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Objectives: To compare consultations at the Otorhinolaryngological Department at a tertiary referral centre between the COVID-19 lockdown in 2020 and the same period in 2019, as well as to study the impact of deferring visits on disease progression., Methods: The emergency consultations during these time periods were analysed retrospectively. The effect of postponing appointments on disease progression was examined for 122 patients with chronic rhinosinusitis, for 50 patients with a benign tumour and for 22 patients with the diagnosis of a malignant tumour. To compare disease progression, patients with the diagnosis of a malignant tumour were matched to patients seen over the same period in 2019., Results: During the lockdown, a reduction of 44.1% in emergency consultations compared with 2019 was observed. The largest significant decrease of consultation numbers was seen for otitis media and for Eustachian tube dysfunction. Fewer patients with tonsillitis sought emergency assistance; however, no difference in frequency of abscesses was observed. Disease progression was seen in 44.4% of patients with chronic rhinosinusitis. In 2020, 18.8% of patients with the diagnosis of a malignant tumour showed disease progression, yet no difference from the previous year was observed., Conclusion: Fewer emergency consultations took place during the COVID-19 lockdown; among others, there were fewer visits due to otitis media and tonsillitis. However, no change in the incidence of complications was noted. Almost 50% of patients with chronic rhinosinusitis showed disease progression, leading to prolonged suffering due to the rescheduling of appointments. The treatment of patients with the diagnosis of a malignant tumour was not affected by the postponement of consultations.

Objectives: The COVID-19 pandemic bears the risk of delayed cancer diagnoses., Methods: Study on the diagnostic pathway of sinonasal malignancies during the COVID-19 pandemic., Results: Median time from first symptom to treatment initiation was not increased during the pandemic: 137 days (interquartile range [IQR] 104-193) vs 139 days (IQR 103-219) ( P  = .60). Median time from first appointment at our institution to treatment initiation was even reduced in 2020: 18 days (IQR 11-25) vs 11 days (IQR 7-17) ( P  = .02). A trend toward advanced tumor stages during the pandemic was seen: 11/30 patients (36.7%) ≥ stage 4 in 2018 to 2019 vs 12/19 patients (63.2%) ≥ stage 4 in 2020 ( P  = .064)., Conclusion: Both, time to diagnosis and time to treatment initiation were similar during the pandemic. However, a higher proportion of advanced tumors stages was observed. Despite the pandemic, we provided a swift diagnostic workflow, including a virtual tumor board decision and a prompt treatment initiation. Level of Evidence: 4., Competing Interests: The authors declare no potential conflict of interest., (© 2021 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Background: For olfactory neuroblastoma (ONB), the combination of surgical tumor resection and radiation therapy (RT) has been considered the "gold standard" in treatment protocols intended to cure., Objective: To summarize evidence on the treatment of ONB using surgery alone., Methods: A retrospective institutional case series, a systematic review of the literature, and an individual patient data (IPD) meta-analysis on only surgically treated ONB patients., Results: At our institution, a total of 10 patients were treated through surgery alone and remained alive and free of disease at last follow-up. The IPD meta-analysis on 128 patients revealed a disease-free survival (DFS) and overall survival (OS) of 67.7% and 75.4% at 5 years and 57.1% and 71.9% at 10 years, respectively. Univariate analysis showed that Kadish stage C/D and Hyams grading III//IV significantly affected OS (P = 0.000 and P = 0.000) and DFS (P = 0.000 and P = 0.002). For low-risk patients, the DFS was 80.6% at 5 years and 67.8% at 10 years, respectively., Conclusions: Surgery alone is an equivalent alternative to combined treatment in carefully selected low-risk ONB patients with better outcome measures than previously reported.

Mucosal melanoma can be driven by various driver mutations in genes such as NRAS , KIT , or KRAS . However, some cases present with only weak drivers, or lacking known oncogenic drivers, suggesting immunotherapy over targeted therapy. While resistance mechanisms to immunotherapy in cutaneous melanoma have been uncovered, including alterations in JAK1 / 2 , B2M, or STK11 , a switch of oncogenic drivers under immunotherapy has not yet been observed. We report three cases of metastatic sinonasal melanoma that switched oncogenic drivers from KRAS , KIT, or no driver to NRAS during or after immunotherapy, thereby showing progressive disease. One of the cases presented with three spatially separate driver mutations in the primary tumor, whereas the NRAS clone persisted under immunotherapy. In comparison, three different control cases receiving radiotherapy only did not show a change of the detectable molecular drivers in their respective recurrences or metastases. In summary, these data provide an important rationale for longitudinal molecular testing, based on evidence for an unforeseen recurrent event of molecular driver switch to NRAS in progressing sinonasal melanoma. These findings provide the basis for further studies on a potential causal relation of emerging NRAS mutant clones and immunotherapy.

