BRAFV600E mutation test on fine-needle aspiration specimens of thyroid nodules: Clinical correlations for 4600 patients.

BACKGROUND: The BRAFV600E mutation is valuable for the diagnosis, prognosis, and therapy of papillary thyroid cancer (PTC). However, studies related to this mutation have involved only a small number of patients. Therefore, we performed a large-scale analysis from a single institute to evaluate the accuracy of combined fine-needle aspiration (FNA) and BRAFV600E mutation tests for PTC diagnosis. METHODS: A total of 4600 patients with thyroid nodules who underwent both FNA cytology and BRAFV600E mutation analysis on FNA specimens were enrolled. The association between the BRAFV600E mutation and clinicopathological features was analyzed. A separate analysis was performed for the 311 patients who underwent repeated FNA for comparison of cytological evaluation and BRAFV600E mutation results. The diagnostic efficacy of the BRAFV600E mutation test and cytologic diagnoses was evaluated for 516 patients who underwent preoperative FNA tests in comparison with conclusive postoperative histopathologic results. RESULTS: The cytology results of all 4600 FNA samples were categorized according to The Bethesda System for Reporting Thyroid Cytology (TBSRTC) stages I-VI, which accounted for 11.76%, 60.02%, 6.46%, 3.61%, 6.71%, and 11.43% of the samples, respectively. The BRAFV600E mutation was detected in 762 (16.57%) FNA samples, with rates of 1.48%, 0.87%, 20.20%, 3.01%, 66.02%, and 87.81% for TBSRTC I-VI lesions, respectively. Among the 311 repeat FNA cases, 81.0% of the BRAFV600E -positive and 4.3% of the BRAFV600E -negative specimens with an initial indication of cytological non-malignancy were ultimately diagnosed as malignant by repeat FNA (p < 0.001). Among the 516 patients who underwent thyroidectomy, the sensitivity and specificity of the BRAFV600E mutation test alone for PTC diagnosis were 76.71% and 100.0%, respectively, which increased to 96.62% and 88.03%, respectively, when combining the BRAFV600E mutation test with cytology. BRAFV600E mutation was significantly associated with lymph node metastasis (p < 0.001), but not with age, gender, or tumor size. CONCLUSIONS: The BRAFV600E mutation test in FNA samples has potential to reduce false negatives in PTC diagnosis, and therefore plays an important role in the diagnosis of thyroid nodules, especially those with an indeterminate or nondiagnostic cytology, which should be considered for repeat FNA.

Distal-type bronchiolar adenoma of the lung harboring an EGFR exon 21 p.L858R mutation: A case report.

Here, we present a case of a distal-type bronchiolar adenoma (BA) of the lung. BAs are benign lung tumors characterized by nodular proliferation of bilayered bronchiolar-type epithelium with a continuous layer of basal cells. This patient underwent S3 segmentectomy following detection by computed tomography (CT) scan of a gradually enlarging ground-glass nodule (GGO) over a five month period. Nodule morphology and immunophenotype were consistent with those of distal-type BA of the lung. An epidermal growth factor receptor (EGFR) exon 21 p.L858R missense mutation was identified which, to the best of our knowledge, is the first case to be reported of a common gene mutation associated with non-small cell lung cancer (NSCLC) being found in a BA lesion. Following surgery, the patient remains relapse-free. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Pathological assessment of a lung nodule confirmed a papillary tumor with a double-layered cell structure, less than typical cytoplasm, and a mixture of ciliated columnar and globular cells, consistent with a distal-type bronchiolar adenoma. WHAT THIS STUDY ADDS: This is the first report of an EGFR exon 21 p.L858R mutation in a bronchiolar adenoma.

Automated classification of cancer from fine needle aspiration cytological image use neural networks: A meta-analysis.

