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Background/aim To analyze ex vivo effects of combined targeting of the epidermal growth factor-receptor (EGFR) by cetuximab (E) plus αVβ3 and αVβ5 integrins by cilengitide (Cil) on colony formation of epithelial cells (CFec) and release of pro-angiogenetic and pro-inflammatory cytokines in head and neck squamous cell carcinoma (HNSCC) cells. Materials and methods Collagenase-IV digests of 43 histopathological confirmed HNSCC cases were seeded into laminin-coated 96-well plates containing E, Cil, or Cil+E in final concentrations of 66.7 μg/ml, 10 μM, and 10 μM+66.7 μg/ml, respectively. Following the FLAVINO-assay protocol, supernatants were harvested after 3 days and adherent cells fixed in ethanol. Counting of CFec was facilitated by FITC-labeled pan-cytokeratin antibodies. Out of 43 HNSCC cases, 39 had adherent growth (mean CFec≥4/well in triplicate controls). Cytokines in supernatants were measured using ELISA were interleukin 6 (IL-6), monocyte chemoattractant protein 1 (MCP-1) and vascular endothelial growth factor A (VEGFA). Results CFec on laminin was significantly reduced by Cil, E, and Cil+E. Cytokine measurements also revealed significant suppression of MCP-1, IL-6 and VEGFA. The strongest suppression of CFec, MCP-1 and VEGFA release was exerted by Cil and E combined. Efficacy of Cil+E exceeded those of the solely applied pharmaceutics but failed regarding significant synergism of both treatments as E was unable to significantly boost the effects of Cil. In contrast, IL-6 release was significantly suppressed by E but not by Cil, while their combination strongly reduced it. Conclusion Combined targeting of EGFR and integrins with E and Cil heightens their suppressive effects regarding CFec as well as release of pro-angiogenetic and pro-inflammatory cytokines.

Background Long-term laryngectomy-free (LFS), tumour-specific (TSS) and overall survival (OS) is achieved by non-surgical larynx preservation (LP) only in a proportion of patients with locally advanced laryngeal or hypopharyngeal cancer. A score facilitating decision-making after 1 cycle induction chemotherapy (IC-1) may improve LFS and TSS. Methods Early response to IC-1 with TPF ± cetuximab was assessed in 52 patients using endoscopic tumour staging for selecting total laryngectomy for non-responders with endoscopic tumour surface shrinkage max , SUV mean ) were measured by 18 F-FDG-PET/CT. Baseline and residual values after IC-1 were calculated and correlated with LFS, TSS and OS. Results After IC-1, 39/52 patients (75%) were early responders. Early response predicted complete response to IC + RT ( p = 8.48 × 10 −9 ). Early laryngectomised non-responders and responders with endoscopic tumour surface shrinkage > 70% had best OS. Significant independent predictors for LFS in responders are number of CT-staged suspect positive neck nodes (N+), residual primary tumour volume, residual total tumour volume and the ratio of residual SUV max and SUV mean (resSUV max /resSUV mean ). Our LFS-score combines >2N+, residual primary tumour volume > 20%, residual total tumour volume > 5.6 mL and resSUV max /resSUV mean > 1.51 weighted by their hazard ratio (12, 6, 5 and 4); LFS-score ≤ 16 predicts increased LFS, OS and TSS ( p Conclusion LFS-score ≤ 16 identifies in responders to IC-1 the patients with maximum benefit of non-surgical LP achieving long-term LFS. Even more importantly, a LFS-score > 16 defines patients unsuitable for LP applying the TPF/TP IC + RT protocol.

