Endobronchial Ultrasonography With Guide Sheath for the Diagnosis of Peripheral Pulmonary Lesions in Japan: A Literature Review.

We evaluated the usefulness of endobronchial ultrasonography with guide sheath (EBUS-GS) for the diagnosis of peripheral pulmonary lesions (PPLs) in Japan. We searched the PubMed/Medline database using the keywords "EBUS guide sheath" for Japanese studies on EBUS-GS published between January 2004 and August 2023. We included 32 original articles that evaluated the diagnostic yield of EBUS-GS for PPLs. Case reports and conference abstracts were excluded due to limited information available for quality assessment. The diagnostic yield of EBUS-GS was 73.6% for 2996 malignant lesions, 65.4% for 752 ground-glass nodules, 59.4% for 414 benign lesions, 61.3% for 1114 lesions of size ≤2 cm, and 75.6% for 1246 lesions of size >2 cm; it was 69.4% for lesions located in the upper lobe (n=793), 71.9% for the middle lobe/lingula (n=121), and 62.5% for the lower lobe (n=334). None of the patients experienced severe complications. In this review, EBUS-GS is effective for the diagnosis of malignant and benign PPLs. A multimodality approach is needed to further enhance its diagnostic performance.

Effectiveness of AERO Stent Placement for Malignant Airway Disorder in Patients with a Poor Performance Status.

Objective Airway stenting is an established procedure for treating various airway disorders. The AERO stent (Merit Medical Systems, South Jordan, UT, USA) is a fully covered self-expandable metallic stent approved for use in Japan in 2014. However, its effectiveness in treating malignant airway disorders in patients with a poor performance status remains unclear. Therefore, we investigated the safety and efficacy of the AERO stent in patients with malignant airway disorders and a poor performance status. Patients and Methods We retrospectively reviewed the medical records of all patients who underwent AERO stent placement at our institute between April 2016 and March 2022, and 21 patients underwent 25 procedures for malignant airway disorders. All AERO stenting procedures were performed using an over-the-wire delivery system with flexible and/or rigid bronchoscopy. Results Eighteen of the 21 patients (85.7%) had a poor general condition (Eastern Cooperative Oncology Group performance status 3 or 4). AERO stents were successfully placed in 23 of the 25 procedures and migrated in the remaining 2 cases. Complications occurred in 10 cases, with infection being the most common (3 cases). Fourteen patients (66.6%) showed an improvement in their performance status. In addition, 5 of the 6 intubated patients were extubated following AERO stenting, and 11 patients subsequently received anticancer treatment. Conclusion The placement of the AERO stent is useful in patients with a poor performance status, including those who are intubated and afflicted with malignant airway disorders.

Dramatic Response to Tezepelumab as an Initial Biologic Agent for Refractory Asthma Associated with Type 2 and Non-type 2 Traits.

A 74-year-old Japanese woman presented with a 45-year history of refractory asthma. She had been treated with inhaled corticosteroids, a long-acting ß2-agonist, and a long-acting muscarinic antagonist for 6 months. She also had a repeated viral infection. Her condition had been characterized as a refractory asthma associated with type 2 and non-type 2 traits. We began treatment with tezepelumab. The control of the patient's asthma symptoms and quality of life improved greatly within 1 month (changes in eosinophil count from 748 to 96 /µL, in FeNO from 32 to 17 ppb, in the Asthma Quality of Life Questionnaire score from 3.59 to 6.68, and in the Asthma Control Test score from 13 to 23). Tezepelumab was effective as an initial biologic agent for a patient with refractory asthma associated with type 2 and non-type 2 traits.

A surgical case of pulmonary adenocarcinoma in the right upper lobe associated with a systemic artery-to-pulmonary artery fistula.

A 52-year-old female never-smoker with an abnormal shadow in the right lung detected on radiography was referred to our institution. Contrast-enhanced computed tomography revealed an irregular nodule in the upper lobe of the right lung, suggestive of a pulmonary vascular abnormality. Angiography revealed a direct communication between the right internal mammary artery (IMA) and the right upper lobe pulmonary artery branches, with dilated and tortuous vascular proliferation. As multiple branch arteries were seen flowing into the upper lobe from the IMA, transcatheter selective embolization of these vessels and right upper lobectomy by video-assisted thoracoscopic surgery were performed. Contrary to the clinical diagnosis, the pathological finding was a pulmonary adenocarcinoma of the right upper lobe. Additional lymph node dissection was performed later. We report an extremely rare and unprecedented case of pulmonary adenocarcinoma fed by the right IMA, with a literature review.