BACKGROUND: The role of retrospective analysis has been evolved greatly in cancer research. We undertook this meta-analysis to evaluate the diagnostic value of Neural networks (NNs) in Fine needle aspiration cytological (FNAC) image of cancer. METHODS: We systematically retrieved 396 literatures on cytodiagnosis of NNs from Cochrane, PubMed, and EMBASE. After screening, only six studies were included in meta-analysis finally. Data was comprehensively analyzed by RevMan and meta-Disc software. RESULTS: A total of 1165 cases were extracted from six articles. Among them, 593 cases were in the abnormal/positive group and 572 cases in the normal/negative group. The pooled estimates for the NNs cytology were Area under ROC curve (AUC): 0.99, Sensitivity: 0.85 (95% CI:0.82-0.88), Specificity: 0.96 (95% CI:0.94-0.97), Positive Likelihood Ratio (LR):18.43 (95% CI:6.83-49.74), Negative Likelihood Ratio (LR): 0.06 (95% CI:0.001-0.58), and Diagnostic odds ratio (DOR): 343.21 (34.41-3422.77). CONCLUSIONS: This meta-analysis confirms that NNs Automated Classification algorithm can facilitate to some extent the FNCA diagnosis of cancer.

IgG4-related disease with tracheobronchial miliary nodules and asthma: a case report and review of the literature.

BACKGROUND: IgG4-related disease (IgG4-RD) is a systemic autoimmune disease that can affect multiple organs of the body. Pulmonary manifestations of IgG4-RD include pulmonary solid nodules, thickening of bronchovascular bundles, interstitial involvement, and ground glass opacities. Here we present a rare case of IgG4-RD with tracheobronchial nodules and review the relevant literature. CASE PRESENTATION: A 52-year-old man was admitted to our hospital with a history of intermittent cough for 27 months and recurrent wheezing for 17 months. He had been diagnosed with asthma prior to admission and was responsive to oral prednisone (30 mg/day, with gradual tapering). Bronchoscopy performed 2 years prior to admission showed tracheal and bronchial mucosal hyperemia, edema, and miliary nodules. Pathological tests showed chronic inflammation with focal lymphocytic infiltration in the bronchial mucosa. The patient had recurrent cough and wheezing after prednisone was stopped or the dose reduced. At the time of admission to our hospital, his serum immunoglobulin G4 (IgG4) level had increased to 7.35 g/L. Following bronchoscopy, the IgG4 expression in the bronchial mucosa was compared with that observed during the last two bronchoscopies. Bronchoscopy performed 7 months prior to admission revealed IgG4+ plasma cell infiltration in the bronchial tissue, with > 10 IgG4+ plasma cells per high power field and an IgG4+/IgG+ cell ratio of > 40%. The current bronchoscopy revealed a decrease in IgG4 expression in the bronchial tissue, probably because of the intermittent prednisone treatment. The case fulfilled the comprehensive clinical diagnostic criteria for IgG4-RD. He received prednisone and azathioprine, and he has never developed recurrence. CONCLUSIONS: Our case exhibited three important clinical indication: First, tracheobronchial miliary nodules could be the presentation of IgG4-related disease. Second, IgG4-related disease with pulmonary involvement has close connection with asthma. Last, IgG4-related disease can be very sensitive to prednisone, the infiltration of IgG4 positive plasma cells decreased after prednisone treatment and symptoms significantly improved in our case. In conclusion, we reported the first case of IgG4-RD presenting with miliary nodules on the tracheal and bronchial tube walls combined with asthma. The findings will further our understanding of the characteristics of IgG4-RD.

Pleuroparenchymal fibroelastosis secondary to autologous hematopoietic stem cell transplantation: A case report.

