Ultrathin bronchoscopic cryobiopsy of peripheral pulmonary lesions.

BACKGROUND AND OBJECTIVE: Ultrathin bronchoscopy aids in the diagnosis of peripheral pulmonary lesions. However, both the working channel and the specimens are small. A 1.1-mm ultrathin cryoprobe that can enter the working channel of the ultrathin bronchoscope is now available, which may overcome the limitations of small specimen size. The aim of this study was to evaluate the feasibility, efficacy and safety of ultrathin bronchoscopic cryobiopsy using an ultrathin cryoprobe for diagnosing peripheral pulmonary lesions. METHODS: Patients with peripheral pulmonary lesions ≤30 mm in diameter were prospectively enrolled in the study. All patients underwent forceps biopsy followed by cryobiopsy using a 3.0-mm ultrathin bronchoscope under radial probe endobronchial ultrasound guidance, virtual bronchoscopic navigation and fluoroscopic guidance. The primary endpoint was the feasibility of cryobiopsy. RESULTS: In total, 50 patients with peripheral pulmonary lesions were enrolled in the study; the median longest diameter on computed tomography was 17.9 mm. Cryobiopsy was performed successfully in 49 patients (98%). Forceps biopsy, cryobiopsy and the combination of these two methods provided a specific diagnosis in 54% (27/50), 62% (31/50) and 74% (37/50) of patients, respectively. The median size of specimens obtained via cryobiopsy was significantly larger than the median size obtained via forceps biopsy (7.0 vs. 1.3 mm2 , respectively, p < 0.001). Mild bleeding during cryobiopsy occurred in 47 patients (94%). No moderate/severe bleeding or pneumothorax occurred. CONCLUSION: Ultrathin bronchoscopic cryobiopsy is feasible, effective and sufficiently safe for the diagnosis of peripheral pulmonary lesions.

Changes in Pulmonary Function Test Results and Respiratory Symptoms before and after Airway Stent Removal.

BACKGROUND: Airway stenting is a useful form of palliation for patients with airway stenosis/fistulas; the stent can be removed after addressing the cause of the airway disorder. Patients with airway stents often complain of coughing and difficulty with expectoration, so the use of such stents can negatively affect pulmonary function and worsen symptoms. OBJECTIVES: The aim of this study was to compare pulmonary function and respiratory symptoms before and after stent removal. METHODS: Patients who would later undergo simple airway stent removal were prospectively recruited in two institutions. All stents were removed using both rigid and flexible bronchoscopes with patients under general anesthesia. Pulmonary function tests were performed before stent removal and at 1 and 4 weeks after stent removal. All patients self-reported their respiratory symptoms using a 100-mm visual analog scale (VAS). RESULTS: Of the 31 patients enrolled, 28 (23 with malignant stenoses, 3 with benign stenoses, and 2 with fistulas [21 silicone and 7 metallic stents]) were included in analyses. Pulmonary function measurements before stent removal and at 1 and 4 weeks after stent removal were as follows: vital capacity, 3.00, 3.04, and 3.08 L (p = 0.387); forced expiratory volume in 1 s, 1.96, 1.96, and 2.12 L (p = 0.034); and peak expiratory flow, 3.60, 4.28, and 5.06 L/s, respectively (p < 0.001). Symptoms (cough, sputum production, difficulty with expectoration, and dyspnea) evaluated using the VAS improved significantly after stent removal. No complications were encountered during removal. CONCLUSION: Removal of unnecessary airway stents improves pulmonary function and respiratory symptoms. Any stent that is no longer functioning should be removed.

Thin bronchoscopic cryobiopsy using a nasobronchial tube.

