Three-dimensional imaging of the larynx for pre-operative planning of laryngeal framework surgery

Modern laryngeal framework surgery (LFS) requires an exact understanding of the laryngeal biomechanics and precise pre-operative planning, for which bi-planar imaging is not sufficient. The aim of the study was to test whether MIMICS®, a commercially available software package for three-dimensional (3D) rendering of high-resolution computerised tomography (HRCT), is suitable for 3D imaging of the larynx, analysis of laryngeal biomechanics and pre-operative planning. We examined four cadaver larynx and one patient larynx. In the five larynges, all relevant structures and landmarks could be 3D visualised. Superimposing of two HRCT scans shows that when the arytenoids move from ‘respiration' to ‘phonation', they perform a rotating, translating and tilting motion. Moreover, we could demonstrate that the vocal fold elongates by 7% with cricothyroid approximation. We conclude that MIMCS® is well suited for 3D imaging of the larynx, analysis of laryngeal biomechanics and pre-operative planning of LFS procedure

The role of the cricothyroid joint anatomy in cricothyroid approximation surgery

Cricothyroid approximation (CTA) surgery aims at raising the voice pitch in male-to-female transsexuals. However, 30% of the patients are not satisfied with the result. The purpose of our study was to examine the cricothyroid joint (CTJ) biomechanics and to analyze if (and how) the CTJ anatomy influences the movement of the cricoid and, consequently, the elongation of the vocal fold and the voice pitch after CTA

Biomechanics of the cricoarytenoid joint : three-dimensional imaging and vector analysis

Laryngeal framework surgery requires a good understanding of the biomechanics of the cricoarytenoid (CA) joint, the precise function of which is still only poorly understood. The aim of the study was (1) to show that, by superimposing two or more three-dimensional (3D) images, we can visualize the exact position of the arytenoid cartilages within the larynx at different phases of their movement; and (2) to demonstrate that it is possible to analyze the arytenoid cartilage movements mathematically with the help of vector analysis

Developing a 3D model of the laryngeal cartilages using HRCT data and MIMICS's segmentation software

Discussions relating to the biomechanics of the larynx are still generally controversial. The purpose of this study is to develop a 3D model of the larynx based on high-resolution computer tomography (HRCT) data identifying and visualizing anatomical landmarks and structures of the larynx. We examined four fresh cadaver larynges with HRCT. The DICOM (Digital Imaging and Communication in Medicine) data were post-processed with the software package MIMICS for three-dimensional visualization. All relevant structures of the laryngeal cartilages could be identified on HRCT and visualized in a 3D model. We conclude that 1) HRCT provides excellent data for three-dimensional visualization of the laryngeal anatomy, and 2) the combined technology of HRCT and MIMICS is useful to study the biomechanics on 3D images and for preoperative planning of laryngeal framework surgery

The clinical impact of p16 status in fine-needle aspirates of cervical lymph node metastasis of head and neck squamous cell carcinomas

Lymph node involvement is prognostically the most determinant clinical factor for patients with head and neck squamous cell carcinomas (HNSCCs). Ultrasound of the neck and fine-needle aspiration (FNA) cytology is one of the first diagnostic procedures and the most accurate diagnostic staging tool for the neck. Patients with HPV-positive oropharyngeal carcinomas (OPSCC) show a significantly better prognosis when compared with HPV-negative OPSCC. P16 overexpression is accepted as surrogate marker for HPV-positive in OPSCC. These HPV/p16-positive OPSCC are localized either in the palatal tonsils or the base of tongue and frequently present with lymph node metastases. We analyzed the correlation and reliability of p16 expression of the FNA of the lymph node metastasis with the immunohistochemical expression of p16 of the same lymph node metastasis and its corresponding primary tumor, as it could be of importance for determining the localization and different prognosis of the primary tumor. 54 HNSCC patients were evaluated, p16 expression of the primary tumors and their lymph node metastases correlated precisely. In 25 of the 54 HNSCC patients, a FNA of the lymph node metastases was taken before the treatment. The positive cytological and immunohistochemical p16 staining correlated exactly. Of the 17 histologically p16-negative lymph node metastases 15 FNA were p16-negative, whereas two samples were p16-positive. In our view, a cytological p16 analysis of cervical lymph node metastasis can facilitate the correct localization of the primary tumor and discriminate reliably HPV-positive OPSCC from HPV-negative HNSCC with their significantly diverse prognosis

Is immunohistochemical epidermal growth factor receptor expression overestimated as a prognostic factor in head-neck squamous cell carcinoma? A retrospective analysis based on a tissue microarray of 365 carcinomas