Pleuroparenchymal fibroelastosis (PPFE) is a rare interstitial lung disease. Although an increased number of PPFE cases have been reported recently, the characteristics of this condition have not been well described. The present study reports on the case of a 34-year-old male patient who presented with unilateral lung abnormalities. The patient was admitted due to a 9-year history of progressive cough and exertional dyspnea, as well as a history of Hodgkin's lymphoma treated by autologous hematopoietic stem cell transplantation (HSCT). The patient had been initially diagnosed with tuberculosis and received regular anti-tuberculosis therapy for 18 months; however, the symptoms progressed. Serial chest computed tomography scans indicated a gradually worsening diffuse pleural thickening, dense subpleural opacification and volume loss, associated with evidence of fibrosis in the right lung. On physical examination the patient was cachectic, with a body mass index of 18.5 kg/m2, and he had a flattened thoracic cage. Arterial blood gas analysis revealed hypoxia. Pulmonary function tests revealed restrictive ventilation dysfunction and decreased diffusion capacity. The microbiological and cytological examinations were negative. Lung biopsy revealed a thickened pleura consisting of large amounts of collagen and elastic fibers, coexisting with subpleural intra-alveolar fibrosis with alveolar septal elastosis, without inflammatory infiltrates. The patient was diagnosed with PPFE secondary to HSCT and eventually succumbed to respiratory failure and infection while waiting for a lung transplant. Physicians should be aware of the typical and atypical characteristics of this rare disease, as its clinical and radiological characteristics may lead to misdiagnosis, particularly as chronic infections. The prognosis remains poor without effective long-term treatment.

Lung cancer in patients with combined pulmonary fibrosis and emphysema revisited with the 2015 World Health Organization classification of lung tumors.

OBJECTIVE: Combined pulmonary fibrosis and emphysema (CPFE) is a newly defined entity that comprises upper lobe emphysema and lower lobe fibrosis. Patients with CPFE are at high risk for lung cancer and have poor prognoses. To investigate the clinical and pathological characteristics of lung cancer with CPFE, lung cancers with CPFE and non-CPFE interstitial lung disease (ILD) were reevaluated by 2015 WHO classification and compared. METHODS: A total of 60 patients with histologically proven lung cancer were selected from the database of two institutional medical centers. The subjects included 35 patients with combined lung cancer and CPFE, and 25 patients with lung cancer and non-CPFE ILD. The clinical and pathological characteristics were evaluated and compared between the two groups. RESULTS: CPFE group had more current smokers but relatively normal pulmonary function compared with non-CPFE group. The majority of the cancers in CPFE were located in the lower lobes (24 of 35 cases), where the pulmonary fibrosis visualized as reticular opacities was predominant. Keranitizing subtype of squamous cell carcinoma was prevalent in lung cancers with CPFE. Poor prognoses were found both for CPFE and non-CPFE group because of advanced stage. CONCLUSIONS: Lung cancers with CPFE show some unique clinical characteristics, and the distinct histological subtype may have therapeutic implication.

Analytic and Clinical Validation of an Ultrasensitive, Quantitative Polymerase Chain Reaction Assay for EGFR Mutation Analysis With Circulating Tumor DNA.

CONTEXT: - The mutation analysis of epidermal growth factor receptor (EGFR) has become a common test to guide therapeutic decision making for lung cancer. Molecular testing with circulating tumor DNA in plasma allows diagnosis of mutations when tumor tissue is not available as well as monitoring treatment response with repeat biopsies. OBJECTIVES: - To develop a timely and cost-effective assay that can accurately detect EGFR mutations in circulating tumor DNA and to evaluate the analytic and clinical performance of the assay. DESIGN: - Analytic assessment was conducted with a set of reference materials carrying classic EGFR mutations. A recently developed Poisson distribution-based approach was employed to understand the assay sensitivity. Clinical evaluation was performed with 224 pairs of plasma and matched tissues from patients with stage I to IV disease. EGFR mutation rates of 390 consecutive plasma samples processed in the central service laboratory were compared with previously reported prevalence in an Asian population. RESULTS: - Our results suggested that limit of detection for the EGFR quantitative polymerase chain reaction assay was 10 mutation copies, and the lowest detectable copy numbers could be extended to a single-digit level. The clinical sensitivity was 53.3% for all stages combined and 81.4% for late stages, with a high specificity of 100%. Clinical observations showed an overall positive finding rate of 32.5% and 41.4% for stage IV disease, which is consistent with previously reported EGFR mutation prevalence in an Asian population. CONCLUSIONS: - Our results supported the clinical utility of the ultrasensitive, quantitative polymerase chain reaction assay for EGFR mutation analysis with circulating tumor DNA.