BACKGROUND: Transbronchial lung cryobiopsy is useful when diagnosing lung lesions. However, prevention of associated bleeding complications is essential. This study aimed to evaluate the safety and efficacy of our novel bronchoscopic cryobiopsy technique, which uses a long nasobronchial tube to prevent blood flooding the central airway. METHODS: Patients with localized or diffuse lung lesions were prospectively enrolled and underwent cryobiopsy using a 1.9 mm diameter cryoprobe and a 4.0 mm diameter thin bronchoscope under conscious sedation. For cryobiopsy, a long silicone tube (inner diameter, 5.0 mm) was advanced through the nose to the target bronchus, then wedged to drain blood under thin-tube bronchoscopic control. The primary endpoint was the frequency of bleeding complications. RESULTS: Of the 80 patients initially enrolled, 73 that underwent at least one cryobiopsy were ultimately included. Mild bleeding during cryobiopsy occurred in 58 patients (79.5%), but there was no moderate or severe bleeding. Other complications occurred in four patients (two pneumothorax, one pneumomediastinum, and one pneumonia). Tube dislocation was noted in eight patients (11%). Cryobiopsy specimens were significantly larger than forceps biopsy specimens (9.0 mm2 vs. 2.7 mm2, P < .001) and allowed specific diagnoses in 50 patients (68.5%). CONCLUSIONS: Thin bronchoscopic cryobiopsy using a nasobronchial tube in consciously sedated patients is safe and effective. Trial registration Date of registration: 24/06/2019. UMIN-Clinical Trials Registry; Identifier: UMIN000037156 https://www.umin.ac.jp/ctr/index.htm.

Assessment of habitat for disturbance-dependent species using light detection and ranging and multispectral sensors mounted on a UAV.

Recently, technological advances in UAV-mounted sensors, such as light detection and ranging (LiDAR) and multispectral sensors, have expanded the applications of unmanned aerial vehicles (UAVs) in ecosystem monitoring. LiDAR is suitable for analyzing the underlying microtopography of wetlands because it can produce a digital terrain model (DTM) with high spatial resolution. If a multispectral sensor that can also capture near-infrared wavelengths is used, it is possible to calculate the normalized difference vegetation index (NDVI), which is related to the amount of vegetation present, and the normalized difference water index (NDWI), which is related to the dryness and wetness of the soil. The purpose of this study was to understand the distribution of a disturbance-dependent species in wetlands using high spatial resolution images acquired with a consideration of phenology, and to evaluate the habitat of this disturbance-dependent species using data acquired by LiDAR and multispectral sensors. The wetland around the Omimaiko Inland Lake in Minamikomatsu, Otsu City, Shiga Prefecture, Japan, was chosen as the site for this study. I chose to examine the distribution of Euphorbia adenochlora as a disturbance-dependent species growing in the wetlands of the study area. Using high spatial resolution images acquired with a consideration of phenology, we were able to determine the distribution of the disturbance-dependent species E. adenochlora. Using the data obtained using LiDAR and multispectral sensors, we were able to evaluate its habitat and deduce its viability at six growth sites. This study aims to introduce a new way of applying UAVs in monitoring disturbance-dependent species in wetlands.

The Role of Rigid Bronchoscopic Intervention for Bronchial Carcinoid.

Bronchial carcinoid is a rare malignant tumor that is categorized as a typical carcinoid or atypical carcinoid. Many institutions use flexible bronchoscopy for diagnosis. However, due to the hemorrhagic nature of the tumor, the amount of specimen obtained is often small, making it difficult to obtain an accurate diagnosis. The use of rigid bronchoscopy may not only contribute to obtaining a diagnosis but also be beneficial in the treatment plan. The aim of this study was to evaluate the efficacy of rigid bronchoscopic interventions for the diagnosis and treatment of bronchial carcinoids. All patients with bronchial carcinoids who underwent rigid bronchoscopic intervention under general anesthesia at our institution between June 2006 and August 2018 were analyzed retrospectively. Eight patients [3 men and 5 women; median age, 71 years (range 45-82 years)] were eligible for the analysis. None of the cases had accurate subtyping preoperatively before intervention. In contrast, all cases were diagnosed as carcinoid with subtypes (5 patients had typical carcinoid and 3 had atypical carcinoid) following rigid bronchoscopic intervention. All respiratory symptoms improved immediately after the procedure. One instance of bleeding occurred, and was easily controlled by argon plasma coagulation and intraluminal administration of epinephrine under flexible and rigid bronchoscopy. Four patients (3 with typical carcinoid and 1 with atypical carcinoid) underwent radical surgery sequentially, and no recurrences were observed. We conclude that rigid bronchoscopic intervention is safe and effective for accurate diagnosis and improvement of respiratory symptoms in patients with bronchial carcinoids.

