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Osimertinib is a highly active agent for patients with progression of lung cancer despite epidermal growth factor receptor (EGFR)tyrosine kinase inhibitor treatment. This resistance is usually due to EGFR exon 20 T790M mutation, which can be detected by repeat biopsy. We report a case in which EGFR exon 20 T790M mutation was detected by repeat ascitic fluid examination. A 71-year-old woman with lung adenocarcinoma harboring EGFR exon 19 deletion was started on erlotinib(25 mg/day)as second-line therapy. Two years later, there was increase in pleural effusion, with concomitant malignant ascites; however, pathologic examination of the pleural and ascitic fluids did not detect EGFR T790Mmutation. Afatinib(2 0mg/day) was started, but there was no decrease in the severity of ascites. Two months later, her condition was extremely deteriorated. Finally, a much larger amount of ascitic fluid obtained by paracentesis was processed for cellblock, which demonstrated EGFR exon 20 T790M mutation. Thereafter, the ascites and the primary lesion dramatically decreased after treatment with osimerti- nib(80mg/day).

Background Endobronchial ultrasound with a guide sheath (EBUS-GS) has resulted to better diagnostic outcome for peripheral pulmonary lesions (PPLs), although the yield is not satisfactory for lesions that cannot be located by EBUS. We aimed to evaluate whether the addition of a new technique, transbronchial needle aspiration through a guide sheath (GS-TBNA), can increase the yield for these cases. Methods This was a retrospective review of cases that were not located by EBUS during EBUS-GS for PPL diagnosis. From September 2012 to August 2014, 67 PPLs had ‘invisible’ EBUS-GS location prior to transbronchial sampling. The patients were divided into two groups according to the use of additional GS-TBNA: GS-TBNA group (n=22) and non-GS-TBNA group (n=45). Diagnostic yields were compared and multivariate analysis was performed to determine the factors associated with increased diagnostic yield. Results The diagnostic yield was significantly higher in the GS-TBNA group than in the non-GS-TBNA group (54.5% vs 17.8%, P

Background and Aims The application of radial probe endobronchial ultrasound (R-EBUS) and virtual bronchoscopic navigation has improved the diagnostic outcome of bronchoscopy for peripheral pulmonary lesions (PPLs). Nonetheless, while existing navigation systems are very useful for selecting the bronchus containing the target lesion, the associated introductory costs are high. Therefore, we focused on virtual bronchoscopy (VB) using the workstation, ziostation that was already available in many countries as an adjunct modality. Methods Consecutive patients who underwent bronchoscopy with R-EBUS for PPLs (major diameter ≤30 mm) were enrolled. From late June 2013 to November 2013, 121 patients were examined with ziostation, and from September 2012 to early June 2013, 113 patients were examined without ziostation. We compared the diagnostic yield, EBUS detection rate and procedure time between two groups to evaluate the utility of the VB. Results The ziostation group had significantly higher diagnostic yield than the non-ziostation group (77.7% vs 64.6%, P = 0.030). Following the multivariate analysis, use of ziostation was a significant factor affecting the diagnostic yield. Meanwhile, EBUS detection rate was significantly higher in the ziostation group (94.2% vs 75.2%, P

Radial endobronchial ultrasound (R-EBUS) is a useful tool for precise localisation of peripheral pulmonary lesions, but there have been no detailed reports about the use of R-EBUS images for ground-glass opacity (GGO).The R-EBUS images of 116 patients with GGO, who were diagnosed as having adenocarcinoma by R-EBUS with a guide sheath (EBUS-GS), were compared with the respective chest computed tomography findings. In 103 patients, R-EBUS images were correlated with the histological surgical specimens.R-EBUS images of GGO were identified based on the internal structure of the lesion and classified into two groups. Blizzard showed an enlarged, diffuse hyperintense acoustic shadow. Mixed blizzard showed a combination of blizzard and some diffuse heterogeneity with several hyperechoic dots and vessels. All pure GGO lesions (nine out of nine) were blizzard on R-EBUS. For part-solid GGOs, the percentage of mixed blizzard was inversely related to the amount of the GGO component. Histological findings from surgery revealed that all blizzard lesions were on the spectrum of adenocarcinoma in situ to well differentiated adenocarcinoma while majority (33 out of 64) of mixed blizzard lesions were moderately to poorly differentiated adenocarcinoma.R-EBUS types are important to locate GGOs prior to transbronchial sampling with EBUS-GS.

Background: Diagnostic bronchoscopy has been considered as a safe and effective procedure. Endobronchial ultrasound with a guide sheath (EBUS-GS) for the diagnosis of peripheral pulmonary lesions (PPLs) is becoming a common procedure, but reports about its safety are missing. Objectives: The aim of this study was to evaluate the safety profile of EBUS-GS for the diagnosis of PPLs. Methods: All patients with PPLs who underwent EBUS-GS between September 2012 and August 2014 at the National Cancer Center Hospital were included. Postprocedural complications and the durability of devices were retrospectively reviewed. Results: During the study period, EBUS-GS procedures were performed for 965 PPLs. The overall complication rate was 1.3% (13/965): 0.8% (8/965) for pneumothorax and 0.5% (5/965) for pulmonary infection. There was no significant hemorrhage, air embolism, tumor seeding or procedure-related death, and there was no breakage of the guide sheath. Only four radial probes were broken during the study period without any adverse reactions. Conclusions: EBUS-GS is a tolerable procedure, and the devices are durable.

Background With the release of the National Lung Screening Trial results, the detection of peripheral pulmonary lesions (PPLs) is likely to increase. Computed tomography (CT)-guided percutaneous transthoracic needle biopsy (PTNB) and radial probe endobronchial ultrasound (r-EBUS)-guided transbronchial lung biopsy (TBLB) are recommended for tissue diagnosis of PPLs. Methods A systematic review of published literature evaluating the accuracy of r-EBUS-TBLB and CT-PTNB for the diagnosis of PPLs was performed to determine point sensitivity and specificity, and to construct a summary receiver-operating characteristic curve. Results This review included 31 publications dealing with EBUS-TBLB and 14 publications dealing with CT-PTNB for the diagnosis of PPLs. EBUS-TBLB had point sensitivity of 0.69 (95% CI: 0.67-0.71) for the diagnosis of peripheral lung cancer (PLC), which was lower than the sensitivity of CT-PTNB (0.94, 95% CI: 0.94-0.95). However, the complication rates observed with EBUS-TBLB were lower than those reported for CT-PTNB. Conclusions This meta-analysis showed that EBUS-TBLB is a safe and relatively accurate tool in the investigation of PLC. Although the yield remains lower than that of CT-PTNB, the procedural risks are lower.

