Epithelial-mesenchymal transition as a fundamental underlying pathogenic process in COPD airways: fibrosis, remodeling and cancer.

Chronic obstructive pulmonary disease (COPD) is a complex condition, frequently with a mix of airway and lung parenchymal damage. However, the earliest changes are in the small airways, where most of the airflow limitation occurs. The pathology of small airway damage seems to be wall fibrosis and obliteration, but the whole airway is involved in a 'field effect'. Our novel observations on active epithelial-mesenchymal transition (EMT) in the airways of smokers, particularly in those with COPD, are changing the understanding of this airway pathology and the aetiology of COPD. EMT involves a cascade of regulatory changes that destabilise the epithelium with a motile and mesenchymal epithelial cell phenotype emerging. One important manifestation of EMT activity involves up-regulation of specific key transcription factors (TFs), such as Smads, Twist, and ß-catenin. Such TFs can be used as EMT biomarkers, in recognisable patterns reflecting the potential major drivers of the process; for example, TGFß, Wnt, and integrin-linked kinase systems. Thus, understanding the relative changes in TF activity during EMT may provide rich information on the mechanisms driving this whole process, and how they may change over time and with therapy. We have sought to review the current literature on EMT and the relative expression of specific TF activity, to define the networks likely to be involved in a similar process in the airways of patients with smoking-related COPD.

Mining pattern sequences in respiratory tumor motion data.

Management of respiration induced tumor motion during radiation therapy is crucial to effective treatment. Pattern sequences in the tumor motion signals can be valuable features in the analysis and prediction of irregular tumor motion. In this study, we put forward an approach towards mining pattern sequences in respiratory tumor motion data. We discuss the use of pattern sequence distributions as effective representations of motion characteristics, and find similarities between individual tumor motion instances. We also explore grouping of patients based on similarities in pattern sequence distributions exhibited by their respiratory motion traces.

Clinical course of thoracic cancers in Hodgkin's disease survivors.

BACKGROUND: Hodgkin's disease survivors have a high risk of subsequently developing thoracic cancers. Our goal was to evaluate the prognosis and treatment outcomes of thoracic cancers after Hodgkin's disease. PATIENTS AND METHODS: Thirty-three patients treated for Hodgkin's disease at Harvard-affiliated hospitals subsequently developed small-cell lung carcinoma, non-small-cell lung carcinoma (NSCLC) or mesothelioma. Information was obtained from medical records about the initial treatment for Hodgkin's disease, any salvage therapy, smoking history, and the stage, histology, treatment and survival for thoracic cancers. RESULTS: Of the 33 patients, 29 (88%) had a history of radiotherapy to the thorax, 17 (52%) had received alkylating chemotherapy, and 24 (73%) had a known history of smoking. The median time between diagnosis of Hodgkin's disease and diagnosis of thoracic cancer was 17.3 years (range 1.2-27.9 years). Among patients with NSCLC and a known stage, 85% presented with stage III or stage IV disease. Among patients whose treatment details were available, 40% underwent surgery, 40% received radiotherapy and 65% received chemotherapy. The median survival was 9 months (range 1-47 months). CONCLUSIONS: Most patients with thoracic cancers after Hodgkin's disease have a history of exposure to risk factors and present at an advanced stage. Patients with thoracic cancers after Hodgkin's disease have a poor survival.

Clinical course of recurrent respiratory papillomatosis in Danish children.

OBJECTIVE: To evaluate the clinical course of juvenile-onset recurrent respiratory papillomatosis (RP) with respect to age, disease duration, and maternal condylomas. DESIGN: Inception cohort study. SETTING: All ear, nose, and throat departments in public Danish hospitals. PATIENTS: Fifty-seven Danish children diagnosed with RP and born between 1974 and 1993 were observed for an average of 14 years after diagnosis. MAIN OUTCOME MEASURE: Removal of respiratory papillomas by knife biopsy, laser surgery, or cryotherapy. RESULTS: Children younger than 5 years diagnosed with RP underwent an average of 4.1 surgeries in the first year of disease, the highest rate among all our patients. The overall surgery rate decreased over time after initial diagnosis but remained significantly higher for children with a younger age of onset for the first 4 years of disease (P <.001) and for children with a maternal history of condylomas in pregnancy for years 4 to 10 of the disease (P <.001). We also observed an independent and statistically significant (P <.001) decreasing surgery rate with increasing age and time from initial diagnosis. The trend for children with recurrent disease was a decreasing rate of surgical procedures (28 of 42 patients with recurrent disease); however, a third of patients (14/42) demonstrated a constant or increasing rate of surgical procedures over time. CONCLUSIONS: The clinical course of RP is characterized by a high frequency of surgeries soon after diagnosis that diminishes over time and with increasing age. Additional studies are warranted to identify factors associated with cases that do not conform to the usual disease course.