Smoking History as a Predictor of Pemetrexed Monotherapy in Patients with Non-Squamous Non-Small Cell Lung Cancer.

BACKGROUND: Pemetrexed monotherapy has come to be recognized as the standard of care for second-line therapy of non-squamous non-small cell lung cancer (NSCLC). Thymidylate synthase (TS) expression is recognized as a potential predictor of the response to pemetrexed-based chemotherapy in patients with advanced NSCLC. The purpose of this study was to identify useful predictors of the response to pemetrexed other than TS expression. METHODS: The records of non-squamous NSCLC patients without driver mutations who received pemetrexed monotherapy as a second or later line of chemotherapy at Kitasato University Hospital between March 2009 and October 2015 were retrospectively reviewed, and the treatment outcomes were evaluated. RESULTS: In the 116 patients with non-squamous NSCLC, the overall response rate and progression-free survival (PFS) were 10.3% and 2.1 months, respectively. The disease control rate and PFS differed significantly among current smokers and never-smokers/former light smokers (44.9 vs. 65.8%, and 1.8 vs. 4.0 months, respectively). Furthermore, multivariate analysis identified Eastern Cooperative Oncology Group Performance Status and smoking status as independent predictors of the PFS. CONCLUSION: The clinical data obtained in this study may provide a valuable basis for the use of smoking status as a predictor of pemetrexed monotherapy in wild-type NSCLC patients.

A case of community-acquired Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus (MRSA) necrotizing pneumonia successfully treated with two anti-MRSA drugs.

A 22-year-old Vietnamese man was referred to our hospital owing to cough, dyspnea, and difficulty moving. The patient was diagnosed with community-acquired Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and necrotizing pneumonia. Treatment involved vancomycin (VCM) and meropenem, and the MRSA bacteremia improved. However, lung tissue destruction progressed. Therefore, linezolid was added to the VCM regimen, and this intervention led to the patient's recovery, and he was discharged from the hospital. Here, we report a case in which the patient was treated with a combination of two anti-MRSA drugs and was cured.

Safety and efficacy of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for patients aged 80 years and older.

BACKGROUND: The safety and efficacy of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in patients aged 70 years and older has been established. However, few studies have evaluated the safety, usefulness, and significance of EBUS-TBNA in patients aged 80 years and older. METHODS: We retrospectively investigated patients aged 80 years and older who underwent EBUS-TBNA under local anesthesia. The study period was 10 years; from November 1, 2010 to October 31, 2020. The primary endpoint was the safety of EBUS-TBNA, which was measured as the incidence of complications associated with the procedure. The secondary endpoints were the overall diagnostic rate, malignant disease diagnosis rate, and malignant disease treatment rate. RESULTS: A total of 111 patients were enrolled in the study, and the median age was 82 years (range: 80-89 years). The incidence of complications (the primary endpoint) was 5% (5/111) and comprised oversedation in one case, chest pain in one case, hypoxemia in two cases, and arrhythmia in one case. Regarding the secondary endpoints, the diagnostic rate for all patients was 75% (83/111), and the diagnostic rate of malignant disease was 89% (75/84). Of the 75 patients with malignant disease diagnosed with EBUS-TBNA, 61 (81%) received tumor-specific therapy in accordance with their diagnoses. CONCLUSION: EBUS-TBNA can be considered safe and effective even in patients aged 80 years and older.

External fixation of airway stents for upper tracheal stenosis and tracheoesophageal fistula.