Objective: Endobronchial ultrasound elastography is a new technique for describing the stiffness of tissue during endobronchial ultrasound-guided transbronchial needle aspiration. The aims of this study were to evaluate the utility of endobronchial ultrasound elastography for mediastinal and hilar lymph nodes, and to compare the elastographic patterns of lymph nodes with results from endobronchial ultrasound-guided transbronchial needle aspiration. Methods: Seventy-five lymph nodes were evaluated. A convex probe endobronchial ultrasound was used with a new endoscopic ultrasound processor to assess elastographic patterns that were classified based on color distribution as follows: Type 1, predominantly non-blue (green, yellow and red); Type 2, part blue, part non-blue (green, yellow and red); Type 3, predominantly blue. The elastographic patterns were compared with the final pathologic results from endobronchial ultrasound-guided transbronchial needle aspiration. Results: On pathological evaluation of the lymph nodes, 33 were benign and 42 were malignant. The lymph nodes that were classified as Type 1 on endobronchial ultrasound elastography were benign in 24/24 (100%); for Type 2 lymph nodes, 6/14 (46.9%) were benign and 8/14 (57.1%) were malignant; Type 3 lymph nodes were benign in 2/37 (5.4%) and malignant in 35/37 (94.6%). In classifying Type 1 as ‘benign’ and Type 3 as ‘malignant,’ the sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy rates were 100, 92.3, 94.6, 100 and 96.7%, respectively. Conclusions: Endobronchial ultrasound elastography of mediastinal and hilar lymph nodes is a noninvasive technique that can be performed reliably and may be helpful in the prediction of nodal metastasis during endobronchial ultrasound-guided transbronchial needle aspiration.

Desmoplastic malignant mesothelioma (DMM) is a rare subtype of malignant pleural mesothelioma (MPM) and is often difficult to distinguish from pleural fibrosis and reactive mesothelial hyperplasia, especially if the biopsy samples are small. We performed full-thickness pleural biopsy on a lesion suspected to be DMM using an insulated-tip diathermic knife-2 (IT knife-2) during flex-rigid pleuroscopy. IT knife-2 is a novel electrosurgical device for endoscopic submucosal dissection in the early gastrointestinal cancer. It consists of a needle knife with 3 short blades at the distal end attached to an insulated ceramic tip. A 54-year-old man presenting with chest wall mass and thickened pleura, in whom a computed tomography-guided percutaneous needle aspiration had remained negative, underwent flex-rigid pleuroscopy for definitive diagnosis. While applying electric current, we used the IT knife-2 to incise the pleura in a circular shape just above the endothoracic fascia. The incised pleura was removed by forceps and examined pathologically. The microscopic examination was compatible with DMM. We discovered that pleuroscopic punch biopsy using IT knife-2 can diagnose DMM. Use of IT knife-2 during flex-rigid pleuroscopy can obtain sufficient samples from densely thickened pleura, which is difficult to diagnose with small biopsies.

Background Many cancers metastasize to bone, which may cause an increase in bone resorption because of the direct effects of the tumor itself or osteoclastic activation. Patients and Methods Levels of urinary cross-linked N-telopeptide of type I collagen (uNTx) and serum cross-linked N-telopeptide of type I collagen (sNTx) were measured in 100 patients with lung cancer and 50 patients with benign respiratory disease using the Osteomark NTx urine and serum assays (Osteomark, Princeton, NJ). Bone metastasis was diagnosed by bone scintigraphy. Receiver operating characteristic (ROC) analysis was used to evaluate the detection of bone metastasis. Sensitivity and specificity to detect bone metastasis were calculated when cutoff points were set to 64 nmol bone collagen equivalents (BCE)/mmol Cr for uNTx and 22 nmol BCE/L for sNTx. Results Patients with lung cancer and bone metastasis had significantly higher levels of both uNTx and sNTx (uNTx median [range], 61.3 [22.7-593.1] nmol BCE/mmol creatinine [Cr]; sNTx median [range], 19.7 [10.7-97.1] nmol BCE/L) than did patients with lung cancer without bone metastasis (uNTx median [range], 45.2 [19.8-153.0] nmol BCE/mmol Cr; sNTx median [range], 16.7 [11.0-28.4] nmol BCE/L), or patients with benign respiratory diseases (uNTx median [range], 40.6 [15.2-155.9] nmol BCE/mmol Cr; sNTx median [range], 14.8 [9.5-55.5] nmol BCE/L.). There was good correlation between uNTx and sNTx ( R = 0.807). Area under the curve (AUC) for ROC was 0.743 for uNTx and 0.712 for sNTx. The sensitivity and specificity for the diagnosis of bone metastasis were 48.0% and 86.0%, respectively, using uNTx, and 40.0% and 87.0%, respectively, using sNTx. Conclusion This prospective study indicates equivalency between sNTx and uNTx in sensitivity and specificity to detect bone metastasis, and both uNTx and sNTx may have value as aids in the diagnosis of bone metastasis in patients with lung cancer.

Background and objective The yield of biopsy performed during bronchoscopy is reduced if the lesion is smaller than 30 mm. We evaluated the performance of a new diagnostic technique combining endobronchial ultrasonography with a guide sheath (EBUS-GS) and a virtual bronchoscopic navigation system, LungPoint (Broncus Technologies, Inc., Mountain View, CA, USA), for the diagnosis of small (≤30 mm) peripheral pulmonary lesions (PPL). Methods Between May 2011 and December 2011, we recruited 68 consecutive patients presenting with a PPL 30 mm or less in diameter determined by chest computed tomography. We used the LungPoint system before bronchoscopy to identify the bronchus into which the bronchoscope should be advanced. We used a thin bronchoscope. EBUS-GS was performed using an endoscope ultrasonography system equipped with a 20-MHz mechanical radial-type probe. We used a guide sheath with an external diameter of 1.95 mm, thin forceps and brushing. Results The diagnostic yield of the 68 PPL was 77.9%; it was 83.7% and 68.0% for the malignant and benign lesions, respectively. Notably, three cases were diagnosed by transbronchial needle-aspiration cytology alone. Univariate and multivariate analyses showed that the EBUS probe localization was the most significant contributor to successful diagnosis (diagnostic yield: within vs adjacent to the lesion = 92.1% vs 60.0%, respectively; P = 0.004 and P = 0.003, respectively). Conclusions The combination of EBUS-GS and LungPoint was useful for diagnosing small PPL.

