Explainable artificial intelligence (XAI) for exploring spatial variability of lung and bronchus cancer (LBC) mortality rates in the contiguous USA.

Machine learning (ML) has demonstrated promise in predicting mortality; however, understanding spatial variation in risk factor contributions to mortality rate requires explainability. We applied explainable artificial intelligence (XAI) on a stack-ensemble machine learning model framework to explore and visualize the spatial distribution of the contributions of known risk factors to lung and bronchus cancer (LBC) mortality rates in the conterminous United States. We used five base-learners-generalized linear model (GLM), random forest (RF), Gradient boosting machine (GBM), extreme Gradient boosting machine (XGBoost), and Deep Neural Network (DNN) for developing stack-ensemble models. Then we applied several model-agnostic approaches to interpret and visualize the stack ensemble model's output in global and local scales (at the county level). The stack ensemble generally performs better than all the base learners and three spatial regression models. A permutation-based feature importance technique ranked smoking prevalence as the most important predictor, followed by poverty and elevation. However, the impact of these risk factors on LBC mortality rates varies spatially. This is the first study to use ensemble machine learning with explainable algorithms to explore and visualize the spatial heterogeneity of the relationships between LBC mortality and risk factors in the contiguous USA.

[Investigation and Analysis of Primary Lung Cancer with Endotracheal and Endobronchial Metastases].

BACKGROUND: Endotracheal and endobronchial metastases (EEM) is a rare manifestation in primary lung cancer. It has not yet been reported in Chinese literatures. The aim of this study was to summarize and analyze the clinical feature of lung cancer with EEM. METHODS: We retrospectively reviewed 6 patients who presented with EEM of lung cancer from Peking University Third Hospital from January 2015 to December 2018. With "endotracheal metastases, endobronchial metastases, lung cancer" as the keywords, 13 cases were retrieved from PubMed database until February 2020. The clinical, radiologic and bronchoscopic data were collected. RESULTS: Six patients were selected from 967 patients with lung cancer, and all were diagnosed with lung cancer and EEM simultaneously. There were 4 cases of squamous cell carcinoma, 1 case of adenocarcinoma, and 1 case of small cell lung cancer. One patient had stage IIIb and 5 patients had stage IV. There were 5 cases of central lung cancer and 1 case of peripheral lung cancer. EEM on bronchoscope examination presented as endoluminal nodular or polypoid lesion in 5 patients, and abnormal white bulge in 1 patient. 5 cases metastasized to the contralateral bronchus, 1 case to the ipsilateral bronchus and 1 case to the trachea. The median overall survival was 7.5 months. Totally 13 cases of lung cancer with EEM were retrieved from PubMed database. 12 cases were diagnosed during the follow up after lung cancer resection. There were 8 cases of squamous cell carcinoma and 9 cases of central type. Endotracheal or endobronchial nodules showed in 10 cases and eccentric wall thickening in 2 cases were seen on chest computed tomography (CT), which corresponding to the nodular or polypoid lesion bronchoscopically. 5 cases metastasized to the contralateral bronchus, 10 cases to the trachea and 1 case to the ipsilateral bronchus. CONCLUSIONS: EEM is a rare metastasis of lung cancer, which can occur at the initial diagnosis of lung cancer or after surgical resection. It is often seen in the patients of squamous cell carcinoma with central type in advanced stage. The prognosis is poor.

[Primary lung cancer and occupational exposure in a North African population]. / Cancer bronchique primitif et risques professionnels dans une population Nord-Africaine.

Bronchopulmonary tumors (BPTs) are the most common cancers. They are associated with poor prognosis. They are usually caused by occupational exposure, but this is often underestimated. The purpose of this study is to assess the rate of bronchopulmonary tumors (BPT) probably due to occupational exposure and to investigate the relationship between the type of exposition and the histological type of BPT. We conducted a retrospective epidemiological study, in the Department of Pneumology at the Public Hospital Institution (EPH) in Rouïba. Between January 2014 and June 2019, we collected 357 cases with histologically confirmed BPT. Medical and professional history collections were carried out. The job-exposure matrix was used to identify the various exposures. The study population consisted of 357 patients, with an average age of 63.9±11.1 years and a male to female sex-ratio of 7.4; 76.5% of patients were smokers or former smokers, on average 42 P/A. Non-small-cell lung carcinoma was confirmed histologically in 88.8% of patients. All occupational categories studied would be responsible for 50.7% of exposure-related primary lung cancers, of which 26.5% were due to occupational exposure of heavy-duty drivers and gear drivers. Occupational exposure as a leading cause of bronchopulmonary cancers (CBP) is not negligible but often unrecognized due to its multifactorial factors and the latency period from the time of exposure to onset of disease symptoms, with an impact on the histological type of bronchopulmonary cancer.