Association between histopathological subtype, 18F-fluorodeoxyglucose uptake and epidermal growth factor receptor mutations in lung adenocarcinoma.

The aim of the present study was to investigate the association between histopathological subtypes, epidermal growth factor receptor (EGFR) mutations and 18F-fluorodeoxyglucose (FDG) uptake in patients with lung adenocarcinoma (ADC). The cases of 97 patients with lung ADC who underwent 18F-FDG positron emission tomography-computed tomography prior to surgical resection were retrospectively reviewed. The patients were stratified according to the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification, and graded using a histopathological scoring system. EGFR mutations were identified. Clinicopathological characteristics associated with EGFR mutation status were evaluated using univariate and multivariate analyses. EGFR mutation was identified in 45.4% of the patients and was associated with gender, smoking history, maximum standardized uptake value (SUVmax) and histopathological score. ADC patients with a low SUVmax were more likely to exhibit EGFR mutations compared with patients with a high SUVmax (P=0.018). Patients with a lower histopathological score possessed a significantly lower SUVmax compared with patients with a higher score (P<0.001). Furthermore, the histopathological score and smoking history of the patients were identified to be independent predictors for EGFR mutations, according to multivariate logistic regression analysis. In conclusion, SUVmax and EGFR mutations were associated with lung ADC patients stratified according to the IASLC/ATS/ERS classification. Overall, SUVmax has the potential to be a useful marker in stratifying pre-operative patients with lung ADC and identifying EGFR mutations.

[Diagnosis value of TTF-1, Napsin A and Ki-67 index in primary salivary gland-type lung carcinomas].

OBJECTIVE: To study the clinicopathologic characteristics of primary salivary gland-type lung carcinomas, and the immunophenotypic value of TTF-1, Napsin A and Ki-67 in their differential diagnosis. METHODS: Totally 48 special type lung cancer surgical removal specimens were collected in China-Japan Friendship Hospital during September 2009 to December 2014. A panel of immunohistochemical markers (TTF-1, Napsin A, Ki-67, CK5/6, CK7 and p63) were conducted on these specimens. RESULTS: The 48 cases of special type lung cancer included 25 cases of primary salivary gland-type lung carcinoma (18 cases of adenoid cystic carcinoma and 7 cases of mucoepidermoid carcinoma), 5 cases pulmonary adenocarcinoma with mucoepidermoid carcinoma-like or adenoid cystic carcinoma-like structure, and 18 cases of pulmonary adenosquamous carcinoma. Compared with pulmonary adenocarcinoma with mucoepidermoid carcinoma-like or adenoid cystic carcinoma-like structure and pulmonary adenosquamous carcinoma, primary salivary gland-type lung carcinomas have special characteristics in median age, sex, location, tumor size, LN involvement and pleura invasion, with negative TTF-1 and Napsin A expression as well as lower Ki-67 index detected by immunohistochemistry. Primary salivary gland-type lung carcinomas usually have an indolent behavior. CONCLUSIONS: Primary salivary gland-type lung carcinomas are low-aggressive entities. The origins of primary salivary gland-type lung carcinomas were different from that of pulmonary adenocarcinoma with mucoepidermoid carcinoma-like or adenoid cystic carcinoma-like structure and pulmonary adenosquamous carcinoma. Negative TTF-1 and Napsin A expression as well as Ki-67 index lower than 20% have special value for primary salivary gland-type lung carcinomas in their differential diagnosis.

[The prognostic impact of preoperative PET-CT on postoperative recurrence for completely resected stage I non-small cell lung cancer].

