Clinical utility of rapid on-site evaluation of brush cytology during bronchoscopy using endobronchial ultrasound with a guide sheath.

Previous studies have shown that rapid on-site evaluation (ROSE) improves the diagnostic yield of bronchoscopy using endobronchial ultrasound with a guide sheath (EBUS-GS) for peripheral pulmonary lesions (PPL). While ROSE of imprint cytology from forceps biopsy has been widely discussed, there are few reports on ROSE of brush cytology. This study investigated the utility of ROSE of brush cytology during bronchoscopy. We retrospectively analyzed data from 214 patients who underwent bronchoscopy with EBUS-GS for PPL. The patients in the ROSE group had significantly higher diagnostic sensitivity through the entire bronchoscopy process than in the non-ROSE group (96.8% vs. 83.3%, P = 0.002). The use of ROSE significantly increased the sensitivity of brush cytology with Papanicolaou staining (92.9% vs. 75.0%, P < 0.001). When ROSE was sequentially repeated on brushing specimens, initially negative ROSE results converted to positive in 79.5% of cases, and the proportion of specimens with high tumor cell counts increased from 42.1 to 69.0%. This study concludes that ROSE of brush cytology improves the diagnostic accuracy of bronchoscopy and enhances specimen quality through repeated brushing.

A Quantitative Computed Tomography Analysis of Fissure Integrity and Emphysema Destruction in Japanese Patients with Severe Chronic Obstructive Pulmonary Disease.

Objective Bronchoscopic lung volume reduction (BLVR) using a one-way endobronchial valve (EBV) can provide clinically meaningful benefits to chronic obstructive pulmonary disease (COPD) patients. Although the Japanese Pharmaceuticals and Medical Devices Agency approved EBVs in November 2022, information regarding the number of Japanese patients with severe COPD eligible for BLVR treatment is still lacking. We therefore screened computed tomography (CT) images of patients with severe COPD using a quantitative CT (QCT) analysis to estimate the proportion of candidates eligible for BLVR treatment with an EBV. Methods CT scans of COPD patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 3 and 4 were retrospectively analyzed using QCT to evaluate fissure integrity and tissue destruction. The difference in volume-weighted percentage was measured using the density scores of the target lobe and ipsilateral non-target lobe at -910 Hounsfield units. The target lobe was defined as the most affected lobe, with an emphysema destruction score of >50% for each patient. Results High-resolution CT scans of 32 patients (GOLD 3=19, GOLD 4=13) were analyzed. The target lobe could not be identified in 1 patient, whereas the target lobes for 8 patients were not surrounded by fissures with ≥80% completeness. Conversely, in 13 patients, the target lobes were surrounded by fissures with >95% completeness. The remaining 10 patients had fissure completeness between 80% and 95% at the target lobes and were considered candidates for collateral ventilation assessment. Conclusion A QCT analysis showed that 23 of 32 patients with severe COPD could be considered for a thorough examination of BLVR treatment with EBV.

Talc slurry pleurodesis in patients with secondary intractable pneumothorax: A phase 2 study.

BACKGROUND: Secondary pneumothorax, which occurs most commonly in the elderly, is caused by underlying diseases. Cardiac dysfunction and other organ inefficiencies may render surgical repair impossible. Such non-operative and poor-risk cases are targets for pleurodesis, which involves the instillation of chemicals or irritants to the thoracic cavity through injection, bronchoscopic bronchial occlusion, or other procedures. Sterile graded talc has been used for pleurodesis mainly in Europe and the United States; however, only a few studies and case series investigating this topic have been published. This study evaluates the efficacy and safety of talc slurry pleurodesis. METHODS: Patients with inoperable secondary intractable pneumothorax, who were not candidates for surgical repair, were recruited. Four grams of sterilized talc was suspended in 50 mL of physiological saline and injected through a tube into the pleural cavity. Additional 50 mL of saline was subsequently injected through the same channel to clean the residual saline in the injection tube. Another additional talc instillation was allowed to control persistent air leakage. The primary endpoint was the proportion of drainage tube removal within 30 days after talc pleurodesis. RESULTS: Thirty-one patients were included in this study. In 23 out of 28 patients, the drainage tube could be removed within 30 days of talc instillation (82.1 %, 95 % CI = 63.1-93.9), exceeding the threshold of 36.0 % (p < 0.0001). The most common event was pain (11/28 patients, 39.3 %). CONCLUSIONS: Talc slurry pleurodesis is effective for intractable secondary pneumothorax, with minor side effects.

