A 57-Year-Old Man With Stridor and Critical Tracheal Narrowing.

CASE PRESENTATION: A 57-year-old man with a history of polysubstance use presented with shortness of breath, wheezing, productive cough, subjective fever, and chills of 3-day duration. Additionally, he reported worsening shortness of breath for the last 3 months. Of note, the patient was reported to have had, in the previous 6 months, two episodes of pneumonia that was treated with antibiotics and steroids. He was also diagnosed several years prior with adult-onset asthma due to intermittent wheezing and was prescribed an albuterol inhaler. The albuterol did not help relieve his wheezing, and he stopped refilling it.

Primary cardiac low-grade neuroendocrine tumor: a case report and review of the literature.

Primary tumors of the heart are uncommon; even rarer are primary cardiac neuroendocrine tumors. To our knowledge, only two cases have been described to date, both being high-grade tumors. We report a solitary low-grade neuroendocrine tumor of the heart, unexpectedly discovered during aortic valve repair for infectious bacterial endocarditis on the wall of the right ventricle in a 44-year-old man with a history of balloon valvulotomy as a child. Frozen section was sent intraoperatively and demonstrated a plasmacytoid neoplasm. Final pathology of the biopsies showed a tumor composed of both cohesive and discohesive plasmacytoid cells separated by a vascular network and strands of fibrosis. The tumor showed strong reactivity for AE1/3, synaptophysin, and CDX2 with focal reactivity for chromogranin-A and CD56. Neither necrosis nor a mitotic rate of greater than 2 mitoses per 2 mm2 was seen. A colonoscopy was performed and demonstrated only a tubular adenoma. An esophagogastroduodenoscopy was unremarkable. PET-CT DOTATATE, performed after complete resection of the tumor, demonstrated no abnormal radiotracer uptake. The patient continues to do well at present, 1 year later, and reports no symptoms attributable to carcinoid syndrome or disease progression. The patient was assigned by medical oncology to yearly follow-up and imaging, and is considered to have no evidence of disease.

Invasive Lobular Carcinoma With Extensive Clear Cells: A Pitfall in Diagnosis.

Carcinomas in the breast with a predominantly clear cytoplasm are rare. In this article, we review the differential diagnosis of clear cell breast neoplasms and report a case of invasive lobular carcinoma with extensive clear cell morphology that was diagnosed as invasive ductal carcinoma, not otherwise specified, on ultrasound-guided biopsy. Lobular carcinomas with extensive clear cell change are unusual, but must be considered when evaluating a clear cell neoplasm in the breast.

Hepatic overexpression of abcb11 promotes hypercholesterolemia and obesity in mice.

BACKGROUND & AIMS: ABCB11 is a canalicular transport protein that controls the rate-limiting step in hepatic bile acid secretion. Its expression levels vary in humans, and it is not clear how these variations affect lipid metabolism. We investigated whether overexpression of Abcb11 in mice increases lipid absorption in the intestine and affects the development of obesity or hypercholesterolemia. METHODS: Transgenic mice that overexpress Abcb11 in liver (TTR-Abcb11) and FVB/NJ mice (controls) were fed a high-cholesterol or high-fat diet for 12 weeks. Intestinal lipid absorption was measured by the dual fecal isotope method. Energy expenditure was measured by indirect calorimetry. The bile acid pool was analyzed by high-performance liquid chromatography. RESULTS: TTR-Abcb11 mice had a nearly 2-fold increase in intestinal cholesterol absorption compared with controls. TTR-Abcb11 mice fed a high-cholesterol diet had greater increases in plasma and hepatic levels of cholesterol and became more obese than controls; they also had increased intestinal absorption of fatty acids and decreased energy expenditure. In the TTR-Abcb11 mice, the sizes of plasma and total bile acid pools were reduced; the bile acid pool contained more species of hydrophobic bile acids compared with controls. CONCLUSIONS: Hepatic overexpression of Abcb11 in mice promotes diet-induced obesity and hypercholesterolemia; increased intestinal cholesterol absorption by hydrophobic bile acids might cause these features. Increased absorption of fatty acids in the intestine and reduced expenditure of energy could increase weight gain in TTR-Abcb11 mice. In humans, variations in expression of ABCB11 might confer genetic susceptibility to diet-induced hyperlipidemia and obesity.

A chronic high-cholesterol diet paradoxically suppresses hepatic CYP7A1 expression in FVB/NJ mice.

Cholesterol 7α-hydroxylase (CYP7A1) encodes for the rate-limiting step in the conversion of cholesterol to bile acids in the liver. In response to acute cholesterol feeding, mice upregulate CYP7A1 via stimulation of the liver X receptor (LXR) α. However, the effect of a chronic high-cholesterol diet on hepatic CYP7A1 expression in mice is unknown. We demonstrate that chronic cholesterol feeding (0.2% or 1.25% w/w cholesterol for 12 weeks) in FVB/NJ mice results in a >60% suppression of hepatic CYP7A1 expression associated with a >2-fold increase in hepatic cholesterol content. In contrast, acute cholesterol feeding induces a >3-fold upregulation of hepatic CYP7A1 expression. We show that chronic, but not acute, cholesterol feeding increases the expression of hepatic inflammatory cytokines, tumor necrosis factor (TNF)α, and interleukin (IL)-1ß, which are known to suppress hepatic CYP7A1 expression. Chronic cholesterol feeding also results in activation of the mitogen activated protein (MAP) kinases, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK). Furthermore, we demonstrate in vitro that suppression of CYP7A1 by TNFα and IL-1ß is dependent on JNK and ERK signaling. We conclude that chronic high-cholesterol feeding suppresses CYP7A1 expression in mice. We propose that chronic cholesterol feeding induces inflammatory cytokine activation and liver damage, which leads to suppression of CYP7A1 via activation of JNK and ERK signaling pathways.