Endobronchial involvement as an extremely rare manifestation of the Waldenström's disease.

Pulmonary infiltration is an infrequent organ involvement in Waldenström's disease (WD). Diffuse infiltration, isolated parenchymatous nodules, and pleural effusion are the most common manifestations of WD, while endobronchial mass is extremely rare. We present a case report of a 66-year-old man with a long-standing history of WD, who developed febrile neutropenia after therapy with rituximab, cyclophosphamide, and dexamethasone. X-ray and CT scan showed consolidation consistent with right-sided pneumonia. Surprisingly, bronchoscopy revealed an endobronchial tumor obstructing the right lower lobe (RLL) and two smaller granulations. Biopsies were obtained and recanalization of the RLL bronchus was performed. Immunohistological staining of the samples was consistent with lymphoplasmacytic lymphoma. Despite the change in therapy the patient died 6 weeks later. A review of published literature revealed only two case reports of endobronchial involvement in WD to this day. While one of the case reports described a patient with diffuse submucosal infiltration of the airways, the other one presented a patient with bronchus-obstructing tumor similar to the case reported here.

[The two major complications of tobacco in a single image!] / Les deux complications majeures du tabac en une seule image!

Smoking is the leading cause of preventable death worldwide, it is responsible for 90% of bronchopulmonary cancers and is the main cause of chronic bronchitis and emphysema, two disorders which contribute to chronic obstructive pulmonary disease (COPD). We here report the case of a 58-year old not weaned chronic tabagic patient with a 2-month history of diffuse abdominal pain evolving in a context of alteration of the general state. Clinical examination showed generally poor health. Pleuropulmonary examination objectified reduction of vesicular breath sounds in the right hemithorax and diffuse abdominal susceptibility and massive left subclavicular lymphadenopathy. Thoraco-abdominal CT scan showed pleural, intra-abdominal and retroperitoneal tissue infiltration and diffuse bilateral lung emphysema (Figure). Bronchial fibroscopy objectified bud obstructing the orifice of the apical bronchus of the right upper lobar bronchus. Anatomopathologic study of bronchial biopsy and lymph node biopsy showed non-differentiated carcinoma. Evolution was marked by patient's death after two weeks. This study aims to highlight fatal outcome due to these two complications due to tobacco use in the same patient in order to emphasize the importance of prevention awareness of the damages of tobacco use and on smoking cessation.

Extranodal Marginal Zone Endobronchial Lymphoma Associated With Hepatitis C.

We describe two patients with hepatitis C and a diagnosis of pulmonary extranodal marginal zone B cell lymphoma. Both patients demonstrated a chronic nonproductive cough without hemoptysis. Diagnosis was obtained after a computed tomographic chest scan and flexible bronchoscopic biopsy. We discuss the staging and prognosis of this disease, its correlation with hepatitis C, and potential benefits of treating the associated hepatitis C.

[The different pleuro-pulmonary pathologies related to asbestos: definitions, epidemiology and evolution]. / Les différentes pathologies pleuropulmonaires liées à l'amiante: définitions, épidémiologie et évolution.

Pleural plaques (fibrosis of the parietal pleura) are sometimes seen following light exposure. Their prevalence may reach 70% in heavily exposed populations. Fibrosis of the visceral pleura is much less common and it is not specifically related to asbestos. The incidence of asbestosis (pulmonary fibrosis induced by asbestos exposure) is diminishing in France. According to the data of the National Programme for the Surveillance of Mesothelioma, the annual number of cases of pleural mesothelioma varied from 646 to 800 for the period 1998-2003. Primary lung cancer due to asbestos does not have specific clinical, radiological or anatomical-pathological features. The number of cases attributable to asbestos has been estimated as between 2086 and 4172 for 1999. A report of the National Academy of Medicine, the Academy of Sciences and the International Centre of Cancer Research has calculated the incidence of primary lung cancer due to asbestos in 2000 as 969 for men and 133 for women. The risk of primary lung cancer is increased in populations exposed to asbestos even in the absence of radiological signs of pulmonary fibrosis. For an identical total exposure, asbestosis increases the risk of primary lung cancer. On the basis of radiological studies, pleural plaques are associated with an increased risk of lung cancer and mesothelioma. For identical levels of total asbestos exposure, it has not been established that the presence of pleural plaques increases the risk of developing thoracic cancer.

