Airway interventions for tracheobronchial involvement in esophageal carcinoma: a retrospective cohort outcome study and algorithmic approach.

Background: In advanced esophageal carcinoma (EC), there is limited data on risk factors predicting tracheobronchoesophageal fistula (TEF) formation and survival among patients who required airway interventions. Methods: A retrospective analysis of consecutive patients with EC, who had airway involvement requiring intervention, was conducted from 1998 to 2018. Demographics, clinical progress, disease stage, treatment and survival outcomes were recorded. Patients were followed up till death or until completion of the study. Survival was estimated with the Kaplan-Meier method and curves compared by log-rank test. Multivariate analyses of risk factors were performed using Cox proportional hazard regression. Results: A total of 122 patients were included. The median (IQR) survival from time of airway intervention was 3.30 (1.57-6.88) months, while the median (IQR) survival from time of histological diagnosis was 8.90 (4.91-14.45) months. Tumour location within 20 mm of the carina, prior radiotherapy and/or esophageal stenting were significantly associated with formation of TEF. Mid EC [adjusted hazard ratio (HR) 1.9; 95% confidence interval (CI): 1.1-3.2] or presence of TEF (adjusted HR 1.8; 95% CI: 1.0-3.2) were associated with lower survival. Patients receiving chemotherapy (adjusted HR 0.46; 95% CI: 0.25-0.84), or esophageal stenting whether before or after airway intervention (adjusted HR 0.32; 95% CI: 0.15-0.68 and adjusted HR 0.51; 95% CI: 0.29-0.90) were associated with increased survival. Conclusions: Factors associated with TEF formation include airway location, radiotherapy and prior esophageal stenting, and the development of TEF was associated with poorer survival. An algorithmic approach towards tracheobronchial involvement in EC is proposed based on these findings and a review of the literature.

Characteristics and Outcomes of Airway Involvement in Esophageal Cancer.

BACKGROUND: Airway involvement, such as airway invasion, compression, and tracheobronchoesophageal fistula (TEF), in esophageal cancer is associated with significant morbidity. However, the risk factors and outcomes of airway complications remain unclear, with limited evidence to guide management. METHODS: This retrospective analysis included 804 patients with a diagnosis of esophageal cancer from 1998 to 2018 at a tertiary care medical center (Singapore General Hospital, Singapore). Patients' demographics, treatment details, and airway involvement, as determined by bronchoscopic evaluation or computed tomographic imaging, were recorded and analyzed to determine risk factors and outcomes of airway involvement. RESULTS: The incidence of airway involvement and TEF was 36.6% and 13.1%, respectively. Airway involvement was associated with reduced survival from the time of diagnosis (hazard ratio, 1.52; 95% confidence interval [CI], 1.30 to 1.79) and increased hospitalizations per year (4.53 ± 4.80 vs 2.75 ± 3.68; P < .001). On multivariate analysis, midesophageal tumors (odds ratio [OR], 11.0; 95% CI, 6.3 to 19.0) and upper esophageal tumors (OR, 8.5; 95% CI, 4.7 to 15.6), previous treatment with esophageal stenting (OR, 17.8; 95% CI, 4.1 to 77.6), and chemotherapy or radiotherapy were associated with development of airway involvement. In patients with TEF, treatment with chemotherapy (OR, 0.34; 95% CI, 0.20 to 0.60) and combined airway and esophageal stenting (OR, 0.48; 95% CI, 0.25 to 0.91) were independently associated with improved survival. CONCLUSIONS: Airway involvement and TEF are common and are associated with increased morbidity and poorer survival. Clinicians should remain vigilant for airway complications after treatment with esophageal stenting, chemotherapy, or radiotherapy, especially in patients with midesophageal and upper esophageal cancers. In patients with TEFs, survival is improved when they are treated with airway stenting, esophageal stenting, or chemotherapy.

Long-term outcomes of tracheobronchial stenosis due to tuberculosis (TSTB) in symptomatic patients: airway intervention vs. conservative management.

