Resection of intralobar pulmonary sequestration after coil embolization of aberrant arteries: report of a case.

Pulmonary sequestration describes a rare congenital mass of nonfunctional pulmonary tissue with an aberrant systemic arterial supply. Conventionally, the mass is removed surgically, but this carries a risk of serious and potentially fatal hemorrhage from the aberrant arteries during the operation. We describe how we performed coil embolization of the aberrant arteries immediately before surgery to overcome this problem. Coil embolization is safe, feasible and effective in preventing intraoperative bleeding. This case is reported to introduce a new preoperative procedure for pulmonary sequestration.

Strain-specific phenotypes of airway inflammation and bronchial hyperresponsiveness induced by epicutaneous allergen sensitization in BALB/c and C57BL/6 mice.

BACKGROUND: Allergen sensitization through a disrupted skin barrier appears to play a prominent role in the development of atopic diseases, including allergic asthma. The role of the genetic background in immunological and physiological phenotypes induced by epicutaneous sensitization is undetermined. METHODS: BALB/c and C57BL/6 mice were sensitized either epicutaneously by patch application of ovalbumin (OVA) or systemically by intraperitoneal injection of OVA with alum before exposure to aerosolized OVA. The concentrations of OVA-specific immunoglobulin in serum and cytokines in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay. The severity of airway inflammation was evaluated by cell counts in BALF, and bronchial responsiveness to methacholine was measured by the flexiVent system. RESULTS: The production of OVA-specific IgG1 and IgE was greater in the epicutaneously sensitized BALB/c than C57BL/6 mice. In contrast, both eosinophilic airway inflammation and bronchial responsiveness to methacholine were more prominent in the C57BL/6 than in the BALB/c mice. The concentrations of interleukin-4 increased significantly in the BALF from C57BL/6 mice only. No between-strain differences were observed after intraperitoneal sensitization. CONCLUSIONS: The C57BL/6 mouse is a more appropriate model than the BALB/c mouse to study the relationship between skin barrier dysfunction and the pathogenesis of allergic asthma.

[Usefulness of serum procalcitonin measurement in the diagnosis of respiratory infectious diseases].

The serum concentration of procalcitonin (PCT) is specifically elevated in severe bacterial infections. In Japan, PCT has been used as a serum marker for bacterial sepsis since February, 2006. However, the evidence of it in respiratory infectious diseases is limited. In the present study, we analyzed 57 episodes of systemic inflammatory response syndrome in 53 inpatients to investigate the usefulness of serum PCT measurement in respiratory infectious diseases. Although the sensitivity and a negative predictive value in common bacterial infections were low, the specificity and positive predictive value were 95% and 93%, respectively. This suggests that the significance of serum PCT measurement relies on confirming the diagnosis of common bacterial infections. Analysis using a receiver operating characteristic (ROC) curve demonstrated that serum PCT was a more reliable measure of bacterial sepsis than leukocyte counts in the peripheral blood or serum C-reactive protein. In cases of community-acquired pneumonia, except atypical pneumonia, the hospital mortality rate was significantly higher in PCT-positive patients than in PCT-negative patients (38% vs. 0%), indicating that serum PCT could be a factor predicting in-hospital death.

[A case of pulmonary aspergillosis subacutely forming a cavity during the course of microscopic polyangiitis].

A 77-year-old woman was referred to our department with hemoptysis. Microscopic polyangiitis (MPA) with resultant alveolar hemorrhage was diagnosed because of diffuse infiltrate of the right lung, proteinurea, renal dysfunction and the presence of MPO-ANCA. The disease responded well to corticosteroid therapy. She was discharged, but as corticosteroid was gradually tapered, an irregularly-shaped nodule appeared in the right upper lung field within 2 weeks. She was re-admitted because the nodule increased in size with cavity formation in spite of the administration of antibacterial agent. Pulmonary aspergillosis was diagnosed, since bronchial washing and transbronchial lung biopsy revealed the presence of Aspergillus fumigatus. Serum beta-D-glucan was decreased and the cavity was reduced in size, responding to the treatment with micafungin. However, she died later of systemic infection by a herpesvirus. We report this case because of the interesting course of pulmonary aspergillosis that subacutely formed a cavity.