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.

Lung cancer is the leading cause of cancer-related death. Many patients with lung cancer are in its advanced stages at the time of diagnosis. The 5-year survival rate for lung cancer is 10% to 20%, and the prognosis for patients with lung cancer is still poor. The crosslinked N-terminal telopeptide of type I collagen (NTx) is a metabolite of type I collagen, the main constituent of bone matrix.We measured serum NTx levels in patients who underwent staging during hospitalization for the initial treatment of lung cancer in our department. We examined whether serum NTx levels would be relevant to the prognosis of non-small-cell lung cancer (NSCLC).This study included 176 patients with lung cancer (125 men and 51 women), including 109 with adenocarcinoma, 53 with squamous cell carcinoma, 6 with large-cell carcinoma, and 8 with other cancer types. Univariate and multivariate analysis using the Cox proportional hazards model revealed a particularly close association between sex, performance status, disease stage, and serum NTx levels and overall survival (OS). A median OS of 368 days was observed for patients with a serum NTx level22 nmol BCE/L, which was significantly longer than the 197 days for patients with a serum NTx level ≥ 22 nmol BCE/L (hazard ratio [HR], 2.02; 95% confidence interval [CI], 1.36-2.99; log-rank P = .00037).We have revealed that a high serum NTx level (22 nmol BCE/L) appears to be a risk factor for a reduction in OS in patients with NSCLC.

Background: Differentiating between Pneumocystis jiroveci pneumonia (PCP) and drug-induced pulmonary parenchymal disease (DIPPD) is difficult after chemotherapy for solid tumors. The aim of this study was to evaluate the utility of bronchoalveolar lavage fluid (BALF) analysis for the diagnosis of PCP and DIPPD.Methods: We evaluated patients who underwent bronchoscopy at our institution from April 2012 to December 2014. Patients’ characteristics, comorbidity, previous treatment of solid tumor, and BALF findings were examined from the medical records.Results: From a total of 2625 consecutive patients who underwent bronchoscopy, 89 underwent BALF examination; among these, 33 cases had prior chemotherapy for malignancy. PCP was diagnosed in 6 patients and DIPPD was diagnosed in 21 patients. Six patients were diagnosed to have other pathologies or were undiagnosed. The white blood cell count in BALF (PCP (median (%) (range), DIPPD (median (%) (range)) consisted of macrophages (24.7 (6.9-46.1), 26.5 (2.1-86.0)), lymphocytes (71.3 (49.6-84.8), 57.0 (4.3-96.4)), neutrophils (4.6 (1.0-14.0), 5.0 (0.5-69.8)), and eosinophils (0.3 (0-1.3), 2.5 (0-37.0)). Only the proportion of eosinophils in the BALF of DIPPD patients was significantly higher (p = 0.016) than that of PCP patients. BAL was performed without serious complications.Conclusions: BALF differential count, especially eosinophils, may be useful in distinguishing between PCP and DIPPD to avoid unnecessary treatment. Further prospective studies would be needed to confirm this benefit of BAL.

The flex-rigid pleuroscope, which has a handle that is similar in design to a standard flexible bronchoscope, is easy to handle and covers a wide field. It is important to perform the procedure in cooperation with a surgeon, while noting that there is a limit. Systematic surveillance during medical thoracoscopy will shorten procedure time and can reduce errors. During pleuroscopy for dry pleural dissemination, identification of the mobility between the parietal and visceral pleura during breathing (sliding sign) by linear probe transthoracic ultrasonography can prevent damage to the lung parenchyma during insertion of the trocar. Full-thickness biopsy is essential in the differential diagnosis of densely thick pleura. Pleuroscopic punch biopsy using insulated-tip diathermic knife (IT knife 2) is a feasible technique for a successful diagnosis of unknown pleural disease. One tip is to hook the short blades of the IT knife 2 into the pleura, then incise while lifting the pleura obliquely.

Central airway obstruction from the trachea to the segmental bronchi is an indication for therapeutic bronchoscopy. It is important to understand the techniques, advantages, and disadvantages of each procedure. Noting the accompanying serious risk in any treatment modality, the bronchoscopist should always be prepared in managing the worst scenario.

Do not forget that every new technology has been born out of a basic procedure that has long been introduced. A fast way to proficiency is to master bronchoscope handling.

Diagnostic bronchoscopy for peripheral pulmonary lesions is not yet established. At present, the method varies according to the preferences of the physicians. A new middle-range diameter bronchoscope with a large working channel (prototype thin 1T scope) combines the function of a large scope and a thin or ultrathin scope to enable farther reach to the periphery while maintaining the ability to collect adequate specimen.

Airway stenosis may occur in both benign and malignant diseases, but is most often due to lung cancer. Stent placement is carried out properly with the use of the flexible and/or rigid bronchoscopes. Close cooperation of respiratory physician, respiratory surgeon, radiologist, and anesthesiologists is essential.

Background Some trials recently demonstrated the benefit of targeted treatment for malignant disease; therefore, adequate tissues are needed to detect the targeted gene. Pleural biopsy using flex-rigid pleuroscopy and pleural effusion cell block analysis are both useful for diagnosis of malignancy and obtaining adequate samples. The purpose of our study was to compare the diagnostic utility between the two methods among patients with malignant pleural disease with effusion. Methods Data from patients who underwent flex-rigid pleuroscopy for diagnosis of pleural effusion suspicious for malignancy at the National Cancer Center Hospital, Japan between April 2011 and June 2014 were retrospectively reviewed. All procedures were performed under local anesthesia. At least 150 mL of pleural fluid was collected by pleuroscopy, followed by pleural biopsies from the abnormal site. Results Thirty-five patients who were finally diagnosed as malignant pleural disease were included in this study. Final diagnoses of malignancy were 24 adenocarcinoma, 1 combined adeno-small cell carcinoma, and 7 malignant pleural mesothelioma (MPM), and 3 metastatic breast cancer. The diagnostic yield was significantly higher by pleural biopsy than by cell block [94.2% (33/35) vs. 71.4% (25/35); p = 0.008]. All patients with positive results on cell block also had positive results on pleural biopsy. Eight patients with negative results on cell block had positive results on pleural biopsy (lung adenocarcinoma in 4, sarcomatoid MPM in 3, and metastatic breast cancer in 1). Two patients with negative results on both cell block and pleural biopsy were diagnosed was sarcomatoid MPM by computed tomography-guided needle biopsy and epithelioid MPM by autopsy. Conclusion Pleural biopsy using flex-rigid pleuroscopy was efficient in the diagnosis of malignant pleural diseases. Flex-rigid pleuroscopy with pleural biopsy and pleural effusion cell block analysis should be considered as the initial diagnostic approach for malignant pleural diseases presenting with effusion.