SURGICAL MANIPULATORS IN EAR SURGERY A FUTURE VISION?INTRODUCTION: Middle ear surgery bears a high risk for injury of difficult to differentiate risk structures. Thus, a precise preparation in this area must be the surgical task. LIMITATIONS: However, there are human (tremor) and systematic limitations (OR setup, narrow access). Assistance systems in terms of manipulators are so far not part of the clinical routine. Although, they could compensate for the above mentioned limitations. MANIPULATORS: This work reviews existing surgical manipulator systems. The expected value is an elevated patient safety through improving surgical accuracy and the reduction of ergonomic deficits. CLINICAL APPLICATION AND DEVELOPMENT: In clinical application there are simply modified industrial robots, highly complex master slave systems and small miniature master slave systems which are directly located at the patient. CONCLUSION: A disadvantage of most systems is the limited number of applicable instruments. Often, only especially designed instruments can be used. The goal in development should be to create a compact, short distance operated master slave system. The usability of standard (already available) instruments with an easy integration into the surgical and sterilisation procedure would lower the threshold for acceptance of such systems.The surgeon will remain the key player. He can only work efficiently in an ergonomic environment and will always have the responsibility for the intervention. From the authors perspective, highly automated systems should not be the research goal.

BACKGROUND This work examines the application possibilities of the panoramic visualization system (HD-PVS) in ENT surgery. The HD-PVS is a new optical system that is neither an endoscope nor a microscope. It has a focal length of 200 mm and a wide field of view. PATIENT AND METHODS The analysis of the visualization quality took place under laboratory conditions at 4 close-to-surgery scenarios with a total of 40 result values. Furthermore, the system was used for 45 operative procedures on patients (tympanoplasty, parotidectomy, neck dissection, septumplasty, transfacial approaches). The results were analyzed following the ICCAS workflow-scheme and with standardized questionnaires. RESULTS The analysis of the visualization quality of the PVS exhibited the best total evaluation in 2 out of 4 scenarios, in 1 scenario HD-PVS attained the maximum score possible, as did the microscope and the endoscope was better than HD-PVS in 1 scenario. The microscope was never evaluated as being better than HD-PVS. Apart from its use in middle ear surgery, the HD-PVS can be considered operational in 4 out of 5 clinical applications with only slight modifications. CONSEQUENCES The advantages of HD-PVS over gold standards such as the surgical microscope are lower initial costs for the optical system with frequently already existing HD-video system, smaller space requirements, equal or sometimes better visualization quality, possibility of videoendoscopic representation of surgery and better ergonomic conditions.

BACKGROUND: The goal of this study is the improvement of the surgical accuracy of a navigate-controlled drill for mastoidectomy in a lab test. METHODS: For lab tests an artificial model of the temporal bone with color-coded injury identification of the facial nerve (solution of 0.5 mm) was used.Two different registration methods were examined: (group 1) navigation bow with 4 integrated markers at the upper jaw; (group 2) landmark registration with 4 titanium micro screws. An optical navigation system was used. The targets were illustrated by 3 titanium screws within the range of the planum mastoideum. The accuracy of the navigate-controlled drill in drilling the planned cavity were evaluated at 20 temporal bone models. The measurement of the registration accuracy was evaluated by deviation between the target screw and the calculated position in the navigation system. The evaluation of the resulted cavities was done by 5 senior surgeons with the help of the microscope. RESULTS: The registration accuracy shows a maximum deviation between the real position and the calculated position of 1,73 MM in group of 1 and 0.93 MM in group 2. In group 1 the nerve was hurt in 5/20 cases and a maximum deviation of - 1.5 mm (Std 0.25 mm) (drilled beyond the nerve) was measured. In group 2 the nerve was not hurt, a maximum deviation of 0.5 mm (too early stopped before the nerve) was measured. CONCLUSIONS: Significantly better results of the registration and drilling accuracy show up in group group 2. Thus the preconditions for clinical use are fulfilled.

