Is proflavine exposure associated with disease progression in women with cervical dysplasia? A brief report

Proflavine is an acridine dye used with high-resolution microendoscopy for in vivo diagnostic evaluation of cervical epithelial cells. However, there are concerns that even short-term exposure of cervical tissue to dilute proflavine may increase cervical cancer risk. We performed a retrospective analysis of women referred for colposcopy to Barretos Cancer Hospital comparing the risk of cervical disease progression in those whose cervical tissue was (n = 232) or was not exposed (n = 160) to proflavine. Patients in both groups underwent treatment and follow-up based on histopathologic results and per the local standards of care. Progression of disease was evaluated by comparing histopathology from the initial visit to the worst subsequent histopathology result from all follow-up visits. Mean duration of follow-up was 18.7 and 20.1 months for the proflavine-exposed and controls groups, respectively. There were no significant differences in disease progression from normal/CIN1 to CIN2/3 or from any initial diagnosis to invasive cancer between the proflavine exposed and control groups overall. Risks of cervical dysplasia progression observed in this study are in agreement with those of the natural history of cervical cancer. Our results suggest that cervical exposure to dilute proflavine does not increase the risk of cervical precancer and cancer.Research reported in this publication was supportedby the NCI of the NIH under Award Numbers UH2CA189910, UH3CA189910 and CA016672. The content is solely the responsibilityof the authors and does not necessarily represent the official views of the NIH.info:eu-repo/semantics/publishedVersio

Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis

<p>Abstract</p> <p>Background</p> <p>Usher syndrome (USH) combines sensorineural deafness with blindness. It is inherited in an autosomal recessive mode. Early diagnosis is critical for adapted educational and patient management choices, and for genetic counseling. To date, nine causative genes have been identified for the three clinical subtypes (USH1, USH2 and USH3). Current diagnostic strategies make use of a genotyping microarray that is based on the previously reported mutations. The purpose of this study was to design a more accurate molecular diagnosis tool.</p> <p>Methods</p> <p>We sequenced the 366 coding exons and flanking regions of the nine known USH genes, in 54 USH patients (27 USH1, 21 USH2 and 6 USH3).</p> <p>Results</p> <p>Biallelic mutations were detected in 39 patients (72%) and monoallelic mutations in an additional 10 patients (18.5%). In addition to biallelic mutations in one of the USH genes, presumably pathogenic mutations in another USH gene were detected in seven patients (13%), and another patient carried monoallelic mutations in three different USH genes. Notably, none of the USH3 patients carried detectable mutations in the only known USH3 gene, whereas they all carried mutations in USH2 genes. Most importantly, the currently used microarray would have detected only 30 of the 81 different mutations that we found, of which 39 (48%) were novel.</p> <p>Conclusions</p> <p>Based on these results, complete exon sequencing of the currently known USH genes stands as a definite improvement for molecular diagnosis of this disease, which is of utmost importance in the perspective of gene therapy.</p

Assessing the utility of autofluorescence-based pulmonary optical endomicroscopy to predict the malignant potential of solitary pulmonary nodules in humans

Solitary pulmonary nodules are common, often incidental findings on chest CT scans. The investigation of pulmonary nodules is time-consuming and often leads to protracted follow-up with ongoing radiological surveillance, however, clinical calculators that assess the risk of the nodule being malignant exist to help in the stratification of patients. Furthermore recent advances in interventional pulmonology include the ability to both navigate to nodules and also to perform autofluorescence endomicroscopy. In this study we assessed the efficacy of incorporating additional information from label-free fibre-based optical endomicrosopy of the nodule on assessing risk of malignancy. Using image analysis and machine learning approaches, we find that this information does not yield any gain in predictive performance in a cohort of patients. Further advances with pulmonary endomicroscopy will require the addition of molecular tracers to improve information from this procedure

Diagnostic endoscopique des nodules pulmonaires périphériques grâce au repérage en échographie par minisonde radiale (Expérience de la Clinique Pneumologique du Centre Hospitalier et Universitaire de Rouen, 2008 - 2013)