Foreign body granulomas in the left main bronchus resulting from the sutures for esophageal cancer surgery: the report of two cases.

In this report, we present two cases of bronchial foreign body granulomas caused by the suture ties used in bronchial surgery for esophageal cancer. Both of them was hospitalized as "tumor transfer or an invasion", but pathological examination of the neoplasms indicated an inflammatory granuloma showing reaction to the foreign body. These two cases give us an attention that the neoplasms in tracheal or bronchial was not only the invasion or transfer of the primary tumor, but also the possibility of granuloma development due to the surgical sutures.

Smoking, occupational risk factors, and bronchial tumor location: a possible impact for lung cancer computed tomography scan screening.

INTRODUCTION: The aim of this study was to describe associations between lung tumor location and smoking as well as selected occupational exposures. In the context of lung cancer screening by computed tomography scan, tumor location may have an interest. Computed tomography scan is known to better detect more peripheral tumors. METHODS: Lung cancer cases diagnosed in two French University hospitals between 1997 and 2009 were included. Tumors visible on white-light bronchoscopy were defined as central. Occupational exposures were assessed by the same expert. Data were analyzed by case-case comparisons using unconditional logistic regressions. RESULTS: A total of 1701 cases were included, comprising mainly men (86.3%), current smokers (52.8%), or former smokers (42.8%). Main histological subtypes of cancer were adenocarcinomas (33.8%) and squamous cell carcinomas (32.6%). The tumor location was found to be central in 61% of cases, and never smokers and women had more often peripheral tumors. Exposure to asbestos was significantly associated with central location with dose-response relationship (odds ratio [OR] for peripheral tumors = 0.45, 95% confidence interval [CI] 0.29-0.70) for the highest level of exposure. Exposure to silica dust was significantly associated with peripheral tumor (OR for peripheral tumors = 3.28, 95%CI 1.50-7.17) for the highest level of exposure. Exposure to welding fumes was associated with central location (OR for peripheral tumors = 0.51, 95% CI 0.26-0.96) for the first level of exposure). CONCLUSIONS: Smoking characteristics and occupational exposures have to be considered to define more accurately high-risk populations suitable for lung cancer screening or early detection programs.

[Natural course of preneoplastic bronchial lesions]. / Evolutia naturala a leziunilor bronsice preneoplazice.

Advances in endoscopic technology have improved the detection of precancerous bronchial lesions associated with the occurence of proximal squamous cell lung cancer (SCC) in high-risk individuals for broncho-pulmonary neoplasm. The debates and controversies regarding the control and treatment of intraepitelial bronchial lesions is due to the fact that the regression rate of all preneoplastic bronchial lesions is 54%. But the progression to carcinoma in situ or to cancer is significantly higher for severe dysplasia, than for preneoplastic lesions showing lower-grade dysplasia, such as squamous metaplasia and mild or moderate dysplasia. The progression rate to carcinoma in situ or cancer with squamous cells varies between 19% and 46% for patients with severe dysplasia. The diagnosis and resection of pulmonary cancer in incipient stages increases spectacularly the survival rates of the resected patients, by comparison to the non-operated patients.

[Cyclooxigenase-2 levels are increased in the lung tissue and bronchial tumors of patients with chronic obstructive pulmonary disease]. / La ciclooxigenasa-2 está regulada al alza en el pulmón y en los tumores bronquiales de pacientes con enfermedad pulmonar obstructiva crónica.

