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- Ageing Fxr Deficient Mice Develop Increased Energy Expenditure, Improved Glucose Control and Liver Damage Resembling NASH. [JOURNAL ARTICLE]
- PLoS One 2013; 8(5):e64721.
Nuclear receptor subfamily 1, group H, member 4 (Nr1h4, FXR) is a bile acid activated nuclear receptor mainly expressed in the liver, intestine, kidney and adrenal glands. Upon activation, the primary function is to suppress cholesterol 7 alpha-hydroxylase (Cyp7a1), the rate-limiting enzyme in the classic or neutral bile acid synthesis pathway. In the present study, a novel Fxr deficient mouse line was created and studied with respect to metabolism and liver function in ageing mice fed chow diet. The Fxr deficient mice were similar to wild type mice in terms of body weight, body composition, energy intake and expenditure as well as behaviours at a young age. However, from 15 weeks of age and onwards, the Fxr deficient mice had almost no body weight increase up to 39 weeks of age mainly because of lower body fat mass. The lower body weight gain was associated with increased energy expenditure that was not compensated by increased food intake. Fasting levels of glucose and insulin were lower and glucose tolerance was improved in old and lean Fxr deficient mice. However, the Fxr deficient mice displayed significantly increased liver weight, steatosis, hepatocyte ballooning degeneration and lobular inflammation together with elevated plasma levels of ALT, bilirubin and bile acids, findings compatible with non-alcoholic steatohepatitis (NASH) and cholestasis. In conclusion, ageing Fxr deficient mice display late onset leanness associated with elevated energy expenditure and improved glucose control but develop severe NASH-like liver pathology.
- Uniquely Lethal: Pulmonary Sarcomatoid Carcinoma, a Case Report. [JOURNAL ARTICLE]
- Chest 2012 Oct 1; 142(4_MeetingAbstracts):611A.
SESSION TYPE: Cancer Global Case Report PostersPRESENTED ON: Tuesday, October 23, 2012 at 01:30 PM - 02:30 PM
INTRODUCTION:Malignant neoplasms are the third leading cause of mortality in the Philippines. Lung cancer is the leading cause of cancer-related mortality throughout the world. However, there are variants to this disease that are rarely seen. Presented is a case of a 75 year old male who was diagnosed with pulmonary sarcomatoid carcinoma at the Philippine Heart Center.
CASE PRESENTATION:A 75 year old male, heavy smoker, presented 6 months prior with non-productive cough, chest x-ray showed a nodule on the left upper lobe. Persistence of cough, associated with anorexia and weight loss prompted consult. Upon admission, chest x-ray showed a mass on the left upper lobe. Chest CT scan with contrast was done which revealed a left upper lobe mass with surrounding lymphangitic spread and nodules on the left hilar and right lower lobe. Consideration was malignancy. CT guided fine needle aspiration biopsy of the left upper lobe mass was done. Metastatic work-ups were requested. Cranial CT scan showed enhancing nodules in the subcortical and cortical region of the left frontal lobe. Whole abdominal CT scan revealed enhancing nodules in the liver, bilateral adrenal glands, bilateral subcutaneous abdominal wall, and left gluteal region, also indicative of metastasis. Histopathologic findings were cytomorphologic features and immunohistochemical profile consistent with Sarcomatoid Carcinoma, of Lung Primary. Patient was diagnosed as stage IV disease and palliative treatment was recommended. Patient underwent whole brain radiation therapy and was started on chemotherapy with Gemcitabine then discharged.
