The Incidence of Hemorrhagic Complications Was Lower With the Guide Sheath Than With the Conventional Forceps Biopsy Method: Results of Bronchoscopy in the 2016 Nationwide Survey by the Japan Society for Respiratory Endoscopy.

BACKGROUND: The Japan Society for Respiratory Endoscopy performed a nationwide survey to evaluate the current status and complications of bronchoscopy. Data on deaths due to bronchoscopy, complications after bronchoscopy, and particularly, complications of forceps biopsy were surveyed. METHODS: The survey form was mailed to 532 facilities accredited by the society. The numbers of procedures, complications, and deaths were investigated. RESULTS: The response rate was 79.1% (421 facilities). Deaths attributable to diagnostic bronchoscopy occurred in 11 (0.011%) of 98,497 cases.In regards to forceps biopsy, the guide sheath method was applied in 23,916 cases and the conventional method in 31,419 cases was done with conventional method. Complications of forceps biopsy developed in 1019 cases in total, with an incidence rate of 1.84%. The most frequent complication was pneumothorax (0.70%), followed by pneumonia/pleurisy (0.46%) and hemorrhage (0.45%). The incidence of hemorrhagic complication was significantly lower in the guide sheath group than in the non-guide sheath group (0.29% vs. 0.58%; P<0.001). The overall incidence of complications (1.63% vs. 2.00%; P=0.002) and the mortality rate (0% vs. 0.02%; P=0.04) were significantly lower in the guide sheath group. CONCLUSION: The incidence of hemorrhagic complications in forceps biopsy of peripheral pulmonary lesions was lower when the guide sheath method was applied. It is necessary to increase the awareness for safety control in diagnostic bronchoscopy for new procedures.

Impact of pathological stage and histological subtype on clinical outcome of adjuvant chemotherapy of paclitaxel plus carboplatin versus oral uracil-tegafur for non-small cell lung cancer: subanalysis of SLCG0401 trial.

BACKGROUND: Pathological stage (pStage) and histological subtype are strong determinants of the treatment strategy for non-small cell lung cancer (NSCLC). Setouchi Lung Cancer study Group (SLCG) recently reported the results of a multicenter trial (SLCG0401) indicating that paclitaxel plus carboplatin (CBDCA/PTX) as adjuvant chemotherapy does not yield better survival than uracil-tegafur (UFT) in NSCLC patients with pStage IB-IIIA disease, while stratified analyses considering the pStage and histological subtype have not been performed. METHODS: We reanalyzed the overall survival (OS) and relapse-free survival (RFS) in 402 patients who had been randomly assigned to receive CBDCA/PTX or UFT by multivariate analysis with adjustments for the pStage and histological subtype. RESULTS: There were no significant differences in the OS or RFS between the two treatment settings either in the entire cohort (n = 402) and in some of subsets: pStage IB (n = 228), pStage II (n = 117), adenocarcinoma (AD, n = 265), and squamous cell carcinoma (SQ, n = 101). In pStage IIIA patients (n = 57), CBDCA/PTX yielded superior RFS to UFT [hazard ratio (HR) 0.44; P = 0.016]. Among the patients with non-AD and non-SQ histology (n = 36), UFT yielded both superior OS and RFS to CBDCA/PTX (HRs 0.16 and 0.23; P = 0.046 and 0.011, respectively). CONCLUSIONS: There are subsets of patients in which one or the other between UFT and CBDCA/PTX is significantly more effective. Selection of adjuvant therapy for NSCLC patients needs to be made taking into consideration the pStage and histological subtype.

Current status of diagnostic and therapeutic bronchoscopy in Japan: 2016 national survey of bronchoscopy.

