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

In vivo quantification of photosensitizer fluorescence in the skin-fold observation chamber using dual-wavelength excitation and NIR imaging

A major challenge in biomedical optics is the accurate quantification of in vivo fluorescence images. Fluorescence imaging is often used to determine the pharmacokinetics of photosensitizers used for photodynamic therapy. Often, however, this type of imaging does not take into account differences in and changes to tissue volume and optical properties of the tissue under interrogation. To address this problem, a ratiometric quantification method was developed and applied to monitor photosensitizer meso-tetra (hydroxyphenyl) chlorin (mTHPC) pharmacokinetics in the rat skin-fold observation chamber. The method employs a combination of dual-wavelength excitation and dualwavelength detection. Excitation and detection wavelengths were selected in the NIR region. One excitation wavelength was chosen to be at the Q band of mTHPC, whereas the second excitation wavelength was close to its absorption minimum. Two fluorescence emission bands were used; one at the secondary fluorescence maximum of mTHPC centered on 720 nm, and one in a region of tissue autofluorescence. The first excitation wavelength was used to excite the mTHPC and autofluorescence and the second to excite only autofluorescence, so that this could be subtracted. Subsequently, the autofluorescence-corrected mTHPC image was divided by the autofluorescence signal to correct for variations in tissue optical properties. This correction algorithm in principle results in a linear relation between the corrected fluorescence and photosensitizer concentration. The limitations of the presented method and comparison with previously published and validated techniques are discussed

Image-guided surgery in oral cancer:toward improved margin control

Purpose of review The aim of this review is to discuss recent studies on the assessment of tumor extension and resection margins by different intraoperative techniques allowing for image-guided surgery of oral cancer. Recent findings There are different in-vivo and ex-vivo intraoperative techniques to improve margin control of which intraoperative ultrasound and targeted fluorescence-guided resections have high potential clinical value and are closest to clinical implementation. In oral cancer surgery, resection margins, particularly deep margins, are often inadequate. Intraoperative frozen section does not improve resection margin control sufficiently. Specimen-driven intraoperative assessment for gross analysis of suspected margins reduces the amount of positive resection margins substantially but leaves still room for improvement. Mucosal staining methods, optical coherence tomography and narrow band imaging can only be used for superficial (mucosal) resection margin control. Spectroscopy is under investigation, but clinical data are scarce. Intraoperative ex-vivo imaging of the resection specimen by magnetic resonance and PET/computed tomography may be used to assess resection margins but needs more research. Intraoperative in-vivo ad ex-vivo ultrasound and targeted fluorescence imaging have high potential clinical value to guide oral cancer resections and are closest to clinical implementation for improved margin control

Checkpoint kinase inhibitor AZD7762 strongly sensitises urothelial carcinoma cells to gemcitabine

Background: More effective chemotherapies are urgently needed for bladder cancer, a major cause of morbidity and mortality worldwide. We therefore explored the efficacy of the combination of gemcitabine and AZD7762, a checkpoint kinase 1/2 (CHK1/2) inhibitor, for bladder cancer. Methods: Viability, clonogenicity, cell cycle distribution and apoptosis were assessed in urothelial cancer cell lines and various non-malignant urothelial cells treated with gemcitabine and AZD7762. DNA damage was assessed by ?H2A.X and 53-BP1 staining and checkpoint activation was followed by Western blotting. Pharmacological inhibition of CHK1 and CHK2 was compared to downregulation of either CHK1 or CHK2 using siRNAs. Results: Combined use of gemcitabine and AZD7762 synergistically reduced urothelial carcinoma cell viability and colony formation relative to either single treatment. Non-malignant urothelial cells were substantially less sensitive to this drug combination. Gemcitabine plus AZD7762 inhibited cell cycle progression causing cell accumulation in S-phase. Moreover, the combination induced pronounced levels of apoptosis as indicated by an increase in the fraction of sub-G1 cells, in the levels of cleaved PARP, and in caspase 3/7 activity. Mechanistic investigations showed that AZD7762 treatment inhibited the repair of gemcitabine-induced double strand breaks by interference with CHK1, since siRNA-mediated depletion of CHK1 but not of CHK2 mimicked the effects of AZD7762. Conclusions: AZD7762 enhanced sensitivity of urothelial carcinoma cells to gemcitabine by inhibiting DNA repair and disturbing checkpoints. Combining gemcitabine with CHK1 inhibition holds promise for urothelial cancer therapy

Patient-specific finite element models of the human mandible:Lack of consensus on current set-ups

The use of finite element analysis (FEA) has increased rapidly over the last decennia and has become a popular tool to design implants, osteosynthesis plates and prostheses. With increasing computer capacity and the availability of software applications, it has become easier to employ the FEA. However, there seems to be no consensus on the input variables that should be applied to representative FEA models of the human mandible. This review aims to find a consensus on how to define the representative input factors for a FEA model of the human mandible. A literature search carried out in the PubMed and Embase database resulted in 137 matches. Seven papers were included in this current study. Within the search results, only a few FEA models had been validated. The material properties and FEA approaches varied considerably, and the available validations are not strong enough for a general consensus. Further validations are required, preferably using the same measuring workflow to obtain insight into the broad array of mandibular variations. A lot of work is still required to establish validated FEA settings and to prevent assumptions when it comes to FEA applications

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

Three-dimensional virtual surgical planning in the oncologic treatment of the mandible

OBJECTIVES: In case of surgical removal of oral squamous cell carcinomas, a resection of mandibular bone is frequently part of the treatment. Nowadays, such resections frequently include the application of 3D virtual surgical planning (VSP) and guided surgery techniques. In this paper current methods for 3D VSP, leads for optimisation of the workflow, and patient specific application of guides and implants are reviewed. RECENT FINDINGS: Current methods for 3D VSP enable multi-modality fusion of images. This fusion of images is not restricted to a specific software package or workflow. New strategies for 3D VSP in Oral and Maxillofacial Surgery include finite element analysis, deep learning and advanced augmented reality techniques. These strategies aim to improve the treatment in terms of accuracy, predictability and safety. CONCLUSIONS: Application of the discussed novel technologies and strategies will improve the accuracy and safety of mandibular resection and reconstruction planning. Accurate, easy-to-use, safe and efficient three-dimensional VSP can be applied for every patient with malignancies needing resection of the mandible