tumours yielding a core biopsy report of histological grade 2 ductal no special type to grade 3 on excision.

PURPOSE: The aim of the study was to identify clinical, radiological and immuno-histochemical factors that may help predict upgrade of invasive ductal cancers of no special type (IDC-NST) with a core biopsy grade of 2 to grade 3 on final histology. METHODS: A prospectively maintained database of ultrasound visible solid masses was used to identify lesions yielding a core biopsy result of IDC-NST grade 2 who underwent immediate surgery yielding a grade 2 or grade 3 tumour. Associations were sought between the source of patient (screening/symptomatic), core biopsy receptor status and imaging findings and the grade of the excision specimen tumour. Statistical analysis, which included the chi-squared test, ROC curves and Cox regression analysis, was used to compare upgrade vs no upgrade for each factor. RESULTS: 463 IDC-NST breast cancers of core biopsy grade 2 gave 344 grade 2 and 119 grade 3 tumours at excision. Factors significantly associated with upgrade were large ultrasound (US) size, hyperechogencity, stiffness at shearwave elastography (SWE), calcification on mammography and oestrogen receptor (ER) and progesterone receptor (PR) negativity. Patient source, Human epidermal growth factor receptor 2 (HER-2) status, ultrasound (US) distal effect and mammographic spiculation were not significantly associated with chance of upgrade. On multivariate analysis, only US size maintained statistical significance. CONCLUSION: Oncologists and surgeons should be aware that lesions with a core biopsy diagnosis of grade 2 IDC-NST measuring over 15 mm on US have a 37% chance of being grade 3 on excision and this should be considered when deciding pre-operative management.

Pre-operative stromal stiffness measured by shear wave elastography is independently associated with breast cancer-specific survival.

INTRODUCTION: With the increased use of neoadjuvant therapy for breast cancer, there is a need for pre-operative prediction of prognosis. We aimed to assess the prognostic value of tumour stiffness measured by ultrasound shear wave elastography (SWE). METHODS: A consecutive cohort of patients with invasive breast cancer underwent breast ultrasound (US) including SWE. The following were recorded prospectively: US diameter, stiffness at SWE, presentation source, core biopsy grade, oestrogen receptor (ER) status and pre-operative nodal status. Breast cancer-specific survival (BCSS) was analysed with regard to US size and stiffness, tumour grade on core biopsy, ER status, presentation mode and pre-operative nodal status. Analysis used Cox proportional hazards regression. RESULTS: Of the 520 patients, 42 breast cancer and 53 non-breast cancer deaths were recorded at mean follow-up of 5.4 years. Hazard ratios (HR) for tertiles of stiffness were 1, 4.8 and 8.1 (P = 0.0001). HR for 2 groups based on US size < or ≥ 20 mm were 1 and 5.1 (P < 0.0001). HR for each unit increase in tumour grade on core biopsy was 3.9 (P < 0.0001). The HR for ER positivity compared to ER negativity was 0.21 (P < 0.001). BCSS was also associated with presentation mode and pre-operative nodal status. In a multivariable model, stiffness, US size and ER status were independently associated with BCSS. CONCLUSION: Multiple pre-operative factors including stromal stiffness at SWE have independent prognostic significance. A larger dataset with longer follow-up could be used in the future to construct a pre-operative prognostic model to guide treatment decisions.

Diagnostic dilemma posed by severe pelvic actinomycosis associated with prolonged use of copper intrauterine contraceptive device.

Actinomycosis has been recognized to be associated with the use of intrauterine contraceptive device. We are reporting a case where a patient with severe pelvic actinomycosis presented with the clinical picture of an ovarian tumour. A 44-year-old lady attended the A&E with progressively worsening lower abdominal pain. A computerized tomography (CT) scan showed the presence of a large pelvic mass, right hydronephrosis and prominent para-aortic lymph nodes and an elevated C-reactive proteine (CRP) and white cell count (WCC). When there was no improvement with antibiotic therapy, a laparotomy was performed, where bilateral tubo-ovarian abscess and dense adhesions were found. A subtotal hysterectomy, bilateral salpingoophorectomy and small bowel resection was performed. Histopathology of the specimen confirmed the diagnosis of actinomycosis. The case highlighted the diagnostic dilemma for ascertaining the nature of the pelvic mass in this patient. Due to its invasion of surrounding tissues and the formation of masses severe infection is often confused with an ovarian neoplasm.

Left ventricular dysfunction is associated with intraventricular dyssynchrony by 3-dimensional echocardiography in children.

INTRODUCTION: We used 3-dimensional (3D) echocardiography to identify and quantify left ventricular (LV) dyssynchrony in children with LV dysfunction compared with control subjects. METHODS: The 3D echocardiography LV full volumes were acquired in 18 children, 9 with LV dysfunction and 9 control subjects. The LV was subdivided into 16 segments (apex excluded). Time from end diastole to the minimal systolic volume for each segment was expressed as a percent of the R-R interval. The SD of these times provided a 16-segment dyssynchrony index (16-SDI). The second index (12-SDI) was similarly calculated using 6 basal and 6 mid segments. The third index consisted of 6 basal segments (6-SDI). RESULTS: The dysfunction group exhibited significantly increased 16-SDI (P = .008) and 12-SDI (P = .01). The 16-SDI was negatively correlated with 3D ejection fraction and 2-dimensional fractional shortening. CONCLUSIONS: Children with LV dysfunction demonstrate increased intraventricular LV dyssynchrony by 3D echocardiography, in a pattern that is negatively correlated with LV systolic function.