DISCUSSION:Pulmonary sarcomatoid carcinomas are poorly differentiated non-small cell carcinomas that contain at least 10% of sarcoma or sarcoma-like elements. These tumors are believed to arise from epithelial to mesenchymal transition of cells and and represent only 0.1% to 0.4% of all cases of non-small cell lung cancer. There is no record of a previous case of sarcomatoid carcinoma in our center. Average age of diagnosis for these patients is about 60 years of age, with a male preponderance of 4:1. The disease is noted to be more prevalent in patients with history of smoking. It is said to present more commonly as a mass in the upper lobes, as was noted in our patient. Median size is 4.5 cms, but diameters of up to 19 cms have been noted. They can invade adjacent structures by forming large necrotic and hemorrhagic masses and can metastasize to conventional sites such as the brain bone adrenals and liver, but may also include unusual locations such as the skin, as noted in our patient, as well as the esophagus, stomach, pancreas and heart. Treatment of localized disease relies on surgical resection, with adjuvant chemotherapy and radiation for patients with bulky tumors, or nodal involvement. Those with stage III or stage IV sarcomatoid carcinomas are managed non-operatively and given palliative treatment. However, cases show consistent poor response to systemic chemotherapy. These patients are said to have poorer prognosis compared with conventional NSCLCs, with a 5-year survival of only 24.5% versus 46.5% for other NSCLC. Future goals may be to target the epithelial mesenchymal transition pathways of these sarcomatoid carcinomas to eliminate surviving cancer cells in order to prevent recurrence and improve survival.
CONCLUSIONS:Pulmonary sarcomatoid carcinoma is a rare variant of non-small cell lung carcinoma, seen to have a sarcomatoid component. It commonly presents as advanced disease, and combined with aggressive metastases, as well as poor response to conventional chemotherapeutic agents, makes it a uniquely lethal disease and thus leads to poorer outcomes in our patients. Our only hope is to better understand the epithelial-mesenchymal transition pathways of these cancer cells and hopefully develop targeted therapies, that will improve the survival for these patients.1) L. Martin, et al. Sarcomatoid Carcinoma of the Lung: A Predictor of Poor Prognosis. Ann Thorac Surgery. 2007;84:973-980.2) Pelosi G, et al. Pleomorphic carcinomas of the lung show a selective distribution of gene products involved in cell differentiation, cell cycle control, tumor growth, and tumor cell motility: a clinicopathologic and immunohistochemical study of 31 cases. Am J Surg Pathol 2003;27:1203-15.3) Vibha T. Thomas, Stacy Hinson and Kartik Konduri. Epithelial - mesenchymal transition in pulmonary carcinosarcoma. Therapeutic Advances in Medical Oncology. 2012 4: 31.DISCLOSURE: The following authors have nothing to disclose: Jessamine Dacanay, Fernando AyuyaoNo Product/Research Disclosure InformationPhilippine Heart Center, Quezon, Philippines.
- Metastatic Lung Adenocarcinoma Presenting as Thumb Pain. [JOURNAL ARTICLE]
- Chest 2012 Oct 1; 142(4_MeetingAbstracts):567A.
SESSION TYPE: Cancer Case Report Posters IIPRESENTED ON: Tuesday, October 23, 2012 at 01:30 PM - 02:30 PM
INTRODUCTION:The incidence of solid organ cancer with metastasis to bones of the digits (acrometastasis) is exceedingly rare, occurring in only 0.1% of cases with osseous involvement. We describe a 52 year-old female who was found to have metastatic lung adenocarcinoma with acrometastasis during evaluation of left thumb pain.
CASE PRESENTATION:A 52 year-old female with history of migraines and 20 pack-year smoking was evaluated by orthopedics for left thumb swelling, pain, and absent flexion, and determined to have a trigger finger. Hand radiographs revealed no osseous abnormalities. She received a flexor sheath injection of corticosteroids, with subsequent improvement in pain and range of motion. However, 6 weeks later she developed new thumb erythema, relapse of symptoms, and a palpable mass. Surgical exploration revealed complete destruction of the proximal phalanx and no viable bone remaining. Histologic evaluation of the mass revealed a poorly differentiated adenocarcinoma, suggestive of a primary lung tumor by immunohistochemical staining. Survey imaging with CT chest revealed a large left upper lobe mass, extensive adenopathy of the mediastinum and left hilum, and suggestion of lymphangitic carcinomatosis. Additionally, PET imaging illustrated widespread disease, with involvement of the brain, adrenal glands, pelvis, and spine.