BACKGROUND: Patients with tracheobronchial stenosis due to tuberculosis (TSTB) have a variable clinical course and response to treatment including airway intervention. There are no clear guidelines on the best approach to manage such patients. This study examines long-term outcomes of patients with TSTB and factors associated with recurrent symptoms or need for repeat airway intervention following initial bronchoscopic intervention. METHODS: This is a retrospective analysis of patients with TSTB over an 18-year period. Symptoms, radiological, bronchoscopic findings, airway interventions and complications were obtained. Multivariate logistic regression analysis was performed to identify factors predictive of recurrence of symptoms or need for repeat airway intervention. RESULTS: A total of 131 patients with mean age 50±18 years and median follow-up 5 (interquartile range, 2-10) years were included. Nineteen (29.7%) patients underwent balloon dilatation alone, 22 (34.4%) had additional resection or stenting, and 19 (29.7%) underwent all 3 procedures. Among patients conservatively managed, a larger proportion (55.6%) of patients with no recurrence of symptoms had active TB. Patients who developed recurrent symptoms had longer symptom duration (12 vs. 3 months, P=0.025), and more had recurrent lower respiratory tract infections (50% vs. 5.6%, P=0.003), lung collapse (90.0% vs. 41.7%, P=0.011) or linear fibrosis (70.0% vs. 30.6%, P=0.033) compared to those without recurrent symptoms. Bronchomalacia (OR =17.18; 95% CI, 3.43-86.18) and prior bronchoscopic airway resection (OR =4.97; 95% CI, 1.20-20.60) were strongly associated with the recurrence of symptoms or need for repeat airway intervention on multivariate logistic regression analysis. CONCLUSIONS: Bronchomalacia and prior bronchoscopic airway resection are associated with the recurrence of symptoms despite airway intervention. Patients who are diagnosed with TSTB early in the course of active TB may be conservatively managed.

A diver's dilemma - a case report on bronchopulmonary sequestration.

BACKGROUND: An asymptomatic SCUBA (Self-contained underwater breathing apparatus) diver was discovered to have an intralobar bronchopulmonary sequestration during routine pre-course screening. This is the first reported case of a diver who, having previously completed several recreational and military diving courses, was subsequently diagnosed with a congenital lung condition, possibly contraindicating diving. Presently, there is no available literature providing guidance on the diving fitness of patients with such a condition. CASE PRESENTATION: An asymptomatic 26-year-old male diver was nominated to attend an overseas naval diving course. Prior to this, he had been medically certified to participate in, and had successfully completed other military and recreational diving courses. He had also completed several hyperbaric dives up to a depth of 50 m and 45 recreational dives up to a depth of 30 m. He did not have a history of diving-related injuries or complications. He had never smoked and did not have any medical or congenital conditions, specifically recurrent respiratory infections. As part of pre-course screening requirements, a lateral Chest X-ray was performed, which revealed a left lower lobe pulmonary nodule. This was subsequently diagnosed as a cavitatory left lower lobe intralobar bronchopulmonary sequestration on Computed Tomography Thorax. The diver remains asymptomatic and well at the time of writing and has been accepted to participate in another overseas course involving only dry diving in a hyperbaric chamber, with no prerequisites for him to undergo surgery. CONCLUSION: Although bronchopulmonary sequestrations lack communication with the tracheobronchial tree, they may still contain pockets of air, even if not radiologically visible. This can be attributed to anomalous connections which link them to other bronchi, lung parenchyma and/or pores of Kohn. As such, there is a higher theoretical risk of pulmonary barotrauma during diving, leading to pneumothorax, pneumomediastinum, or cerebral arterial gas embolism. Taking these into consideration, the current clinical consensus is that bronchopulmonary sequestrations and all other air-containing lung parenchymal lesions should be regarded as contraindications to diving. Patients who have undergone definitive and uncomplicated surgical resection may be considered fit to dive.

Genomic landscape of lung adenocarcinoma in East Asians.