BACKGROUND: The safety management committee of the Japan Society for Respiratory Endoscopy (JSRE) conducted national surveys to clarify the state of diagnostic and therapeutic bronchoscopy in 2016. METHODS: Questionnaire forms were mailed to 532 JSRE-accredited facilities throughout Japan. We surveyed the actual condition of clinical practice and cases of bronchoscopy during 2016. RESULTS: Four hundred and thirty-three facilities responded giving a response rate of 81.4%; 67.6% held more than 400 beds. The average number of board accredited senior Fellows and Fellows per facility was 1.9 and 3.2, respectively. Diagnostic bronchoscopy was performed in a hospitalized setting in 74.6% of all facilities. The radial type ultrasound probe was operated in 51.7% of all facilities. The number of facilities has markedly increased compared with that reported in the 2010 survey (19.6%). The bronchoscopic navigation system had been in operation in 41.7% of all facilities. Antithrombotic drugs were adjusted before biopsy in 96.8% of all facilities. For intravenous sedation, midazolam was the first choice in 76.9% of all facilities. Endobronchial ultrasound guided transbronchial lymph node needle aspiration (EBUS-TBNA) has become popular over the decade (19.6% in 2010 to 68.1% in 2016). The mean number of the board accredited senior Fellows and board accredited Fellows increased in comparison with that in 2010. As a new technique, radial type ultrasound-guided peripheral approach has become popular. CONCLUSIONS: Through this survey, the advanced safety of bronchoscopic examination has been secured in many facilities. A continuous monitoring of bronchoscopic practices with respect to safety management is recommended.

A Multicenter Randomized Controlled Study of Paclitaxel plus Carboplatin versus Oral Uracil-Tegafur as the Adjuvant Chemotherapy in Resected Non-Small Cell Lung Cancer.

INTRODUCTION: We conducted a randomized controlled study to compare the survival benefit of paclitaxel plus carboplatin and oral uracil-tegafur (UFT) as adjuvant chemotherapy in resected NSCLC. METHODS: In an open-label multicenter trial, patients with pathological stage IB to IIIA NSCLC were randomized into a group receiving paclitaxel (175 mg/m2) plus carboplatin (area under the curve 5) every 3 weeks for four cycles (arm A) or a group receiving orally administered UFT (250 mg/m2) daily for 2 years (arm B). The primary and secondary end points were overall survival and relapse-free survival and toxicity, respectively. RESULTS: Between November 2004 and November 2010, 402 patients from 40 institutions were included (201 in each arm). The median follow-up period was 6.5 years. The 5-year overall survival rate was 70% (95% confidential interval [CI]: 63-76] in arm A versus 73% (95% CI: 66-78) in arm B (hazard ratio = 0.92, 95% CI: 0.55-1.41, p = 0.69). There was no significant difference in the 5-year relapse-free survival rate between arms A and B (56% versus 57% [hazard ratio = 0.92, 95% CI: 0.63-1.34, p = 0.50]). Toxicities were well tolerated and there was no treatment-related death. Toxicities of any grade or grade 4 were significantly more frequent in the paclitaxel plus carboplatin group (95.7% and 22.1%, respectively) than in the UFT group (76.5% and 1.0%, respectively [p < 0.0001 in both]). CONCLUSIONS: As adjuvant chemotherapy, paclitaxel plus carboplatin was no better than UFT in terms of survival among patients with stage IB to IIIA NSCLC tumors who underwent complete resection (UMIN000000810).

Randomized feasibility study of S-1 for adjuvant chemotherapy in completely resected Stage IA non-small-cell lung cancer: results of the Setouchi Lung Cancer Group Study 0701.

