Performance Characteristics of Endometrial Sampling in Diagnosis of Endometrial Carcinoma.

Outpatient endometrial biopsy can give false-negative results, with a 0.9% reported posttest probability for endometrial carcinoma (EC) after a negative result. Our objective was to determine if there has been any improvement in the performance characteristics of endometrial biopsy over the last 15 yr. All hysterectomy specimens with a diagnosis of EC or atypical hyperplasia (AH), reported between May 2011 and May 2015, were identified and cross-referenced for any negative endometrial sampling results during the 5 yr before hysterectomy. Negative endometrial samples were defined as either benign findings or insufficient/nondiagnostic, excluding those diagnosed as AH or EC and those for which follow-up sampling was recommended because of atypia. Of 1677 hysterectomy specimens showing AH or EC there were previous negative biopsies in 172: 116 benign and 56 insufficient/nondiagnostic. Over the same period 22,875 negative endometrial biopsy specimens were reported in our region. The posttest probability of having EC or AH in the hysterectomy specimen, given a negative endometrial biopsy result, was 0.74%. In a subset of 90 cases in which a negative biopsy was followed by a diagnosis of AH or EC in a hysterectomy specimen, the slides were independently reviewed. There were no cases where a diagnosis of carcinoma was missed. In 12 samples atypia or possible atypia was identified, and the level of agreement with the original diagnosis was excellent κ=0.83±0.05. In a prospective comparison of examination of 3 levels from each block versus a single slide in 319 cases, the routine preparation of additional slides did not yield clinically significant information. Although there has been evolution in the diagnostic criteria for AH and for recognition of morphologically subtle forms of AH or EC, our results demonstrate a significant lack of sensitivity of outpatient endometrial sampling in the diagnosis of endometrial malignancy/premalignancy. The sensitivity problems are mainly attributable to failure to sample abnormal endometrium. Independent review of slides or examination of additional levels did little to increase the diagnostic yield.

Metastatic non-small cell lung carcinoma a mimic of primary breast carcinoma-case series and literature review.

Metastatic tumors to the breast are rare but constitute a major diagnostic dilemma. Of these, non-mammary carcinomatous metastases to the breast are particularly challenging and, without a clinical history, may be extremely difficult to distinguish from primary breast carcinoma (PBC). We specifically studied metastatic tumors of pulmonary origin, as the lung is one of the major primary sites for carcinomatous metastasis to breast. Sixteen metastatic lung tumors to the breast were identified in our archives between 1996 and 2017 including 12 non-small cell lung carcinomas (NSCLC), one large-cell neuroendocrine, one atypical carcinoid, and two small-cell carcinomas. Adenocarcinoma was the most frequent amongst the NSCLCs (11/14). We retrieved the clinical information of these cases and reviewed the pathological characteristics to provide practical tools for pathologists to aid in their identification. Even in the absence of a clinical history of lung cancer, metastatic pulmonary adenocarcinoma to the breast should be considered in at least one of the following scenarios: (1) single or multiple well-circumscribed lesions of the breast that lack an in situ component and that are accompanied by distant metastases but negative axillary lymph nodes, (2) breast tumors that are triple negative yet not high-grade, or (3) breast tumors presenting as stage 4 disease and/or having an unusually aggressive clinical course on standard breast therapy. Accurate and timely diagnosis of these tumors is mandatory because of treatment and prognostic implications.

Coronary artery calcification score as tool for risk assessment among families with premature coronary artery disease.

INTRODUCTION: There is discussion about incorporating a family history (FamHis) of premature coronary artery disease (CAD) in risk score algorithms. However, FamHis provides information on individual risk. Coronary artery calcification score (CACS) is a metric of atherosclerosis that may determine the individual risk within families at high risk of premature CAD. METHODS: In asymptomatic individuals (n = 704), we assessed the association between FamHis of CAD and elevated CACS. To assess the predictive value of CACS in individuals with a FamHis of CAD, we performed a post-hoc analysis on the St. Francis Heart Study (n = 834). We assessed, in a case control design, the risk of future CAD in individuals with a FamHis of CAD and either CACS >80th percentile or no CACS at all. RESULTS: Individuals with a FamHis for CAD had an increased risk for elevated CACS (adjusted odds ratio (OR) 2.23 (95% CI 1.48-3.36); p < 0.05), compared to those without a FamHis. In the prospective study (3.5 years follow-up), the event rate equally low in those with a positive FamHis and a negative FamHis (0% vs. 1%), if they had a CAC of 0. However, in those with CACS >80(th) percentile, a FamHis of CAD doubled the CAD event rate (positive FamHis 12.5% vs. negative FamHis 6.8%; adjusted HR 2.08 (95% CI 1.09-3.87; p < 0.05). CONCLUSION: CAC scoring leads to risk discrimination among those with a positive FamHis for premature CAD. These results support testing CAC score in asymptomatic individuals with a positive FamHis to identify a high risk population.

Variations in the management of acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a significant cause of morbidity and mortality for patients with COPD. AECOPD are the leading cause of hospital admissions in Canada. Although multiple guidelines have been developed for the acute and chronic management of COPD, there are few quality assurance studies investigating adherence to these guidelines. METHODS: A retrospective chart review of all patients admitted to a tertiary care hospital in 2009 for an AECOPD was performed. Using a standardized data abstraction tool, adherence to current guidelines across different physician groups and patient outcomes were assessed. Particular focus was centred on differences in management across physician groups. RESULTS: Overall, 293 patients were evaluated. Of these, 82.6% were treated with one or more chronic COPD medication(s) in the community, with only 17.7% of patients treated with a long-acting inhaled anticholinergic medication. For treatment of AECOPD, 58% of patients received corticosteroids and 84% received antibiotics. Compared with general medicine and the hospitalist service, the respiratory medicine service demonstrated significantly better adherence with current treatment guidelines; however, even this was less than optimal. In addition, there was poor follow-up of patients cared for outside of the respiratory service. CONCLUSIONS: The present study identified significant care gaps in the treatment of patients admitted with AECOPD and on their discharge.

