Molecular abnormalities in ovarian carcinoma: clinical, morphological and therapeutic correlates.

The histopathological classification of ovarian surface epithelial carcinomas (referred to hereafter as 'ovarian carcinoma') has shifted over the past 10 years to reflect more clearly our understanding of molecular events during carcinogenesis. Ovarian carcinoma is no longer viewed as a single entity but as multiple disease processes, with each having different molecular pathways altered during oncogenesis, resulting in differences in clinical and pathological features, such as biomarker expression, pattern of spread and response to chemotherapy. There are five subtypes of ovarian carcinoma that are sufficiently distinct and well-characterized that they should be considered to be different diseases, i.e. high-grade serous, clear cell, endometrioid, mucinous and low-grade serous, from most to least common, respectively. This review summarizes the molecular abnormalities of these five ovarian carcinoma subtypes, relating them to clinical and pathological features.

Angiotropism in primary cutaneous melanoma with brain metastasis: a study of 20 cases.

Previous clinical and experimental studies suggested that invasion of the brain by metastatic melanoma may follow the external surfaces of vascular channels, that is, angiotropic extravascular migratory metastasis. Such angiotropic invasion seemss analogous to that of neoplastic glial invasion of the nervous system. We, therefore, have retrospectively investigated 20 primary melanoma cases and their respective metastatic brain lesions. The following parameters were analyzed in each primary melanoma: presence of angiotropism, Breslow thickness, Clark level, mitotic rate, sentinel lymph node (SLN) status, and time interval between the primary lesion and the metastasis. The metastatic brain lesions were examined for the presence of angiotropism. Of the 20 cases, 14 showed angiotropism in the primary lesion. The angiotropic group had a significantly deeper Breslow thickness (median 4.4 mm vs. 1.4 mm, P < 0.01) and was more mitotically active (median 11 vs. 4.7 mitoses/mm, P = 0.04). Interestingly, the angiotropic group had an average time lapse of 33 months from the primary lesion to the brain metastasis, whereas the nonangiotropic group had a 57-month time interval. Although the Kaplan-Meier analysis failed to show a survival difference in this small cohort (P = 0.235), there was a trend toward significance. Seven of 20 brain metastases showed angiotropism; however, no significant correlation between angiotropism in the primary melanomas and the corresponding metastatic lesions could be demonstrated. Indeed, angiotropism in the brain metastases was difficult to assess because the available material were generally small partial biopsy samplings and many showed conspicuous necrosis. Ten melanoma patients underwent SLN biopsy. The 3 of 6 positive cases in the angiotropic group had an average time lapse of 32 months from the primary lesion to the brain metastasis, whereas the 4 positive SLN biopsies in the nonangiotropic group had an average of 63 months. This preliminary study of angiotropism in primary melanomas and their corresponding brain metastasis shows a striking trend suggesting that angiotropism in primary melanomas may predict the rapid development of brain metastases. This study also has demonstrated the difficulty in studying angiotropism in melanoma brain metastases because of small sample sizes and abundance of necrotic tissue. The authors are in the process of collecting larger and more representative numbers of melanoma brain metastases for further investigations.

Deaths Associated With Community Donation Bins: A Ten-Year Retrospective Review Describing Five Cases in British Columbia and Ontario.

INTRODUCTION: Community donation bins have become more common in the urban setting over the past several years. Many nonprofit organizations use these sturdy metal enclosures for unobserved collection of various donated items such as clothing, books, and household items. Although the donated items are often of low individual value, donation bins may become a target of individuals in low socioeconomic situations seeking desired items for personal use or resale, or for personal shelter within the bin. METHODS: To identify donation bin-associated deaths, we reviewed cases taken under the jurisdiction of the coroner for investigation in the provinces of British Columbia and Ontario, Canada, over the years 2009 to 2019. RESULTS: We present the circumstances and postmortem findings of five deaths that occurred in British Columbia and Ontario (Canada) between 2009 and 2019, wherein the decedents were each believed to have been reaching into donation bins and became caught within the door mechanism and died as a consequence of compression asphyxia involving the chest and/or neck. DISCUSSION: Donation bins have the potential for harm when individuals attempt to access the bin contents through the entry portal. We advocate for greater attention and changes in the placement location and/or design of these potentially dangerous devices.

Effect of exercise training on myocardial blood flow in patients with stable coronary artery disease.

BACKGROUND: The mechanisms by which exercise training benefits patients with coronary artery disease (CAD) are unclear but may include improved myocardial circulation. The aim of this study was to investigate the effect of exercise training on myocardial blood flow (MBF) and coronary flow reserve (CFR) in patients with stable CAD. METHODS: Twelve patients with documented CAD and ischemic ST-segment depression during exercise testing were randomized to exercise training (n = 7) or sedentary life style (control; n = 5) and underwent rubidium-82 positron emission tomography pre- and postintervention. Global left ventricle MBF and regional MBF in 17 left ventricular segments were calculated. Segments with <75% uptake (2 SD below normal) on stress uptake images were defined as abnormal. RESULTS: Exercise training increased global CFR by 20.8% +/- 27.9% versus control (10.5 +/- 24.1%, P = .0001). In normal segments (exercise training: n = 91; control: n = 46), exercise training did not change resting MBF (-14.1% +/- 16.3% vs -8.8% +/- 15.6%) and hyperemic MBF (-1.93% +/- 19.1% vs 2.86% +/- 20.5%, P = NS) and increased in CFR compared to control (17.0% +/- 25.5% vs 11.3% +/- 23.5%, P = .01). In abnormal segments, the change in resting MBF was not significantly different (-12.6% +/- 18.5% exercise [28 segments] vs -2.9% +/- 18.0% control [39 segments], P = NS). A significant increase was seen in hyperemic MBF with exercise (12.5% +/- 22.1% vs 2.6% +/- 16.3%, P = .02) and CFR (32.8% +/- 32.3% vs 9.5% +/- 24.8%, P = .001). CONCLUSIONS: Exercise training increased CFR in normal and diseased segments, and increased hyperemic flow in diseased segments. These data provide preliminary evidence in support of a favorable effect of exercise training on blood flow to ischemic myocardium.

Sudden death due to undiagnosed primary amyloidosis.

Amyloidosis is a disease characterized by abnormal deposition of amyloid protein within tissues throughout the body. The site of deposition can differ between patients, and therefore, clinical presentation can vary. Here, we present a case of previously undiagnosed amyloidosis presenting with sudden death. Autopsy demonstrated amyloid infiltration of intramural myocardial vessels, in the absence of myocardial involvement, leading to acute myocardial infarction and death. Postmortem analysis on femoral blood demonstrated an increase in the concentration of free lambda light chains with a significantly decreased kappa-to-lambda ratio, confirming the amyloidosis to be of AL type. While cardiac involvement in AL amyloidosis is not uncommon, isolated intramural vessel involvement is rarely seen, and to our knowledge, no reported cases have resulted in sudden death. This case highlights the importance of investigating angina-like symptoms in patients with amyloidosis. It also demonstrates that free light chain analysis can be a useful tool for diagnosing and classifying amyloidosis in postmortem investigations.