Objective The utility of rapid on-site evaluation during endobronchial ultrasound with a guide sheath for peripheral pulmonary lesions is unclear. The aim of this study was to evaluate the role of rapid on-site evaluation during endobronchial ultrasound with a guide sheath for peripheral pulmonary lesions. Methods Consecutive patients who underwent endobronchial ultrasound with a guide sheath for the diagnosis of peripheral pulmonary lesions at our hospital between September 2012 and July 2014 were included in this retrospective study. Cytology slides were air-dried, and modified Giemsa (Diff-Quik) staining was used for rapid on-site evaluation. Additional smears were prepared for Papanicolaou staining and tissue samples were placed in formalin for histologic evaluation. The results of rapid on-site evaluation were compared with the final diagnoses of endobronchial ultrasound with a guide sheath. Results A total of 718 cases were included in the study population. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of rapid on-site evaluation during endobronchial ultrasound with a guide sheath for peripheral pulmonary lesions was 88.6%, 65.9%, 81.2%, 77.7% and 80.1%, respectively. There were no procedure-related deaths. Conclusions Rapid on-site evaluation during endobronchial ultrasound with a guide sheath had high sensitivity for peripheral pulmonary lesions. When carrying out rapid on-site evaluation of transbronchial biopsy samples from peripheral pulmonary lesions, careful interpretation and clinical correlation are necessary.

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.

Small cell lung cancer with interstitial lung disease (ILD-SCLC) is difficult to treat because of the risk of fatal pneumonitis. Our study aims to evaluate the validity of topotecan (TOP) as chemotherapy for patients with relapsed ILD-SCLC. Overall survival was compared between TOP and other drugs as second-line treatments for ILD-SCLC patients. Forty-seven patients began chemotherapy and second-line treatment was administered in 48.5% of relapsed cases. The response rate of TOP for second-line therapy was 16.7%. Hematologic toxicities were grade 4 anemia, grade 3 neutropenia and grade 3 thrombocytopenia. Mild pulmonary toxicity was observed in 1 case. Patients receiving TOP as second-line treatment showed no significant difference in survival when compared to patients who underwent other regimens (median survival time 179 vs. 76 days; p =0.76). TOP is a well tolerated drug and is a viable candidate for second-line treatment of ILD-SCLC patients.

Background The aim of this study was to evaluate the factors contributing to an accurate diagnosis of small (≤15 mm) peripheral pulmonary lesions (PPLs) by standard bronchoscopy and to determine the most suitable technology for such a diagnosis. Objective Bronchoscopy was performed for 115 PPLs (≤15 mm diameter) on chest computed tomography (CT) between August 2003 and December 2006. Methods Univariate and multivariate analyses were conducted retrospectively with the R software. Results The diagnostic yield of the 115 PPLs was 65.2%; the yield was 61.9% and 69.2% for the malignant and benign lesions, respectively. In the univariate analysis, the approach to the lesion contributed the most to successful diagnosis, followed by skill and the use of hemostasis. In the multivariate analysis, the most important factor was approach, followed by lower lobe lesion and the use of hemostasis. Although it was better to use a sedative, operator skill was not a contributing factor. Conclusion The approach to the lesion is the most important factor for a successful diagnosis of PPLs by bronchoscopy. Bronchoscopy is time consuming and painful; therefore, it is very important to establish an accurate diagnosis as soon as possible. Further, endobronchial ultrasonography with a guide sheath (EBUS-GS) and navigation systems are useful tools for the diagnosis of small PPLs.

目的．当センターにおける外来化学療法の現状を評価し，非小細胞肺がんの外来化学療法の治療レジメンとその投与回数，および長期生存者について検討した．方法．2004年9月から2009年5月の間に当センターで外来化学療法を1レジメン以上行った症例を後ろ向きで検討した．結果．450症例が安全に外来化学療法を受けていた．450例の内訳は，306例が非小細胞肺がん，71例が小細胞肺がん，63例がその他のがん，10例が慢性関節リウマチであった．非小細胞肺がん症例のうち187例が根治的放射線照射を受けていないIIIB期またはIV期であった．187例中22例が3年以上生存し，長期生存者の多くは多レジメンで多サイクルの治療を受けていた．結論．当センターにおける外来化学療法は化学療法の期間を延長し，それによって予後が改善された可能性がある．

Targeted therapy against epidermal growth factor receptor (EGFR) represents a major therapeutic advance in lung cancer treatment. Somatic mutations of the EGFR gene, most commonly L858R (exon 21) and short in-frame exon 19 deletions, have been found to confer enhanced sensitivity toward the inhibitors gefitinib and erlotinib. We have recently identified an EGFR mutation E884K, in combination with L858R, in a patient with advanced lung cancer who progressed on erlotinib maintenance therapy, and subsequently had leptomeningeal metastases that responded to gefitinib. The somatic E884K substitution appears to be relatively infrequent and resulted in a mutant lysine residue that disrupts an ion pair with residue R958 in the EGFR kinase domain C-lobe, an interaction that is highly conserved within the human kinome as demonstrated by our sequence analysis and structure analysis. Our studies here, using COS-7 transfection model system, show that E884K works in concert with L858R in-cis, in a dominant manner, to change downstream signaling, differentially induce Mitogen-activated protein kinase (extracellular signaling-regulated kinase 1/2) signaling and associated cell proliferation and differentially alter sensitivity of EGFR phosphorylation inhibition by ERBB family inhibitors in an inhibitor-specific manner. Mutations of the conserved ion pair E884-R958 may result in conformational changes that alter kinase substrate recognition. The analogous E1271K-MET mutation conferred differential sensitivity toward preclinical MET inhibitors SU11274 (unchanged) and PHA665752 (more sensitive). Systematic bioinformatics analysis of the mutation catalog in the human kinome revealed the presence of cancer-associated mutations involving the conserved E884 homologous residue, and adjacent residues at the ion pair, in known proto-oncogenes (KIT, RET, MET and FAK) and tumor-suppressor gene (LKB1). Targeted therapy using small-molecule inhibitors should take into account potential cooperative effects of multiple kinase mutations, and their specific effects on downstream signaling and inhibitor sensitivity. Improved efficacy of targeted kinase inhibitors may be achieved by targeting the dominant activating mutations present.