Intimal Sarcoma of the Pulmonary Artery Treated with Pazopanib.

Intimal sarcoma is a rare disease with a poor prognosis. We herein report the case of a 71-year-old man with intimal sarcoma of the pulmonary artery treated with pazopanib. The tumor showed regression after 1 month of treatment. Hand-foot syndrome led to cessation of pazopanib, which triggered a disease flare. Pazopanib should be considered in patients with intimal sarcoma of the pulmonary artery that is unresectable or recurrent after surgery or cytotoxic chemotherapy. We must be careful about drug cessation, as it can lead to a disease flare.

Benign metastasizing leiomyoma of the lung.

A 44-year-old woman was found to have an abnormal shadow on a chest X-ray during a regular health checkup, and visited our department. Chest computed tomography showed multiple nodular shadows in both lungs. The patient had no history of neoplasm except for myomectomy for uterine leiomyoma 6 years previously. Eighteen months later, the nodules showed a gradual increase in size, and video-assisted thoracoscopic biopsy of a nodule was performed. Histopathologically, the pulmonary nodule was composed of benign smooth muscle cells proliferating in fascicles, consistent with the diagnosis of benign metastasizing leiomyoma. Benign metastasizing leiomyoma is defined as a histologically benign uterine smooth muscle tumor that acts in a somewhat malignant fashion and produces benign metastases. Although it is a rare condition, it should be considered in asymptomatic women of reproductive age with a history of uterine leiomyoma, who present with solitary or multiple pulmonary nodules. Herein, we report a case of pulmonary benign metastasizing leiomyoma.

Bronchial pleomorphic adenoma coexisting with lung cancer.

Pleomorphic adenoma usually occurs in the salivary glands but rarely in the trachea or bronchi. A 71-year-old man had abnormal shadows on a chest X-ray. Chest CT revealed one tumor in the right basal segment of the lung and another, in the left main bronchus. Bronchoscopic biopsy of the right tumor revealed well-differentiated squamous cell carcinoma. Right lower lobectomy and lymph node dissection were performed (pT2N0M0, stage IB). At the orifice of the left main bronchus, bronchoscopy identified a polypoid lesion nearly obstructing the airway. The lesion was resected with hot snare ablation. The histological examination revealed a mixture of epithelial and myxoid mesenchymal elements, characterized by ductal structures, squamous metaplasia, and cartilage tissue. The diagnosis was bronchial pleomorphic adenoma coexisting with squamous cell carcinoma of the lung.

Tracheobronchomalacia treated by inserting a long T-tube into the left main bronchus.

An 88-year-old woman with advanced Parkinson's disease (stage V on the Yahr scale) had difficulty in expectoration and underwent tracheostomy in 1999. In July 2004, granulation tissue was formed in the tracheal lumen at the tip of the tracheostomy tube, and a standard type silicone T-tube was inserted. Thereafter, she was cared for at home, where she was doing well until early March 2009, when a decrease in SaO(2) and difficulty in sputum aspiration were noted. Bronchoscopy showed crescent type tracheobronchomalacia involving the trachea down to the orifice of the left main bronchus. Considering its localization, an intact right main bronchus, a history of tracheostomy tube placement resulting in granulation tissue formation in the lower trachea, and the future need for frequent sputum aspiration, we inserted a long T-tube into the left main bronchus, which is easily replaceable and facilitates sputum aspiration. Right-lung ventilation was maintained through a side aperture made in the long T-tube. After its insertion, her respiratory status stabilized, secretion drainage improved, and she was discharged for treatment at home. Herein, we describe a tracheobronchomalacia patient in whom airway patency was achieved by inserting a long T-tube with a side aperture into the left main bronchus.

A surgical case of quadruple lung cancer.