OBJECTIVE: The aim of this multicenter study was to determine the appropriate administration schedule for S-1, an oral fluoropyrimidine, for adjuvant chemotherapy in patients with completely resected pathological-Stage IA (tumor diameter, 2-3 cm) non-small-cell lung cancer. METHODS: Patients were randomly assigned to receive adjuvant chemotherapy consisting of either the 4-week oral administration of S-1 (80-120 mg/body/day) followed by a 2-week rest (Group A), or the 2-week oral administration of S-1 (80-120 mg/body/day) followed by a 1-week rest (Group B). The duration of adjuvant chemotherapy was 1 year in both arms. The primary endpoint was compliance, namely drug discontinuation-free survival, which was calculated using the Kaplan-Meier method with log-rank test. RESULTS: Eighty patients were enrolled in this study, and 76 patients actually received S-1 treatment. The drug discontinuation-free survival rates at 1 year were 49.1% in Group A and 52.7% in Group B (P = 0.373). The means of the relative dose intensities were 55.3% in Group A and 64.6% in Group B (P = 0.237). There were no treatment-related deaths. Patients with grade 3/4 toxicities were significantly more frequent in Group A (40.5%) than in Group B (15.4%, P = 0.021). The 2-year relapse-free survival rates were 97.5% in Group A and 92.5% in Group B, and the 2-year overall survival rates were 100% in both groups. CONCLUSIONS: The feasibility showed no significant difference between the two groups among patients with completely resected Stage IA (tumor diameter, 2-3 cm) non-small-cell lung cancer.

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.

Recurrent rupture of intercostal artery aneurysms in neurofibromatosis type 1.

Vasculopathy associated with neurofibromatosis type 1 (NF-1) can cause a spontaneous hemothorax, which is an uncommon but life-threatening complication of the disease. We report a case of recurrent rupture of intercostal artery aneurysms in an NF-1 patient. A 40-year-old man with NF-1 suffered from a right spontaneous hemothorax. The bleeding source was not identified by dynamic contrast-enhanced computed tomography (CT), so he was initially treated by conservative therapy. However, repeated contrast CT revealed aneurysms of the right 10th intercostal artery. They were successfully occluded by transcatheter arterial embolization (TAE). Seven months afterward, he presented with sudden lower back pain and was diagnosed with a contralateral spontaneous hemothorax due to a ruptured aneurysm of the left 12th intercostal artery. TAE was successfully performed.

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.

Video-assisted thoracic resection for intralobar pulmonary sequestration.

We present a case in which video-assisted thoracic resection for intralobar pulmonary sequestration (ILPS) was successfully performed. A 36-year-old woman had repeated pneumonia. Chest computed tomography (CT) showed a round mass in the right lower lobe of the lung. Subsequent three-dimensional CT revealed that a large anomalous artery arising from the descending thoracic aorta was distributing to the posterior basal segment containing the lesion and was draining into the inferior pulmonary vein. The patient was diagnosed with ILPS and underwent surgery. The anomalous artery was divided, and the sequestered segment was completely resected by video-assisted thoracic surgery (VATS). We think that VATS resection for ILPS is feasible and is a major therapeutic option as noninvasive surgery.

Bronchial and cardiac ruptures due to blunt trauma.

Tracheobronchial and cardiac injuries following blunt thoracic trauma are uncommon but can be life-threatening. We report a case in which the patient with bronchial and right atrial ruptures due to blunt trauma survived after emergent repairs. An 18-year-old female driver was transported to our hospital after a traffic accident and was hemodynamically stable on arrival. Chest computed tomography revealed cervicomediastinal emphysema and hemopericardium, and fiberoptic bronchoscopy showed a tear in the right main bronchus. She was intubated with a double-lumen endotracheal tube guided by bronchoscopy. A median sternotomy was undertaken, and a laceration of the right atrium was oversewn without the use of cardiopulmonary bypass. After that, right-sided thoracotomy was performed. The tear in the membranous portion of the right main bronchus was repaired with interrupted sutures, and the suture lines were wrapped with a pedicled flap of intercostal muscle.

Primary lung cancer arising from the wall of a giant bulla in which positron emission tomography was useful for preoperative diagnosis.