Introduction: The Clavien-Dindo classification is a broadly accepted surgical complications classification system, grading complications by the extent of therapy necessary to resolve them. A drawback of the method is that it does not consider why the patient was operated on primarily. Methods: We designed a novel index based on Clavien-Dindo but with respect to the surgical indication. We surveyed an international panel of otolaryngologists who filled out a questionnaire with 32 real case-inspired scenarios. Each case was graded for the surgical complication, surgical indication, and a subjective rating whether the complication was acceptable or not. Results: Seventy-seven otolaryngologists responded to the survey. Mean subjective rating and surgical complication grading for each scenario showed an inverse correlation ( r 2 = 0.147, p = 0.044). When grading the surgical complication with respect to the surgical indication, the correlation with the subjective rating increased dramatically ( r 2 = 0.307, p = 0.0022). Conclusion: We describe a novel index grading surgical complications with respect to the surgical indication. In our survey, most respondents judged a complication as acceptable or not according to its grade but kept in mind the surgical indication. This subjective judgment could be quantified with our novel index., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Morand, Anderegg, Kleinjung, Bohlender, Veraguth, Broglie, Holzmann, Huber, Röösli and Soyka.)

Background: Most studies on sinonasal inverted papillomas (SNIPs) regarding risk factors for recurrence, recurrence rates (RRs) and malignant transformation are biased by a significant proportion of revision cases., Methods: Retrospective study on patients with consecutive, treatment-naïve SNIPs at a tertiary referral center between 1999 and 2019., Results: Overall, RR was 9.8% (10 of 102 patients), with 2 of 10 recurrences (20%) occurring after more than 5 years. Histopathological workup revealed synchronous malignancy in 2 of 102 patients (2%). Subgroup analysis revealed a significantly higher RR for SNIPs involving the frontal sinus (26.3% vs 6.0%, P = .02). No SNIPs primarily originating from the frontal sinus were observed., Conclusion: Overall, RR of treatment-naïve SNIPs is comparably low; however, long-term follow-up is mandatory due to late recurrences. Secondary involvement of the frontal sinus was identified as risk factor for recurrence. No SNIPs primarily originating from frontal sinus were observed., (© 2020 Wiley Periodicals LLC.)

Background: To assess hybrid positron emission tomography (PET) imaging in the initial staging and outcome prediction of sinonasal malignancies., Methods: Retrospective study on patients with sinonasal malignancies undergoing hybrid PET imaging for initial staging., Results: Complete remission (CR) was achieved in 45 of 65 patients (69.2%). Overall sensitivity for detection of primaries using 18F-fluoro-deoxy-d-glucose PET (FDG-PET) was 95.4%, for lymph node metastases 100% and distant metastases (DM) 100%. On univariate analysis, PET parameter total lesion glycolysis (TLG) was associated with achieving CR after primary treatment (176.8 ± 157.2 vs 83.7 ± 110.8, P = .03). Multivariate logistic regression demonstrated that TLG adjusted for the T classification best predicted achievement of CR., Conclusions: Hybrid PET imaging yields an excellent sensitivity in detecting primary tumors, lymph node metastases and DM in sinonasal malignancies. TLG of the primary tumor is an independent prognostic factor for achieving CR after initial treatment., (© 2020 Wiley Periodicals LLC.)

HPV-related multiphenotypic sinonasal carcinoma (HMSC) is a recently described distinct tumor entity of the sinonasal tract associated with high-risk subtypes of human papilloma virus (HPV), predominantly type 33. The biological behavior seems to be less aggressive than the often high-grade, highly proliferative morphology implies; however, recurrences are frequent. Most of the cases present as polypoid tumors within the nasal cavity. Microscopic morphology frequently encompasses adenoid cystic-like features or features reminiscent of other salivary gland tumors. Here, we describe four cases of this rare entity, all observed in women. The polypoid tumors were within the nasal cavity, leading to obstruction, facial pain and epistaxis. The morphology was predominantly basaloid, solid and adenoid cystic-like in two of four cases, one with additional glomeruloid features. Another case showed basaloid tumor cells with prominent mature squamous differentiation and extensive keratinization. A single case showed a predominantly solid and reticular growth pattern. All cases were diffusely positive for p16 (100%), expressed SOX10, LEF-1 and partially S-100, and harbored HPV high-risk types 33, 56 (2×) and 82. No recurrences or metastases were detectable after 3-50 months of follow-up. Of note, three of four patients were nurses/nursing assistant. We expand the morphological spectrum by describing a glomeruloid growth pattern and extensive mature keratinization, and add HPV type 82 to the molecular spectrum. The finding of HMSC among predominantly nurses in our cohort warrants further epidemiological studies in larger cohorts.