Lung cancer is the world's leading cause of cancer death and shows strong ancestry disparities. By sequencing and assembling a large genomic and transcriptomic dataset of lung adenocarcinoma (LUAD) in individuals of East Asian ancestry (EAS; n = 305), we found that East Asian LUADs had more stable genomes characterized by fewer mutations and fewer copy number alterations than LUADs from individuals of European ancestry. This difference is much stronger in smokers as compared to nonsmokers. Transcriptomic clustering identified a new EAS-specific LUAD subgroup with a less complex genomic profile and upregulated immune-related genes, allowing the possibility of immunotherapy-based approaches. Integrative analysis across clinical and molecular features showed the importance of molecular phenotypes in patient prognostic stratification. EAS LUADs had better prediction accuracy than those of European ancestry, potentially due to their less complex genomic architecture. This study elucidated a comprehensive genomic landscape of EAS LUADs and highlighted important ancestry differences between the two cohorts.

Resection with preserved histologic morphology of a rare tumour via bronchoscopic cryosurgery.

Tracheobronchial leiomyoma is a rare pulmonary neoplasm accounting for <2% of benign tumours of the lower airway. Published case series reported bronchoscopic resectability with laser ablation for lesions located in the large airway. Surgery was performed for tumours with wide-based and tumours located in segmental bronchus or lung parenchyma. This is the first reported case of complete bronchoscopic cryoresection of leiomyoma arising from the subsegmental bronchi and illustrating the cryopreservation of its histologic morphology. A 55-year-old Chinese male who was a life-long non-smoker presented with chronic cough, left-sided chest pain and loss of weight. Chest radiograph showed left lower lobe (LLL) collapse, with the accompanying computed tomography scan of the thorax showing a non-enhancing soft tissue lesion in the LLL bronchus. Rigid bronchoscopy was performed, with rigid forceps resection followed by cryosurgery of the tumour to its base. Histology was consistent with a primary bronchial leiomyoma. Surveillance bronchoscopy performed 6 months later revealed no tumour recurrence. The patient also had complete resolution of his symptoms. Cryosurgery is a promising treatment modality, in complement with conventional forceps resection, for benign airway neoplasms.

Nonsteroidal anti-inflammatory drug (NSAID) exacerbated respiratory disease phenotype: Topical NSAID and asthma control - A possible oversight link.

BACKGROUND: Patients with aspirin-exacerbated respiratory disease (AERD) also recently known as nonsteroidal anti-inflammatory drug (NSAID) exacerbated respiratory disease (NERD) must avoid aspirin and all other oral NSAIDs. The effect of topical NSAID (tNSAID), especially salicylates which are commonly present in topical medicated preparations, on asthma control of this phenotype is studied. METHODS: The study inclusion criteria were adults with: 1) NSAID hypersensitivity; 2) nasal polyposis/chronic rhinosinusitis; 3) not well-/poorly controlled asthma and 4) exposure to tNSAID. Patients were given verbal and written instructions to cease tNSAIDs exposure and asthma control was evaluated during the 6 months prior and after intervention. RESULTS: There were eleven patients (ten females) with a mean age of 56.5 (range 37-71) years. Prior known oral NSAIDs hypersensitivity included aspirin (5), mefenamic acid (2), diclofenac (2), Synflex (2) and ibuprofen (1). All, except 2, had arthropathies or spinal disorders and were using tNSAID for a mean of 4.2 years. One, four and six patients were using over-the-counter medicated oil containing salicylates, NSAID gel/plasters and both respectively. All patients had cutaneous, with 4 having concomitant inhalational exposure to these tNSAIDs. The mean duration of asthma diagnosis and uncontrolled asthma were 25.2 and 4.5 years respectively. Except for 2 patients, there was no change in asthma maintenance medications pre and post-intervention. Asthma control significantly (p < 0.05) improved based on pre and post-intervention ACT score, number of exacerbations, FEV1 were 14.9 and 22.1, 1.9 and 0.43, 1.28L and 1.67L respectively. CONCLUSIONS: It is paramount to eliminate not only oral but topical NSAID exposure in NERD phenotype asthmatic patients. When a long-standing asthma progressed to uncontrolled, a meticulous evaluation of tNSAIDs exposure is warranted especially if the patient has developed chronic pain.

Endoscopic intervention of lower airway foreign matter in adults-a different perspective.

