Virtual 3D planning of tracheostomy placement and clinical applicability of 3D cannula design:A three-step study

AIM: We aimed to investigate the potential of 3D virtual planning of tracheostomy tube placement and 3D cannula design to prevent tracheostomy complications due to inadequate cannula position. MATERIALS AND METHODS: 3D models of commercially available cannula were positioned in 3D models of the airway. In study (1), a cohort that underwent tracheostomy between 2013 and 2015 was selected (n = 26). The cannula was virtually placed in the airway in the pre-operative CT scan and its position was compared to the cannula position on post-operative CT scans. In study (2), a cohort with neuromuscular disease (n = 14) was analyzed. Virtual cannula placing was performed in CT scans and tested if problems could be anticipated. Finally (3), for a patient with Duchenne muscular dystrophy and complications of conventional tracheostomy cannula, a patient-specific cannula was 3D designed, fabricated, and placed. RESULTS: (1) The 3D planned and post-operative tracheostomy position differed significantly. (2) Three groups of patients were identified: (A) normal anatomy; (B) abnormal anatomy, commercially available cannula fits; and (C) abnormal anatomy, custom-made cannula, may be necessary. (3) The position of the custom-designed cannula was optimal and the trachea healed. CONCLUSIONS: Virtual planning of the tracheostomy did not correlate with actual cannula position. Identifying patients with abnormal airway anatomy in whom commercially available cannula cannot be optimally positioned is advantageous. Patient-specific cannula design based on 3D virtualization of the airway was beneficial in a patient with abnormal airway anatomy

Differences in the diagnostic value between fiberoptic and high definition laryngoscopy for the characterisation of pharyngeal and laryngeal lesions:A multi-observer paired analysis of videos

Objectives High definition laryngoscopy (HDL) could lead to better interpretation of the pharyngeal and laryngeal mucosa than regularly used fiberoptic laryngoscopy (FOL). The primary aim of this study is to quantify the diagnostic advantage of HDL over FOL in detecting mucosal anomalies in general, in differentiating malignant from benign lesions and in predicting specific histological entities. The secondary aim is to analyse image quality of both laryngoscopes. Design Retrospective paired analysis with multiple observers evaluating endoscopic videos simulating daily clinical practice. Setting A tertiary referral hospital. Participants In 36 patients, both FOL and HDL videos were obtained. Six observers were provided with additional clinical information, and 36 FOL and HDL videos were evaluated in a randomised order. Main outcome measures Sensitivity, specificity, positive and negative predictive value and diagnostic accuracy of observers using both flexible laryngoscopes were calculated for detection of mucosal lesions in general and uncovering malignant lesions. Sensitivities were calculated for prediction of specific histological entities. Image quality (scale 1-10) was assessed for both flexible laryngoscopes. Results HDL reached higher sensitivity compared to FOL for detection of mucosal abnormalities in general (96.0% vs 90.4%; P = .03), differentiating malignant from benign lesions (91.7% vs 79.8%; P = .03) and prediction of specific histological entities (59.7% vs 47.2%; P <.01). Image quality was judged better with HDL in comparison with FOL (mean: 8.4 vs 5.4, P <.01). Conclusions HDL is superior to FOL in detecting mucosal anomalies in general, malignancies and specific histological entities. Image quality is considered as superior using HDL compared to FOL

High-definition videolaryngoscopy is superior to fiberoptic laryngoscopy:a 111 multi-observer study

PURPOSE: This study aims to analyse differences in fiberoptic laryngoscopy (FOL) versus high definition laryngoscopy (HDL) by examining videolaryngoscopy images by a large group of observers with different levels of clinical expertise in ear, nose and throat (ENT) medicine. METHODS: This study is a 111 observer paired analysis of laryngoscopy videos during an interactive presentation. During a National Meeting of the Dutch Society of ENT/Head and Neck Surgery, observers assessed both FOL and HDL videos of nine cases with additional clinical information. Observers included 41 ENT consultants (36.9%), 34 ENT residents (30.6%), 22 researchers with Head and Neck interest (19.8%) and 14 with unspecified clinical expertise (12.6%). For both laryngoscopic techniques, sensitivity, specificity, positive and negative predictive value and diagnostic accuracy were determined for identifying a normal glottis, hyperkeratosis, radiotherapy adverse effects and squamous cell carcinoma. The sensitivities for FOL and HDL were analysed with regard to the different levels of clinical expertise. RESULTS: The overall sensitivity for correctly identifying the specific histological entity was higher in HDL (FOL 61% vs HDL 66.3%, p < 0.05). HDL was superior to FOL in identifying a normal glottis (FOL 68.1% vs HDL 91.6%, p < 0.01) and squamous cell carcinoma (FOL 70.86% vs HDL 79.41%, p = 0.02). Residents and researchers with Head and Neck interest diagnosed laryngeal lesions more correctly with HDL (p < 0.05). CONCLUSIONS: In a large population of observers with different levels of clinical expertise, HDL is superior to FOL in identifying laryngeal lesions

