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.

Detection of cerebral amyloid angiopathy by 3-T magnetic resonance imaging and amyloid positron emission tomography in a patient with subcortical ischaemic vascular dementia.

The patient was an 81-year-old man who had been treated for hypertension for several decades. In 2012, he developed gait disturbance and mild amnesia. One year later, his gait disturbance worsened, and he developed urinary incontinence. Conventional brain magnetic resonance imaging using T 2 -weighted images and fluid-attenuated inversion recovery showed multiple lacunar infarctions. These findings fulfilled the diagnostic criteria for subcortical ischaemic vascular dementia. However, susceptibility weighted imaging showed multiple lobar microbleeds in the bilateral occipitoparietal lobes, and double inversion recovery and 3-D fluid-attenuated inversion recovery images on 3-T magnetic resonance imaging revealed cortical microinfarctions in the left parietal-temporo-occipito region. Pittsburgh compound B-positron emission tomography revealed diffuse uptake in the cerebral cortex. Therefore, we diagnosed the patient with subcortical ischaemic vascular dementia associated with Alzheimer's disease. The use of the double inversion recovery and susceptibility weighted imaging on 3-T magnetic resonance imaging may be a supplemental strategy for diagnosing cerebral amyloid angiopathy, which is closely associated with Alzheimer's disease.

A case of musical anhedonia due to right putaminal hemorrhage: a disconnection syndrome between the auditory cortex and insula.

A 63-year-old, right-handed professional chorus conductor developed right putaminal hemorrhage, and became unable to experience emotion while listening to music. Two years later, neurological examination revealed slight left hemiparesis. Neuromusicological assessments revealed impaired judgment of "musical sense," and the inability to discriminate the sound of chords in pure intervals from those in equal temperament. Brain MRI and tractography identified the old hemorrhagic lesion in the right putamen and impaired fiber connectivity between the right insula and superior temporal lobe. These findings suggest that musical anhedonia might be caused by a disconnection between the insula and auditory cortex.

Regional Lung Sound Asynchrony in Chronic Obstructive Pulmonary Disease Patients.

BACKGROUND: Regional lung sound distribution in chronic obstructive pulmonary disease (COPD) is reported to be asynchronous. Mathematical analyses using vibration response imaging (VRI), such as left and right lung asynchrony (gap index; GI) and regional lung asynchrony (asynchrony score; AS), are useful measures to evaluate lung sound asynchrony. OBJECTIVES: The aim of this study was to investigate the association of lung sound asynchrony with pulmonary functions and emphysematous lesions in COPD patients. METHODS: VRI recordings and pulmonary function tests were performed in 46 stable male COPD patients and in 40 healthy male smokers. Lung sound asynchrony was evaluated using GI, AS of the left and right lung (AS L-R), and AS of the upper and lower lung (AS U-L). In 38 patients, computed tomography taken within 6 months was available and analyzed. RESULTS: AS L-R and AS U-L were significantly higher in COPD patients than in healthy smokers, with no significant difference in GI. There were no significant correlations with either AS and pulmonary functions, excluding a negative correlation between AS U-L and diffusion capacity. Although there were no significant correlations between both AS and severity of emphysema, significant positive correlations were observed between heterogeneity of emphysematous lesions and AS L-R (ρ = 0.38, p < 0.05) or AS U-L (ρ = 0.51, p < 0.005). CONCLUSIONS: Regional lung sounds are distributed more asynchronously in COPD patients than in healthy smokers, which correlates with the heterogeneous distribution of emphysematous lesions.

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.

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.

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.

Assessing the site of maximal obstruction in the trachea using lateral pressure measurement during bronchoscopy.