Coronary artery calcium findings in asymptomatic subjects with family history of premature coronary artery disease.

BACKGROUND: To evaluate the frequency of positive coronary arteries calcium (CAC) scores in a unique population of asymptomatic first degree relatives (FDRs) of patients with angiographically confirmed early onset of coronary artery disease (CAD) and to assess their association with carotid ultrasound findings and other cardiovascular risk factors. METHOD AND RESULTS: We scanned, using 64-slice multi-detector computed tomography, 57 asymptomatic FDRs (47 ± 9 years old; 44% male, 56% female), out of the 111 FDRs previously phenotyped for cardiovascular (CV) risk factors. The controls were 616 individuals (57 ± 10 years old; 76% male, 24% female) with no family history of cardiovascular disease, chest pain or diabetes selected out of the 3500 subjects scanned between 2002 and 2007. FDRs had higher risk of abnormal CAC scores compared to controls; odds ratio (OR) for the 75th percentile was 1.96 (95% CI 1.04-3.67, p < 0.05). CONCLUSION: The frequency of abnormal CAC scores is two-fold higher in asymptomatic FDRs than in controls. CAC scan provides additional information on CV risk assessment in asymptomatic FDRs, particularly for those in the intermediate risk category. CLINICAL TRIAL REGISTRATION: NCT00387595.

Incidence of pancreatitis, secondary causes, and treatment of patients referred to a specialty lipid clinic with severe hypertriglyceridemia: a retrospective cohort study.

BACKGROUND: Severe hypertriglyceridemia (HTG) is one cause of acute pancreatitis, yet the level of plasma triglycerides likely to be responsible for inducing pancreatitis has not been clearly defined. METHODS AND RESULTS: A retrospective cohort study was conducted on patients presenting non-acutely to the Healthy Heart Program Lipid Clinic at St. Paul's Hospital with a TG level > 20 mM (1772 mg/dl) between 1986 and 2007. Ninety-five patients with TG > 20 mM at the time of referral were identified, in who follow up data was available for 84. Fifteen patients (15.8%), with a mean outpatient TG level of 38.1 mM, had a history of acute pancreatitis. Among 91 additional patients with less severe HTG, none had a history of pancreatitis when TG were between 10 and 20 mM. Among patients with TG > 20 mM on presentation, 8 (8.5%), with a mean TG level of 67.8 mM, exhibited eruptive xanthomata. A diet high in carbohydrates and fats (79%) and obesity (47.6%) were the two most frequent secondary causes of HTG at initial visit. By 2009, among patients with follow up data 53% exhibited either pre-diabetes or overt Type 2 diabetes mellitus. Upon referral only 23 patients (24%) were receiving a fibrate as either monotherapy or part of combination lipid-lowering therapy. Following initial assessment by a lipid specialist this rose to 84%, and remained at 67% at the last follow up visit. CONCLUSIONS: These results suggest hypertriglyceridemia is unlikely to be the primary cause of acute pancreatitis unless TG levels are > 20 mM, that dysglycemia, a diet high in carbohydrates and fats, and obesity are the main secondary causes of HTG, and that fibrates are frequently overlooked as the drug of first choice for severe HTG.

Subclinical atherosclerosis in subjects with family history of premature coronary artery disease.

BACKGROUND: First-degree relatives (FDRs) of subjects with early onset of coronary heart disease (CHD) have higher risk of developing cardiovascular disease. We verified early CHD by angiography in index patients and extensively phenotyped their FDRs to investigate the relationship of traditional and nontraditional cardiovascular risk factors to carotid ultrasound measures of subclinical atherosclerosis. METHODS AND RESULTS: B-mode carotid ultrasound was used to assess the combined intimamedia thickness and plaque burden in 111 FDRs (65 men, 44.4 +/- 11 and 46 women, 44.7 +/- 13 years old) of 82 index patients (men <50 and women <60 years of age at the time of the event). The biochemical and anthropometrical characteristics of the FDRs were compared with those of healthy controls matched for sex, age, ethnicity, and body mass index. First-degree relatives had increased average total thickness (a combined measure of intimamedia thickness and plaque) compared to controls (0.76 mm, interquartile range [IQR] 0.69-1.01 vs 0.69 mm, IQR 0.60-0.88, P < .001) even after adjusting for age, total cholesterol-to-high-density lipoprotein cholesterol ratio, systolic blood pressure, waist circumference, and smoking (beta = 0.143, P < .05). No differences were observed in average intimamedia thickness measurements alone. Of the nontraditional risk factors, only plasma homocysteine was higher in FDRs then in controls (9.6 mg/L, IQR 8.0-11.1 versus 7.5 mg/L, IQR 6.4-8.7, P < .001), after adjusting for all other confounding variables. CONCLUSION: First-degree relatives of patients with angiographically confirmed CHD have higher burden of subclinical atherosclerosis even when considered in the context of traditional risk factors. Noninvasive assessment of carotid artery plaques and intimamedia thickness and plasma homocysteine measurements may be useful in such patients.