Activation of human synovial mast cells from rheumatoid arthritis or osteoarthritis patients in response to aggregated IgG through Fcγ receptor I and Fcγ receptor II.

OBJECTIVE: Substantial evidence suggests that human synovial mast cells (MCs) are involved in the pathogenesis of rheumatoid arthritis (RA). A plausible pathway for the activation of synovial MCs is through IgG receptors, given the prevalence of circulating IgG isotype autoantibodies and synovial immune complexes in patients with RA. However, IgG receptor expression on human synovial MCs remains uncharacterized. The aim of this study was to identify which IgG receptor(s) on synovial MCs are responsible for MC activation in immune complexes. METHODS: Synovial tissue specimens were obtained from patients with RA or patients with osteoarthritis (OA) who were undergoing joint replacement surgery, and synovial MCs were enzymatically dispersed. Cultured synovium-derived MCs were generated by culturing synovial cells with stem cell factor, and receptor expression was analyzed using fluorescence-activated cell sorting. Mediators released from MCs were measured using enzyme immunoassays or enzyme-linked immunosorbent assays. RESULTS: Primary synovial MCs and cultured synovium-derived MCs obtained from both patients with RA and patients with OA expressed Fcε receptor I (FcεRI), FcγRI, and FcγRII but not FcγRIII. Cultured synovium-derived MCs induced degranulation and the production of prostaglandin D2 and tumor necrosis factor α (TNFα) through FcγRI. The aggregation of FcγRII caused histamine release from cultured MCs but not from primary MCs. Histamine release induced by aggregated IgG was significantly inhibited by neutralizing anti-FcγRI monoclonal antibody and anti-FcγRII monoclonal antibody. CONCLUSION: With regard to the FcR expression profile, synovial MCs from patients with RA and patients with OA were similar. FcγRI was responsible for producing abundant TNFα from synovial MCs in response to aggregated IgG. Immune complexes may activate synovial MCs through FcγRI and FcγRII.

Complications associated with endobronchial ultrasound-guided transbronchial needle aspiration: a nationwide survey by the Japan Society for Respiratory Endoscopy.

BACKGROUND: With the recent widespread use of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), there have been occasional reports on complications associated with its use. Previous reviews on EBUS-TBNA have been limited to studies by skilled operators, thus the results may not always be applicable to recent clinical practice. To assess the safety of EBUS-TBNA for the staging and diagnosis of lung cancer in Japan, a nationwide survey on its current usage status and complications associated with its use was conducted by the Japan Society for Respiratory Endoscopy (JSRE). METHODS: A questionnaire about EBUS-TBNA performed between January 2011 and June 2012 was mailed to 520 JSRE-accredited facilities. RESULTS: Responses were obtained from 455 facilities (87.5%). During the study period, EBUS-TBNA was performed in 7,345 cases in 210 facilities (46.2%) using a convex probe ultrasound bronchoscope, for 6,836 mediastinal and hilar lesions and 275 lung parenchymal lesions. Ninety complications occurred in 32 facilities. The complication rate was 1.23% (95% confidence interval, 0.97%-1.48%), with hemorrhage being the most frequent complication (50 cases, 0.68%). Infectious complications developed in 14 cases (0.19%) (Mediastinitis, 7; pneumonia, 4; pericarditis, 1; cyst infection, 1; and sepsis, 1). Pneumothorax developed in 2 cases (0.03%), one of which required tube drainage. Regarding the outcome of the cases with complications, prolonged hospitalization was observed in 14 cases, life-threatening conditions in 4, and death in 1 (severe cerebral infarction) (mortality rate, 0.01%). Breakage of the ultrasound bronchoscope occurred in 98 cases (1.33%) in 67 facilities (31.9%), and that of the puncture needle in 15 cases (0.20%) in 8 facilities (3.8%). CONCLUSIONS: Although the complication rate associated with EBUS-TBNA was found to be low, severe complications, including infectious complications, were observed, and the incidence of device breakage was high. Since the use of EBUS-TBNA is rapidly expanding in Japan, an educational program for its safe performance should be immediately established.