OBJECTIVE: To analyze the prognostic impact of preoperative (18)F-fluorodeoxyglucose (FDG) PET-CT on postoperative recurrence in patients with completely resected stage I non-small cell lung cancer (NSCLC). METHODS: The clinic data of 182 patients with stage I NSCLC who underwent (18)F-FDG PET-CT scan before surgical resection between June 2005 and June 2012 were reviewed retrospectively. There were 121 male and 61 female patients, with an average age of 68 years (range from 34 to 85 years). The pathological stage was I A in 98 patients, I B in 84 patients; the histology were adenocarcinoma in 137 patients, squamous cell carcinoma in 35 patients, and others in 10 patients. Clinicopathological factors including gender, age, smoking history, SUV(max), surgical procedure, pathological features and adjuvant chemotherapy were evaluated to identify the independent factors predicting postoperative recurrences by univariate and multivariate analysis. The survivals were calculated by the Kaplan-Meier method and differences in variables were analyzed by the Log-rank test. RESULTS: The postoperative recurrence rate was 15.9%. The univariate analysis identified that the SUV(max) (t=3.278, P<0.001), p-stage (χ² =5.204, P=0.026), blood vessel invasion (χ² =5.333, P=0.027) and visceral pleural invasion (χ² =7.697, P=0.009) are factors for predicting postoperative recurrence. Only SUV(max) was found to be a significant independent factor according to multivariate analysis (HR=1.068, 95%CI: 1.015 to 1.123, P=0.001). The study population was stratified into three groups by SUV(max), patients with SUV(max) > 5.0 had significantly higher risk of recurrence (23.9%) than those with 2.5 < SUV(max) ≤ 5.0 (15.0%) and SUV(max) ≤ 2.5 (7.3%) (P=0.043); patients with SUV(max) ≤ 2.5 had significantly better 5-year recurrence-free survival rate (90.9%) than those with 2.5 < SUV(max) ≤ 5.0 (82.7%) and SUV(max) ≤ 2.5 (71.0%) (P=0.030). There was a trend toward higher probability of blood vessel invasion (χ² =20.267, P < 0.001), visceral pleural invasion (χ² =6.185, P=0.045) and pathological stage I B (χ² =13.589, P=0.001) with increased SUV(max). CONCLUSIONS: Preoperative SUV(max) of primary tumor is a predictor of postoperative relapse for stage I NSCLC after surgical resection. Therefore, it can contribute to the risk stratification for patients with the same pathological stage and selecting the optimal postoperative follow-up and therapeutic strategy.

[Immunohistochemical evaluation of mutant p53 protein over-expression in non-mucinous adenocarcinoma in-situ and invasive adenocarcinoma, NOS of lung].

OBJECTIVE: To study the over-expression of mutant p53 protein in non-mucinous adenocarcinoma in-situ (NMAIS) and invasive adenocarcinoma, NOS of lung. METHODS: Immunohistochemical study for p53 protein was performed on 17 cases of NMAIS and 70 cases of invasive adenocarcinoma, NOS of lung. The difference in p53 over-expression between the two tumor subtypes was analyzed. RESULTS: The over-expression of mutant p53 protein was observed in 0 case (0%) of NMAIS and 37 cases (52.9%) of invasive adenocarcinoma, NOS of lung. The difference was of statistical significance (P = 0.000). CONCLUSION: Mutant p53 protein over-expression may play a role in the progression of NMAIS to invasive adenocarcinoma, NOS.

Folate receptor α associated with triple-negative breast cancer and poor prognosis.

CONTEXT: Folate receptor α (FRA) has been shown to be selectively expressed in several types of human cancer, including breast cancer. Currently, several FRA target therapies are under intensive study. OBJECTIVE: To investigate the expression pattern of FRA in a large cohort of patients with breast cancer and analyze its relationship with different clinicopathologic features, with expression of several key biomarkers, and with clinical outcome. DESIGN: Four hundred forty-seven cases of infiltrating ductal carcinoma diagnosed between 1997 and 2008 at the University of Rochester Medical Center were identified and reviewed, and 25 blocks of tissue microassays were constructed. The association between expression of FRA and clinicopathologic features; expression of estrogen receptor (ER), progesterone receptor (PR), HER2/neu, and Ki-67; and clinical outcome of these tumors were evaluated. RESULTS: The expression of FRA was significantly associated with tumors with high histologic grade, higher nodal stages, ER/PR negativity, and high proliferative activity (Ki-67 ≥ 15%), and was independent of HER2/neu overexpression. In all, 74% of ER/PR-negative and 80% of triple-negative breast cancers expressed FRA. The expression of FRA was significantly associated with a worse disease-free survival. CONCLUSIONS: Our data demonstrate that a significant subgroup of ER/PR-negative and triple-negative breast cancers express FRA, and its expression is associated with worse clinical outcome.