DISCUSSION:Bony metastases are common and frequently occur from a wide array of primary tumors, including lung, prostate, kidney, breast, and gastrointestinal. However, bones of the hand rarely harbor metastatic disease, accounting for only 0.1% of metastatic osseous involvement. Acrometastasis was first identified in 1906 in a female with breast cancer and metastases to the metacarpals. The etiology of acrometastasis is almost exclusively a lung primary tumor, accounting for approximately 44% of all reported cases. The mechanism of spread to the digits is unknown, but hypotheses include increased blood flow and chemotaxis of prostaglandins during trauma. The high predilection towards a primary lung tumor among acrometastases is thought to be secondary to direct systemic arterial supply, whereas tumor emboli of other primary malignancies must first pass through capillary beds of the liver or the lung.
CONCLUSIONS:Acrometastasis is a rare occurrence, and typically suggests concomitant widespread malignancy with poor prognosis. Our patient presented with thumb pain, and subsequent evaluation revealed metastatic lung adenocarcinoma. She died 6 weeks later. This emphasizes the importance of identifying non-benign causes of finger symptoms in a timely manner.1) Flynn CJ, et al. Two Cases of Acrometastasis to the Hands and Review of the Literature. Current Oncology 2008;15(5):51-58.DISCLOSURE: The following authors have nothing to disclose: David Ferraro, Pedro LuceroNo Product/Research Disclosure InformationSan Antonio Military Medical Center, Fort Sam Houston, TX.
- Intussusception: A Rare Presentation of Non-small Cell Lung Cancer. [JOURNAL ARTICLE]
- Chest 2012 Oct 1; 142(4_MeetingAbstracts):566A.
SESSION TYPE: Cancer Case Report Posters IIPRESENTED ON: Tuesday, October 23, 2012 at 01:30 PM - 02:30 PM
INTRODUCTION:Non-small cell lung cancers (NSCLC) constitute between 85 to 90 % of all lung cancers; the rest 10 to 15 % are small cell lung cancers. Extrathoracic metastasis to brain, bones, liver, bone marrow, lymph nodes & adrenal glands is well known in case of non-small cell lung cancer (1).
CASE PRESENTATION:A 56-year-old African American gentleman with no past medical history presented with complaint of constipation associated with progressively worsening left periumbilical pain and one episode of vomiting undigested food material. He reported decreased appetite and 15 pounds weight loss in last few months. He had 40 pack year history of smoking and occasional alcohol intake. On physical examination he was afebrile with stable vital signs, had mild tenderness in the left periumbilical location with no guarding or rigidity. CT scan of abdomen revealed a long segment of intussusception involving proximal jejunal loop in left hemiabdomen leading to proximal small bowel obstruction secondary to a submucosal mass. CT scan of the chest revealed severe emphysema with bullous changes and a 1.4 cm spiculated mass in left apex along with bilateral necrotic appearing hilar lymphadenopathy (Image 1). Patient underwent exploratory laparotomy during which the diseased part of small intestine (fungating, friable mass measuring 6.0 x 4.2 x 3.8 cms) and part of the attached mesentery (with multiple lymph nodes enlargement) were resected. Histopathology revealed poorly differentiated neoplasm and immunohistochemical markers (positive for CD34, cytokeratin & vimentin, negative for CD117, CK20) were consistent with a metastatic non-small cell carcinoma (Image 2). An MRI of the brain also revealed vasogenic edema with five enhancing lesions compatible with metastatic disease. Patient was started on palliative chemotherapy and radiotherapy (whole brain irradiation) and discharged from the hospital with outpatient follow ups.
DISCUSSION:Intussusception is an "internal prolapse" of the bowel that leads to obstruction and compromise of mesenteric blood flow, with resultant inflammation and the potential for ischemia of the bowel wall (2). Surgical resection is recommended because of the high percentage of associated malignancy (3).