Simvastatin does not exhibit therapeutic anti-inflammatory effects in asthma.

BACKGROUND: Statins lower cholesterol and also exhibit anti-inflammatory properties. In vitro and animal studies have suggested they may be useful for the treatment of a number of inflammatory conditions. OBJECTIVE: To evaluate the in vivo therapeutic potential of simvastatin as an anti-inflammatory agent in patients with asthma. METHODS: Potential signal from treatment effect was optimized by withdrawing all anti-inflammatory treatment for the duration of the study. Participants received 1 month of daily simvastatin and 1 month of daily placebo in a randomized, double-blind crossover trial. A total of 16 patients completed per protocol. Asthmatic inflammation was evaluated by measuring exhaled tidal nitric oxide, alveolar nitric oxide, sputum and peripheral eosinophil count, methacholine hyperresponsiveness, salivary eosinophilic cationic protein, and C-reactive protein. Measurements of dynamic and static lung volumes and of cholesterol were also made. RESULTS: After initial withdrawal of usual asthma medication, there was a 1.43 geometric mean fold increase (ie, 43% difference) in fraction of exhaled nitric oxide (95% CI, 1.15 to 1.78; P = .004). Compared with placebo, simvastatin led to a 0.86 geometric mean fold decrease (95% CI, 0.7 to 1.04; P = .15) in exhaled nitric oxide (ie, a 14% difference), and a -0.18 doubling dilution shift (95% CI, -1.90 to 1.55; P = 1.0) in methacholine hyperresponsiveness. There were no significant differences in other inflammatory outcomes, lung volumes, or airway resistance between simvastatin and placebo. Treatment with simvastatin led to a significant reduction (P < .005) of total and low-density lipoprotein cholesterol. CONCLUSION: There is no evidence to suggest simvastatin has anti-inflammatory activity in patients with asthma. CLINICAL IMPLICATIONS: Simvastatin is not useful for the treatment of asthma.

Variability and resource utilization of bedside three-dimensional echocardiographic quantitative measurements of left ventricular volume in congenital heart disease.

OBJECTIVES: This study evaluated the variability and time resource utilization of bedside 3-dimensional echocardiographic left ventricular volume analysis (3D-LVVA) in congenital heart disease (CHD). Background. There are currently limited data on the resource utilization and variability of 3D-LVVA in the CHD. METHODS: Four reviewers of varying experience levels were timed performing 15 on-scanner 3D-LVVAs. Inter- and intraobserver variability for left ventricular end-diastolic volume (LVEDV), end-systolic volume (LVESV), and ejection fraction (LVEF) was evaluated. RESULTS: Median age was 12.7 years (0.6-33 years). Diagnoses were: normal (n = 4), cardiomyopathy (n = 4), ventricular septal defect (n = 2), and atrioventricular canal, tricuspid atresia, bicuspid aortic valve, left ventricular hypertrophy, and heart transplant (n = 1 each). For interobserver variability, intraclass correlation coefficients (ICCs) for all possible combinations of reviewers were: LVEDV, 0.991-0.999 (P < .01); LVESV, 0.98-0.99 (P < .01); LVEF, 0.95-0.98 (P < .01). Bland-Altman plot mean differences (+/-2SD) were: LVEDV, -3 +/- 14%; LVESV, -5.4 +/- 21.4%; LVEF, 1.2 +/- 14.7%. Interobserver variability of LVESV was not dependent on ventricular volumes (P = .25; r(2) = 0.01) or heart rate (P = .43; r(2) = 0.003). For intraobserver variability, ICCs for 2 reviewers were LVEDV, 0.99, 0.99 (P < .01); LVESV, 0.99, 0.99 (P < .01); and LVEF, 0.94, 0.94 (P < .01), respectively. Bland-Altman plot mean differences (+/-2SD) were: LVEDV, -1 +/- 9.2%; LVESV, 0 +/- 19.6%; LVEF, -2.2 +/- 24%. CONCLUSION: Reviewers with varying experience levels can accomplish 3D-LVVA at the bedside with acceptable inter- and intraobserver reproducibility, providing the rationale for integrating 3D-LVVA into the care of CHD patients.

A statistical model to predict nonsurvival in congenital diaphragmatic hernia.

OBJECTIVE: To develop a predictive model using echocardiographic indices to identify nonsurvivors from survivors in preoperative patients with congenital diaphragmatic hernia (CDH). STUDY DESIGN: Eight cases of CDH, with a mortality rate of 38%, underwent echocardiographic study before surgical repair. Left ventricular mass (LVMASS) using the area-length method of Wyatt et al. and fractional shortening (FS) by M-mode measurements were determined. RESULTS: We identified a nonlinear nonoverlapping distribution that predicted nonsurvivors from survivors, p=0.04. Multiple regression analysis demonstrated the quantity (LVMASS x FS)(1/2) to be correlated with nonsurvival with a coefficient of determination r(2)=0.55. Comparison of the means of the quantity (LVMASS x FS)(1/2) for the two groups suggested two distinct populations, p=0.04. CONCLUSION: The mathematical quantity (LVMASS x FS)(1/2) calculated from echocardiographic measurements obtained preoperatively in babies with CDH may predict nonsurvival despite maximal intervention.