A 79-year-old man presented with back pain. Chest CT scan showed elevated nodular lesions in the right parietal pleurae with pleural effusion. There were no intrapulmonary or mediastinal abnormalities. Under local anesthesia, right thoracoscopy and subsequent thoracoscopic pleural resection were performed using an insulation-tipped diathermic knife (IT-knife). The resected pleura, 2.2 cm in diameter, had a rough granular surface. Lymphoid cells histologically infiltrated diffusely into the pleura. They were composed of centrocyte-like and monocytoid cells. On immunohistochemistry they were found to be positive for Bcl2, CD20, CD45RB and CD79a, but negative for CD3, CD5, CD10 and cyclin D1. EBV-encoded small RNA-1 (EBER-1) in situ hybridization was negative. A diagnosis of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) arising in the pleura was therefore made. To the authors' knowledge this is the first case in which IT-knife was used for diagnosis of a pleural lesion. This large, single-piece, only slightly crushed pleural specimen, enabled study of histopathological findings (listed here) that could not have been obtained on conventional biopsy: (i) lack of apparent evidence of plasmacytic differentiation; (ii) no recognition of lymphoid follicles; (iii) mesothelial cells not infiltrated by lymphoma cell clusters; (iv) thin layer of hyperplastic mesothelial cells continuously covering the surface; and (v) no proliferation of fibroblast-like submesothelial cells.

Objective: Introduction of NPC-05 (sterile graded talc) into Japanese clinical practice is expected to lead to persistent prevention of re-accumulation of MPE and alleviation of concomitant symptoms in patients, including dyspnea and chest pain. We conduct an investigator-initiated trial in Japan to clarify the efficacy and safety of NPC-05 for use as a pleurodesis agent. Methods: This study is a multicenter uncontrolled open-label phase II study. An uncontrolled open-label joint clinical study is conducted in 6 institutes, involving 30 patients with MPE. Conclusion: Sterile graded talc has been described as the most useful pleurodesis drug for treating malignant pleural effusion in many guidelines and meta-analyses; thus, it is used as a standard pleurodesis agent in Western countries. However, its efficacy and safety have not been examined in Japan. This study assessed the efficacy and safety of NC-05, sterile graded talc, in 30 Japanese patients with malignant pleural effusion.

Paclitaxel often causes severe hypersensitivity reactions (HSRs) rapidly after infusion, even in patients given prophylactic therapy. The purpose of this study was to analyze the incidence of paclitaxel-related HSRs in patients with non-small cell lung cancer (NSCLC) retrospectively, and to assess the feasibility of a modified premedication protocol. One hundred and seven patients who were pretreated with either a conventional premedication regimen (two doses of dexamethasone) or a short premedication regimen (single dose of dexamethasone with oral diphenhydramine and intravenous ranitidine), prior to paclitaxel infusion were retrospectively analyzed. A modified premedication regimen, consisting of 12.5 ml of Rescalmin (intravenous diphenhydramine 50 mg and calcium bromide 437.5 mg), intravenous ranitidine 100 mg, and intravenous dexamethasone 20 mg, was given 30 min prior to paclitaxel, with oral dexamethasone 8 mg given on the night before the paclitaxel. Patients received paclitaxel intravenously at 175 mg/m2 over 3 h, followed by carboplatin, AUC 5, over 1 h on day 1 every 3 weeks. In the conventional premedication group, 21 patients had HSRs (32.3%); in 1 of these patients the HSR was considered to be severe (1.5%). In the short premedication group, 19 patients had HSRs (45.2%); in 6 of these patients the HSRs were considered to be severe (14.3%). The incidence of severe HSRs was significantly higher in the short premedication group than in the conventional premedication group (P = 0.027). In the modified premedication protocol study, HSR events were recorded in 14 patients (63.6%); 14 showed flushing, 2 had skin rash, and 1 had tachycardia. No severe HSRs were seen. The incidence of HSRs in the short premedication group tended to be higher than that in the conventional premedication group. The modified premedication protocol was found to be feasible for preventing paclitaxel-related HSR, but case accumulation is needed.

Objective: EBUS elastography (E-ELT) is a new technique for describing the stiffness of tissue during EBUS-TBNA. This study was to evaluate the utility of E-ELT type classification for thoracic lymph nodes (LNs). Methods: Seventy-five LNs were evaluated. E-ELT patterns were classified as follows: Type 1, predominantly non-blue; Type 2, part blue, part non-blue; Type 3, predominantly blue. The E-ELT patterns were compared with the pathologic results. Results: The LNs that were classified as Type 1 on E-ELT were benign in 24/24 (100%); for Type 2 LNs, 6/14 (46.9%) were benign and 8/14 (57.1%) were malignant; Type 3 LNs were benign in 2/37 (5.4%) and malignant in 35/37 (94.6%). In classifying Type 1 as “benign” and Type 3 as “malignant,” the sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy rate were 100%, 92.3%, 94.6%, 100% and 96.7%, respectively. The median values of FDG-PET SUV max were 2.49 for E-ELT Type 1, 4.95 for Type 2, and 8.50 for Type 3. The computed Spearman rank coefficient ( r ) was 0.54 (P Conclusions: EBUS elastography type classification is a useful tool with very high sensitivity, specificity and accuracy for differential diagnosis of mediastinal and hilar LNs. Aside from providing complementary information to conventional EBUS imaging, it may potentially increase the diagnostic yield of EBUS-TBNA and reduce the number of unnecessary biopsies.