INTRODUCTION: The expression of cyclooxygenase 2 (COX-2) is usually increased in inflammation and cancer. This study examines the expression of COX-2 in the lung of chronic obstructive pulmonary disease (COPD) patients with lung cancer. METHODS: We studied 44 male patients with bronchial cancer (27 squamous carcinoma and 17 adenocarcinoma). Samples were obtained from the pulmonary parenchyma, from the bronchial mucosa adjacent to the tumor and from the tumor itself. Lung tissue specimens from 14 patients with pneumothorax were used as control. The mRNA and the COX-1 and COX-2 proteins were assessed by RT-PCR and Western blot, respectively. RESULTS: COX-1 and COX-2 mRNA levels were significantly higher in the lung parenchyma of COPD patients than in the control subjects. COX-2 mRNA levels were also higher in the lung parenchyma than in both tumor and airway tissue samples procured from COPD patients. There were no differences in the COX-2 mRNA levels between squamous carcinoma and adenocarcinoma. In contrast, COX-2 protein levels were significantly higher in tumors than in lung parenchyma and airways. COX-2 protein levels were higher in adenocarcinoma compared with squamous carcinoma. CONCLUSION: This study shows that in COPD, the pathway of cyclooxygenase is activated and associated with an increase in the expression of COX-2 in lung tumors. These observations suggest that COX-2 is possibly involved in the association between COPD and cancer.

Radiation-induced sarcoma in bronchial stump after thoracic radiation therapy for small-cell lung cancer.

We report a rare case of radiation-induced sarcoma (RIS) that arose in the right bronchial stump, 8 years after right pneumonectomy followed by adjuvant chemotherapy and thoracic radiotherapy for a localized small-cell lung cancer. The patient was treated in 2002 with 6 MV X-ray irradiation in a total dose of 60 Gy. Eight years after the end of radiotherapy, he presented with an undifferentiated high-grade pleomorphic sarcoma. Although an increased rate of soft tissue sarcoma has been reported after radiotherapy for some solid cancers or lymphomas, to our knowledge, this is the first report of RIS related to small-cell lung cancer.

Cellular burdens and biological effects on tissue level caused by inhaled radon progenies.

In the case of radon exposure, the spatial distribution of deposited radioactive particles is highly inhomogeneous in the central airways. The object of this research is to investigate the consequences of this heterogeneity regarding cellular burdens in the bronchial epithelium and to study the possible biological effects at tissue level. Applying computational fluid and particle dynamics techniques, the deposition distribution of inhaled radon daughters has been determined in a bronchial airway model for 23 min of work in the New Mexico uranium mine corresponding to 0.0129 WLM exposure. A numerical epithelium model based on experimental data has been utilised in order to quantify cellular hits and doses. Finally, a carcinogenesis model considering cell death-induced cell-cycle shortening has been applied to assess the biological responses. Present computations reveal that cellular dose may reach 1.5 Gy, which is several orders of magnitude higher than tissue dose. The results are in agreement with the histological finding that the uneven deposition distribution of radon progenies may lead to inhomogeneous spatial distribution of tumours in the bronchial airways. In addition, at the macroscopic level, the relationship between cancer risk and radiation burden seems to be non-linear.

Hypoxia and nickel inhibit histone demethylase JMJD1A and repress Spry2 expression in human bronchial epithelial BEAS-2B cells.

Epigenetic silencing of tumor suppressor genes commonly occurs in human cancers via increasing DNA methylation and repressive histone modifications at gene promoters. However, little is known about how pathogenic environmental factors contribute to cancer development by affecting epigenetic regulatory mechanisms. Previously, we reported that both hypoxia and nickel (an environmental carcinogen) increased global histone H3 lysine 9 methylation in cells through inhibiting a novel class of iron- and α-ketoglutarate-dependent histone demethylases. Here, we investigated whether inhibition of histone demethylase JMJD1A by hypoxia and nickel could lead to repression/silencing of JMJD1A-targeted gene(s). By using Affymetrix GeneChip and ChIP-on-chip technologies, we identified Spry2 gene, a key regulator of receptor tyrosine kinase/extracellular signal-regulated kinase (ERK) signaling, as one of the JMJD1A-targeted genes in human bronchial epithelial BEAS-2B cells. Both hypoxia and nickel exposure increased the level of H3K9me2 at the Spry2 promoter by inhibiting JMJD1A, which probably led to a decreased expression of Spry2 in BEAS-2B cells. Repression of Spry2 potentiated the nickel-induced ERK phosphorylation, and forced expression of Spry2 in BEAS-2B cells decreased the nickel-induced ERK phosphorylation and significantly suppressed nickel-induced anchorage-independent growth. Taken together, our results suggest that histone demethylases could be targets of environmental carcinogens and their inhibition may lead to altered gene expression and eventually carcinogenesis.