RATIONALE: Lateral airway pressure can provide valuable physiological information during bronchoscopy. OBJECTIVES: To evaluate tracheal obstruction during intervention. METHODS: To prospectively measure lateral airway pressure during bronchoscopy using a double-lumen catheter in 15 healthy subjects and 30 patients with tracheal obstruction. Pressure difference was used to evaluate the site of maximal obstruction. The angle between pressure recordings on either side of the stenosis was measured simultaneously (pressure-pressure curves) to assess the degree of tracheal obstruction. MEASUREMENTS AND MAIN RESULTS: In the experimental study, the angle of the pressure-pressure curve was unaffected by breathing maneuvers whereas the pressure difference was affected. In healthy subjects, no pressure difference between the carina and trachea was observed during tidal breathing, and the angle was close to 45°. In patients with tracheal obstruction, the dyspnea scale, pressure difference, and angle changed significantly beyond 50% obstruction (P<0.0001). After stenting, the pressure difference disappeared and the angle was close to 45°. The degree of tracheal obstruction was significantly correlated with the pressure difference (r=0.83, P<0.0001) and angle (r=-0.84, P<0.0001). The cross-sectional area, dyspnea scale, pulmonary function tests, pressure difference, and the angle significantly improved after procedures (P<0.0001). Responder rates on the modified Medical Research Council Scale were 84.6% for obstructions above 80%, and 58.8% for obstructions between 50 and 80%. CONCLUSIONS: The direct measurement of pressure difference and the angle of the pressure-pressure curve represent a new assessment modality for the success of interventional bronchoscopy. Measuring lateral airway pressure could estimate the need for additional procedures better than bronchoscopy alone.

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.

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.

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.

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.

Kinematic evaluation of the adjacent segments after lumbar instrumented surgery: a comparison between rigid fusion and dynamic non-fusion stabilization.

The aim of the current study was to evaluate changes in lumbar kinematics after lumbar monosegmental instrumented surgery with rigid fusion and dynamic non-fusion stabilization. A total of 77 lumbar spinal stenosis patients with L4 degenerative spondylolisthesis underwent L4-5 monosegmental posterior instrumented surgery. Of these, 36 patients were treated with rigid fusion (transforaminal lumbar interbody fusion) and 41 with dynamic stabilization [segmental spinal correction system (SSCS)]. Lumbar kinematics was evaluated with functional radiographs preoperatively and at final follow-up postoperatively. We defined the contribution of each segmental mobility to the total lumbar mobility as the percent segmental mobility [(sagittal angular motion of each segment in degrees)/(total sagittal angular motion in degrees) × 100]. Magnetic resonance imaging was performed on all patients preoperatively and at final follow-up postoperatively. The discs were classified into five grades based on the previously reported system. We defined the progress of disc degeneration as (grade at final follow-up) - (grade at preoperatively). No significant kinematical differences were shown at any of the lumbar segments preoperatively; however, significant differences were observed at the L2-3, L4-5, and L5-S1 segments postoperatively between the groups. At final follow-up, all of the lumbar segments with rigid fusion demonstrated significantly greater disc degeneration than those with dynamic stabilization. Our results suggest that the SSCS preserved 14% of the kinematical operations at the instrumented segment. The SSCS may prevent excessive effects on adjacent segmental kinematics and may prevent the incidence of adjacent segment disorder.

Decrease in birth weight and gestational age by arsenic among the newborn in Shanghai, China.

OBJECTIVES: To assess the effects of trace metals on birth weight and gestational age among newborn babies of mothers without occupational exposure. METHODS: The subjects examined were 142 newborn babies (71 males and 71 females) delivered at two university hospitals in Shanghai, China and their parents. Relationships of newborn birth weight and gestational age to concentrations of arsenic, lead, cadmium, manganese, zinc, and cobalt in maternal and cord blood were investigated. RESULTS: Birth weight was 3379.5 +/- 440.8 (2090-4465) g and the gestational age was 39.7 +/- 1.3 (35-43) weeks. Stepwise regression analysis indicated that, in the male newborn, birth weight and gestational age were inversely related to the logarithm arsenic concentration (4.13 +/- 3.21 microg/l) in mothers' whole blood. CONCLUSION: Arsenic might have a negative influence on newborn birth weight and gestational age at a relatively low exposure level. This effect was observed in male but not female babies, suggesting a sex differential in susceptibility to arsenic at an early stage of development. Although birth weight is believed to be related to gestational age, arsenic may directly affect both birth weight and gestational age.

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.