BACKGROUND: Lower airway foreign matter (FM) is uncommonly encountered in adults. This study reviews FM in the lower airway that required bronchoscopic intervention. METHODS: A retrospective review of patients with FM in the lower airway seen at a tertiary hospital between 1996 and 2014 was undertaken. RESULTS: Lower airway FM was removed in 80 out of 18,650 bronchoscopies performed. Forty-seven were males, with mean age of 50.8 (range, 29-78) years and mean symptom duration of 10.3 months (range, 1 day -20 years). The most common symptoms were persistent cough, followed by dyspnea, hemoptysis, episodes of choking and fever. Three-quarters of the patients had risk factors of either aspiration or iatrogenic cause for FM in the airway. FM identified following bronchoscopy was classified as: organic (31.3%), inorganic (46.3%) and endogenous matter (22.4%). Iatrogenic etiology was evident in four-fifths of the patients with inorganic FM (stents being the most common). Forty-eight (60.0%) patients had FM removed via flexible bronchoscopy, and the remainder via rigid bronchoscopy. The majority (27 out of 32) of FM removed by rigid bronchoscopy could not be removed using the flexible scope. This was primarily due to retrieval of stents [24] could only be done with the rigid bronchoscope. There were four FM-related complications (three bronchostenosis, one actinomycosis). CONCLUSIONS: There is an increasing indication for bronchoscopists to retrieve FM, particularly of iatrogenic and endogenous sources, lodging in the lower airway of adults. There may be a reversing trend in the utilization of rigid bronchoscopy, mainly due to the increasing need to remove airway stents as more are deployed.

Impact of Smoking and Brain Metastasis on Outcomes of Advanced EGFR Mutation Lung Adenocarcinoma Patients Treated with First Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors.

OBJECTIVES: This purpose of this study was to examine clinical-pathologic factors--particularly smoking and brain metastases--in EGFR mutation positive (M(+)) lung adenocarcinoma (ADC) to determine their impact on survival in patients treated with first line EGFR TKI. METHODS: A retrospective review of EGFR mutation reflex testing experience for all ADC diagnosed at a tertiary Asian cancer centre from January 2009 to April 2013. Amongst this cohort, patients with advanced EGFR M(+) ADC treated with first line EGFR TKI were identified to determine factors that influence progression free and overall survival. RESULTS: 444/742 (59.8%) ADC reflex tested for EGFR mutations were EGFR M(+.) Amongst never-smokers (n=468), EGFR M(+) were found in 74.5% of females and 76.3% of males, and amongst ever smokers (n=283), in 53.3% of females and 35.6% of males. Exon 20 mutations were found more commonly amongst heavy smokers (> 50 pack years and > 20 pack years, Pearson's chi square p=0.044, and p=0.038 respectively). 211 patients treated with palliative first line TKI had a median PFS and OS of 9.2 and 19.6 months respectively. 26% of patients had brain metastasis at diagnosis. This was significantly detrimental to overall survival (HR 1.85, CI 1.09-3.16, p=0.024) on multivariate analysis. There was no evidence that smoking status had a significant impact on survival. CONCLUSIONS: The high prevalence of EGFR M(+) in our patient population warrants reflex testing regardless of gender and smoking status. Smoking status and dosage did not impact progression free or overall survival in patients treated with first line EGFR TKI. The presence of brain metastasis at diagnosis negatively impacts overall survival.

Negative pressure pulmonary oedema in the medical intensive care unit.

OBJECTIVE: Negative pressure pulmonary oedema (NPPE) occurring in the medical intensive care unit (MICU) is an uncommon, probably under-diagnosed, but life-threatening condition. DESIGN: Retrospective data collection. SETTING: Medical intensive care unit in a 1,500-bedded tertiary care hospital. PATIENTS AND PARTICIPANTS: Five patients were diagnosed between January 1998 and January 2002. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Five patients were diagnosed to have NPPE from different aetiologies. These were acute epiglottitis, post-stenting of right bronchus intermedius stenosis, strangulation, compression from a goitre and one patient developed diffuse alveolar haemorrhage after biting the endotracheal tube during recovery from anaesthesia. All patients responded rapidly to supplemental oxygen, positive pressure ventilation and correction of underlying aetiologies. Pulmonary oedema resolved rapidly. CONCLUSIONS: There is a large spectrum of aetiologies causing NPPE in the medical intensive care unit.