CONCLUSIONS:Adult intussusception is rare accounting for 1 to 5% of bowel obstruction and commonly involves a distinct pathologic lead point, which is malignant in over half of the cases (3). Hence, adult patient with intussusception should be evaluated for underlying malignancy.1) Kuo CW et al. Non-small cell lung cancer in very young and very old patients. Chest 2000; 117:354.2) Marinis A et al. Intussusception of the bowel in adults: a review. World J Gastroenterol 2009; 15:407.3) Nagorney DM et al. Surgical management of intussusception in the adult. Ann Surg 1981; 193:230.DISCLOSURE: The following authors have nothing to disclose: Vipin Mittal, Anish Shah, Arya Karki, Muhammad Ali, Amer Akmal, Walid BaddouraNo Product/Research Disclosure InformationSt Joseph's Regional Medical Center, Paterson, NJ.
- Metastatic Papillary Thyroid Carcinoma With Tracheal Obstruction. [JOURNAL ARTICLE]
- Chest 2012 Oct 1; 142(4_MeetingAbstracts):899A.
SESSION TYPE: Bronchology Student/Resident Case Report PostersPRESENTED ON: Tuesday, October 23, 2012 at 01:30 PM - 02:30 PM
PURPOSE:Despite its location, well-differentiated thyroid carcinoma rarely invades local structures. Prognosis worsens with tracheal invasion. Nearly one-half of deaths from papillary carcinoma stem from tracheal obstruction. Management of airway obstruction can be life saving.
METHODS:A 71 year-old male experienced dyspnea and hemoptysis for one month. CT revealed a soft tissue mass arising from the thyroid and invading the tracheal lumen. In addition, there was a soft tissue mass on the right anterior first rib with sclerotic margins and areas of cortical breakthrough and cervical lymphadenopathy. Flexible bronchoscopy demonstrated a near-obstructing tracheal mass 2 cm in length located 3 cm below the cricoid. Rigid bronchoscopy allowed endoluminal resection followed by argon plasma coagulation (APC).
RESULTS:The dyspnea and stridor improved significantly. He was discharged. The pathology was papillary adenocarcinoma. Thyroglobulin was 708 ng/ml with absent thyroglobulin antibody. Thyroid Stimulating Hormone and Free T4 were within reference laboratory values. PET-CT revealed FDG-avidity in both lobes of the thyroid with tracheal and esophageal invasion, and FDG-avidity in cervical lymph nodes, the right anterior first rib, and left adrenal gland, indicating T4aN1b staging. He underwent external beam radiation therapy then total thyroidectomy and bilateral neck dissections along with tracheostomy. The final pathology was papillary thyroid carcinoma with tracheal invasion, involved margins, and lymphovascular invasion. 14 out of 61 lymph nodes were positive. Follow-up thyroglobulin level was undetectable. Radioactive iodine treatment followed.
CONCLUSIONS:Nearly one half of mortality related to papillary thyroid carcinoma is due to airway obstruction. Thus, even with tracheal invasion, intervention is indicated. Depth of tracheal invasion, longitudinal extent of disease, and involvement of local structures impact therapy. Surgical options range from limited "shave" excision of the trachea to en bloc resection and tracheal reconstruction. Patients with locally invasive papillary carcinoma require treatment with radioiodine therapy and TSH suppression following total or near-total thyroidectomy.
CLINICAL IMPLICATIONS:With symptomatic tracheal obstruction from papillary thyroid carcinoma, bronchoscopic intervention can achieve a stable airway, thus facilitating subsequent safe surgical resection.DISCLOSURE: The following authors have nothing to disclose: Steven Khov, Michael Reed, Jennifer TothNo Product/Research Disclosure InformationPenn State Milton S. Hershey Medical Center, Hershey, PA.
- Diagnostic Yield of EBUS TBNA for the Evaluation of Centrally Located Peribronchial Pulmonary Lesions. [JOURNAL ARTICLE]
- Chest 2012 Oct 1; 142(4_MeetingAbstracts):871A.