Bronchoscopic practice in Japan: a survey by the Japan Society for Respiratory Endoscopy in 2010.

BACKGROUND AND OBJECTIVE: To ensure the safety of bronchoscopic practice, the Japan Society for Respiratory Endoscopy conducted a national survey to investigate the current state of procedure for this technique. METHODS: A questionnaire survey about procedures carried out during the whole of the year 2010 was mailed to 538 facilities accredited by the society. RESULTS: Responses were obtained from 511 facilities (95.0%). Rigid bronchoscopes were used in only 18.5% of the facilities, while mobile/thin bronchoscopes were used in ≥ 50%, and fluoroscopy systems were used in 99.8%. Biopsies were performed after discontinuation of therapy in patients receiving antiplatelet drugs and anticoagulants in 96.7% and 97.4% of the facilities, respectively. Atropine was administered for premedication in 67.5% of the facilities, a decrease from previous surveys. Intravenous sedation was given in 36.1% of the facilities. In 21.9% of these, the procedure was conducted in the outpatient clinic for ≥ 70% of patients. A bronchoscope was orally inserted in ≥ 70% of patients in 95.7% of the facilities. Intravenous access was maintained during the examination in 92.5% of the facilities, oxygen saturation was monitored during examinations in 99.0%, oxygen was administered in 97.6% and resuscitation equipment was available in 96%. In 98.6% of the facilities, bronchoscopes were disinfected using an automatic washing machine, with glutaraldehyde used in 42.2%. CONCLUSIONS: Japan-specific characteristics of bronchoscopic practice were identified. Whether procedures used in Japan meet international guidelines with respect to safety should be monitored continuously. In addition, a Japanese evidence-based consensus is needed.

Omalizumab inhibits acceleration of FcεRI-mediated responsiveness of immature human mast cells by immunoglobulin E.

BACKGROUND: A large body of evidence has demonstrated that treatment with omalizumab is clinically effective for the management of moderate to severe allergic asthma, emphasizing the importance of IgE in the pathogenesis of allergic asthma. We hypothesized that IgE accelerates FcεRI-mediated responsiveness of "immature" human mast cells (MCs) and that omalizumab downregulates the acceleration. OBJECTIVES: To examine when MC progenitors acquired the ability to degranulate following FcεRI aggregation, whether IgE accelerates the responsiveness of immature MCs following FcεRI aggregation, and whether omalizumab regulates such an acceleration. METHODS: Gene expression was examined using a microarray and quantitative reverse transcription polymerase chain reaction. Protein expression was investigated using FACS. Histamine release was examined using an EIA. RESULTS: The time-course analysis of the mRNA expression of MC-related genes, including FcεRI, in Kit(+) sorted cells during the differentiation and histamine experiments revealed that the expression level of FcεRI in 5 week (w)-cultured MCs was not sufficient to induce degranulation following FcεRI aggregation but that 5 w-cultured MCs were fully responsive to calcium ionophore. By addition of IgE in culture medium FcεRI expression level and FcεRI-mediated histamine release of 5 w-cultured MCs were significantly increased compared with those without addition of IgE, whereas the expression level of tryptase and number of MCs was not affected. Omalizumab significantly inhibited IgE-dependent enhancement of FcεRI expression level and FcεRI-mediated histamine release. CONCLUSIONS: High levels of IgE in the microenvironment in vivo may upregulate the responsiveness of immature MCs to allergens. Omalizumab may inhibit the IgE-mediated responsiveness of not only mature MCs, but also immature MCs.

Deaths and complications associated with respiratory endoscopy: a survey by the Japan Society for Respiratory Endoscopy in 2010.