We report a case of lung cancer arising from the wall of a giant bulla. A 58-year-old man consulted a physician because of bloody sputum. Chest computed tomography (CT) revealed a left upper giant bulla with partial thickness of the wall. Cytology of both sputum and transbronchial brushing was negative at that time. After 6 months follow-up CT scans showed more thickness of the wall, and positron emission tomography (PET) revealed high accumulation of fluorodeoxyglucose in the thickened wall. Because lung cancer was highly suspected, we performed an operation without a definitive diagnosis. The postoperative pathological diagnosis was large cell carcinoma arising from the wall of a giant bulla. Because a preoperative diagnosis is difficult in the case of lung carcinoma associated with bullous disease due to the lack of a characteristic radiological appearance and the difficulty of pathological examination, we emphasize that PET is a useful diagnostic tool.

Localized extraosseous Ewing's sarcoma of the chest wall resected by video-assisted thoracoscopic surgery.

Extraosseous Ewing's sarcoma (ES) is a small round cell tumor arising in soft tissue that was undifferentiated histologically from classic ES of bone. It frequently affects children and adolescents, with an unfavorable prognosis. Herein, we report a case of localized extraosseous ES of the chest wall resected by video-assisted thoracoscopic surgery (VATS). An asymptomatic 40-year-old man presented with an abnormal shadow on chest radiography. Chest computed tomography showed a 1.5-cm solid tumor on the chest wall. VATS was undertaken for the undiagnosed tumor. Thoracoscopic findings showed a hemispheric tumor with a smooth surface on the chest wall. The tumor was diagnosed with an extraosseous ES by pathological and cytogenetic examinations. As adjuvant therapy, the patient was treated with radiotherapy, followed by multiagent chemotherapy. There have been few reported cases in which VATS was used for extraosseous ES of chest wall, so our case was thought to be very rare.

Native lung-sparing lobar transplantation for pulmonary emphysema.

The living-donor lobar lung transplantation procedure has been developed clinically as an alternative approach for patients considered too ill to await cadaveric transplantation. With this procedure, 2 lobes are implanted in the recipient in place of whole right and left lungs, respectively. However, the shortage of graft volume can be a problem when compared with full-sized cadaveric grafts. In an attempt to solve this problem, we have developed a native lobe-preserving lobar transplant technique using a large animal model. We report a first successful case of a patient undergoing native lobe-preserving lobar lung transplantation for severe pulmonary emphysema.

Sirolimus amelioration of clinical symptoms of recurrent lymphangioleiomyomatosis after living-donor lobar lung transplantation.

In this study we report the case of a 28-year-old female patient with recurrent lymphangioleiomyomatosis (LAM) in the allografts after bilateral living-donor lobar lung transplantation. Although her post-operative course under immunosuppression with tacrolimus and prednisolone had been uneventful without rejection episodes, she had developed shortness of breath and a progressive chylous effusion with diffuse cystic changes in both lungs 5 years after transplantation. In spite of a diagnosis of having a recurrence of LAM based on radiologic findings and deteriorating pulmonary function, her clinical symptoms, which included dyspnea and chylothorax, were significantly improved after treatment with sirolimus. Although a beneficial effect of sirolimus in the treatment of LAM has not been definitively determined, this report may provide useful information for management of recurrent LAM after lung transplantation.

Dry small pleural dissemination of adenocarcinoma of the lung preoperatively detected by PET/CT: a report of two cases.

Dry pleural dissemination in non-small cell lung cancer, defined as solid pleural metastasis of lung cancer without pleural effusion, is a condition occurring in T4 lung cancer. Positron emission tomography (PET) has been reported to be useful for the diagnosis and staging of lung cancer. It has been reported that positive findings on PET scans of indeterminate pleural abnormalities at computed tomography (CT) are sensitive to malignancy. We encountered two cases of dry small pleural dissemination of adenocarcinoma of the lung preoperatively detected by PET/CT. A 75-year-old man and a 66-year-old man underwent CT scan, which demonstrated solitary tumor in the lung, an enlarged mediastinal lymph node, and a small pleural nodule less than 10 mm in size, all of which were positive findings on the fluorine 18 fluorodeoxyglucose (FDG) PET portion of an integrated PET/CT. Both patients underwent thoracoscopic biopsy of the dry pleural nodule revealing dissemination of adenocarcinoma of the lung (T4). Whereas histological thoracoscopic diagnosis remains mandatory before planning treatment, our cases may suggest that PET/CT will be useful as a screening modality for dry pleural dissemination of lung cancer.

