Bleomycin, a widely used antineoplastic agent, has been associated with severe pulmonary toxicity, primarily fibrosis. Previous work has shown a reduction in bleomycin-induced lung pathology by long-chain omega-3 fatty acids. Treatment by short-chain omega-3 fatty acids, α-linolenic acid, found in dietary flaxseed oil may also reduce lung fibrosis, as previously evidenced in the kidney. To test this hypothesis, 72 rats were divided between diets receiving either 15% (w/w) flaxseed oil or 15% (w/w) corn oil (control). These groups were further divided to receive either bleomycin or vehicle (saline) via an oropharyngeal delivery, rather than the traditional intratracheal instillation. Lungs were harvested at 2, 7, and 21 days after bleomycin or saline treatment. Animals receiving flaxseed oil showed a delay in edema formation (P = 0.025) and a decrease in inflammatory cell infiltrate and vasculitis (P = 0.04 and 0.007, resp.). At days 7 and 21, bleomycin produced a reduction in pulmonary arterial lumen patency (P = 0.01), but not in rats that were treated with flaxseed oil. Bleomycin-treated rats receiving flaxseed oil had reduced pulmonary septal thickness (P = 0.01), signifying decreased fibrosis. Dietary flaxseed oil may prove beneficial against the side effects of this highly effective chemotherapeutic agent and its known toxic effects on the lung.
Objective: Endobronchial ultrasound-guided fine-needle aspiration (EBUS-FNA) cytology and EBUS-miniforceps biopsy (MFB) have emerged as less invasive tools for evaluating mediastinal lymph nodes and pulmonary lesions. The aim of this study is to compare the diagnostic yields of EBUS-FNA cytology to EBUS-MFB. Study Design: A retrospective cohort study was performed by reviewing the database at our institution between December 12, 2010, and August 10, 2012. A total of 476 consecutive cases were identified. Of these, 227 patients had concurrent FNA and MFB taken during the procedure. The results and diagnostic yields of both techniques are calculated. Results: Of the 476 cases, the mean age was 62 ± 14 years with 53% being males. In 453 of the total cases, the less invasive FNA technique alone produced enough diagnostic cytology material negating the need for concurrent MFB. Of these FNA cases, 280 were diagnosed as malignant neoplasms. The diagnostic yield of EBUS-FNA cytology was comparable to EBUS-MFB (95% FNA and 94% MFB). There were discordant diagnoses between cytology and histology in 19 of the 227 (∼8.4%) cases. Conclusions: EBUS-FNA cytology is a more efficacious diagnostic modality compared to EBUS-MFB.
Cyclin D, an upregulated gene of colorectal cancers is used as a diagnostic marker for colon carcinomas. BCL‐6 is a transcriptional regulator important for lymphocyte survival. Microarrays show BCL6 is seven‐fold upregulated in colorectal cancers compared to controls. We tested whether BCL‐6 could be used as a diagnostic marker in moderately differentiated colonic adenocarcinomas by comparing the proportion of BCL‐6 staining to Cyclin D control. With IRB approval, human neoplastic colorectal masses were obtained from surgical pathology specimens on 31 subjects. Antibodies for BCL‐6 and Cyclin D were tested in control tissues and on all sections with antigen baring, secondary and tertiary staining for both markers, n=62. Sections were graded by 2 pathologists unaware of the slides' identity. Data were also evaluated for inflammation, mucin, positive lymph nodes and polyp origin. Analysis by ANOVA included 4 groups, BCL‐6 positive, cyclin D positive, tumors positive for both or negative for both markers. Of the 100% surgically diagnosed cases, BCL‐6 was positive in 16% and cyclin D positive in 29%. BCL‐6 was significantly related to cases “mucinous” cases (p<0.001). Marked inflammation (p<0.01) was noted in tumors positive for both markers. This study attempted the validation of another biomarker for colon cancer. A need exists to predict treatment responsiveness. Sponsor: Sarah Morrison grant, UMKC
Elevated numbers of mast cells were found in a rat model of fat embolism and pulmonary vasculitis and fibrosis where the vasculitis was related to increased secretion of angiotensin II. Our early work suggests that this increase could be consequent to an increase in renin secretion produced by an increased number of mast cells. This study reports mast cell response in another lung damage model also associated with severe vasculitis and fibrosis: Bleomycin administration.Twenty four rats were divided between diets receiving 15% flax seed oil or corn oil controls. The groups were further divided to receive intratracheally 8 units/kg of bleomycin or vehicle. After 7 days, rats were euthanized and lungs harvested for histological studies. Arteries were measured for lumen patency and the ratio of media/adventitia diameter. Mast cells were counted in Evans Blue stained sections.Bleomycin induced marked reduction of vascular lumen patency and media/adventitia ratio (p< 0.01), similar to that obtained with fat embolism. Mast cell number, however, was not increased. Flax seed oil treatment markedly reduced vasculitis and fibrosis without influencing mast cell number and location (mostly around peribronchial arteries and subpleural septa). Contrarily to what was observed in the fat embolism model mast cells did not correlate with vasculitis and fibrosis, suggesting a different pathogenic mechanism.Wheaton College
INTRODUCTION: Actinomyces is a commensal in aero-digestive tracts which rarely causes infection. The commonest site is cervicofacial region. Risk factors are low immunity and pre-existing tissue damage. Esophageal involvement is rare. We report a case of esophageal actinomycosis in an immunocompetent patient. CASE DESCRIPTION/METHODS: A 71-year-old male presented with recurrent dysphagia. The patient had multiple prior EGDs for management of refractory peptic stricture due to gastrin secreting pancreatic neuroendocrine tumor. He undewent multiple prior procedures with placement of fully-covered self-expanding metal stents (SEMS) for therapy of refractory stricture, as surgical esophagectomy was not possible due to co-morbidities and patient preference. On previous EGD, one of the stents could not be removed due to tissue ingrowth at the distal end, and another SEMS was placed overlapping the imbedded stent and extending to the gastric cardia. The patient was lost to follow up for 7 months until presenting with recurrence of dysphagia. EGD now showed proximal migration of the distal stent with severe stenosis, inflammation, and nodularity distal to the esophageal stents. The distal stent was imbedded in the abnormal mucosa and could not be removed. Following balloon dilation another SEMS was placed in the distal esophagus. Pathology revealed ulcerated acute esophagitis with actinomycetes colonies. The patient was placed on a long course of IV penicillin-G. At subsequent EGD a month later, the tissue ingrowth improved allowing removal of the esophageal stents. Repeat biopsies did not reveal actinomyces. DISCUSSION: Actinomyces, a gram positive anaerobic rod, is unable to penetrate healthy tissue. It requires mucosal compromise to invade tissue, leading to abscess and sinus formation across tissue planes. Our patient had multiple risk factors - mucosal damage, endoscopic dilations and stenting. Esophageal stent in situ for longer than 3 months increases the risk of embedment. Discovery of esophageal ulceration or tissue ingrowth in this setting should raise suspicion for possible actinomycosis (among other diagnoses) and biopsies should be obtained. Gram stain and histology would reveal necrosis with yellow sulfur granules and gram-positive filamentous pathogen. Early diagnosis is necessary to initiate treatment in a timely manner to prevent the potentially debilitating sequelae of chronic infection. Treatment includes penicillin G or amoxicillin for 3-12 months.
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