High efficacy of brigatinib for brain metastases in ALK fusion gene-positive non-small cell lung cancer: A case series.

Anaplastic lymphoma kinase (ALK) fusion gene-positive lung cancer often shows brain metastasis at initial diagnosis or during the course of treatment. However, molecular-targeted drugs are known to pass through the blood-brain barrier and present positive effects for central nervous system lesions. There are few reports suggesting how effective molecular-targeted drug therapy alone is for brain metastasis lesions of ALK fusion-positive lung cancer, especially after the first use of ALK-tyrosine kinase inhibitor (TKI) or for bulky brain metastases. A patient in his mid-fifties with stage IV pleural dissemination developed brain metastases after 10 years of crizotinib use, but showed a complete response after switching to brigatinib. Moreover, a patient in her early sixties with stage III recurrent large brain metastases 5 years after chemoradiation therapy experienced dramatic tumor shrinkage with brigatinib. In each case of ALK fusion gene-positive lung cancer with brain metastases, brigatinib showed a high efficacy and was well-tolerated after previous ALK-TKI and for bulky lesions.

EML4-ALK Gene Mutation Detected with New NGS Lung Cancer Panel CDx Using Sputum Cytology in a Case of Advanced NSCLC.

The detection of driver gene mutations has become essential for lung cancer; however, insufficient sample sizes make gene panel tests difficult to use. We previously reported that the lung cancer compact panel TM (LCCP) could detect EGFR and MET gene mutations with sputum cytology. To date, the detection of gene mutation using RNA from sputum samples is considered practically difficult. We report a case in which the EML4-ALK fusion gene was successfully detected from a sputum sample using the LCCP that was just released in Japan as a new next-generation sequencing lung cancer panel, CDx.

Efficacy of combined transbronchial lung cryobiopsy and conventional forceps biopsy for lung malignancies: a prospective cohort study.

There are few prospective reports of transbronchial lung cryobiopsy (TBLC) for malignant tumors in combination with forceps biopsy. We investigated the clinical parameters in which TBLC is superior to forceps biopsy. This is a prospective cohort study to analyse the efficacy of TBLC for suspected malignancy. TBLC was performed after brushing cytology and forceps biopsy, and the diagnostic yield for TBLC, brushing cytology, and forceps biopsy were examined. Adverse events were defined as those requiring additional procedures. Next-generation sequencing (NGS) analysis was performed in each case of non-small cell lung cancer. Of the 100 patients, malignancy was confirmed in 94 cases. The diagnostic yield for TBLC/forceps biopsy/brushing cytology was 86/81/82% respectively, while the diagnostic yield for all procedures combined was 94%. There was no significant difference in the diagnostic yield between TBLC and forceps biopsy. When comparing the biopsy site, the diagnostic yield for TBLC at the lower lobe was significantly higher than forceps biopsy (P < 0.01). Endobronchial ultrasonography imaging using a guide-sheath did not significantly differ in the diagnostic yield of TBLC. The success rate of NGS for TBLC specimens was 100% (26 cases). Adverse events included two cases of severe bleeding. TBLC of peripheral lesions may improve the diagnostic yield when combined with forceps biopsy and brushing cytology. The diagnostic yield of TBLC was higher at the lower lobes. Furthermore, TBLC provided sufficient specimen quality for NGS.

A Prospective Validation Study of Lung Cancer Gene Panel Testing Using Cytological Specimens.