BACKGROUND AND OBJECTIVE: In order to survey the current status of the use and complications associated with respiratory endoscopy, the Japan Society for Respiratory Endoscopy conducted a nationwide postal questionnaire survey. METHODS: The survey was mailed to all 538 facilities certified by the society. The subjects were patients who underwent respiratory endoscopy in 2010. The numbers of procedures, and associated complications and deaths were investigated according to lesion and procedure using a specific inventory. RESULTS: The inventory was completed by 483 facilities (89.8%). The total number of diagnostic flexible bronchoscopy procedures performed was 103 978, and four patients died (0.004%). The complication rate according to lesion ranged from 0.51% to 2.06%, with the highest rate being observed in patients with diffuse lesions. The complication rate according to procedure ranged from 0.17% to 1.93%, with the highest rate being observed in patients who underwent forceps biopsy. The complication rate after forceps biopsy of solitary peripheral pulmonary lesions was 1.79% (haemorrhage: 0.73%, pneumothorax: 0.63%), and that after endobronchial ultrasound-guided transbronchial needle aspiration of hilar and/or mediastinal lymph node lesions was 0.46%. Therapeutic bronchoscopy was performed in 3020 patients; one patient (0.03%) died due to haemorrhage induced by insertion of an expandable metallic stent. The complication rate according to procedure was highest for foreign body removal (2.2%). Medical pleuroscopy was performed in 1563 patients. The highest complication rate was for biopsy without electrocautery (1.86%). A total of 228 facilities (47.2%) experienced breakage of bronchoscopes and/or devices. CONCLUSIONS: Respiratory endoscopy was performed safely, but education regarding complications caused by new techniques is necessary.

Treatment strategies for chronic expanding hematomas of the thorax.

PURPOSE: To investigate retrospectively the treatment strategies for chronic expanding hematoma (CEH) of the thorax. METHODS: We reviewed the medical records of six patients treated for CEH of the thorax at our institution between October 1996 and October 2006. RESULTS: All of the patients had a history of thoracic surgery or tuberculosis with a latent period of 12-55 years before onset. One elderly patient with ischemic heart disease and in poor general health demonstrated a substantial improvement of symptoms after undergoing arterial embolization twice instead of surgery. The remaining five patients underwent either pleuropneumonectomy or a total capsule excision, following which their clinical condition improved remarkably. All six patients were discharged from the hospital. Arterial embolization was performed before surgery, and the amount of intraoperative bleeding ranged from 905 ml to 6,590 ml (average: 2,396 ml). CONCLUSION: Chronic expanding hematoma of the thorax may occur after thoracic surgery and a tuberculosis infection; however, considering the risk of massive bleeding during surgery, the decision to perform surgery should be made with extreme care.

Activation of human mast cells through the platelet-activating factor receptor.

BACKGROUND: In human subjects platelet-activating factor (PAF) concentrations are markedly increased in the plasma after anaphylactic reactions, and these correlate strongly with the severity of the response. The mechanism for the systemic spread of mast cell (MC) activation in anaphylaxis is often assumed to relate to the hematogenous spread of allergen, but this is implausible, and amplification mechanisms need to be considered. OBJECTIVE: We have investigated the ability of PAF to induce human MC degranulation using skin, lung, and peripheral blood (PB)-derived cultured MCs and the signaling pathways activated in PB-derived MCs in response to PAF. METHODS: The expression of PAF receptor was investigated by means of RT-PCR and Western blot analysis. Cell-signaling pathways in PB-derived MCs in response to PAF were investigated by analyzing the effect of various inhibitors and the silencing of phospholipase C (PLC) mRNA on PAF-mediated histamine release. RESULTS: We show for the first time that PAF induces histamine release from human lung MCs and PB-derived MCs but not skin MCs. Activation of PAF receptor-coupled G(alphai) leads to degranulation through PLCgamma1 and PLCbeta2 activation in human MCs. PAF-induced degranulation was rapid, being maximal at 5 seconds, and was partially dependent on extracellular Ca(2+). CONCLUSION: Our findings provide a mechanism whereby PAF mediates an amplification loop for MC activation in the generation of anaphylaxis.

Hyperexpression of NOD2 in intestinal mast cells of Crohn's disease patients: preferential expression of inflammatory cell-recruiting molecules via NOD2 in mast cells.