Avec les progrès de l imagerie et le développement des scanners thoraciques en coupes millimétriques, nous sommes de plus en plus confrontés à la découverte de nodules pulmonaires périphériques. Ils sont souvent asymptomatiques mais il est nécessaire d obtenir un diagnostic surtout lorsqu ils ont les critères morphologiques de malignité. Ces lésions sont difficilement explorées en bronchoscopie conventionnelle. L endoscopie couplée à l utilisation d une mini-sonde d échographie radiale permet de prélever les nodules distaux après les avoir repérés en échographie. Objectifs : Déterminer la rentabilité de la bronchoscopie couplée à l échographie par mini-sonde pour le diagnostic de nodules pulmonaires périphériques et caractériser les nodules diagnostiqués par cette technique endoscopique. Matériel et méthodes : C est une étude rétrospective concernant 345 patients ayant eu une échoendoscopie avec un endoscope fin de 4.4mm de diamètre, une minisonde 17S et un kit K201 comprenant un cathéter-guide. Les examens ont eu lieu à la Clinique Pneumologique de Rouen entre mai 2008 et mai 2013. Nous avons recueilli les caractéristiques des patients (âge, tabagisme, exposition à l amiante, données fonctionnelles respiratoires), des nodules explorés (diamètre, distance à la plèvre, signe de la bronche, fixation au PET scanner, localisation lobaire, visualisation échographique) ainsi que les résultats des prélèvements cyto-histologiques (brosse bronchique, biopsie, rinçage du cathéter) obtenus au cours de l endoscopie avec mini-sonde. Les analyses statistiques ont été effectuées avec le test exact de Fisher et le test de Kruskall-Wallis. Le seuil de significativité était p<0,05. Résultats : 345 patients ont eu une endoscopie avec mini-sonde à visée diagnostique et 13 patients ont eu la pose d un fiduciaire intra-tumoral avant irradiation stéréotaxique. Nous avons recueilli un diagnostic pour 316 nodules : 252 lésions malignes, 38 nodules infectieux, 11 nodules en rapport avec une maladie systémique et 13 nodules sans diagnostic spécifique, 2 tumeurs bénignes. 21 nodules sont actuellement sous surveillance et 8 patients ont été perdus de vue. Le diamètre médian des lésions était de 25 millimètres [5-32mm]. 296 lésions ont été visualisées en échographie et 309 lésions ont été prélevées dans le cadre de la bronchoscopie avec mini-sonde. Dans 266 cas, ont été réalisées une brosse bronchique et une biopsie, contributives conjointement dans 36% (97/266) et respectivement dans 23% (60/266) et 13% (34/266). Chez 186 patients, un rinçage du cathéter a été associé aux 2 prélèvements précédents, mais il n a conduit seul au diagnostic que dans 1 cas. L examen a mené au diagnostic dans 60.9% des cas (210/345): 199 lésions néoplasiques, 4 infections, 2 sarcoïdoses et 5 autres diagnostics. La sensibilité de l échoendoscopie pour les lésions malignes a été de 78.9% (199/252). Les facteurs ayant influencé la rentabilité diagnostique ont été : la visualisation échographique du nodule (p= 3,99.10-17), la taille du nodule supérieure à 20mm (p= 0,0073), et la présence d un signe de la bronche sur la scanner (p= 3,19.10-5). Les nodules malins ont été plus souvent diagnostiqués que les nodules bénins (78,9% vs 17,2%, p= 5,62.10-20). La localisation lobaire des nodules n a pas influencé la visualisation ni la rentabilité diagnostique de l examen. Les nodules situés à moins de 10mm de la plèvre ont été aussi bien visualisés (85.7% vs 88.6%, p=0,494) et diagnostiqués que les nodules plus centraux (59.4% vs 52%, p=0,559). Aucune complication n est survenue. Conclusion : La bronchoscopie échoguidée avec minisonde est d apprentissage rapide, sans risque, et rentable pour le diagnostic de nodules pulmonaires périphériques. Elle permet également la pose de marqueur fiduciaire, permettant le repérage des nodules avant un geste thérapeutique par radiothérapie stéréotaxique.ROUEN-BU Médecine-Pharmacie (765402102) / SudocSudocFranceF

Photodynamic therapy using methylene blue in lung adenocarcinoma xenograft and hamster cheek pouch induced squamous cell carcinoma

International audiencePhotodynamic therapy (PDT) is used to treat early proximal bronchial cancer during a flexible bronchoscopy. The technique relies on the excitation of a photosensitizer by an appropriate wavelength, which is delivered into the bronchus in close contact with the tumor

Safety and performance analysis of acriflavine and methylene blue for in vivo imaging of precancerous lesions using fibered confocal fluorescence microscopy (FCFM): an experimental study

International audienceFibered confocal fluorescence microscopy (FCFM) allows in vivo investigation of pulmonary microstructures. However, the bronchial epithelium can only be imaged using exogenous fluorophores. The objective of this study is to compare methylene blue (MB) and acriflavine genotoxicity and to assess FCFM performance for in vivo imaging of precancerous lesions. Genotoxicity was assessed using the comet assay on both cultured human lymphocytes and NCI-H460 cells, which had been exposed to MB or acriflavine before being illuminated at 660 or 488 nm, respectively. FCFM was performed on precancerous lesions in the hamster cheek pouch model, following topical application of the fluorophores. FCFM data were analyzed according to histology. No genotoxicity was found using 0.01% (w/v) MB after illumination at 660 nm for 2 and 15 min (5 mW). Acriflavine exposure (0.025%) led to DNA damages, increasing from 2 to 15 min of light exposure at 448 nm in both lymphocytes (83.4 to 88%, p = 0.021) and NCI H460 cell populations (79.9 to 84.6%, p = 0.045). In total, 11 invasive carcinoma, 24 reserve cell hyperplasia, and 17 dysplasia lesions were imaged using FCFM in vivo. With both fluorophores, the cellular density increased from hyperplasia to high-grade dysplasia (p < 0.05). With MB, the cellular diameter significantly decreased (48.9 to 13.9 μm) from hyperplasia to carcinoma (p < 0.05). In this model, a cut-off diameter of 30 μm enabled the diagnosis of high-grade lesions with a sensitivity of 94.7% and a specificity of 97%. Methylene blue can be used safely to image precancerous lesions in vivo. This study does not support the use of acriflavine in humans

Molecular analysis of peripheral non-squamous non-small cell lung cancer sampled by radial EBUS

International audienceTreatment optimization of non-squamous non-small-cell lung cancers (nonSq-NSCLC) relies on the molecular analysis of the tumour. We aimed to assess the predictive factors of molecular analysis feasibility (MAF) from samples of peripheral nonSq-NSCLC obtained by radial endobronchial ultrasound bronchoscopy (r-EBUS) and 1.5 mm microbiopsy forceps

Assessment of Per-Endoscopic Placement of Fiducial Gold Markers for Small Peripheral Lung Nodules < 20 mm Before Stereotactic Radiation Therapy

International audienceStereotactic radiotherapy is used to treat peripheral lung cancer in inoperable patients. Placement of fiducial gold markers (FMs) is crucial for tracking small lesions that are not visible on chest radiographs. Our objective was to assess endoscopic FM placement in small peripheral lung nodules (PLNs) that are not trackable using automated tracking software