OBJECTIVES: Stent migration is a common complication of airway stent placement for upper tracheal stenosis and tracheoesophageal fistula. Although several researchers have reported that external fixation is effective in preventing stent migration, the usefulness and safety of external fixation have not been proved because their cohorts were small. We therefore investigated the efficacy and safety of external fixation during upper tracheal stenting. METHODS: Records of patients who underwent airway stent placement from May 2007 to August 2018 in a single centre were retrospectively reviewed. We included only patients whose stent had been placed in the upper trachea with external fixation to the tracheal wall. The primary endpoint of this study was the rate of stent migration. RESULTS: Altogether, 51 procedures were performed in 45 patients (32 males, 13 females; median age 60 years, range 14-91 years). The median follow-up period was 9 months (range 0.3-90 months). Among the procedures, 15 were performed for benign disease and 36 for malignancy. Stents were composed of either silicone (n = 42) or metal (n = 9). Stent migration occurred in 3 (6%) patients. The stents with migration were all composed of silicone. Other sequelae were granulation tissue formation in 10 (20%) patients, sputum obstruction in 6 (12%), cellulitis in 3 (6%) and pneumonia in 1 (2%). CONCLUSIONS: External fixation was an effective method for preventing migration of airway stents placed for upper tracheal stenosis and tracheoesophageal fistula. The complications were acceptable in terms of safety.

Solvent-based paclitaxel or nab-paclitaxel for heavily treated relapsed/refractory small cell lung cancer: Retrospective single-institution observational study.

Treatment options for patients with relapsed/refractory small cell lung cancer (R/R SCLC) are limited, and the efficacy of salvage therapies for heavily treated patients should be assessed. Here, we evaluated the efficacy of paclitaxel (PTX) in R/R SCLC patients.A single-institute retrospective chart review was conducted. The primary endpoint was overall survival (OS), whereas the secondary endpoints were progression-free survival (PFS), overall response rate, disease control rate (DCR), and safety.Thirty-one patients (median age, 69 [range, 56-80] years) were analyzed. The median follow-up period was 122 (range, 28-1121) days. The median OS and PFS were 4.4 and 2.2 months, respectively. Adverse events of grade 3 or higher, other than hematological toxicity, were febrile neutropenia and neuropathy. Multivariate analyses identified the following independent predictors of poor OS: performance status and lactate dehydrogenase at the upper limit of normal.PTX monotherapy showed moderate efficacy with acceptable toxicity in heavily treated patients with R/R SCLC patients.

A promising response to osimertinib in a patient with erlotinib-resistant lung adenocarcinoma with an uncommon EGFR mutation.

Most patients with non-small cell lung cancer with common epidermal growth factor receptor (EGFR) mutations respond dramatically to EGFR tyrosine kinase inhibitors (TKIs), but data are limited on the response of tumours with uncommon mutations. We present the case of a 68-year-old man with stage IV lung adenocarcinoma with an uncommon EGFR mutation in exon 21 (L861Q). The disease progressed 2 years after he started erlotinib (150 mg daily). Using a transbronchial lung biopsy, we detected additional mutations in exon 20 (T790M) and exon 21 (L858R). He was treated with osimertinib (80 mg daily) and achieved a partial remission. This case demonstrates the value of repeating a biopsy after EGFR-TKI therapy in patients with uncommon EGFR mutations.

Nab-paclitaxel plus carboplatin as an effective and safe chemotherapy regimen for pulmonary carcinosarcoma with interstitial lung disease: A case report.

Carcinosarcoma is a rare histological type of non-small cell carcinoma (NSCLC), and its prognosis has been reported to be worse compared with other NSCLCs. Nanoparticle albumin-bound paclitaxel (nab-PTX) + carboplatin (CBDCA) achieves a favorable response rate in patients with non-small cell lung cancer (NSCLC). We administered nab-PTX + CBDCA to a 68-year-old man with postoperative recurrent carcinosarcoma with interstitial lung disease (ILD). A partial response was evident after four cycles of chemotherapy. To the best of our knowledge, the present study is the first to report the safety and efficacy of nab-PTX + CBDCA for treating carcinosarcoma with ILD.

Real-world evaluation of carboplatin plus a weekly dose of nab-paclitaxel for patients with advanced non-small-cell lung cancer with interstitial lung disease.