Safe sedation during diagnostic and therapeutic flexible bronchoscopy in Japan: A review of the literature.

We explored whether a combination of an opioid (fentanyl or pethidine) and midazolam could safely sedate Japanese patients undergoing bronchoscopic procedures. We searched the PubMed Medline and Igaku Chuo Zasshi (ICHUSHI) databases from 1980 to 2022 for papers on sedatives used during bronchoscopy, especially opioids (fentanyl and pethidine) and midazolam. The keywords were "bronchoscopy" and "sedation" ("kikanshikyo" and "chinsei", respectively, in Japanese). The results showed that midazolam was the preferred sedation agent during flexible bronchoscopy; with midazolam sedation is rapid, and the drug is associated with anterograde amnesia and decreased discomfort. A combination of an opioid (fentanyl or pethidine) and midazolam improved the patient tolerance and willingness to undergo a repeat procedure and also improved the working conditions for the physician. The British Thoracic Society guideline of 2013 suggested that a combination of an opioid (fentanyl or alfentanil) and midazolam should be considered to improve bronchoscopic tolerance. The American College of Chest Physicians Consensus Statement of 2011 suggested that fentanyl should be preferred; the onset of action and peak effect are rapid, and the effects are of relatively short duration. Emphasis has been placed on safety aspects, such as patient monitoring, the precautions that should be taken in patients with certain conditions, prevention and management of complications, adequate staffing, and optimal sedation and disinfection. In conclusion a combined opioid (fentanyl or pethidine) and midazolam sedation is optimal for diagnostic and therapeutic flexible bronchoscopy in Japanese patients.

Case Report: Use of endobronchial Watanabe spigot and coagulation factor XIII supplementation in the treatment of persistent pneumothorax due to pneumocystis pneumonia with human immunodeficiency virus infection.

Pneumocystis jiroveceii pneumonia is one of the most common opportunistic infections associated with human immunodeficiency virus. Endobronchial Watanabe spigot has been recommended for refractory pneumothorax, even with persistant air leak despite continuous negative pressure control via thoracic drainage. Moreover, coagulation factor XIII is considered effective in wound healing.

Use of a highly sensitive lung cancer compact panel to detect KRAS G12D in the wash fluid from a lung tumor: A case report.

Here, we report a case of a pulmonary invasive mucinous adenocarcinoma harboring KRAS G12D, diagnosed from tumor samples containing a very small amount of tumor cells using next-generation sequencing (NGS) and the recently developed Lung Cancer Compact Panel. A 79-year-old woman without any respiratory symptoms underwent chest computed tomography, which revealed a tumor in the left lower lobe. During endobronchial ultrasound (EBUS)-guided transbronchial biopsy (TBB) using a guide sheath (GS), a sufficient specimen for pathological diagnosis could not be obtained because the patient had a severe cough and pulmonary bullae located adjacent to the tumor. In the absence of EBUS transbronchial biopsy findings using a guide sheath, brush cytology was used to categorize the tumor as class II (Papanicolaou classification). However, the wash fluid from the cytological examination contained enough cells to obtain sufficient nucleic acid for use in sequencing analysis. The latter revealed KRAS G12D expression. Although the patient underwent surgery without pathological evidence, the evaluation of the surgical specimen confirmed a diagnosis of pulmonary invasive mucinous adenocarcinoma. Use of the Lung Cancer Compact Panel enabled the detection of KRAS G12D in the wash fluid of a brush cytology sample and thus a diagnosis of pulmonary invasive mucinous adenocarcinoma.

Guide sheath versus non-guide sheath method for endobronchial ultrasound-guided biopsy of peripheral pulmonary lesions: a multicentre randomised trial.

BACKGROUND: Guide sheaths (GSs) have been widely used during radial probe endobronchial ultrasound-guided transbronchial biopsy (rEBUS-TBB) of peripheral pulmonary lesions. However, it remains unknown whether a GS enhances the diagnostic yield. We compared the diagnostic yields of small peripheral pulmonary lesions between rEBUS-TBB with and without a GS. METHODS: In eight institutions, patients with peripheral pulmonary lesions ≤30 mm in diameter were enrolled and randomised to undergo rEBUS-TBB with a GS (GS group) or without a GS (non-GS group) using a 4.0-mm thin bronchoscope, virtual bronchoscopic navigation and fluoroscopy. The primary end-point was the diagnostic yield of the histology specimens. RESULTS: A total of 605 patients were enrolled; ultimately, data on 596 (300 in the GS group and 296 in the non-GS group) with peripheral pulmonary lesions having a longest median diameter of 19.6 mm were analysed. The diagnostic yield of histological specimens from the GS group was significantly higher than that from the non-GS group (55.3% versus 46.6%; p=0.033). Interactions were evident between the diagnostic yields, procedures, lobar locations (upper lobe versus other regions; p=0.003) and lesion texture (solid versus part-solid nodules; p=0.072). CONCLUSIONS: The diagnostic yield for small peripheral pulmonary lesions afforded by rEBUS-TBB using a GS was higher than that without a GS.