Background: Genetic panel tests require sufficient tissue samples, and therefore, cannot always be performed. Although collecting cytological specimens is easier than tissue collection, there are no validation studies on the diagnostic accuracy of lung cancer gene panel tests using cytology samples. Methods: Using an amplicon-based high-sensitivity next-generation sequencing panel test capable of measuring eight druggable genes, we prospectively enrolled consecutive patients who underwent diagnostic procedures. We evaluated the analysis accuracy rate, nucleic acid yield, and the quality of cytological specimens under brushing, needle aspiration, and pleural effusion. We then compared these specimens with collected tissue samples. Results: In 163 prospectively enrolled cases, nucleic acid extraction and analysis accuracy was 100% in cases diagnosed with adenocarcinoma. Gene mutations were found in 68.7% of cases with 99.5% (95% CI: 98.2-99.9) concordance to companion diagnostics. The median DNA/RNA yield and DNA/RNA integrity number were 475/321 ng and 7.9/5.7, respectively. The correlation coefficient of the gene allele ratio in 64 cases compared with tissue samples was 0.711. Conclusion: The success of gene analysis using cytological specimens was high, and the yield and quality of the extracted nucleic acid were sufficient for panel analysis. Moreover, the allele frequency of gene mutations in cytological specimens showed high correlations with tissue specimens.

Preliminary Results of NGS Gene Panel Test Using NSCLC Sputum Cytology and Therapeutic Effect Using Corresponding Molecular-Targeted Drugs.

As more molecular-targeted drugs for advanced non-small cell lung cancer are brought to market, batch tests for the identification of gene mutations are needed at initial diagnosis. However, since current gene panel tests require a sufficient amount of tissue sample, there are many instances where panel tests cannot be performed. Therefore, we have developed a highly sensitive next generation sequencing (NGS) panel test to facilitate cytological specimens. Herein, we describe three cases positive for epidermal growth factor receptor (EGFR) exon 19 deletion, MET exon 14 skipping, and KRAS G12A using NGS analysis from sputum. In each case, genetic information was consistent with companion diagnostic analysis obtained from tissue samples collected under bronchoscopy. In cases of EGFR and MET mutations, the corresponding tyrosine kinase inhibitors were highly effective. This is the first report to demonstrate that a novel panel test could detect gene mutations in sputum samples in clinical practice and compare the gene allele ratio with the sample directly collected from the lesion.

Flexible bronchoscopy for lung cancer diagnosis in patients aged ≥85 years.

AIM: Flexible bronchoscopy (FB) is a common modality for the diagnosis of lung cancer. Recently, the number of older patients with lung cancer is increasing, and FB is being utilized more for these patients. METHODS: FB carried out in patients aged ≥85 years at St. Marianna University Hospital, Kawasaki, Japan, were reviewed. The indication of FB was decided on a case-by-case basis, taking into consideration the condition of the patient, which included mental status and accessibility of the lesion. Outcomes included complications, diagnostic yields, treatment options and survival after FB evaluation. RESULTS: From April 2015 to March 2019, 1604 diagnostic FBs were carried out. A total of 28 were carried out for the diagnosis of lung cancer (19 transbronchial lung biopsy, 9 transbronchial needle aspiration) in patients aged ≥85 years. Although there were three complications reported (pneumonia, fever, asthma exacerbation), they were successfully treated. A total of 19 cases were diagnosed with malignancy; five were treated with stereotactic body radiation therapy, five were prescribed targeted therapy, two underwent surgery and one was treated by cytotoxic monotherapy. Six patients were not included for active treatment. A total of 12 patients who received active treatment for lung cancer reported a 2-year survival rate of >60%. CONCLUSIONS: FB for lung cancer diagnosis in patients aged ≥85 years were carried out with acceptable safety and diagnostic yield. Considering the development of less invasive therapeutic measures for lung cancer, FB is safe and valuable in individuals aged ≥85 years suspected of lung cancer with therapeutic indications. Geriatr Gerontol Int 2022; 22: 32-35.

Pleurodesis After Bronchial Occlusion for Inoperable Secondary Spontaneous Pneumothorax.