BACKGROUND: The optimal chemotherapy regimen for non-small-cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) remains unknown. Therefore, in this study, we investigated the real-world efficacy and safety of carboplatin (CBDCA) plus nab-paclitaxel (nab-PTX) as a first-line regimen for NSCLC patients with ILD. PATIENTS AND METHODS: We retrospectively reviewed advanced NSCLC patients with ILD who had received CBDCA plus nab-PTX as a first-line chemotherapy regimen between April 2013 and March 2018. Patients were diagnosed with ILD based on the findings of a pretreatment high-resolution computed tomography of the chest. RESULTS: The 34 patients enrolled in this study were included in the efficacy and safety analysis. Collagen vascular disease or a history of exposure to dust or asbestos was not reported for any patients. The median age of patients was 71 years (range, 59-83 years), and 32 patients had a performance status of 0 or 1. The overall response rate was 38.2%. The median progression-free survival and overall survival were 5.8 months and 12.7 months, respectively. Chemotherapy-related acute exacerbation of ILD was observed in two patients (5.7%). Other toxicities were feasible, and no treatment-related deaths occurred. CONCLUSION: CBDCA plus nab-PTX, as a first-line chemotherapy regimen for NSCLC, showed favorable efficacy and safety in patients with preexisting ILD.

Safety and efficacy of carboplatin plus nab-paclitaxel for treating advanced non-small-cell lung cancer with interstitial lung disease.

There are few established treatments for patients with non-small-cell lung cancer (NSCLC) with interstitial lung disease (ILD). The safety and efficacy of albumin-bound paclitaxel (nab-paclitaxel) in combination with carboplatin is uncertain, although the combination of carboplatin and paclitaxel is the most common regimen for treating NSCLC patients with ILD. A total of 9 NSCLC patients with ILD, treated between April 2013 and March 2016, were retrospectively investigated. Carboplatin (AUC 5-6) was administered on day 1 and nab-paclitaxel on days 1, 8 and 15, every 4-6 weeks. The median age of the patients upon initiating chemotherapy was 67 years. The pathological examination revealed 6 patients with squamous cell carcinoma, and 6 patients exhibited the typical pattern of ILD. The response rate was 55.6%, and the median progression-free and overall survival time was 174 and 344 days, respectively. Acute exacerbation of ILD was not observed in any of the patients, and febrile neutropenia developed in 3 patients (3/9, 33.3%). Thus, treatment with carboplatin plus nab-paclitaxel was found to be safe and effective for NSCLC patients with ILD, although management of hematological adverse events, such as febrile neutropenia, was required. However, these encouraging results require confirmation by a large-scale clinical trial.

Endobronchial involvement of mantle cell lymphoma: A case report.

Mantle cell lymphoma (MCL) is a subtype of B-cell non-Hodgkin's lymphoma. Most cases of MCL have extranodal involvement at the time of the initial diagnosis; however, endobronchial involvement is rare. An 87-year-old man was referred to our hospital because of dyspnea on exertion. A chest CT revealed diffuse irregular wall thickening of the trachea and bilateral bronchi. A bronchoscopy revealed a diffuse irregular surface of the tracheal and bilateral bronchial mucosa and polyposis-like lesions. He was diagnosed as having MCL based on an endobronchial biopsy, and the diagnosis was confirmed using immunohistochemical staining.

Successful oral desensitization against skin rash induced by alectinib in a patient with anaplastic lymphoma kinase-positive lung adenocarcinoma: A case report.

Alectinib has been approved for the treatment of patients with anaplastic lymphoma kinase (ALK) gene rearrangement-positive advanced non-small cell lung cancer. In terms of adverse effects, the occurrence of a severe skin rash induced by alectinib is reportedly rare, compared with the occurrence of skin rash induced by epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). In the present case report, a 76-year-old woman with ALK-positive lung adenocarcinoma experienced disease progression after undergoing first-line chemotherapy. Subsequently, alectinib was administered as a second-line therapy. However, she discontinued alectinib therapy after 11days because of the occurrence of an alectinib-induced skin rash. Since the skin rash improved within one week, we attempted to perform oral desensitization to alectinib. The patient has not shown any recurrence of the rash or disease progression for 7 months since the successful oral desensitization to alectinib. Here, we describe the first case of successful oral desensitization against a skin rash induced by alectinib in a patient with ALK-positive lung adenocarcinoma. Desensitization to overcome adverse effects and to enable sustained treatment with alectinib should be considered in patients who develop alectinib sensitivities.