The patient was a 50-year-old male psychiatrist with a history of smoking 3 packs of cigarettes per day for 30 years. Chest computed tomography (CT) showed a nodular shadow in the left S6 segment in April 2002, for which thoracoscopic partial resection of the lung was performed. Because adenocarcinoma was diagnosed by intraoperative frozen sectioning, a left lower lobectomy and lymph node dissection were performed. The pathological diagnosis was adenocarcinoma with mixed subtypes (AMS, pT1N0M0). Cytologically, the tumor cells exhibited tall columnar eosinophilic cytoplasm. In March 2005, chest CT showed a nodular shadow in the right S3 segment, and thoracoscopic partial resection of the lung was performed. Histopathological examination revealed AMS (pT1N0M0). Cytologically, cancer cells showed cuboidal cytoplasm. In November 2007, a nodular shadow appeared in the right S4 segment on chest CT, and thoracoscopic partial resection of the middle lobe and the portion of the upper lobe that had adhered to the middle lobe was performed. Histologically, the middle-lobe tumor was solid adenocarcinoma with mucin (pT1N0M0). Although no gross tumor could be identified in the upper lobe, histological examination revealed nonmucinous bronchioloalveolar carcinoma (pT1N0M0). The patient is currently following a favorable course. Herein, we report a surgical case of quadruple lung cancer.

Uracil-Tegafur-induced pleural effusion following lung cancer surgery.

The patient was a 75-year-old female with a history of no smoking. Under a diagnosis of lung cancer, she underwent a right lower lobectomy in March 2008. She was started on oral Uracil-Tegafur (UFT) (400 mg/day) from April and in May developed fatigue, respiratory discomfort, and tachycardiac atrial fibrillation. Chest X-ray film showed an increase in right pleural effusion. Thoracentesis revealed a yellowish, serous exudate containing predominantly lymphocytes, with no evidence of malignancy. Despite continued diuretic administration for 5 months from July, it was difficult to control the pleural effusion, and her activities of daily living remained low. In December of the same year, the oral administration of UFT was terminated, which 2 weeks later resulted in a marked decrease in pleural effusion on chest X-ray film. Respiratory discomfort and fatigue also subsided, and her general condition improved markedly. Herein we report a case of oral UFT-induced pleural effusion following lung cancer surgery.

Cyclooxygenase-2/prostaglandin D2/CRTH2 pathway mediates double-stranded RNA-induced enhancement of allergic airway inflammation.

Respiratory RNA viruses responsible for the common cold often worsen airway inflammation and bronchial responsiveness, two characteristic features of human asthma. We studied the effects of dsRNA, a nucleotide synthesized during viral replication, on airway inflammation and bronchial hyperresponsiveness in murine models of asthma. Intratracheal instillation of poly I:C, a synthetic dsRNA, increased the airway eosinophilia and enhanced bronchial hyperresponsiveness to methacholine in OVA-sensitized, exposed rats. These changes were associated with induction of cyclooxygenase-2 (COX-2) expression and COX-2-dependent PGD2 synthesis in the lungs, particularly in alveolar macrophages. The direct intratracheal instillation of PGD2 enhanced the eosinophilic inflammation in OVA-exposed animals, whereas pretreatment with a dual antagonist against the PGD2 receptor-(CRTH2) and the thromboxane A2 receptor, but not with a thromboxane A2 receptor-specific antagonist, nearly completely eliminated the dsRNA-induced worsening of airway inflammation and bronchial hyperresponsiveness. CRTH2-deficient mice had the same degree of allergen-induced airway eosinophilia as wild-type mice, but they did not exhibit a dsRNA-induced increase in eosinophil accumulation. Our data demonstrate that COX-2-dependent production of PGD2 followed by eosinophil recruitment into the airways via a CRTH2 receptor are the major pathogenetic factors responsible for the dsRNA-induced enhancement of airway inflammation and responsiveness.

TLR3-mediated synthesis and release of eotaxin-1/CCL11 from human bronchial smooth muscle cells stimulated with double-stranded RNA.

