Cell cycle association and hypoxia regulation of excision repair cross complementation group 1 protein (ERCC1) in tumor cells of head and neck cancer.

Excision repair cross complementation group 1 (ERCC1) is a key component of homologous recombination-based repair of interstrand DNA cross-links (ICLs). As a consequence, ERCC1 mediates resistance to mitomycin C (MMC) and platinum chemotherapeutic agents and may predict treatment failure. Clinical response to MMC or cisplatin (CDDP)-based radiochemotherapy (RCT) was assessed in 106 head and neck squamous cell carcinoma (HNSCC) patients and correlated with cell nuclear immunoreactivity of the mouse monoclonal (clone: 8 F1) ERCC1 antibody in tumor tissue samples. BEAS-2B epithelial and Detroit 562 pharyngeal squamous carcinoma cells were treated with CDDP, MMC, and 5-fluorouracil (5-FU) at 50 % growth inhibitory (IC-50) concentrations. ERCC1 protein synthesis was compared with cell cycle distribution using combined immunocytochemistry and flow cytometry. ERCC1 messenger RNA (mRNA) and protein expression was investigated in normoxic and hypoxic conditions in Detroit 562 cells. Clinically, the nonresponder revealed significantly lower HNSCC tissue ERCC1 immunoreactivity than the responder (p = 0.0064) or control normal mucosa, which led to further mechanistic investigations. In vitro, control cells and cells treated with cytotoxic agents showed increasing ERCC1 levels from the G1 through S and G2 phases of the cell cycle. In CDDP-treated cells, ERCC1 mRNA and protein expression increased. Under hypoxic conditions, ERCC1 gene expression significantly decreased. Although ERCC1(+) cells show increased chemoresistance, they might be particularly radiosensitive, representing G2 cell cycle phase and less hypoxic. ERCC1 expression might be indirectly related with some conditions important for RCT treatment, but it is not a clear predictor for its failure in HNSCC patients.

Chondrosarcoma of the nasal cavity in a patient with Maffucci syndrome: case report and review of the literature.

INTRODUCTION: Maffucci syndrome is a rare, congenital, non-hereditary mesodermal dysplasia, manifested by multiple enchondromas and hemangiomas. Malignant transformation of these lesions is seen in up to 40% of the cases. CASE REPORT: We present a case of a patient with Maffucci syndrome and an associated chondrosarcoma of the nose. Treatment consisted of surgical resection. Because of the low grade of the tumor, additional treatment, such as radiotherapy, was not necessary. CONCLUSION: Maffucci syndrome is an exceedingly rare mesodermal dysplasia. Its manifestation in the head and neck region is even less common. Malignant transformation of the associated enchondromas is common, and should be considered whenever a change of the clinical course occurs. Random, periodically performed X-ray examinations give little additional information on malignant transformation and are considered useless.

A new nasopharyngeal dynamic reference frame improves accuracy in navigated skull base targets.

OBJECTIVE: We questioned whether the position of the dynamic reference frame (DRF) influences the application accuracy in electromagnetically navigated cranial procedures. A carrier for an electromagnetic DRF was developed, which could be fixed at the posterior edge of the vomer near the center of the head. This nasopharyngeal DRF was compared with a standard DRF fixed to the surface of the forehead. METHODS: Image coordinates and real-world coordinates were co-registered and the total target error (TTE) was measured in the frontal and the lateral skull base of formalin fixed human head. At each anatomical site, 10 targets served for TTE determinations and 5 different fiducial combinations were used for registration. RESULTS: With the nasopharyngeal DRF, lower TTE values (2.8 ± 1.4 mm; mean ± SD) were observed when compared with the forehead DRF (3.7 ± 2.8 mm; P = .004). TTEs of both anatomical sites investigated were significantly lower when using the nasopharyngeal DRF (frontal skull base 3.4 vs 2.1 mm, P = .005 and lateral skull base 3.9 vs 3.5 mm, P = .013) than with the standard forehead mounted one. CONCLUSION: Positioning the DRF in the center of the head significantly improved the application accuracy of targets in the skull base with electromagnetic navigation by 25%.