Interstitial pneumonia following administration of pegfilgrastim during carboplatin and etoposide chemotherapy for small-cell lung cancer.

Pegfilgrastim is a long-acting granulocyte colony-stimulating factor formulation that has been approved for the prevention of febrile neutropenia. We herein report a case of interstitial pneumonia following administration of pegfilgrastim. A 65-year-old man with stage IV small-cell lung cancer was treated with carboplatin and etoposide as third-line chemotherapy. Pegfilgrastim was administered during the second cycle of chemotherapy. On the day after the administration of pegfilgrastim, interstitial pneumonia developed. The respiratory condition improved with pulse steroid therapy; however, the patient eventually succumbed to cancer progression. In conclusion, interstitial pneumonia due to pegfilgrastim is rare; however, physicians should be aware of the possibility of this adverse effect.

Successful chemotherapy with carboplatin and nab-paclitaxel for thymic large cell neuroendocrine carcinoma: A case report.

Thymic large cell neuroendocrine carcinomas (LCNECs) are rare, and the optimal regimen for second and subsequent lines of chemotherapy for the treatment of LCNECs remains unknown. In the present case study, a 59-year-old male with post-operative recurrent thymic LCNEC was treated with nab-paclitaxel and carboplatin every 4 weeks as third-line chemotherapy, and a partial response was achieved following 4 cycles of this regimen. The patient developed grade 4 neutropenia and grade 3 leukopenia, but none of the other toxicities, including peripheral neuropathy, were severe. Therefore, the patient was able to tolerate this salvage chemotherapy. To the best of our knowledge, the present study is the first case demonstrating clinically meaningful antitumor activity by combination chemotherapy with carboplatin and nab-paclitaxel, resulting in a positive response in a patient with thymic LCNEC.

Successful chemotherapy with nab-Paclitaxel in a heavily treated non-small cell lung cancer patient: a case report.

Non-small cell lung cancer (NSCLC) accounts for the majority of all lung cancers. A 69-year-old female with postoperatively recurrent NSCLC was treated weekly with nanoparticle-albumin-bound paclitaxel (nab-paclitaxel) monotherapy every 4 weeks as a tenth line chemotherapy, and stable disease was achieved by seven cycles of this regimen. The patient developed grade 4 neutropenia and grade 3 leukopenia, but none of the other toxicities, including febrile neutropenia and peripheral neuropathy, were severe, and thus she was able to tolerate this salvage chemotherapy. To our knowledge this is the first report of the efficacy of nab-paclitaxel monotherapy in a heavily treated NSCLC patient.

Evaluation of gefitinib efficacy according to body surface area in patients with non-small cell lung cancer harboring an EGFR mutation.

BACKGROUND: Exon 19 deletions and L858R point mutation are the most commonly encountered active epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC), and they predict greater efficacy of gefitinib therapy. The objective of this study was to evaluate whether body surface area (BSA) affects the efficacy of gefitinib in patients with NSCLC harboring an active EGFR mutation. METHODS: We reviewed the medical records of consecutive patients with advanced NSCLC harboring an active EGFR mutation who received gefitinib monotherapy. The median BSA value was used as the cutoff value to evaluate the impact of BSA on the efficacy of gefitinib. RESULTS: The median BSA of the 103 NSCLC patients harboring an active EGFR mutation was 1.45 m(2). The overall response rate, progression-free survival (PFS), and median survival time (MST) were 65.0 %, 11.3 months, and 26.2 months, respectively. There were no significant differences in clinical outcomes between the high-BSA group (BSA ≥ 1.45 m(2)) and low-BSA group (BSA < 1.45 m(2)), i.e., the response rates was 60.0 % and 69.8 %, respectively (P = 0.20), and their MST was 24.7 and 26.2 months, respectively (P = 0.78). Although BSA was predictive of PFS between high-BSA group and low-BSA group in the univariate analysis (9.0 and 12.2 months, P = 0.04), the multivariate analysis identified only performance status and smoking status as independent predictors of PFS. CONCLUSIONS: The efficacy of gefitinib in patients with NSCLC harboring an EGFR mutation does not differ according to their BSA.