SESSION TYPE: Endobronchial UltrasoundPRESENTED ON: Monday, October 22, 2012 at 04:00 PM - 05:30 PM
PURPOSE:To evaluate the diagnostic yield of endobronchial ultrasound with real-time guided transbronchial needle aspiration (EBUS-TBNA) as a single step method for centrally located lung masses when used solely or in conjunction with either endobronchial forceps biopsy (EBBx) or 2D -fluoroscopic guided transbronchial forceps biopsy (TBLBx).
METHODS:This was a single center retrospective analysis of consecutive patients who had been detected with centrally located peribronchial lesions (medial margin of the mass within inner third of hemithorax on CT imaging). Patients who underwent EBUS-TBNA from 2008 to 2011 were included. EBUS-TBNA was either used as a sole method or simultaneously with either endobronchial forceps biopsy or 2D Fluoroscopy-guided TBLBx for lung masses suspected of malignancy
RESULTS:A total of 32 cases were studied. Mean age was 69.1 years. Half of them were males. EBUS-TBNA detected malignancy in 30 patients (93.8 %). CT-guided biopsy confirmed diagnosis in the two remaining cases. Out of 32 patients, 21 patients had EBUS-TBNA performed simultaneously with either 2D-fluoroscopic guided TBLBx(n=13) or EBBx (n=8). In 13 patients who had 2D-fluoroscopic guided TBLBx ,it was positive in 8/13 cases (61.3%) while EBUS-TBNA was positive in 12/13 cases (95%). In 8 patients with endobronchial lesions, EBBx was positive in 6/8 cases (75%) while EBUS-TBNA was positive in all cases 8/8 (100%). Total cases that would have been missed if EBUS-TBNA was not used concomitantly with TBLBx or EBBx were 6/21 (28%). Additionally, there were 10 patients where EBUS-TBNA was used as a sole method for sampling, due to either lack of an endobronchial target or inability to perform TBLBx due to central nature of the lesion and all of them were positive for malignancy. Two patients had moderate amount of bleeding requiring localized diluted epinephrine.
CONCLUSIONS:EBUS-TBNA showed excellent diagnostic yield in centrally located lung masses.
CLINICAL IMPLICATIONS:In a centrally located lung mass deemed accessible, EBUS-TBNA,should be considered as an important adjunct to other techniques to enhance the diagnostic yield.DISCLOSURE: The following authors have nothing to disclose: Hammad Bhatti, Abubakr Bajwa, James Cury, Adil Shujaat, Lisa Jones, Faisal UsmanNo Product/Research Disclosure InformationUniversity of Florida College of Medicine, Jacksonville, FL.
- [Oncocytic Tumors of The Adrenal Gland.] [JOURNAL ARTICLE]
- Acta Med Port 2013 Jan-Feb; 26(1):61-66.
The oncocytic tumors of the adrenal gland are rare. To date there's only 147 cases published. The authors present a case of a 34 year-old man admitted to the hospital with lumbar pain and fever. At medical examination a mass was found in the left upper quadrant of the abdomen. The hormonal measurements of the adrenal gland were normal and the abdominal angio CT showed a left retroperitoneal lesion measuring 145 x 157 x 128 mm with extensive necrotic and hemorrhagic areas. The patient underwent a complete surgical resection of the lesion. The mass weighted 1495g and the histological exam revealed an oncocytic tumor of the adrenal gland with uncertain potential. Most of the oncocytic tumors are non functioning and must be considered in the differential diagnosis of adrenocortical tumors. The biologic behavior and the prognosis of these tumors are variable and still need a better definition. Due to the rarity of these tumors the authors made a revision on the published bibliography.
- Bone health and aldosterone excess. [JOURNAL ARTICLE]
- Osteoporos Int 2013 May 22.