Differences in Attitudes and Practices of Cancer Pain Management between Medical Oncologists and Palliative Care Physicians.

This study aimed to evaluate whether there are differences in the attitudes and practices of cancer pain manage-ment between medical oncologists and palliative care physicians. An online nationwide survey was used to collect responses from board-certified medical oncologists and palliative care physicians in Japan. The survey questionnaire comprised 30 questions. The differences in responses between medical oncologists and palliative care physicians were examined. Out of the 1,227 questionnaires sent, 522 (42.5%) were returned. After apply-ing the exclusion criteria, 445 questionnaires (medical oncologists: n = 283; palliative care physicians: n = 162) were retained for analysis. Among the questions about potential barriers to optimal cancer pain man-agement, both medical oncologists and palliative care physicians considered the reluctance of patients to take opioids due to fear of adverse effects as the greatest barrier. Significantly different ratings between medical oncologists and palliative care physicians were observed on 5 of the 8 questions in this area. Significantly differ-ent ratings were observed for all questions concerning pain specialists and their knowledge. For effective cancer pain management, it is important to account for differences in attitudes and practice between medical oncolo-gists and palliative care physicians.

End-tidal capnographic monitoring during flexible bronchoscopy under fentanyl and midazolam sedation.

BACKGROUND: Bronchoscopic examination including endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is well established for lung cancer diagnosis and staging. Sedation using fentanyl and midazolam is recommended during bronchoscopic examinations. Meanwhile, inadvertent oversedation is a clinical problem. The objective of this research was to estimate the frequency of apnea episodes by end-tidal capnography under fentanyl and midazolam sedation during bronchoscopy. METHODS: Eighty-five patients were enrolled retrospectively between August 2017 and March 2018 at Okayama Medical Center. Apnea was defined as the cessation of airflow for more than 10 seconds. We reviewed medical records, including capnographic data, by cap-ONE YG-227T (NIHON KOHDEN, Tokyo, Japan) during flexible bronchoscopy under fentanyl and midazolam sedation. RESULTS: Patients received 49.4±20.6 µg of fentanyl [mean ± standard deviation (SD)] and 4.35±2.0 mg of midazolam (mean ± SD). The patients included 52 males and 33 females; the median age was 71 (range, 31-88) years were enrolled. Apnea episodes were recorded (median duration 18 seconds) in 85 patients (100%). Prolonged apnea episodes with more than 30 seconds occurred in 56 patients (65.8%). Furthermore, the median time was 32 (range, 5-102) seconds whose delay between the onset of an apnea episode and decline in the SpO2 level of ≥4% from baseline. CONCLUSIONS: End-tidal capnography, cap-ONE YG-227T was effective for detecting the occurrence of apnea in patients undergoing a bronchoscopic examination under fentanyl and midazolam sedation. Monitoring might be useful for preventing inadvertent oversedation.

Survival of chemo-naïve patients with EGFR mutation-positive advanced non-small cell lung cancer after treatment with afatinib and bevacizumab: updates from the Okayama Lung Cancer Study Group Trial 1404.

BACKGROUND: In a phase I study, afatinib (30 mg/body daily) plus bevacizumab (15 mg/kg every 3 weeks) was well tolerated and showed favourable outcomes in patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small-cell lung cancer. Herein, we report the 2-year progression-free survival, overall survival and safety profile of these patients. METHODS: Chemo-naïve patients with EGFR-mutant advanced non-small-cell lung cancer were enrolled. One group of patients received 40 mg afatinib daily and 15 mg/kg bevacizumab every 3 weeks (level 0) until disease progression or severe toxicity. Another group of patients received 30 mg afatinib daily and the same dose of bevacizumab (level 1). Dose-limiting toxicity was the primary endpoint, whereas long-term progression-free survival, overall survival and tolerability were secondary endpoints. Survival rates were estimated using the Kaplan-Meier method. RESULTS: The study included 19 patients (level 0: 5; level - 1: 14). Until the data cut-off date, seven patients continued the treatment, whereas 12 discontinued due to disease progression (n = 5) or toxicity (n = 7). The median PFS was 24.2 months, while the median overall survival was not reached. All patients developed adverse effects. Diarrhoea and skin rash were frequently observed as severe adverse events (grade 3). A secondary EGFR mutation (T790M) was detected in two patients after progression. CONCLUSIONS: Prolonged follow-up revealed that combination therapy with afatinib and bevacizumab might improve survival outcomes in EGFR-mutant advanced non-small-cell lung cancer patients and seems to be promising. TRIAL REGISTRATION: UMIN000015944.