BACKGROUND: In many cases of secondary spontaneous pneumothorax (SSP), surgery is not feasible. Furthermore, in cases with a collapsed lung or numerous air leaks, pleurodesis is ineffective, and treatment options are severely limited. For these cases, bronchial occlusion might be the only effective treatment, despite the low success rate. If, however, bronchial occlusion can expand the lung and reduce air leakage, it can positively amplify later effects on pleurodesis, resulting in a powerful treatment. We reviewed the clinical data of patients who underwent bronchial occlusion with endobronchial Watanabe spigot (BO-EWS) and pleurodesis to investigate the usefulness of bronchial occlusion therapy in inoperable SSP patients. MATERIALS AND METHODS: This single-center, retrospective study reviewed 36 cases of inoperable SSP patients who underwent pleurodesis after BO-EWS from April 2007 to October 2018. Twenty cases were allocated to the air leak analysis group, and 16 cases were included in the pneumothorax volume analysis group. The Robert David Cerfolio classification and the Collins method were used to evaluate air leak and pneumothorax volume, respectively. RESULTS: Pneumothorax volumes decreased significantly after BO-EWS from 29.1%±17.3% to 12.1%±8.8%, while the air leak score decreased from 2.9±1.4 to 1.2±1.0. The success rate for chest tube removals in cases that underwent pleurodesis after BO-EWS was 85.0% (17/20). CONCLUSIONS: This study demonstrated the synergistic effectiveness of BO-EWS and the usefulness of pleurodesis treatment in inoperable SSP patients with lung collapse or numerous air leaks. We believe that this treatment will benefit patients with inoperable SSP which, until now, has had few treatment options.

Detection of a pinhole-sized bronchoesophageal fistula under bronchoscopic autofluorescence imaging.

Autofluorescence imaging (AFI) is a technique for detecting early-stage lung cancer by amplifying the difference in autofluorescence of the bronchial mucosa. However, there are few reports detailing its other applications. Here, we report the case of a 54-year-old woman with stage IVa esophageal cancer who completed chemoradiation therapy, but developed a bronchoesophageal fistula at the left main bronchus and underwent fasting treatment. Computed tomography confirmed that the fistula had closed; however, she subsequently developed aspiration pneumonia and underwent bronchoscopy for confirmation. Although it was difficult to identify the site of the pinhole bronchoesophageal fistula under white light, AFI could easily identify the fistula and digestive mucus in light magenta. AFI may therefore be worth considering for the detection of pinhole bronchoesophageal fistulas.

Drug-induced Hypersensitivity Syndrome by EGFR-TKI in a Patient with Lung Cancer.

An 83-years-old woman diagnosed with advanced Epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma was administered afatinib as a first-line treatment. On Day 17, the patient presented with grade 3 diarrhea and a blood test analysis showed an increased inflammatory response. Afatinib treatment was discontinued on the same day. On Day 26, the patient displayed blepharedema and multiple irregular erythema covering her entire body. Drug-induced hypersensitivity syndrome (DIHS) was suspected, and the systemic administration of 30 mg/day prednisolone was administered. The symptoms subsided thereafter. A blood test analysis 3 weeks after onset revealed a reactivation of Human herpesvirus 6 (HHV-6) and a diagnosis of DIHS due to afatinib therapy was confirmed.

Drastic healing process after pembrolizumab monotherapy in a case of advanced squamous cell carcinoma with severe bronchial stenosis observed over a two-year period using continuous bronchoscopy: A case report.