Introduction: Diagnostic yield of bronchoscopy for peripheral pulmonary lesions (PPLs) has improved since the application of radial endobronchial ultrasound (R-EBUS). The obtained EBUS image is known to relate the diagnostic yield. However, we sometimes fail to diagnose even if we get the EBUS within image. So we attempted to find out the factors that are difficult to diagnose for these cases. Materials and Methods: Consecutive patients who underwent bronchoscopy with R-EBUS for PPL in 2013 were collected. The cases that EBUS within image was obtained and finally malignant tumor was proven were enrolled. Each transbronchial biopsy results were checked and the biopsy success rates were calculated. And the cases were divided into the following groups; a) easy group: equal and more than one-third of biopsies were success to prove malignancy, b) difficult group: less than one-third of biopsies were success. We compared factors likely to affect the biopsy success rate between the two groups. Results: Total 206 malignant tumors were enrolled and the diagnostic yield of bronchoscopy was 86.4 %. Meanwhile, total 1108 transbronchial biopsies were performed and 656 were success to prove malignancy (59.2 %). The biopsies were found to be significantly easier in PPLs with spiculation ( p = 0.018) and in PPLs with stenosed bronchi ( p = 0.028). These findings indicated that highly invasive tumor had the tendency to expose more to the involved bronchus. Conclusion: In addition to the reachability to the involved bronchus, we should take care that the invasion findings of PPLs.

The bone resorption biomarker cross-linked N-Telopeptides of type I collagen (NTx) has been shown to aid in the diagnosis of metastatic bone disease from lung cancer (MBDLC). Patients with MBDLC are often treated with zoledronic acid (ZA). ZA reduces the levels of NTx and also lowers the risk of skeletal adverse events in patients with MBDLC.Patients with MBDLC at initial diagnosis were included in the study. NTx was measured in serum (sNTx) once a month using the OSTEOMARKTM sNTx assay. MBDLC was assessed by monthly physical examinations and bone scintigraphy every 3 months for 12 months.Twenty patients were enrolled between June and December 2010. The sNTx concentration at baseline was 19.8 ± 5.8 nmol bone collagen equivalents (nmol BCE)/l. In the 16 patients receiving ZA, the level of sNTx significantly decreased after the first month of treatment (baseline vs. 1 month of treatment: 21.3 ± 5.5 vs. 13.6 ± 2.7 nmol BCE/l; p0.01). During the follow-up period, 13 of the patients treated with ZA experienced worsening of bone metastasis. There were statistically significant differences in the levels of sNTx at baseline (20.3 ± 4.8 nmol BCE/l), at the lowest levels after administration of ZA (11.8 ± 2.9 nmol BCE/l vs. baseline; p0.001), and at the time of measurable disease progression (14.1 ± 4.6 nM BCE/l vs. baseline; p0.05).Serial measurements of sNTx in patients with MBDLC treated with ZA may effectively predict disease progression.

Recently, the double contrast technique in a gastrointestinal examination and the transbronchial lung biopsy in an examination for the respiratory system [1-3] have made a remarkable progress. Especially in the transbronchial lung biopsy, better quality of x-ray fluoroscopic images is requested because this examination is performed under a guidance of x-ray fluoroscopic images. On the other hand, various image processing methods [4] for x-ray fluoroscopic images have been developed as an x-ray system with a flat panel detector [5-7] is widely used. New noise reduction processing, Adaptive Noise Reduction [ANR], was announced in SPIE last year.[8] ANR is a new image processing technique which is capable of extracting and reducing noise components regardless of moving objects in fluoroscopy images. However, for further enhancement of noise reduction effect in clinical use, it was used in combination with a recursive filter, which is a time axis direction filter. Due to this, the recursive filter generated image lags when there are moving objects in the fluoroscopic images, and these image lags sometimes became hindrance in performing smooth bronchoscopy. This is because recursive filters reduce noise by adding multiple fluoroscopy images. Therefore, we have developed new image processing technique, Motion Tracking Noise Reduction [MTNR] for decreasing image lags as well as noise. This ground-breaking image processing technique detects global motion in images with high accuracy, determines the pixels to track the motion, and applies a motion tracking-type time filter. With this, image lags are removed remarkably while realizing the effective noise reduction. In this report, we will explain the effect of MTNR by comparing the performance of MTNR images [MTNR] and ANR + Recursive filter-applied images [ANR + Recursive filter].

The combination of chemotherapy and thoracic radiation therapy (TRT) is considered as a standard treatment for locally advanced non-small-cell lung cancer (NSCLC). Although the frequent interaction of anticancer agents and irradiation may produce stronger radio-sensitizing effects, the daily administration of these agents is complicated. We therefore used weekly administration of these agents, and conducted a phase I study of weekly cisplatin, vinorelbine, and concurrent TRT. The purpose of this study was to identify the maximum tolerated dose (MTD), the dose-limiting toxicity (DLT), and the recommended dose of this treatment.Patients with locally advanced NSCLC were enrolled in this study. Both cisplatin and vinorelbine were given intravenously on a weekly schedule for 6 weeks, starting on the first day of TRT, i.e., on days 1, 8, 15, 22, 29, and 36. The total dose of TRT was 60 Gy. The dose of cisplatin was fixed at 20 mg/m(2) per week. The starting dose of vinorelbine was 15 mg/m(2) per week (dose level 1).Nine patients were enrolled in this study. All three patients at dose level 1 experienced DLTs. We decreased the dose of vinorelbine to 10 mg/m(2) per week (dose level 0). Two of the six patients at dose level 0 experienced DLTs. Therefore, dose level 1 was considered as the MTD, and dose level 0 as the recommended dose. The DLTs of this treatment were esophagitis, fatigue, infection, and hyponatremia.The recommended dose of cisplatin is 20 mg/m(2) per week and that of vinorelbine is 10 mg/m(2) per week with standard TRT. A phase II study of this treatment is warranted.

Objectives: To evaluate the usefulness of the Sasada transbronchial angled forceps (STAF) in patients with peripheral pulmonary lesions (PPLs), which are difficult to manipulate with standard forceps. Methods: We have invented the STAF, a forceps with an angled tip. One hundred ten patients with PPLs that were difficult to reach with standard forceps were retrospectively evaluated. The patients first underwent bronchoscopy with a standard forceps and then with the STAF. The specimens obtained with standard forceps and those obtained with STAF were separately fixed and analyzed histologically. We compared the histologic diagnosis of the specimens obtained by STAF with that obtained by the specimens obtained with standard forceps. Statistical significance was calculated with the McNemar χ2 statistic. Results: The diagnostic yield of all lesions from the specimens obtained with STAF (86 of 110 lesions; 78.2%) was significantly higher than that of lesions from the specimens obtained with standard forceps (43 of 110 lesions; 39.1%; p Conclusions: The STAF was shown to be useful for obtaining specimens that were sufficient for histologic diagnosis from PPLs that were difficult to manipulate with standard forceps.