NOD2, an intracellular sensor of bacteria-derived muramyl dipeptide (MDP) has been implicated as a key player in intestinal immune health and disease. Mast cells (MCs) have been reported to be increased in the gut of patients with inflammatory bowel disease. However, NOD2 expression and its role in human primary MCs are unknown. The number of NOD2(+) intestinal MCs was significantly increased in the Crohn's disease (CD) specimens compared to Ulcerative colitis (UC) specimens and controls. IFN-gamma upregulated NOD2 expression in MCs. CXCL10 and urokinase-type plasminogen activator (uPA) upregulation was specific to MCs activated by MDP compared to MCs activated by LPS and IgE/anti-IgE. MDP-induced upregulation of ICAM-1, VCAM-1, and uPA was specific to MCs compared to mononuclear cells. The number of CXCL10(+)NOD2(+) intestinal MCs was significantly increased in the CD patients. Our results suggest that NOD2(+) MCs have specific pathogenic roles that involve the recruitment of inflammatory cells in CD.

[A case of resection of esophageal cancer infiltrating the left main bronchus following preoperative chemo-radiotherapy and resection of metachronous lung metastasis].

We herein report a case of T4 esophageal carcinoma, which was resected after chemo-radiation therapy. In addition, the metachronous lung metastasis was also resected. A 59-year-old female with esophageal carcinoma, which invaded the left main bronchus, underwent chemo-radiation therapy (the combination of systemic chemotherapy of 5-FU/CDDP and external radiation therapy) from January 2004. After the therapy, although the imaging showed a downstaging of esophageal carcinoma, a severe esophageal stricture appeared with ingestion defective. So hyper-alimentation was performed. After the state of nutrition was improved, esophagectomy was performed on March 2004 without a complication. Histopathological study revealed that no viable cells remained. Nine months after esophagectomy, chest CT scan revealed that a solitary pulmonary tumor appeared in S6 of the right. The solitary tumor enlarged gradually. On August 2005, a surgical resection for the solitary pulmonary tumor was performed. Histopathologically, the lesion was compatible for metastasis from esophageal carcinoma. The patient is alive without recurrence more than 23 months after the last surgery.

Mature cystic teratoma with malignant transformation to adenocarcinoma.

An anterior mediastinal tumor had been found in a 65-year-old woman 10 years previously, and she had been followed-up under the diagnosis of a mature cystic teratoma. Changes in the structure of the inside of the mediastinal cystic tumor were observed on a chest computed tomography image, and she was referred to our hospital for surgical intervention. The tumor was removed and was determined to be a mature teratoma. An adenocarcinoma was also observed in part of this cystic lesion. From these findings, the lesion was diagnosed as a malignant change in a mediastinal mature teratoma. Because few if any changes tend to be observed in the cystic wall of such cases, an aggressive resection of such mature cystic teratomas is therefore recommended.

Thoracoscopic resection of mediastinal bronchogenic cysts in adults.

OBJECTIVE: The aim of this study was to discuss the diagnosis and determine the optimal thoracoscopic surgical treatment of mediastinal bronchogenic cysts. METHODS: From May 1996 to April 2008, 13 consecutive patients with mediastinal bronchogenic cysts underwent thoracoscopic surgery at our institution. There were eight men and five women aged 16-74 years (mean age, 41.5 years). RESULTS: In the majority of patients (69.2%), there were no clinical symptoms and the lesions were found incidentally by chest radiography that was performed as part of physical screening. Lesions were found in the posterior mediastinum in five patients (38.5%) and in the upper mediastinum in four (30.8%). In the histopathological examinations, ciliary epithelium was observed in 13 patients (100.0%), bronchial cartilage in 7 patients (53.8%), bronchial glands in 6 patients (46.2%), and smooth muscle in 5 patients (38.5%). No serious postoperative complications were observed. In 3 patients (23.1%), conversion to open thoracotomy was necessary due to major pleural adhesions and intraoperative vascular injury. CONCLUSION: Thoracoscopic resection of mediastinal bronchogenic cyst is minimally invasive and has no serious postoperative complications, and should therefore be considered as the primary therapeutic option.