Effect of pH on the performance of an acidic biotrickling filter for simultaneous removal of H2S and siloxane from biogas.

Acidic biotrickling filters (BTF) can be used for simultaneous removal of hydrogen sulfide (H2S) and siloxane from biogas. In this study, the performance of a BTF under different acidic pH conditions was investigated. The removal profile of H2S showed that 90% of H2S removal was achieved during the first 0.4 m of BTF height with down-flow biogas. Decamethylcyclopentasiloxane (D5) removal decreased from 34.5% to 15.6% when the pH increased from 0.88 to 3.98. Furthermore, the high partition coefficient of D5 obtained in under higher pH condition was attributed to the higher total ionic strength resulting from the addition of sodium hydroxide solution and mineral medium. The linear increase in D5 removal with the mass transfer coefficient (kL) indicated that the acidic recycling liquid accelerated the mass transfer of D5 in the BTF. Therefore, the lower partition coefficient and higher kL under acidic pH conditions lead to the efficient removal of D5. However, the highly acidic pH 0.9 blocked mass transfer of H2S and O2 gases to the recycling liquid. Low sulfur oxidation activity and low Acidithiobacillus sp. content also deteriorated the biodegradation of H2S. Operating the BTF at pH 1.2 was optimal for simultaneously removing H2S and siloxane.

Randomized study comparing mannitol with furosemide for the prevention of cisplatin-induced renal toxicity in non-small cell lung cancer: The OLCSG1406 trial.

AIM: Evidence is lacking on the best standard method for forced diuresis to prevent cisplatin-induced nephrotoxicity. We compared the cisplatin-induced nephrotoxicity prevention effect of furosemide or mannitol in patients with advanced non-small cell lung cancer. METHODS: Patients with advanced non-small cell lung cancer suitable to receive cisplatin-containing regimen were randomly assigned to receive furosemide or mannitol with appropriate hydration. The primary endpoint was the proportion of ≥ grade 1 serum creatinine elevation in the first cycle. RESULTS: The trial was terminated early with 44 (22 per arm) of the planned 66 patients because of slow accrual. Patients' characteristics were well balanced with median baseline creatinine clearance of 98.0 and 95.1 mL/min in the furosemide and mannitol arms, respectively. In the first cycle, two (9%) and four (18%) patients developed grade 1 creatinine elevation (P = .66), respectively, despite no ≥ grade 2 toxicity. The median times to develop the worst creatinine score were 10 and 8 days, respectively. For all cycles, median times to recover to grade 0 were 56 and 20 days, respectively. The furosemide arm was characterized by relatively high urine output after cisplatin administration (900 vs 550 mL/h), low frequency of unplanned additional hydration (14% vs 32%), and high incidence of hyponatremia (18% and 5%) compared with the mannitol arm. Both arms showed similar progression-free survival and overall survival. CONCLUSION: The preventive effect of the two forced diuretics on cisplatin-induced nephrotoxicity was not significantly different. However, the two diuretics have some distinct types of clinical presentations.

Successful Treatment with Benralizumab for Allergic Bronchopulmonary Aspergillosis That Developed after Disastrous Heavy Rainfall in Western Japan.

We herein report a 56-year-old woman who developed allergic bronchopulmonary aspergillosis (ABPA) possibly due to fungal exposure after disastrous heavy rainfall in Western Japan in 2018. She was diagnosed with ABPA complicated with asthma, increased peripheral blood eosinophil count, elevation of specific immunoglobulin E for Aspergillus fumigatus, positive Aspergillus fumigatus precipitation antibody reaction test results, and notable chest computed tomography findings. After treatment with benralizumab, her symptoms, peripheral blood eosinophil count, radiological findings, and respiratory function dramatically improved. The administration of benralizumab appears to be an effective treatment strategy for ABPA.