Background: Knowledge of medial orbital wall (MOW) and anterior skull base (ASB) infiltration is of uttermost importance for staging and therapy planning of advanced sinonasal tumors., Methods: We assessed the diagnostic performance of preoperative computed tomography (CT) and magnetic resonance imaging (MRI) for MOW and ASB infiltration compared to intraoperative exploration., Results: Both CT and MRI yielded higher diagnostic accuracy for MOW infiltration (Reader 1: 83.6% CT; 89.0% MRI, Reader 2: 91.8% CT, 93.2% MRI) than for ASB infiltration (Reader 1: 82.2% CT, 82.2% MRI, Reader 2: 67.7% CT, 67.7% MRI). Both modalities were equal to the gold standard, except for ASB assessment by Reader 2 with MRI. A postoperative change of T classification is common (Reader 1: 28.8%, Reader 2: 31.5%)., Conclusions: CT and MRI are accurate methods for the assessment of MOW infiltration. ASB assessment is challenging and false-positive and false-negative findings are common with both methods, emphasizing the need for intraoperative exploration., (© 2020 Wiley Periodicals, Inc.)

Objective: The "chopsticks" technique is a 3-instrument, 2-hand mononostril technique that has been recently introduced in endoscopic neurosurgery. It allows a dynamic surgical view controlled by one surgeon only while keeping bimanual dissection. Being a mononostril approach, it requires manipulation of the mucosa of one nasal cavity only. The rationale of the technique is to reduce nasal morbidity without compromising surgical results and complication rates. There are, however, no data available on its results in endoscopic surgery (transsphenoidal surgery [TSS]) for pituitary adenoma., Methods: The authors performed a cohort analysis of prospectively collected data on 144 patients (156 operations) undergoing TSS using the chopsticks technique with 3T intraoperative MRI. All patients had at least 3 months of postoperative neurosurgical, endocrinological, and rhinological follow-up (Sino-Nasal Outcome Test-20 [SNOT-20] and Sniffin' Sticks). The surgical technique is described, and the achieved gross-total resection (GTR) and extent of resection (EOR) together with patients' clinical outcomes and complications are descriptively reported., Results: On 3-month postoperative MRI, GTR was achieved in 71.2% of patients with a mean EOR of 96.7%. GTR was the surgical goal in 122 of 156 cases and was achieved in 106 of 122 (86.9%), with a mean EOR of 98.7% (median 100%, range 49%-100%). There was no surgical mortality. At a median follow-up of 15 months (range 3-70 months), there was 1 permanent neurological deficit. As of the last available follow-up, 11.5% of patients had a new pituitary single-axis deficit, whereas 26.3% had improvement in endocrinological function. Three patients had new postoperative hyposmia. One patient had severe impairment of sinonasal function (SNOT-20 score > 40). The operation resulted in endocrine remission in 81.1% of patients with secreting adenomas., Conclusions: This study shows that the chopsticks technique confers resection and morbidity results that compare favorably with literature reports of TSS. This technique permits a single surgeon to perform effective endoscopic bimanual dissection through a single nostril, reducing manipulation of healthy tissue and thereby possibly minimizing surgical morbidity.