Cause and management of recurrent primary spontaneous pneumothorax after thoracoscopic stapler blebectomy.

BACKGROUND: As the number of patients treated by thoracoscopic stapler blebectomy increased, the postoperative recurrence rate had risen unexpectedly. We retrospectively investigated the cause and management of primary spontaneous pneumothorax recurrence after thoracoscopic stapler blebectomy. METHODS: From March 1992 to the end of December 2006, thoracoscopic stapler blebectomy was performed in 357 patients with primary spontaneous pneumothorax at the Nihon University Itabashi Hospital. The causes and management of recurrence were investigated in 30 patients with postoperative recurrence based on items such as the resurgical observations, preoperative chest computed tomography findings, previous operative notes. RESULTS: Among the patients with bilateral pneumothorax, young patients exhibited a higher tendency for postoperative recurrence. The most common cause was new bulla formation (28 slides, 16 of which were apparently related to the staple line and 12 of which were not related to the staple line). CONCLUSION: In thoracoscopic stapler blebectomy for primary spontaneous pneumothorax, the most common cause of recurrence was new bulla formation. It is necessary to establish additional procedures involving either the visceral pleura or the parietal pleura to reduce the recurrence rate.

Surgical treatment of catamenial pneumothorax.

OBJECTIVE: To discuss the aetiology and determine the optimal surgical treatment of catamenial pneumothorax. METHODS: Between January 1980 and December 2007, 17 patients with catamenial pneumothorax were treated at our institution. Regarding the surgical approach, thoracotomy was performed until 1991, and thoracoscopic surgery was performed from 1992 onward. RESULTS: Pneumothorax was on the right side in all but two patients. Surgery was performed on 15 of the 17 patients. The surgical procedure was a diaphragm resection plus a partial bleb resection in eight patients, a diaphragm resection in two patients, a diaphragm resection plus an absorbable polyglycolic acid sheet in four patients, and a partial bleb resection in one patient. Five patients demonstrated a postoperative recurrence (33.0%). However, no recurrence has been observed thus far in the four patients with an absorbable polyglycolic sheet placed on the diaphragmatic surface. CONCLUSION: Although the postoperative recurrence rate of patients undergoing surgical procedures remains high, there were some patients with no postoperative recurrence. Placement of an absorbable sheet on the diaphragmatic surface may therefore prevent recurrence of catamenial pneumothorax.

Staple line reinforcement with fleece-coated fibrin glue (TachoComb) after thoracoscopic bullectomy for the treatment of spontaneous pneumothorax.

BACKGROUND: We investigated the cause of pneumothorax recurrence after thoracoscopic surgery and the effectiveness of staple line reinforcement with fleece-coated fibrin glue (TachoComb) in the prevention of postoperative pneumothorax recurrence. METHODS: From April 3, 1992 to the end of December 2005, thoracoscopic bullectomy was performed on 499 patients of primary spontaneous pneumothorax. The causes of recurrence were investigated on 39 patients on the basis of surgical observations, preoperative chest computed tomography, and so on. The most common cause was new bulla formation (37 cases), 19 of which were apparently related to the staple line (within 1 cm of the staple lines) and 15 of which were not related to the staple line. After 2000, we stopped using forceps to grasp lungs and we have reinforced the staple line by applying fleece-coated fibrin glue. RESULTS: The staple line reinforced with fleece-coated fibrin glue, or sprayed with fibrin glue solution and the untreated group (bullectomy only with staples) were compared, and the recurrence rates were 1.22%, 7.25%, and 10.00%, respectively (P = 0.0006021). CONCLUSIONS: The recurrence rate after thoracoscopic bullectomy with fleece-coated fibrin glue was significantly lowered and we consider this procedure to be the treatment of choice for the management of spontaneous pneumothorax.