Pigmented paraganglioma of the kidney: a case report.

Paragangliomas are rare neoplasms arising from undifferentiated cells of the primitive neural crest. We report a case of a 57-year-old patient with renal pigmented paraganglioma that was an incidental finding. Histopathological examination showed typical morphology of paraganglioma, as well as the unusual feature of large amounts of pigment in the cytoplasm of the tumor cells which was confirmed by bleached Fontana-Masson. Electron microscopy showed abundant, pleomorphic electron-dense granules consistent with neuromelanin. The tumor cells were positive for CD56 and chromogranin A, negative for HMB-45. The unique morphologic appearance represents divergent differentiation from neural crest. To our knowledge, the present case represents the first example of pigmented paraganglioma of the kidney. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2017147293711495.

[Usefulness of CK19, HBME-1 and galectin-3 expressions in differential diagnosis of thyroid papillary microcarcinoma from benign lesions].

OBJECTIVE: To characterize the morphological features of thyroid papillary microcarcinoma (PMC) and assess the significance of expression of CK19, HBME-1, Galectin-3, CD56 and p63 in differential diagnosis of PMC from benign thyroid lesions. METHODS: Clinicopathologic features of 78 cases PMC were reviewed. Immunohistochemical analysis of CK19, HBME-1, Galectin-3, CD56, and p63 in 78 cases of PMC and 48 cases of benign thyroid lesions (18 cases of papillary hyperplasia, 17 cases of nodular goiter and 13 cases of lymphocytic thyroiditis) was conducted. The patients were followed up for from 6 to 269 months after surgical operation. RESULTS: 69 cases nuclear atypia and overlapping nuclei (88.5%), 67 cases nuclear grooves (85.9%), 50 cases nuclear pseudoinclusions (64.1%) and 60 cases papillary architecture (76.9%) were detected in 78 cases of PMC. Moderate to strong co-expression of CK19, HBME-1 and galectin-3 was observed in 98.0% (50/51) in the PMC group but in none of the benign disease group. The expression of CD56 and p63 was negative in both groups. In the postoperative follow-up period of 6-269 months, 7 cases (9.0%) developed intrathyroid recurrence, 3 cases (3.8%) developed lymph node metastasis, no distant metastasis or death was observed. In 12 cases (15.4%) the PMC lesion smaller than 3 mm in diameter was not found by frozen section diagnosis. CONCLUSIONS: Overlapping nuclei, nuclear atypia, polar disorder, ground glass nuclei, nuclear grooves and nuclear pseudoinclusions are most important for the diagnosis of PMC with or without papillary architecture. The appearance of definite interstitial invasion, interstitial sclerosis and true complex papillary architecture are more helpful to make right diagnosis. Intraoperative frozen section is of limited value for a reliable diagnosis of PMC in diameter < or = 3 mm. Moderate to strong co-expression of CK19, HBME-1 and Galectin-3 is a very useful indicator for differential diagnosis of PMC from benign thyroid lesions.

Metastatic potential of lung squamous cell carcinoma associated with HSPC300 through its interaction with WAVE2.

The small protein, HSPC300 (haematopoietic stem/progenitor cell protein 300), is associated with reorganization of actin filaments and cell movement, but its activity has not been reported in human cancer cells. Here, we investigated the association of HSPC300 expression with clinical features of lung squamous cell carcinoma. High levels of HSPC300 protein were detected in 84.1% of tumour samples, and in 30.8% of adjacent morphologically normal tissues. The number of primary tumours with elevated HSPC300 levels was significantly higher in primary tumours with lymph node metastases as opposed to those without, and also in tumours from patients with more advanced disease. HSPC300 modulates the morphology and motility of cells, as siRNA knockdown caused the reorganization of actin filaments, decreased the formation of pseudopodia, and inhibited the migration of a lung cancer cell line. We further showed that HSPC300 interacted with the WAVE2 protein, and HSPC300 silencing resulted in the degradation of WAVE2 in vitro. HSPC300 and WAVE2 were co-expressed in approximately 85.7% of primary tumours with lymph node metastases. We hypothesize that HSPC300 is associated with metastatic potential of lung squamous cell carcinoma through its interaction with WAVE2.