Voice quality of prepubescent children with quiescent recurrent respiratory papillomatosis.

OBJECTIVE: The purpose of this study was to assess the long-term impact of recurrent respiratory papillomatosis (RRP) and its treatment on voice quality in prepubescent children. STUDY DESIGN: Case-control study. METHODS: Prepubescent children with RRP in remission for at least 12 [according to MM section] months were asked to participate. Remission was documented by absence of papillomas on fiberoptic flexible laryngoscopy. An age- and sex-matched control was selected for each patient enrolled. Voice was evaluated using the voice-related quality of life (V-RQOL) questionnaire, perceptual evaluations of voice quality by speech-language pathologists using the GRBAS (grade of hoarseness, roughness, breathiness, asthenia, strain) scale, and acoustic analysis (fundamental frequency, maximal phonation time, and relative average perturbation) using the Visi-Pitch II 3300. RESULTS: Medical records of 84 patients were reviewed and 15 met study criteria. Five agreed to participate but one was excluded due to the presence of papillomas. The four study patients and four matched controls were between 9- and 11-years old. On the V-RQOL questionnaire, each control rated V-RQOL as normal (10/50) and the average patient group score was within the normal range (11.5/50). On perceptual evaluations, the patient's voices were more hoarse, breathy, and rough compared to controls'. Acoustic analysis showed that patients' voices had a lower average fundamental frequency (F(0)) (200 Hz compared to 243 Hz for controls) and a higher relative average perturbation (RAP) (1.10 compared to 0.77), although only one patient's voice actually had elevated RAP (2.89), which had a large impact on raising the average score for the patient group. The average maximal phonation times were similar for the two groups (7.8s for patients and 7.4s for controls) but lower than average normal scores reported in the literature. CONCLUSIONS: Although children with RRP do not perceive their voice quality to have a negative impact on V-RQOL, speech-language pathologist evaluations and acoustic measurements show objective differences between the voices of children with quiescent RRP and those of normal, healthy controls.

[Primary melanoma of the respiratory tract]. / Pervichnaia melanoma dykhatel'nykh putei.

4 cases of melanoma of the respiratory tract (trachea and bronchi) are analysed clinico-morphologically. A case of melanoma with a primary multiple location (trachea and the main bronchus), rapid recurrence after surgery and radiation therapy is described in detail. Melanocytic nature of the tumor is proved immunohistochemically.

The relevance to humans of animal models for inhalation studies of cancer in the nose and upper airways.

While nasal cancer is relatively rare among the general population, workers in the nickel refining, leather manufacturing, and furniture building industries exhibit increased incidences of nasal cancer. To investigate the causes of nasal cancer and to design ameliorative strategies, an appropriate animal model for the human upper respiratory regions is required. The present report describes, compares, and assesses the anatomy and physiology of the nasal passages and upper airways of humans, rats, and monkeys for the purpose of determining a relevant animal model in which to investigate potential causes of nasal cancer. Based on the mode of breathing, overall geometry of the nasal passages, relative nasal surface areas, proportions of nasal surfaces lined by various epithelia, mucociliary clearance patterns, and inspiratory airflow routes, the rat, which is very different from humans, is a poor model. In contrast, the monkey exhibits many similarities to humans. Although the monkey does differ from humans in that it exhibits a more rapid respiratory rate, smaller minute and tidal volumes, larger medial turbinate, and a vestibular wing that creates an anterior vortex during inspiration, it offers a more appropriate model for studying the toxic effects of inhaled substances on the nasal passages and extrapolating the findings to humans.

[Origin of malignant tumors of the upper respiratory and digestive tracts and the ear (from a clinicians-point of view). 2. Pathogenesis of metastases (author's transl)]. / Zur Entstehung bösartiger Geschwülste 2. Entstehung von Metastasen.

Growth and development of metastases depends on 1. Tumor cells themselves, 2. Manipulations on the primary tumor, 3. Lymphatic vessels in the surrounding area of the primary tumor, 4. Blood composition. 5. Extent of tissue resistence through which tumor cells pass. 6. Certain circulatory conditions of the blood. Tumor cells are distinguished from normal cells often by reduced (Verbrauchskoagulopathie, tendency to bleed). An increase in bloodclotting supports the development of haematogenic metastases and the tumor growth. Malignant tumors of the kidney and the intestines may develop micrometastases of the lungs which, for years, as dormant cells, remain undiscovered. Then after 12--14 years metastases (further satelites) are seen e.g. in the ENT-field. In the spreading of tumor cells the flow parameters of lymph and blood play a very important role.