First-line gemcitabine with cisplatin or epirubicin in advanced non-small-cell lung cancer: a phase III trial

The purpose of our study was to compare progression-free survival and quality of life (QOL) after cisplatin-gemcitabine (CG) or epirubicin-gemcitabine (EG) in chemotherapy-naive patients with unresectable non-small-cell lung cancer. Patients (n = 240) were randomised to receive gemcitabine 1125 mg m(-2) (days 1 and 8) plus either cisplatin 80 mg m(-2) (day 2) or epirubicin 100 mg m(-2) (day 1) every 3 weeks for a maximum of five cycles. Eligible patients had normal organ functions and Eastern Cooperative Oncology Group performance status less than or equal to2. QOL was measured with European Organisation for Research and Treatment of Cancer QLQ-C30 and LC13 questionnaires. There were no significant differences in median progression-free survival (CG 26 weeks, EG 23 weeks), median overall survival (CG 43 weeks, EG 36 weeks), or tumour response rates (CG 46%, EG 36%). Toxicity was mainly haematologic. In the EG arm granulocytopenia occurred more frequently, leading to more febrile neutropenia. Also, elevation of serum transaminases, mucositis, fever, and decline in LVEF were more common in the EG arm. In the CG arm, more patients experienced elevated serum creatinine levels, sensory neuropathy, nausea, and vomiting. Global QOL was not different in both arms. Progression-free survival, overall survival, response rate, and QOL were not different between both arms; however, overall toxicity was more severe in the EG arm

PTEN Is Associated With Worse Local Control in Early Stage Supraglottic Laryngeal Cancer Treated With Radiotherapy

Objectives: The aim of this study was to establish the prognostic value of the epidermal growth factor receptor (EGFR) and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression on local control in patients with early stage supraglottic laryngeal squamous cell carcinoma (LSCC) treated with radiotherapy only. Study design: Retrospective cohort study. Methods: Immunohistochemical staining for EGFR and PTEN was performed on pretreatment biopsies of a selected well-defined homogeneous group of 52 patients with T1-T2 supraglottic LSCC treated with radiotherapy between 1990 and 2008. Kaplan-Meier analysis and univariate and multivariate Cox Regression analyses were performed to correlate clinical data and expression levels of EGFR and PTEN with local control. Results: Kaplan-Meier survival analysis and Cox Regression analysis showed a significant association between PTEN expression and local control (hazard ratio [HR] = 3.26, 95% confidence interval [CI] = 1.14-9.33, P = .027) and between lymph node status and local control (HR = 3.60, 95% CI = 1.26-10.31, P = .017). Both were independent prognostic factors in a multivariate analysis (HR = 3.28, 95% CI = 1.14-9.39, P = .027 and HR = 3.62, 95% CI = 1.26-10.37, P = .017, respectively). There was no significant association between EGFR expression and local control (HR = 1.32, 95% CI = 1.17-10.14, P = .79). Conclusion: This study showed an association between both high PTEN expression and the presence of lymph node metastasis and deteriorated local control in early stage supraglottic LSCC treated with radiotherapy. Level of Evidence: NA

Distinct Biomarker Profiles and Clinical Characteristics in T1-T2 Glottic and Supraglottic Carcinomas

Background: In early stage laryngeal squamous cell carcinoma (LSCC) radiotherapy with curative intent is a major treatment modality. TNM classification is used to define patients eligible for radiotherapy. Studies in early stage glottic LSCC identified several predictive biomarkers associated with local control. However, we recently reported that this predictive value could not be confirmed in supraglottic LSCC. Objective: To examine whether clinical behavior and protein expression patterns of these biomarkers differ between glottic and supraglottic LSCC. Study Design: Retrospective cohort study. Methods: Tumor tissue sections of 196 glottic and 80 supraglottic T1-T2 LSCC treated primarily with RT were assessed immunohistochemically for expression of pAKT, Ki-67 and β-Catenin. Expression data of HIF-1α, CA-IX, OPN, FADD, pFADD, Cyclin D1, Cortactin and EGFR in the same cohort of glottic and supraglottic LSCC, were retrieved from previously reported data. The relationship between glottic and supraglottic sublocalization and clinicopathological, follow-up, and immunohistochemical staining characteristics were evaluated using logistic regression and Cox regression analyses. Results: Glottic LSCC were correlated with male gender (P =.001), hoarseness as a primary symptom (P <.001), T1 tumor stage (P <.001), negative lymph node status (P <.001), and an older age at presentation (P =.004). Supraglottic LSCC patients developed more post-treatment distant metastasis when adjusted for gender, age, and T-status. While supraglottic LSCC was associated with higher expression of HIF-1α (P =.001), Cortactin (P <.001), EGFR (P <.001), and Ki-67 (P =.027), glottic LSCC demonstrated higher expression of CA-IX (P =.005) and Cyclin D1 (P =.001). Conclusion: Differences in clinicopathological and immunohistochemical staining characteristics suggest that T1-T2 glottic and supraglottic LSCC should be considered as different entities. Level of Evidence: N/A. Laryngoscope, 2020