Intravascular large B-cell lymphoma with involvement of the abdominal subcutis: a case report and literature review.

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of diffuse large B-cell lymphoma (DLBCL). It commonly presents with a variety of symptoms due to occlusion of small vessels by tumor cells in different organ systems. Clinically patients may present with generalized symptoms such as fever and malaise. In western patients, there is a 'cutaneous variant' of IVLBCL, which demonstrates cutaneous involvement only. However, Asian patients show hemophagocytosis, which is typical of the 'Asian variant'. Here we report a case of IVLBCL in a Chinese individual who presented with a huge mass in the subcutis of the abdomen.

Nitric oxide up-regulates the glucocorticoid receptor and blunts the inflammatory reaction in porcine endotoxin sepsis.

OBJECTIVES: Nitric oxide inhibits the expression of many genes involved in inflammatory diseases. Glucocorticoids inhibit similar transcription factors. We hypothesized that there may be an interaction between nitric oxide and glucocorticoids, with the potential to enhance the anti-inflammatory effect when administered simultaneously. DESIGN: Prospective, randomized, controlled study. SETTING: Animal research laboratory. SUBJECTS: A total of 45 anesthetized and mechanically ventilated pigs. INTERVENTIONS: Lung and systemic injury was induced by intravenous infusion of endotoxin (lipopolysaccharide) for 6 hrs. After 2.5 hrs, one group received 3.5 mg/kg hydrocortisone, another group inhaled nitric oxide (30 ppm), and still another group received both steroid and nitric oxide. Control groups of healthy and endotoxin-exposed piglets were also studied. MEASUREMENTS AND MAIN RESULTS: Central hemodynamics and gas exchange were measured. Detection of the glucocorticoid receptor and inflammatory markers in lung, liver, and kidney tissue were made by immunohistochemistry, and morphology was studied with light microscopy. Endotoxin infusion markedly reduced glucocorticoid receptor expression in lung, liver, and kidney and up-regulated activator protein-1 and the inflammatory markers nuclear factor-kappaB and tumor necrosis factor-alpha. When administered separately, steroids and nitric oxide had modest effect on the inflammatory response. However, nitric oxide up-regulated the glucocorticoid receptor expression. Simultaneous administration of steroids and nitric oxide attenuated the inflammatory response and almost preserved or restored normal histology of both lung and systemic organs. When the glucocorticoid receptor was blocked by a receptor antagonist (mifepristone, 600 mg) and inhaled nitric oxide was subsequently administered, no increase in the expression of the glucocorticoid receptor was seen. CONCLUSION: We suggest that up-regulation of glucocorticoid receptor expression by nitric oxide made steroid therapy more effective.

[Misdiagnosis and mistherapy of ectopic thyroid gland].

OBJECTIVE: To explore the clinic characteristic, diagnosis and treatment of ectopic thyroid gland (ETG) and avoid the misdiagnosis and mistherapy of ETG. METHOD: The clinic materials of 4 cases with ETG were analysed. Four patients were misdiagnosed thyroglossal duct cyst. The clinical features, diagnosis and management of ETG were discussed. RESULT: All of patients had a normal thyroid gland in the neck and underwent a surgical resection of neck mass. Postoperative pathologic examination revealed the neck masses originated from accessory thyroid gland, of them, 1 gland enlargement, 1 adenoma and 2 adenocarcinoma. Fortunately, by the postoperative fellow up, no significant complication was found in the patients. CONCLUSION: The well understanding of ETG and the detailed examination before surgical treatment of neck mass, including ultrasonography, CT or MRI, radioactive isotope scanning and fine needle aspiration biopsy, are keys to adequate diagnosis and management of ETG.