Background: Despite the discordance in the literature concerning the effect of columellar strut grafts on nasal tip rotation, this method is often used when an increase in nasolabial angle or nasal tip projection is desired., Objectives: We aimed to elucidate the change in nasolabial angles and nasal tip projections after exclusive columellar strut graft implantations and in addition to other surgical steps. Furthermore, differences in these parameters between patients with conchal and septal columellar strut grafts were investigated., Methods: A monocentric retrospective cohort study of 173 open septorhinoplasties with columellar strut graft technique, between 2006 and 2016, was conducted. The pre- and postoperative nasal tip projection, nasolabial and nasofrontal angle and interalar distance were determined and the Goode-ratio was calculated., Results: In cases where uprotation was not specifically desired, neither nasolabial angles nor tip projections changed significantly, irrespective of whether a columellar strut graft was used alone or with additional surgical steps. If an uprotation through surgery was desired, a significant mean increase in nasolabial angle of 4.4° was achieved. Furthermore, conchal instead of septal columellar strut grafts showed significantly better results., Conclusion: In our study, a columellar strut graft-without any additional surgical step-does only have an improving impact on nasal tip rotations and projections, if specifically intended to by the surgeon. In other words, if the strut graft was not chosen for an uprotational intention, it did not relevantly impact on the nasolabial angle or nasal tip projection. However, in patients where an uprotation is desired, the columellar strut graft still represents a meaningful tool. Since conchal instead of septal columellar strut grafts showed better results, we suggest using them for these patients., Level of Evidence: 2b.

Background/aim: Among the most important prognostic factors in melanoma is the sentinel lymph node (SLN) status., Materials and Methods: Using our electronic database we identified 109 of 890 SLN-negative patients with progressive disease (PD). These patients were characterized for melanoma type, molecular type, sequence and extent of metastatic spread., Results: A total of 61 of 109 SLN-negative patients had PD in the SLN-basin indicating false-negative SLN (group-1). Forty eight of 109 patients had PD at distant sites and were therefore impossible to be identified using SLN biopsy (group-2). Despite distant spread these patients had significantly more single organ metastasis (p<0.001) and significantly longer disease-free-survival (p=0.001) compared to group-1. Additionally, to significant differences on a molecular basis between the two groups (p=0.01), all lentigo maligna and spindle-cell-melanomas belonged to group-2 and all, except one lentigo maligna melanoma, had single visceral metastasis., Conclusion: Two different biological groups among SLN-negative patients with PD were demonstrated. Extravascular-migratory-metastasis, rather than hematogenous spread, might be responsible for the observed PD with single organ involvement., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: In the rare case of intractable, posterior, non-sphenopalatine artery epistaxis, ligation of ethmoidal arteries using an external approach like a Lynch-type incision is required. Orbital complications, especially extra-ocular motility disorders with diplopia, are known, but in the literature rarely described. Our aim was to analyse the complication type, rate, and outcome of ethmoidal artery ligation for epistaxis., Materials and Methods: Data between 2012 and 2017 of patients treated with ethmoidal artery ligation were analysed retrospectively and through a telephone interview using a non-standardized questionnaire., Results: Data of 18 patients (m/f = 3/15) aged 53-83 years were reviewed. Epistaxis recurred in only one patient after 1 month. Five patients (28%) suffered from diplopia shortly after surgery. Motility analysis revealed full recovery with free motility in four out of five reported cases after 4-8 months, one patient still reports intermittent mild diplopia more than 1 year postoperatively., Conclusion: In patients with intractable, non-sphenopalatine artery epistaxis, anterior ethmoidal artery ligation was highly effective. Diplopia, however, occurred in one-third of our patient group. Information about motility restriction with longer standing diplopia are mandatory when consenting patients for ligation of ethmoidal arteries. Special care needs to be taken during dissection in the region of the trochlea and superior oblique muscle., Level of Evidence: Case Series, level 4.

Background: It is currently unclear if there are subsets of patients undergoing transsphenoidal surgery (TSS) in which intraoperative high-field magnetic resonance imaging (3T-iMRI) is particularly advantageous. We aimed to investigate whether a radiological grading scale predicts the utility of 3T-iMRI in pituitary adenoma (PA) TSS., Methods: From a prospective registry, patients who underwent endoscopic TSS for PA using 3T-iMRI were identified. Adenomas were graded using the Zurich Pituitary Score (ZPS). We assessed improvement after 3T-iMRI in terms of gross total resection (GTR), residual volume (RV), and extent of resection (EOR)., Results: Among 95 patients, rates of conversion to GTR after 3T-iMRI decreased steadily from 33% for grade I to 0% for grade IV adenomas, with a statistically significant conversion rate only for grade I (p = 0.008) and grade II (p < 0.001). All grade I adenomas were completely resected after 3T-iMRI. Median RV change was statistically significant for grades I to III, but not for grade IV (p = 0.625). EOR improvement ranged from a median change of 0.0% (IQR 0.0-4.5%) for grade I to 4.4% (IQR 0.0-9.0%) for grade IV, with a significant improvement only for grades I to III (p < 0.05)., Conclusions: Interestingly, this study shows that clinical utility of 3T-iMRI is highest in the more "simple" adenomas (ZPS grades I-II) than for the more "complex" ones (ZPS grade III-IV). Grade I adenomas are amenable to GTR if 3T-iMRI is implemented. In grade III adenomas, EOR and RV can be improved to clinically relevant levels. Conversely, in grade IV adenomas, 3T-iMRI may be of limited use.