ERCC1 expression and RAD51B activity correlate with cell cycle response to platinum drug treatment not DNA repair

Background: The H69CIS200 and H69OX400 cell lines are novel models of low-level platinum-drug resistance. Resistance was not associated with increased cellular glutathione or decreased accumulation of platinum, rather the resistant cell lines have a cell cycle alteration allowing them to rapidly proliferate post drug treatment. Results: A decrease in ERCC1 protein expression and an increase in RAD51B foci activity was observed in association with the platinum induced cell cycle arrest but these changes did not correlate with resistance or altered DNA repair capacity. The H69 cells and resistant cell lines have a p53 mutation and consequently decrease expression of p21 in response to platinum drug treatment, promoting progression of the cell cycle instead of increasing p21 to maintain the arrest. Conclusion: Decreased ERCC1 protein and increased RAD51B foci may in part be mediating the maintenance of the cell cycle arrest in the sensitive cells. Resistance in the H69CIS200 and H69OX400 cells may therefore involve the regulation of ERCC1 and RAD51B independent of their roles in DNA repair. The novel mechanism of platinum resistance in the H69CIS200 and H69OX400 cells demonstrates the multifactorial nature of platinum resistance which can occur independently of alterations in DNA repair capacity and changes in ERCC1

A randomised phase II trial of docetaxel vs docetaxel and irinotecan in patients with stage IIIb–IV non-small-cell lung cancer who failed first-line treatment

Response rate and toxicity of second-line therapy with docetaxel (75 mg m−2) or docetaxel, irinotecan, and lenogastrim (60 mg m−2, 200 mg m−2, and 150 μg m−2 day−1, respectively) were compared in 108 patients with stage IIIb–IV non-small-cell lung cancer. Addition of irinotecan to docetaxel does not improve response rate, and increases gastrointestinal toxicity

First-Principles Calculations of Hyperfine Interactions in La_2CuO_4

We present the results of first-principles cluster calculations of the electronic structure of La_2CuO_4. Several clusters containing up to nine copper atoms embedded in a background potential were investigated. Spin-polarized calculations were performed both at the Hartree-Fock level and with density functional methods with generalized gradient corrections to the local density approximation. The distinct results for the electronic structure obtained with these two methods are discussed. The dependence of the electric-field gradients at the Cu and the O sites on the cluster size is studied and the results are compared to experiments. The magnetic hyperfine coupling parameters are carefully examined. Special attention is given to a quantitative determination of on-site and transferred hyperfine fields. We provide a detailed analysis that compares the hyperfine fields obtained for various cluster sizes with results from additional calculations of spin states with different multiplicities. From this we conclude that hyperfine couplings are mainly transferred from nearest neighbor Cu^{2+} ions and that contributions from further distant neighbors are marginal. The mechanisms giving rise to transfer of spin density are worked out. Assuming conventional values for the spin-orbit coupling, the total calculated hyperfine interaction parameters are compared to informations from experiments.Comment: 23 pages, 9 figure

Experimental and theoretical investigation on the misalignment tolerance of a micron-sized solid immersion lens tolerance of a micron-sized solid immersion lens

We report an experimental and theoretical study on the alignment error tolerance of a 2 µm-size solid immersion lens (SIL) illuminated by different types of focused spots. Tightly confined focal spots are of great interest for improving the performance of many optical systems, so that a study on the alignment tolerance is of interest. In particular, it was found that micro-SILs can be largely misaligned with respect to the optical axis of an objective lens focusing light onto it and yet allow for a reasonably good immersed spot. In fact, a displacement of approximately 400 nm, i.e. one fifth of the lens diameter, is tolerable. The measurements are compared with a rigorous finite element method model for a micro-SIL, showing an excellent agreemen