Programmed cell death-1 immune checkpoint inhibitor (ICI) antibody has proven to be effective in advanced non-small cell lung cancer (NSCLC) patients positive for programmed cell death-1 ligand-1. However, there are currently no reports which evaluate drug efficacy by continuous bronchoscopic observation. A 75-year-old man with complete right atelectasis was diagnosed with squamous cell carcinoma (SCC) of the right lower lobe (tumor proportion score: TPS 90%, cT4N3M0, stage 3C). For first-line chemotherapy, carboplatin and nab-paclitaxel were effective for the primary lesion and the right lung atelectasis improved. However, due to repeated febrile neutropenia with pneumonia, treatment was modified to pembrolizumab monotherapy. Bronchoscopic rebiopsy prior to second-line treatment revealed high TPS, with a severe stenosis in the right main bronchus. After three courses of pembrolizumab, the right main bronchus opened completely, and no signs of malignancy were observed. Bronchoscopic narrow-band and autofluorescence imaging also confirmed a complete endobronchial response. Subsequent bronchoscopic observation two years after the initial diagnosis showed a complete and continued response to treatment. ICIs can result in a drastic bronchoscopic response. In this case, the healing process was notable with minimal scarring, and resulted in continued locally bronchoscopic and complete pathological response to treatment compared to previous cytotoxic chemotherapy.

Bronchial Occlusion with Endobronchial Watanabe Spigot for Hemoptysis in a Mechanically Ventilated Patient with Extracorporeal Circulation.

Bronchial occlusion with endobronchial Watanabe spigots (EWSs) can be an essential therapeutic measure for treating massive hemoptysis in intensive care patients when no other conventional options are available. A 68-year-old-man on mechanical ventilation and extracorporeal circulation after cardiovascular surgery presented massive hemoptysis. He was deemed unfit for bronchial artery embolization (BAE) and surgery while in the intensive care setting; thus, bronchial occlusion was performed using EWSs. His hemoptysis ceased, and he was successfully weaned from mechanical ventilation and extracorporeal circulation. Bronchial occlusion by EWSs may be considered an optimal, and at times, definitive treatment for obtaining hemostasis in these situations.

Dementia IT screening system (DITS): Practical use of local social resources for early diagnosis of dementia with collaboration between family physicians and dementia specialists.

AIM: To build a dementia screening system in the community to facilitate collaboration among patients/caregiver(s), family clinic physicians and memory clinic specialists. METHODS: We placed a Dementia Network Promoter (DNP) in four cities in Mie prefecture, Japan. Based on requests from patients/caregiver(s), family clinic physicians ordered dementia screening from the DNP. The DNP carried out screenings at the clinic using an IT device (iPad), and sent the results to a dementia specialist at the Mie University Hospital Dementia Center. The dementia specialist assessed the results of the screening tests, and made a treatment recommendation for a follow-up consultation with a memory clinic or continuing observation by the family clinic. The DNP reported the recommendation of the dementia specialist to the family clinic physician, who provided this information to the patients/caregiver(s). We investigated the characteristics of the patients referred for consultation with the memory clinic. RESULTS: A total of 158 patients participated in the screening. The majority of patients were in vulnerable living situations characterized by minimal social and family support. The mean score on the Mini-Mental State Examination was 24.1 ± 5.2. Of patients screened, 62% were referred for consultation at the memory clinic, and 57% of those referred completed a consultation at the memory clinic. Patients referred to the memory clinic showed significantly worse cognitive function and ability to complete activities of daily living. CONCLUSIONS: A dementia screening system might facilitate early consultation and intervention for patients with dementia, and build a more effective network to connect families and memory clinics. Geriatr Gerontol Int 2018; 18: 599-606.

The effectiveness of istradefylline for the treatment of gait deficits and sleepiness in patients with Parkinson's disease.

PURPOSE: Istradefylline is useful in treating the wearing-off state in Parkinson's disease (PD). We investigated the effectiveness of istradefylline (ISD) in improving arousal, sleep, and gait deficits in patients with PD. METHODS: We examined 14 patients with PD treated with ISD. We assessed the patients using the Unified Parkinson's Disease Rating Scale, Parkinson's Disease Questionnaire, Timed Up-and-Go test (TUG), Freezing of Gait Questionnaire (FOG-Q), Epworth Sleepiness Scale (ESS), and Parkinson's Disease Sleep Scale (PDSS) before and 1 month after ISD use. RESULTS: ESS scores were significantly lower 1 month after the start of ISD treatment (6.79±6.50) than before the intervention (8.14±6.15, Wilcoxon signed-rank test, p=0.0033). PDSS scores were not significantly different 1 month after beginning the treatment (112±23mm) when compared to those before the intervention (110±27mm, Wilcoxon signed-rank test, p=0.40). TUG scores were not changed after 1 month of ISD use (14.9±8.3s) when compared to those before the intervention (21.3±30.0s, Wilcoxon signed-rank test, p=0.59). Although these measures were not significantly affected by ISD treatment, some patients remarkably improved after the treatment. FOG-Q scores were significantly lower 1 month after the beginning of treatment (9.79±7.16) than those before the intervention (12.14±5.82, Wilcoxon signed-rank test, p=0.030). CONCLUSIONS: ISD may improve daytime sleepiness and FOG in patients with PD.