Sinonasal melanoma is a rare subtype of melanoma and little is known about its molecular fingerprint. Systemic treatment options are limited, as targetable BRAF mutations are rare compared to cutaneous melanoma. Currently, metastatic sinonasal melanoma is being treated according to the guidelines of cutaneous melanoma. In this study, we investigated the molecular profile of 19 primary sinonasal melanomas, using a novel customized melanoma-specific next generation sequencing (NGS) panel (MelArray) of 190 genes. Results were correlated to histological and clinical features to further characterize this rare, aggressive type of melanoma and screen for prognostic markers and possible treatment options. Molecular profiles encompassed predominantly mutations in NRAS (25%), whereas KIT or BRAF p.V600 mutations were not detected. Tumor mutational burden was overall low. High level of copy number variations (CNVs) were associated with alterations in DNA-repair genes and shorter distant metastasis-free survival ( p = 0.005). Monomorphic (vs. pleomorphic) morphology was found to be significantly associated with worse disease-specific survival ( p < 0.001), however no correlation between morphology and molecular aberrations was found. A variety of alterations in different pathways were detected, justifying molecular testing and opening potential personalized treatment options in current study or compassionate use settings.

Purpose: To present outcome measures of sinonasal mucosal melanoma (SMM) patients with particular focus on current radiological and therapeutic options, especially in the non-curative setting (immunotherapy)., Methods: Retrospective study on SMM patients treated at our institution between January 1992 and December 2018., Results: FDG-PET/MRI has emerged as the new hybrid imaging modality, addressing the need for high local tissue contrast in the paranasal sinuses and the skull base, while allowing for whole-body staging in search for distant metastases, including the brain. Primary treatment protocols consisted of tumor resection in 30/34 patients (88%), palliative radiation therapy (RT) in 3/34 patients (9%) and best supportive care therapy in 1/34 patient (3%). Of all the initially operated patients, 25/30 patients (83%) received adjuvant RT. A total of 9/34 patients (26%) was treated with immunotherapy after the previous combined therapy. For patients treated in curative intention, we observed a 1-year overall survival (OS) of 60% (18/30 patients) and a 3-year OS of 40% (12/30 patients). For patients treated with immunotherapy, median progression-free survival (PFS) was 5 months (IQR 0-13.75), with a maximum PFS of 16 months (combination of nivolumab and ipilimumab). However, there was no difference in OS in patients treated with immunotherapy vs. no immunotherapy (log rank 0.99)., Conclusions: Sinonasal mucosal melanoma is a highly aggressive tumor, requiring multimodal therapy and developing a substantial incidence of distant metastases. The introduction of FDG-PET/MRI offers new possibilities in the radiological assessment of the tumor and immunotherapy has altered the management in the non-curative setting, resulting in a substantial progression-free survival in selected cases.

The detection of infrared radiation is of great interest for a wide range of applications, such as absorption sensing in the infrared spectral range. In this work, we present a CMOS compatible pyroelectric detector which was devised as a mid-infrared detector, comprising aluminium nitride (AlN) as the pyroelectric material and fabricated using semiconductor mass fabrication processes. To ensure thermal decoupling of the detector, the detectors are realized on a Si 3 N 4 /SiO 2 membrane. The detectors have been tested at a wavelength close to the CO 2 absorption region in the mid-infrared. Devices with various detector and membrane sizes were fabricated and the influence of these dimensions on the performance was investigated. The noise equivalent power of the first demonstrator devices connected to a readout circuit was measured to be as low as 5 . 3 × 10 - 9 W / Hz .