Proof-of-concept of a laser mounted endoscope for touch-less navigated procedures.

BACKGROUND AND OBJECTIVES: During navigated procedures a tracked pointing device is used to define target structures in the patient to visualize its position in a registered radiologic data set. When working with endoscopes in minimal invasive procedures, the target region is often difficult to reach and changing instruments is disturbing in a challenging, crucial moment of the procedure. We developed a device for touch less navigation during navigated endoscopic procedures. MATERIALS AND METHODS: A laser beam is delivered to the tip of a tracked endoscope angled to its axis. Thereby the position of the laser spot in the video-endoscopic images changes according to the distance between the tip of the endoscope and the target structure. A mathematical function is defined by a calibration process and is used to calculate the distance between the tip of the endoscope and the target. The tracked tip of the endoscope and the calculated distance is used to visualize the laser spot in the registered radiologic data set. RESULTS: In comparison to the tracked instrument, the touch less target definition with the laser spot yielded in an over and above error of 0.12 mm. The overall application error in this experimental setup with a plastic head was 0.61 ± 0.97 mm (95% CI -1.3 to +2.5 mm). CONCLUSION: Integrating a laser in an endoscope and then calculating the distance to a target structure by image processing of the video endoscopic images is accurate. This technology eliminates the need for tracked probes intraoperatively and therefore allows navigation to be integrated seamlessly in clinical routine. However, it is an additional chain link in the sequence of computer-assisted surgery thus influencing the application error.

Agreement between rhinomanometry and computed tomography-based computational fluid dynamics.

PURPOSE: Active anterior rhinomanometry (AAR) and computed tomography (CT) are standardized methods for the evaluation of nasal obstruction. Recent attempts to correlate AAR with CT-based computational fluid dynamics (CFD) have been controversial. We aimed to investigate this correlation and agreement based on an in-house developed procedure. METHODS: In a pilot study, we retrospectively examined five subjects scheduled for septoplasty, along with preoperative digital volume tomography and AAR. The simulation was performed with Sailfish CFD, a lattice Boltzmann code. We examined the correlation and agreement of pressure derived from AAR (RhinoPress) and simulation (SimPress) and these of resistance during inspiration by 150 Pa pressure drop derived from AAR (RhinoRes150) and simulation (SimRes150). For investigation of correlation between pressures and between resistances, a univariate analysis of variance and a Pearson's correlation were performed, respectively. For investigation of agreement, the Bland-Altman method was used. RESULTS: The correlation coefficient between RhinoPress and SimPress was r = 0.93 (p < 0.001). RhinoPress was similar to SimPress in the less obstructed nasal side and two times greater than SimPress in the more obstructed nasal side. A moderate correlation was found between RhinoRes150 and SimRes150 (r = 0.65; p = 0.041). CONCLUSION: The simulation of rhinomanometry pressure by CT-based CFD seems more feasible with the lattice Boltzmann code in the less obstructed nasal side. In the more obstructed nasal side, error rates of up to 100% were encountered. Our results imply that the pressure and resistance derived from CT-based CFD and AAR were similar, yet not same.

Missed paranasal sinus compartments in sinus surgery with and without image-guidance systems: a pilot feasibility study.