OBJECTIVE: Endobronchial ultrasound with a guide sheath has been a widely used diagnostic procedure for peripheral pulmonary lesions. After sequential sampling with the usual devices, small portions of the collected specimen remain in the guide sheath and these can potentially contribute to diagnosis. We assessed the diagnostic value of each histological and cytological sample, especially the guide sheath flush, for pulmonary malignancies. METHODS: The medical records of patients who were diagnosed to have peripheral lung cancer by endobronchial ultrasound with a guide sheath in our hospital between January 2014 and May 2014 were reviewed. Separate samples from forceps biopsy, bronchial brushing, device wash, guide sheath flush and bronchial lavage were compared and analyzed. RESULTS: A total of 106 consecutive patients (54 men, 52 women, median age 69.0 years) were included. The median long axis size of the lesions was 26.0 mm. A definitive diagnosis was made in 90.6% of forceps biopsy samples and in 85.8% of all cytology samples combined. Individual yields were 61.3% from brushing, 77.4% from device wash, 72.6% from guide sheath flush and 32.1% from bronchial lavage. The diagnosis yield from forceps biopsy was significantly higher than each cytological sampling method (P < 0.05). Among the cytological sampling methods, yield from bronchial lavage was significantly the lowest (P < 0.001). CONCLUSIONS: Forceps biopsy is an important sampling method during endobronchial ultrasound with a guide sheath for peripheral pulmonary lesions. In the collection of diagnostic liquid samples, guide sheath flush is more advantageous than bronchial lavage and provides specimen that may be adequate for molecular testing.

The application of radial probe endobronchial ultrasound (R-EBUS) and virtual bronchoscopic navigation has improved the diagnostic outcome of bronchoscopy for peripheral pulmonary lesions (PPLs). Nonetheless, while existing navigation systems are very useful for selecting the bronchus containing the target lesion, the associated introductory costs are high. Therefore, we focused on virtual bronchoscopy (VB) using the workstation, ziostation that was already available in many countries as an adjunct modality.Consecutive patients who underwent bronchoscopy with R-EBUS for PPLs (major diameter ≤30 mm) were enrolled. From late June 2013 to November 2013, 121 patients were examined with ziostation, and from September 2012 to early June 2013, 113 patients were examined without ziostation. We compared the diagnostic yield, EBUS detection rate and procedure time between two groups to evaluate the utility of the VB.The ziostation group had significantly higher diagnostic yield than the non-ziostation group (77.7% vs 64.6%, P = 0.030). Following the multivariate analysis, use of ziostation was a significant factor affecting the diagnostic yield. Meanwhile, EBUS detection rate was significantly higher in the ziostation group (94.2% vs 75.2%, P 0.001). And, procedure time was significantly shorter in the ziostation group (mean ± standard deviation: 24.0 ± 7.4 min vs 26.9 ± 7.9 min, P = 0.005).VB offered by the workstation was a valuable tool that facilitated more accurate and rapid bronchoscopy procedure for diagnosis of PPLs.

Background Several studies have assessed the expression of programmed death-ligand 1 (PD-L1) in resected surgical specimens of non–small-cell lung cancer (NSCLC). However, the expression of PD-L1 in smaller biopsy samples of advanced NSCLC has not been reported. Patients and Methods A total of 79 patients with NSCLC at our institution with available biopsy samples and resected specimens were retrospectively enrolled in the present study. PD-L1 expression was assessed by immunohistochemistry and scored using the hybrid scoring method. The concordance rates for the expression of PD-L1 between the 2 samples were analyzed. Results The pathologic stage of the patients (51 men, 28 women; median age, 68 years) was stage I in 37, stage II in 18, and stage III in 24. The diagnostic procedures included transbronchial biopsy in 59, transbronchial needle aspiration biopsy in 14, and computed tomography (CT)-guided needle biopsy in 6. The positivity rate of PD-L1 in these samples was 38.0% (27 transbronchial biopsies, 6 transbronchial needle aspiration biopsies, 3 CT-guided needle biopsies) versus 35.4% in the resected specimens. The median hybrid score was 0 (range, 0-170), and the mean score was 28.7 ± 43.4. Comparing the biopsy samples and resected specimens with a score of ≥ 1 as positive for PD-L1 staining, 6 tumors were discordant for PD-L1 expression and 73 were concordant, for a concordance rate of 92.4% and κ value of 0.8366. Conclusion PD-L1 status showed good concordance between the biopsy samples and resected specimens. These small samples, even those derived from transbronchial needle aspiration biopsies, appear adequate for the assessment of PD-L1 expression.

Radial endobronchial ultrasound with a guide sheath (EBUS-GS) has improved the diagnostic accuracy of transbronchial biopsy (TBB) for malignant peripheral pulmonary nodules (PPNs). Many underscore the importance of tumor localization but reproducible results on other aspects that affect yield are few. We aimed to analyze the diagnostic performance of TBB with EBUS-GS and to know what group of patients can benefit most.The database of patients with malignant PPNs (≤30 mm) who underwent EBUS-GS TBB at the National Cancer Center Hospital, Tokyo, Japan from April 2012 to March 2013 was retrospectively reviewed and analysed based on lesion and procedural characteristics.Most PPNs (N=212) were adenocarcinoma, measuring 20 mm [mean, standard deviation (SD) 5.45]. Overall diagnostic accuracy was 67.5% (143 of 212 cases). Factors that significantly affected and predicted diagnostic success were EBUS probe within (P=0.001) and parenchymal location that was not adjacent to the costal visceral pleura (P=0.001). When combined, these variables achieved an 87% (59 of 68 lesions) diagnostic yield. CT scan characteristic, lesion size, lobe location, and GS size were non-contributory.EBUS-GS TBB is an acceptable diagnostic method for small peripheral lung cancer. It can be maximized for PPNs that are away from the pleura and when the EBUS probe can be placed within the lesion.