Respiratory infections with RNA viruses, such as rhinovirus or respiratory syncytial virus, are a major cause of asthma exacerbation, accompanied by enhanced neutrophilic and/or eosinophilic inflammation of the airways. We studied the effects of dsRNA synthesized during RNA virus replication, and of its receptor, TLR3, on the synthesis of eosinophilic chemokines in bronchial smooth muscle cells (BSMC). Synthetic dsRNA, polyinosinic-cystidic acid (poly(I:C)), induced the synthesis of eosinophilic chemokines, eotaxin-1/CCL11 and RANTES/CCL5, from primary cultures of human BSMC, and IL-4 increased synergistically the synthesis of poly(I:C)-induced CCL11. A robust eosinophil chemotactic activity was released from BSMC stimulated with poly(I:C) and IL-4, which was mostly inhibited by preincubation with an anti-CCL11, but not with an anti-CCL5 Ab. Although the immunoreactivity of TLR3 was detectable on the cellular surface of BSMC by flow cytometric analysis, pretreatment with an anti-TLR3-neutralizing Ab failed to block the poly(I:C)-induced synthesis of CCL11. We have determined by confocal laser-scanning microscopy that the immunoreactivity of TLR3 was aggregated intracellularly in poly(I:C)-stimulated BSMC, colocalizing with fluorescein-labeled poly(I:C). The synthesis of CCL11 was prominently inhibited by the transfection of TLR3-specific small interfering RNA or by bafilomycin A1, an endosomal acidification inhibitor, further supporting the essential role played by intracellular TLR3 in the synthesis of poly(I:C)-induced CCL11 in BSMC. In conclusion, these observations suggest that, by activating intracellular TLR3 in BSMC, respiratory RNA virus infections stimulate the production of CCL11 and enhance eosinophilic inflammation of the airways in the Th2-dominant microenvironment.

Prostaglandin D2-induced eosinophilic airway inflammation is mediated by CRTH2 receptor.

Mast cell-derived prostaglandin D(2) (PGD(2)) is one of the essential modulators of eosinophilic airway inflammation in asthma and allergic rhinitis. Two G protein-coupled receptors for PGD(2), prostaglandin D(2) receptor (DP) and chemoattractant receptor-homologous molecule expressed on Th(2) cells (CRTH2), are both expressed on the surface of eosinophils, and CRTH2 has been demonstrated to mediate PGD(2)-induced eosinophil mobilization in vitro. However, it has not yet been determined whether PGD(2) and its receptors mediate in vivo eosinophil trafficking into the airways or other organs. We demonstrated that intratracheal administration of PGD(2) in rats pretreated with systemic interleukin-5 (IL-5) injection induced marked airway eosinophilia, determined by the differential counts of cells in bronchoalveolar lavage (BAL) fluid and lung histology, within 2 h. Systemic IL-5 alone significantly increased the number of eosinophils in the peripheral blood but showed no effect on airway eosinophilia. Three CRTH2-specific agonists (13,14-dihydro-15-keto-PGD(2), 11-deoxy-11-methylene-15-keto-PGD(2), and indomethacin) demonstrated equivalent induction of BAL eosinophilia to that of PGD(2), but a DP agonist (BW 245C [5-(6-carboxyhexyl)-1-(3-cyclohexyl-3-hydroxypropyl)-hydantoin]) or a thromboxane A(2) receptor (TP) agonist ([1S-1alpha,2beta(5Z), 3alpha(1E,3R*),4alpha)]-7-[3-(3-hydroxy-4-(4'-iodophenoxy)-1-butenyl)-7-oxabicyclo-[2.2.1]heptan-2-yl]-5-heptenoic acid) showed no effect. PGD(2) or CRTH2 agonist-induced BAL eosinophilia was almost completely inhibited by pretreatment with a CRTH2/TP antagonist, ramatroban [BAY-u3405; (+)-(3R)-3-(4-fluorobenzenesulfonamido)-1,2,3,4-tetra-hydrocarbazole-9-propionic acid], whereas a TP-specific antagonist, SQ29,548 (5-heptenoic, 7-[3-[[2-[(phenylamino)carbonyl]hydrazino]methyl]-7-oxabicyclo[2.2.1]-hept-2-yl]-[1S-[1alpha,2alpha(Z),3alpha,4alpha]]), or a DP-specific antagonist, BW A868C [3-benzyl-5-(6-carboxyhexyl)-1-(2-cyclohexy-2-hydroxyethylamino)-hydantoin], did not inhibit the effects of PGD(2). These results suggest that CRTH2 plays a significant role in the eosinophil trafficking from the bloodstream into the airways in PGD(2)-related airway inflammation.