BACKGROUND Suitable simulation systems providing realistic conditions are required for preclinical evaluation of computer assisted interventions and surgical training. Techniques are necessary for an objective detection of injuries to the structures at risk. The aim of this study was the technical realization of a simulation system for the ENT intervention, mastoidectomy. MATERIALS AND METHODS The basis of the simulation system was a CT scan of a cadaver skull. Using 3D printing, an anatomical phantom with realistic bone-like properties was created. Electronic detection systems were integrated into the structures at risk. A study with 16 ENT surgeons was conducted to prove the system's suitability for surgical training. RESULTS The creation of simulation systems for the objective evaluation of surgical intervention qualities is feasible. A modular structure enables economic and simple replacement of the simulation area. The modules are cost effective and reproducible with high accuracy. The present study shows that the simulation system can be applied in surgical education and evaluation as an alternative to cadavers. CONCLUSION Objective evaluation of injured structures at risk can be realized in real time. The simulation system permits preclinical evaluation studies of computer assisted instruments and surgical education. Reproducibility of the results makes multi-center studies possible.

Background: This study examines the feasibility of a navigation-controlled (NC) drill for surgery on the petrosal bone in an experimental environment. According to the principle of NC, the drill is to be switched off automatically once the borders of the workspace are exceeded during a mastoidectomy. Materials and Methods: The registration is based on an optical navigation system with navigation software (MiMed). As surgery engine, the Unidrive-system (Karl Storz GmbH & CO. Kg, Tuttlingen, Germany) was integrated. The definition of the workspace was performed manually in axial computed tomography (CT) slices of the petrosal bone phantom. The mastoidectomy on the model was accomplished in three runs with 10 trial surgeons altogether (5 experienced [exp.] in otologic (ear) surgery, 5 inexperienced [nonexp.]). During each run, the following were logged: the total length of time for the procedure as well as the number and extent of injuries to the risk structures (facial nerve, horizontal semicircular canal, sigmoid sinus). The resultant petrosal bone cavities were measured on the CT. Results: The time for the segmentation of the workspace for the mastoidectomy amounted to 17 minutes. The mean value of the drilling (e.g., milling) performance ranges from 6.61 mm3/s (group 1 [nonexp. + NC]), 9.62 mm3/s (group 2 [exp. w/o NC]), to 10.08 mm3/s (group 3 [exp. + NC]). The relative deviation to the segmented volume amounts to +7.4% (794.3 mm3) for group 1, –39.9% for group 2, and –34% (3,647.0 mm3) for group 3. In the groups with NC guidance of the drill, no damage to a risk structure could be logged. In the group of exp. ear surgeons without NC assistance, one injury to the facial nerve in the petrosal bone phantom occurred. Discussion: The results that follow prove the fundamental feasibility of an NC drill for surgery of the petrosal bone using the example of the simple mastoidectomy in the laboratory test. When using NC, tissue resection is faster, more precise, and has fewer related complications than the same procedure without. The results offer a very promising basis for the introduction of a newly conceived system to the procedure of NC surgery on the petrosal bone. The device configuration used here was originally conceived for NC guidance of a shaver in functional endoscopic sinus surgery. Individual errors will have to be mitigated through the new version of the control unit presently in development.

International audience; This paper describes the ElePhant (Electronic Phantom)-an anatomical correct simulation system based on 3D rapid prototyping models for the otologic intervention "Mastoidectomy". The anatomical structures of the head are created with plaster as base material using 3D-printing as rapid prototyping technology (RPT). Structures at risk, represented by electrically conductible material and fiber optics, are realized as an electric circuit and can be detected during the simulation of the surgical procedure. An accuracy study of 15 identical RPT-models compared to the 3D reconstructed CT-dataset of the patient showed that the mean accuracy is lower than the reconstructed CT layer thickness of 0.5 mm. An evaluation study of the ElePhant-system for "Mastoidectomy" was performed by 7 ENT-surgeons. The mean value of the study questionnaire (evaluation range from -2 (not at all) to +2 (very good)) was +1.2. The results showed that the ElePhant can simulate "Mastoidectomy" realistically. It is especially suitable for the simulation of the correct representation and position of the anatomical structures, realistic operation setting, and realistic milling properties of the bone structure. Furthermore it is applicable for training of surgeons.