Epidermal growth factor receptor is overexpressed in more than 80% of head-neck squamous cell carcinoma. Its role as an independent prognostic marker is discussed controversially. No standardized evaluation methods are reported. The aim of our study was to analyze the prognostic relevance of epidermal growth factor receptor expression, using a tissue microarray with more than 300 tumor samples. Epidermal growth factor receptor expression was analyzed by immunohistochemistry and fluorescence in situ hybridization based on a tissue microarray of 365 head-neck squamous cell carcinomas with complete clinicopathologic and follow-up data. Multiple independent observers blinded for clinical data evaluated epidermal growth factor receptor immunostaining semiquantitatively. Cut-off scores for positivity were determined systematically by receiver operating characteristic curve analysis and validated by resampling of the data. Epidermal growth factor receptor expression cut-off scores for loco-regional relapse and overall survival were determined to be 60%. No significant correlation with clinicopathologic data was found. Independent significant differences in loco-regional control and overall survival could not be distinguished by epidermal growth factor receptor expression. Epidermal growth factor receptor expression could not be confirmed as a significant independent prognostic marker in head-neck squamous cell carcinoma using a large tissue microarray with 365 head-neck squamous cell carcinomas with complete clinical data, an evaluation based on immunohistochemistry and fluorescence in situ hybridization by multiple independent observers and systematic determination of cut-off scores

Is the improved prognosis of p16 positive oropharyngeal squamous cell carcinoma dependent of the treatment modality?

The incidence of human papilloma virus (HPV) induced oropharyngeal squamous cell carcinoma (OPSCC) increases in the western countries. These OPSCC show distinct molecular characteristics and are characterized by an overexpression of p16, considered a surrogate marker for HPV infection. When compared to patients with p16 negative OPSCC, patients with HPV induced p16 positive OPSCC show a significantly better prognosis, which is reported to be caused by increased radiosensitivity. The objective of the present study was to analyze the impact of p16 expression status on the prognosis of OPSCC treated by either radiotherapy (RT) or primary surgery. Results are based upon a tissue microarray (TMA) of 365 head neck squamous cell carcinomas (HNSCC) including 85 OPSCC with clinico-pathological and follow-up data. p16 positivity correlated significantly with oropharyngeal tumor localization (p > 0.001). Patients with p16 positive OPSCC exhibited a significantly better overall survival than those with p16 negative tumors (p = 0.007). In a multivariate analysis, survival benefit of patients with p16 positive OPSCC was independent of clinico-pathological parameters such as cT and cN classification and treatment modality. The improved prognosis of p16 positive OPSCC is found after RT as well as after surgery

Clumped isotope fractionation during phosphoric acid digestion of carbonates at 70 oC

The application of clumped isotopes (Δ47) in carbonate minerals as a sensitive temperature proxy in paleo-environments depends on a well-constrained clumped isotope fractionation for the necessary step of phosphoric acid digestion of the carbonate mineral to produce CO2. Published estimates for clumped isotope fractionations vary, and the effect of different carbonate mineralogies is still under debate. Differences in the sample preparation design and sample digestion temperatures are potential sources for varying acid fractionations and could be a source for discrepant Δ47-temperature calibrations observed in different laboratories. To evaluate the clumped isotope acid fractionation at 70 °C and simultaneously account for a potential cation effect we analyzed a set of eight carbonate minerals (calcite, aragonite, dolomite and magnesite) that were driven to a stochastic isotope distribution by heating them to temperatures of 1000 °C. Our study reveals significant cation- and mineral-specific differences for the Δ47 acid fractionation of carbonate minerals digested at 70 °C or 100 °C. The Δ47 acid fractionation at 70 °C for calcite is 0.197±0.002 ‰, for aragonite 0.172±0.003 ‰, whereas dolomite has a significantly larger acid fractionation of 0.226±0.002 ‰. For magnesite digested at 100 °C we observed a Δ47 acid fractionation of 0.218±0.020 ‰. Projected to an acid digestion at 25 °C, our acid fractionation for calcite of 0.260 ‰ is statistically indistinguishable from existing studies. We further show that the Δ47 of the calcite standards ETH-1 and ETH-2 of 0.265 ‰ and 0.267 ‰, respectively, are in the range of the determined acid fractionation projected to 25 °C suggesting that they have an identical and near stochastic isotope distribution. The observed differences in the Δ47 acid fractionation between calcite and aragonite (ΔΔ47 = −0.025 ‰) and between calcite and dolomite (ΔΔ47 = −0.029 ‰) does not correlate with the phosphoric acid fractionation of oxygen isotopes, but rather depends on the radius of the cation as well as on the mineral structure. Our results reveal that the acid fractionation of dolomite at 70 °C is significantly distinct from the one of calcite, but at 90 °C the two are within error of each other due to the different acid fractionation temperature dependence of calcite and dolomite. Thus it is necessary to use a mineral-specific Δ47 acid fractionation factor for dolomite to avoid differences in the final Δ47 signal from dolomites digested at 90 °C and dolomites digested at lower temperatures. Similar effects may apply also to other carbonates such as magnesite and siderite. However, their mineral specific Δ47 acid fractionation at digestion temperatures around 90 °C might be also similar to the one of calcite so that potential differences could be within the range of the analytical error