PURPOSE: Image-guidance systems (IGS) have gained widespread use in endoscopic sinus surgery (ESS) and have been thoroughly analysed. In this study, we looked for a new parameter to determine if patients could directly benefit from the use of IGS during primary ESS. We questioned if IGS could improve the quality of ESS in chronic rhinosinusitis (CRS) patients via allowing a more comprehensive treatment of all involved sinus compartments. METHODS: In a pilot feasibility study, we evaluated uncomplicated CRS patients following primary ESS with and without IGS between January 2011 and June 2012 using preoperative and postoperative CT scans. The preoperative CT scans identified the sinus compartments requiring surgery. The postoperative CT scans were used to evaluate the treatment effect in these compartments. From these data, we calculated a missing ratio (missed compartments/compartments requiring surgery) for each patient. RESULTS: Of the 169 ESS patients who were treated, ten patients were retrospectively identified as complying with the inclusion and exclusion criteria following ESS with IGS. Ten patients treated without IGS were then randomly chosen. The median missing ratio for non-IGS patients was 36%, and for IGS patients, the median missing ratio was 0% (p = 0.046). However, the missing ratio was depended on the number of compartments requiring surgery. Stratification of the number of compartments requiring surgery resulted in an exact p value of 0.13. CONCLUSIONS: IGS could help the surgeon to more completely address diseased sinus compartments. For better scientific merit, a comparative study of ESS with and without IGS seems feasible, using the proposed failing score missed compartments/compartments requiring surgery as the primary outcome parameter.

Probe versus microscope: a comparison of different methods for image-to-patient registration.

PURPOSE: Computer-aided navigation is widely used in ENT surgery. The position of a surgical instrument is shown in the CT/MR images of the patient and can thus be a good support for the surgeon. The accuracy is highly dependent on the registration done prior to surgery. A microscope and a probe can both be used for registration and navigation, depending on the surgical intervention. A navigation system typically only reports the fiducial registration error after paired-point registration. However, the target registration error (TRE)-a measurement for the accuracy in the surgical area-is much more relevant. The aim of this work was to compare the performance of a microscope relative to a conventional probe-based approach with different registration methods. METHODS: In this study, optical tracking was used to register a plastic skull to its preoperative CT images with paired-point registration. Anatomical landmarks and skin-affixed markers were used as fiducials and targets. With both microscope and probe, four different registration methods were evaluated based on their TREs at 10 targets. For half of the experiments, a surface registration and/or external fiducials were used additionally to paired-point registration to study their influence to accuracy. RESULTS: Overall, probe registration leads to a smaller TRE ([Formula: see text]) than registration with a microscope ([Formula: see text]). Additional surface registration does not result in better accuracy of navigation for microscope and probe. The lowest mean TRE for both pointers can be achieved with paired-point registration only and radiolucent markers. CONCLUSION: Our experiments showed that a probe used for registration and navigation achieves lower TREs compared using a microscope. Neither additional surface registration nor additional fiducials on an external reference element are necessary for improved accuracy of navigated ENT surgery on a plastic skull.

Microdebrider-assisted intracapsular tonsillectomy in adults with chronic or recurrent tonsillitis.

OBJECTIVES/HYPOTHESIS: We compared the effectiveness and morbidity of microdebrider-assisted total intracapsular tonsillectomy (ICTE) with conventional extracapsular tonsillectomy (ECTE) in adults with chronic or recurrent tonsillitis. STUDY DESIGN: Prospective randomized surgical trial. METHODS: Adult patients with recurrent or chronic tonsillitis who underwent tonsillectomy between July 2010 and July 2012 in the Department of Otorhinolaryngology-Head and Neck Surgery, Medical University Innsbruck, Innsbruck, Austria, were consecutively included. Patients were randomized to receive either ICTE or ECTE. Patients and examiners were blinded to the surgical procedure. Effectiveness was assessed with the Tonsil and Adenoid Health Status Instrument (TAHSI). Various parameters of perioperative morbidity and the occurrence of tonsillar remnants were recorded. RESULTS: In the 104 randomized patients, the average TAHSI score was 34.6 ± 11.7 before and 2.2 ± 5.7 after 6 months following tonsillectomy (P < 0.001). TAHSI scores improved equally in patients receiving conventional ECTE (33.6 points; 95% confidence interval (CI), 29.5 to 37.6) and in patients with ICTE (31.8 points; 95% CI, 27.7 to 35.9; between groups P = 0.6). Posttonsillectomy hemorrhage was more frequent following conventional ECTE (P = 0.03). Following ECTE, patients required more pain medication then following ICTE (P < 0.05). Tonsillar remnants were significantly more frequent after ICTE (P < 0,001). However, presence of tonsillar remnants had no influence on postoperative THASI scores (P > 0.5). CONCLUSION: Tonsillectomy reduced symptoms of chronic or recurrent tonsillitis in adults with remarkable effectiveness. Microdebrider-assisted ICTE reduced symptoms as effectively as conventional ECTE. ICTE was associated with lower morbidity, but residual tonsils occurred in almost half of patients, costs were higher, and the intracapsular approach was more intricate and time-consuming. LEVEL OF EVIDENCE: 1b.