Immune checkpoint inhibitor efficacy and safety in older non-small cell lung cancer patients.

OBJECTIVES: Immune checkpoint inhibitors offer longer survival than chemotherapy in several clinical trials for advanced non-small cell lung cancer. In subset analyses of clinical trials, immune checkpoint inhibitors extended survival in patients aged ≥65 years, but the effects in patients aged ≥75 years are controversial. We performed multicenter, collaborative and retrospective analyses of immune checkpoint inhibitor efficacy and safety in non-small cell lung cancer patients aged ≥75 years. METHODS: We retrospectively studied 434 advanced non-small cell lung cancer patients who received immune checkpoint inhibitors from December 2015 to December 2017, and retrospectively applied the Geriatric (G) 8 screening tool with medical records. RESULTS: Of the 434 patients who received immune checkpoint inhibitors, 100 were aged ≥75 years. Five patients with performance status 3 were omitted from the final analysis. Immune checkpoint inhibitors were given as a first-line treatment to 20 patients. The objective response rates, median progression-free survival rates and median survival times were 35.0%, 6.1 months and 10.7 months for first-line treatment, and 20.0%, 2.9 months and 14.7 months for second- or later-line treatments, respectively. The median modified G8 score was 11.0. The median survival time was longer in the high modified G8 (≥12.0) group than in the low modified G8 (≤11.0) group (18.7 vs. 8.7 months; P = 0.02). Likewise, the median survival time was 15.5 months (performance status 0-1) vs. 3.2 months (performance status 2) (P < 0.01). The grade ≥ 2 immune-related adverse events incidence was 36.8%. CONCLUSIONS: In this study, immune checkpoint inhibitors were effective and tolerable for patients aged ≥75 years. The modified G8 screening tool and performance status were associated with the outcome of older non-small cell lung cancer patients treated with immune checkpoint inhibitors.

Rapidly Progressive Acute Kidney Injury Associated with Nivolumab Treatment.

A 63-year-old man with pulmonary adenocarcinoma was treated with nivolumab. High fever developed within several hours after the first administration of nivolumab; subsequently, serum creatinine levels kept increasing daily. We diagnosed acute kidney injury (AKI) as an immune-related adverse event; the patient was initially treated with 50 mg prednisolone, and the dose was then tapered. Renal biopsy pathologically revealed tubulointerstitial inflammation with strong infiltration of only T cells that were CD3+, CD4+, and CD8+. The infiltration of CD163+ M2 macrophage was also observed. AKI within 1 week after the administration of nivolumab seems to be rare; therefore, the present case provides important findings useful in daily clinical practice.

Simultaneous removal of siloxanes and H2S from biogas using an aerobic biotrickling filter.

The feasibility of simultaneous removal of siloxane and H2S from biogas was investigated using an aerobic biotrickling filter (BTF). The biodegradation of H2S in the BTF followed a first-order kinetic model and more than 95 % H2S was eliminated within a residence time of 0.3 min. The removal of decamethylcyclopentasiloxane (D5) increased with longer empty bed residence time (EBRT). The partition test and microbial community analysis further reveals that up to 52 % removal of D5 was reached mainly by the chemical-absorption in acid recycling liquid. Finally, D5 was converted into mixtures of dimethylsilanediol (DMSD) and hexamethyldisiloxane (L2) via ring-opening hydrolysis in acid liquid and ring-shrinking polyreaction using CH4 derived from biogas. These operational characteristics demonstrate that the abiotic removal of D5, in addition to biological removal of H2S in an aerobic BTF can significantly decrease the siloxane loading to the downstream siloxane removing units.

Bilateral Testicular Metastases from Lung Adenocarcinoma Showing an Objective Response to Nivolumab: A Case Report and Review of the Literature.

A 69-year-old man who had undergone chemoradiotherapy for advanced pulmonary adenocarcinoma had bilateral testicular and adrenal gland masses on a routine follow-up examination. We performed left orchiectomy, and the histopathological examination confirmed metastatic pulmonary adenocarcinoma involving the extracted testis. He was treated for disease progression with nivolumab after unsuccessful cytotoxic chemotherapy, which resulted in regression of recurrent adrenal and right testicular tumors. We reviewed the existing literature on metastatic testicular tumors and found that testicular metastasis from lung cancer is rare and poses a chemotherapeutic challenge. Based on our experience, immune checkpoint inhibitors seem to have good efficacy for treating testicular metastasis.