Pseudoprogression of lung cancer after concomitant chemoradiotherapy.

We observed re-enlargement of a squamous cell carcinoma without recurrence. The tumour regressed markedly after concomitant chemoradiotherapy, but within 1 month, we supposed that the tumour had enlarged again and resection was performed. The resected tissue showed evidence of haemorrhage and several lymphocytes and macrophages, but no malignant cells were detected. We herein report a rare case of lung cancer showing a pathological complete response despite re-enlargement of tumour lesion.

Measurement of pleural temperature during radiofrequency ablation of lung tumors to investigate its relationship to occurrence of pneumothorax or pleural effusion.

The purpose of this study was to investigate the relationship between pleural temperature and pneumothorax or pleural effusion after radiofrequency (RF) ablation of lung tumors. The pleural temperature was measured immediately outside the lung surface nearest to the tumor with a fiber-type thermocouple during 25 ablation procedures for 34 tumors in 22 patients. The procedures were divided into two groups depending on the highest pleural temperature: P-group I and P-group II, with highest pleural temperatures of <40 degrees C and >/=40 degrees C, respectively. The incidence of pneumothorax or pleural effusion was compared between the groups. Multiple variables were compared between the groups to determine the factors that affect the pleural temperature. The overall incidence of pneumothorax and pleural effusion was 56% (14/25) and 20% (5/25), respectively. Temperature data in five ablation procedures were excluded from the analyses because these were affected by the pneumothorax. P-group I and P-group II comprised 10 procedures and 10 procedures, respectively. The incidence of pleural effusion was significantly higher in P-group II (4/10) than in P-group I (0/10) (p = 0.043). However, the incidence of pneumothorax did not differ significantly (p = 0.50) between P-group I (4/10) and P-group II (5/10). Factors significantly affecting the pleural temperature were distance between the electrode and the pleura (p < 0.001) and length of the lung parenchyma between the electrode and the pleura (p < 0.001). We conclude that higher pleural temperature appeared to be associated with the occurrence of pleural effusion and not with that of pneumothorax.

The association between RAD18 Arg302Gln polymorphism and the risk of human non-small-cell lung cancer.

PURPOSE: The repair enzyme RAD18 plays a key role in the post-replication repair process in various organisms from yeast to human, and the molecular function of the RAD18 protein has been elucidated. Single nucleotide polymorphism (SNP) of arginine (Arg, CGA) or glutamine (Gln, CAA) at codon 302 is known on RAD18; however, the association between the SNP and the risk of any human cancers including non-small-cell lung cancer (NSCLC) has not been reported. We therefore investigated the relationship between the polymorphism and the development and progression of human NSCLC. METHODS: The study population included 159 patients with NSCLC and 200 healthy controls. The SNP was genotyped by polymerase chain reaction with the confronting two-pair primer (PCR-CTPP) assay. Genotype frequencies were compared between patients and controls, and the association of genotypes with clinicopathological parameters was also studied. RESULTS: The Gln/Gln genotype was significantly more frequent in NSCLC patients (20.7%) than in healthy controls (11.5%)(P = 0.003). The increased risk was detected in NSCLC patients with the Gln/Gln genotype [Odds ratio (OR) = 2.63, 95% confidence interval (CI)=1.38-4.98]. As to the relationship of the SNP with clinicopathological parameters of NSCLC, significantly higher risks were detected in lung squamous cell carcinoma (LSC) (OR = 4.40, 95% CI = 1.60-12.1). CONCLUSIONS: Our results suggested that Gln/Gln genotype of the RAD18 SNP has the increased risk of NSCLC, especially of LSC. This is the first report to provide evidence for an association between the RAD18 Arg302Gln polymorphism and human NSCLC risk.