Assessment of Bronchial Obstruction Using Lateral Pressure Measurement during Bronchoscopy.

BACKGROUND: In patients with bronchial obstruction estimating the location of the maximal obstruction is crucial for guiding interventional bronchoscopy. However, flow-volume curves cannot discriminate between the right and left lungs. OBJECTIVES: The aim of this study was to physiologically evaluate bronchial obstruction during interventional bronchoscopy. METHODS: We prospectively measured lateral airway pressure (Plat) at either side of the obstruction using a double-lumen catheter (pressure-pressure [P-P] curve) simultaneously to assess the degree of bronchial obstruction in 22 patients. The shape of the P-P curve was assessed to confirm the site of maximal obstruction. RESULTS: In the experimental study, Plat was uniform between both bronchi in the normal model. For the unilateral and bilateral obstruction models, a phase shift was only seen for the more obstructed side. In healthy subjects, the angle of the P-P curve was close to 45° and linear in shape. In patients with bronchial obstruction, the angle was much smaller but approached 45° after the bronchoscopic procedure. The degree of bronchial obstruction was significantly correlated with the angle of the P-P curve (r = -0.51, p < 0.01). Dyspnea significantly increased when the airway lumen was obstructed by more than 60% (p < 0.0001), and when the P-P curve appeared loop-shaped (p < 0.01). CONCLUSIONS: The shape of the P-P curve could be used to detect the site of maximal obstruction for the optimal positioning of the stent and assess the need for additional procedures in real time in patients with bronchial obstruction.

Background and distribution of lobar microbleeds in cognitive dysfunction.

Objectives: Cerebral microbleeds (CMBs) are often observed in memory clinic patients. It has been generally accepted that deep CMBs (D-CMBs) result from hypertensive vasculopathy (HV), whereas strictly lobar CMBs (SL-CMBs) result from cerebral amyloid angiopathy (CAA) which frequently coexists with Alzheimer's disease (AD). Mixed CMBs (M-CMBs) have been partially attributed to HV and also partially attributed to CAA. The aim of this study was to elucidate the differences between SL-CMBs and M-CMBs in terms of clinical features and regional distribution. Materials: We examined 176 sequential patients in our memory clinic for clinical features and CMB location using susceptibility-weighted images obtained on a 3T-MRI. The number of lobar CMBs in SL-CMBs and M-CMBs was counted in each cerebral lobe and their regional density was adjusted according to the volume of each lobe. Results: Of the total 176 patients, 111 patients (63.1%) had CMBs. Within the patients who had CMBs, M-CMBs were found in 54 patients (48.6%), followed by SL-CMBs in 35 (31.5%) and D-CMBs in 19 (17.1%). The SL-CMB group showed a significantly higher prevalence of family history of dementia, whereas the M-CMB group showed an increasing trend toward hypertension and smoking. The prevalence of AD was significantly higher in the SL-CMBs group, whereas the prevalence of AD with cerebrovascular disease was higher in the M-CMBs group. The regional density of lobar CMBs was significantly higher in the occipital lobe in the M-CMB group, whereas the SL-CMB group showed higher regional density between regions an increasing tendency in the parietal and occipital lobe. Conclusion: The between-group differences in clinical features and regional distribution indicate there to be an etiological relationship of SL-CMBs to AD and CAA, and M-CMBs to both HV and CAA.