A picture of hyperparathyroidism secondary to increased urinary calcium excretion was found in 116 patients with primary aldosteronism (PA), compared with 110 essential hypertensives. After medical or surgical treatment in 40 PA patients, parathyroid hormone (PTH) levels were significantly reduced and bone mineral density (BMD) significantly increased at the lumbar spine, femoral neck, and total hip.
INTRODUCTION:Recent studies have shown that aldosterone induces urinary calcium excretion leading to a reduction of calcemia with consequent secondary hyperparathyroidism and BMD loss. In patients with PA, this picture of hyperparathyroidism is significantly improved by treatment with adrenal surgery or with mineralocorticoid receptor antagonists. On these premises, the aim of the present study was to evaluate calcium and phosphate metabolism parameters in PA patients, compared with patients with essential hypertension (EH) and the effect of treatment of aldosterone excess on bone health in PA patients.
METHODS:We studied 226 patients: 116 with PA (46 with an aldosterone-producing adenoma and 70 with bilateral adrenal hyperplasia) and 110 patients with EH. In 40 patients with PA, we evaluated biochemical parameters and bone mass, using the dual-energy X-ray absorptiometry, at baseline and after a mean follow-up of 24 months from treatment.
RESULTS:In PA patients, compared with EH, PTH levels and urinary calcium excretion significantly increased while serum calcium significantly decreased with comparable vitamin D levels. At follow-up in PA patients, PTH levels were significantly reduced compared with basal evaluation, despite similar vitamin D amounts. At follow-up, we observed a significant improvement of the Z-score at the lumbar spine, femoral neck, and at total hip sites.
CONCLUSIONS:Our results support previous data showing secondary hyperparathyroidism in PA patients, which is reversible after treatment. Moreover, this targeted treatment appears to be able to determine a significant improvement of BMD both at the spine and hip sites.
- Proteomic analysis of NGF-induced transdifferentiation of adrenal medullary cells. [JOURNAL ARTICLE]
- Int J Mol Med 2013 May 21.
Nerve growth factor (NGF) is a polypeptide growth factor with specific trophic function in nerve cells and was initially investigated for its role as a key player in the regulation of peripheral innervations. The aim of this study was to examine the NGF-induced transdifferentiation of adrenal medullary cells, and to screen the major candidate differentially expressed proteins involved in the transdifferentiation. NGF was used to treat primary cultures of neonatal calf adrenal medullary cells and the effects of transdifferentiation were determined in association with cellular morphology, ultrastructure and changes in endocrine function. Differentially expressed proteins were screened and identified through two-dimensional gel electrophoresis and mass spectrometry. The protein spots showing differential expression were verified by western blot analysis. We observed neurite outgrowth in the adrenal medullary cells treated with NGF under a phase contrast microscope. Ultrastructure analysis revealed that there were rich drumstick-like and villiform processes on the cell membranes and vesicles were formed near the cell membranes. The cytoplasm was rich in mitochondria and the secretion of epinephrine was decreased. Two-dimensional gel electrophoresis revealed that among the differentially expressed proteins, 48 protein spots showed an upregulated expression and 37 protein spots showed a downregulated expression, and no 'all-or-none' spots with significant differences in expression were found. Fourteen protein spots with an upregulated expression and 6 with a downregulated expression were randomly selected for identification by mass spectrometry. Western blot analysis revealed that ras homologus oncogene (Rho) GDP dissociation inhibitor α (RhoGDIα) protein expression was significantly downregulated and peripherin protein expression was significantly upregulated. In brief, our data demonstrate that NGF can induce the differentiation of adrenal medullary cells into neurons, and that RhoGDIα and peripherin may play important roles in this process.
- Adrenal cortical adenoma arising from an adrenohepatic union. [JOURNAL ARTICLE]
- Jpn J Radiol 2013 May 18.
Although the observation of an adrenohepatic union is not a rare occurrence during autopsies, cases associated with this clinical entity are rarely described. We report a case with an adrenal cortical adenoma arising from adrenohepatic union tissue in a patient with a past history of a liver mass.