Objective: Endobronchial ultrasound-guided transbronchial needle aspiration is widely used for mediastinal and hilar lesions. Histologic specimens from this procedure are important for specific diagnosis and targeted therapy. Studies on the traditional endobronchial ultrasoundguided transbronchial needle aspiration needles reported yields of only 50‐60% for diagnostic histologic specimens. Recently, a new needle has become available in Europe, USA and Asia. The investigators aimed to evaluate the histologic specimen retrieval yields of the two needles. Methods: Patients who underwent endobronchial ultrasound-guided transbronchial needle aspiration with the new 22 G needle (M group, n ¼ 94) were compared with a historical control group who underwent endobronchial ultrasound-guided transbronchial needle aspiration with the traditional 22 G needle (O group, n ¼ 82). The quality of needle aspirates from both groups was evaluated. Results: There were no significant differences between the two groups in terms of demographics, lesion characteristics, primary disease and examiner experience. The M group had a significantly shorter procedure time than the O group (P ¼ 0.049). Of the 214 punctures by the M group, 159 (74.3%) were diagnostic, 28 (13.1%) were non-diagnostic and 27 (12.6%) had no histologic specimen. The 235 punctures by the O group were diagnostic in 144 (61.3%), nondiagnostic in 60 (25.5%) and had no histologic specimen in 31 (13.2%). The yield for diagnostic histologic specimens of the M group was significantly higher than the O group (P ¼ 0.0035). There were no major complications observed. Conclusions: The yield for diagnostic histologic specimens by the new 22 G endobronchial ultrasound-guided transbronchial needle aspiration needle was high. Further technical improvements of histologic sampling yields are very important when selecting targeted therapy.

Objective Medical thoracoscopy using a flex-rigid pleuroscope under local anesthesia is a recent diagnostic procedure for malignant pleural disease. Although most previous studies have reported its usefulness, especially in wet pleural dissemination, the feasibility of flex-rigid pleuroscopy in patients with dry pleural dissemination is not well established.We assessed the diagnostic performance of flex-rigid pleuroscopy under local anesthesia in patients suspected of dry pleural dissemination on radiography. Methods The pleuroscopic parameters of all patients (n = 56) who underwent flex-rigid pleuroscopy at the National Cancer Center Hospital from October 2011 to September 2013 were retrospectively reviewed. Those with computed tomography findings of asymmetric pleural thickening or pleural nodules without pleural effusion (dry group, n = 16) were compared with the remaining patients with pleural effusion (wet group). Results The dry group consisted of eight men and eight women, with a median age of 61 years (range, 48-79 years). The definitive diagnoses were adenocarcinoma (n = 10), mesothelioma (n = 2) and chronic inflammation (n = 3). The diagnostic accuracy was 93.8% (15/16). Only two minor complications were observed: mild chest pain (n = 1) and transient hypoxia (n = 1). No major complications such as pneumothorax were observed. The mean duration of post-operative chest tube drainage in the dry group was 2.31 ± 2.26 days. Complications, operation duration and diagnostic accuracy did not statistically differ between the two groups. Conclusions Flex-rigid pleuroscopy under local anesthesia can be a well-tolerated diagnostic procedure for radiographic dry pleural dissemination with respect to diagnostic yield and complications.

Purpose Although, endobronchial ultrasonography with a guide sheath is becoming a common procedure for the diagnosis of peripheral pulmonary lesions, there remain to be some inaccuracies in cases wherein the probe is located outside the lesion. We tested whether adding transbronchial needle aspiration through a guide sheath to the conventional technique increases efficacy for diagnosing peripheral pulmonary lesions. Methods We performed transbronchial needle aspiration through a guide sheath for 37 subjects with peripheral pulmonary lesions between September 2012 and April 2013. The devices used were as follows (all Olympus Ltd., Tokyo, Japan): 1T-260 or LF-TP bronchoscope, K203 guide sheath kit and NA-1C-1 needle apparatus, customized by cutting the guide sheath 30 mm from the proximal end to fit well with the needle. Results The endobronchial ultrasound probe was located within the lesion in 21 cases (56.8%) and outside in 16 cases (43.2%). Overall accuracy was 86.5 percent; 90.5% in "within" cases compared to 81.3% in "outside" cases with no significant difference (P = 0.42). Pneumothorax occurred in 2 cases and pneumonia in 1 case. Conclusion Transbronchial needle aspiration through a guide sheath is an effective and safe diagnostic procedure for peripheral pulmonary lesions, especially when the guide sheath is outside the lesion.

A 64-year-old man who underwent sigmoid resection for Stage 4 colon cancer had a growing nodule on the left upper lobe during follow-up. Surgical resection revealed primary pulmonary adenocarcinoma. Subsequently, a new nodule appeared in the contralateral S(1)b, for which endobronchial ultrasonography with a guide sheath (EBUS-GS) was performed for diagnosis. However, histopathologic examinations were inconclusive. Gene analysis of the liquid samples from this lesion revealed KRAS mutation, which on hindsight was not detected in the metachronous left upper lobe cancer but was detected in the resected sigmoid colon. Hence, the right upper lobe nodule was diagnosed by bronchoscopy as colon cancer metastasis, confirmed after wedge resection. For specimen obtained by EBUS-GS, search for gene mutation in the liquid specimen is useful as an ancillary test especially when histological diagnosis is equivocal. Thus, developments on diagnostic tools using liquid samples are highly expected in the future.

Aims Pulmonary ground-glass nodules (GGNs) are frequently observed. Histopathologically, their presentation can indicate a wide range of disorders from an inflammatory process to malignancy. An accurate diagnosis based on GGNs can sometimes be challenging on small-sized biopsies. Mutations in the EGFR gene are detected in pulmonary adenocarcinomas (ADCs). Immunohistochemical analysis using antibodies that detect specific EGFR mutations has been shown to correlate with mutational status as determined by molecular methods. We hypothesized that these antibodies could be used to discriminate between ADCs and benign pneumocyte hyperplasias. Methods and results Surgically resected, pre-invasive to invasive lung ADC (n = 32) and reactive pneumocyte hyperplasia (n = 40) tissue samples were probed with antibodies against EGFR mutations, p53, Mouse double minute 2 and 14-3-3 sigma. Of the 32 lung ADC specimens analysed, 12 (38%) were positive using the EGFR mutation-specific antibodies, while no immunoreactivity was observed in reactive pneumocyte hyperplasia specimens. Analyses of receiver operating characteristic curves showed that the highest area under the curve values were associated with the use of EGFR mutation-specific antibodies. In addition, a high concordance rate was observed between surgically resected and corresponding biopsy materials using these antibodies. Conclusions EGFR mutation-specific antibodies can be used to discriminate between lung ADC and benign pneumocyte hyperplasia, even in small-sized biopsies.