Comparison of optical and electromagnetic tracking for navigated lateral skull base surgery.

BACKGROUND: Navigation with optical tracking sometimes makes it difficult to establish a line-of-sight in cluttered operating theatres. On the other hand, the accuracy of electromagnetic tracking is influenced by ferromagnetic surgical equipment. We compared electromagnetic with optical tracking under controlled conditions for the lateral skull base. METHODS: Six anatomical specimens were dissected to measure the target registration error (TRE) in and around the petrous bone in a wet laboratory to simulate an intraoperative setting. Specimens were registered with passive optical and electromagnetic tracking. RESULTS: Overall accuracy was better using optical tracking than electromagnetic tracking (0.22 mm; 0.07-0.48 vs 0.99 mm; 0.56-1.27 mm; median, lower and upper quartiles, respectively; p < 0.001). CONCLUSION: The accuracy of optical tracking was near the resolution of the camera system, whereas the accuracy of electromagnetic tracking was lower. Only optical tracking allows for an application accuracy of considerably less than 1 mm in high-resolution datasets.

Navigated surgery at the lateral skull base and registration and preoperative imagery: experimental results.

OBJECTIVES: To assess factors that affect the accuracy of navigated surgery at the human lateral skull base, including the choice of registration procedures and preoperative computed tomography (CT) section thickness, and to compare target registration error, a measure of clinical application accuracy, with root mean square, an accuracy variable provided by several surgical navigation systems. DESIGN: Experimental cadaver study. SETTING: Medical university. PARTICIPANTS: Anatomic specimen. MAIN OUTCOME MEASURES: Target registration error. RESULTS: A combination of high-resolution CT images, 0.5-mm section thickness, with pair-point matching of a combination of markers on the anatomical specimen, and the registration element was found to be superior (mean [SD], 0.72 [0.28] mm). No correlation was found between target registration error and root mean square. A statistical analysis that considers image registration and acquisition method did not show any correlation between target registration error and root mean square error (r = -0.175, P = .15). CONCLUSIONS: High-resolution CT images, 0.5 mm, of the petrous bone and a pair-point registration using loci on the patient and registration superstructures worked best under experimental conditions. Only target registration error was found to provide reliable information on accuracy intraoperatively. In line with the literature, these data prove that root mean square bears little relevance for clinical application accuracy.

Registration and fusion of CT and MRI of the temporal bone.

OBJECTIVE: To present and evaluate a registration method to fuse complementary information of CT and MRI of the temporal bone. METHODS: CT and MRI of the temporal bone of 26 patients were independently registered 4 times. A manual, iterative, intrinsic, rigid, and retrospective registration method was used. Mean CREm (consistency registration error) was calculated as a reproducibility measurement. RESULTS: CREm was 0.6 mm (95% CI = 0.52-0.68 mm). T-test revealed no difference between pathologic and normal cases (t[102] = -1.71; P = 0.09). Time needed: 13 minutes. In the registered and fused datasets, important bony surgical landmarks (eg, facial nerve canal, inner ear) could be assessed in 3 dimensions relatively to tumor tissue (eg, acoustic schwannoma). Fluid distribution within partially obliterated cochleae could be assigned to either scalae. CONCLUSION: An accurate, reproducible registration and fusion method that improves tumor surgery and cochlea implantation planning with only minor changes to the clinical workflow was presented and described. We suggest this method in selected cases.