Objectives/hypothesis: To investigate the association between epistaxis and atherosclerotic cardiovascular disease., Study Design: Case-control cohort study., Methods: This study included patients from the tertiary-care ear, nose, and throat department at the University Hospital of Zurich between December 1, 2016 and June 1, 2017. We assessed the cardiovascular risk profiles in a group of 41 patients presenting with epistaxis, and a group of 41 matched controls, focusing on a surrogate parameter for atherosclerosis: the carotid intima-media thickness (CIMT)., Results: With a mean of 1.06 mm (standard deviation [SD] = 0.17), CIMT values were on average 26% higher in epistaxis patients than in their controls, with a mean of 0.84 mm (SD = 0.14; P < .001). Occurrence of severe epistaxis was also associated with lower ankle-brachial index values at 0.96 (SD = 0.12) versus 1.05 (SD = 0.17) (P < .001) and significantly higher QRISK2 relative risks (an algorithm for predicting cardiovascular risk) than found in the control group (1.81, SD = 0.97 vs. 1.35, SD = 0.28; P = .028). A binary logistic regression model, adjusted for possible confounders, showed an odds ratio of 2.5 for the occurrence of epistaxis per increase in CIMT of 0.1 mm in the study population (95% confidence interval: 1.56-4.11; P < .001)., Conclusions: The occurrence of severe epistaxis was shown to be closely associated with the prevalence of atherosclerotic cardiovascular disease. Accordingly, patients affected by epistaxis should be regarded as at an elevated cardiovascular risk, which indicates the need for appropriate further medical assessment and preventive measures., Level of Evidence: 3b TRIAL REGISTRATION: Clinical trials NCT03092973 Laryngoscope, 129:783-787, 2019., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose: To describe the volumetric changes that the pituitary gland (PG) undergoes during and after transsphenoidal surgery (TSS), and to evaluate if unfolding and/or pruning are related to endocrinological outcome measures., Methods: Retrospective evaluation of data prospectively collected of a cohort of patients undergoing TSS for a pituitary adenoma with the adjunctive use of high field 3 Tesla intraoperative MRI. All patients underwent a full endocrinological workup preoperatively, as well as at 6 weeks and 1 year postoperatively. A decrease in PG volume ≥15% between the intraoperative and 3-month, or between the 3-month and 12-month measurements, was considered early and late pruning, respectively., Results: The PG unfolds significantly during TSS, and subsequently undergoes pruning up until 1 year postoperatively, in most cases returning to the preoperatively measured PG volume. A smaller baseline PG volume predicts intraoperative unfolding. Early pruning of the PG after surgery was associated with new functional deficits. Baseline pituitary compression also correlated to newly occurring deficits after surgery. A larger 1-year pituitary volume was associated with biochemical remission in secreting adenomas., Conclusions: The PG shows dynamic change during and after TSS for pituitary adenoma. Small baseline and 3-month PG volumes, as well as early pruning were independently associated with new deficits. Our findings warrant prospective validation in a larger cohort with higher statistical power.

Objective  We compare the open and transnasal approaches for the excision of juvenile nasopharyngeal angiofibromas regarding the rate of morbidity, and residual tumor and its symptomatic recurrence over time. In addition, we present volumetric measurements of juvenile nasopharyngeal angiofibromas over time. Methods  All surgically treated patients of our institution were reviewed back to 1969 for type of surgery, residual tumor by magnetic resonance imaging (MRI)-based volumetry, recurrence, and morbidity. We performed a prospective clinical and radiological follow-up on reachable patients. Results  In total, 40 patients were retrievable from our records. We were able to follow up on 13 patients after a mean of 15.7 years since surgery (range: 1-47 years). Patients operated by the open approach had a higher rate of postoperative complications and thus a higher morbidity than endoscopic patients (4/4 vs 3/9; p  = 0.007), although tumor sizes were equal among groups ( p  = 0.12). Persisting tumor was noted in 3/4 and 4/9 ( p  = 0.56) patients, respectively. The corresponding mean volumes of residual tumors were 16.2 ± 14.4 cm 3 and 10.8 ± 6.6 cm 3 ( p  = 0.27). No progression could be noted in endoscopically treated patients ( p  = 0.24, mean time between scans 2 years). Conclusions  Our analysis shows that the endoscopic approach results in less morbidity. The open approach does not guarantee freedom from persisting tumor tissue. Age seems to be a most important risk factor for the conversion of an asymptomatic persistence into a symptomatic recurrence.

OBJECTIVEGross-total resection (GTR) is often the primary surgical goal in transsphenoidal surgery for pituitary adenoma. Existing classifications are effective at predicting GTR but are often hampered by limited discriminatory ability in moderate cases and by poor interrater agreement. Deep learning, a subset of machine learning, has recently established itself as highly effective in forecasting medical outcomes. In this pilot study, the authors aimed to evaluate the utility of using deep learning to predict GTR after transsphenoidal surgery for pituitary adenoma.METHODSData from a prospective registry were used. The authors trained a deep neural network to predict GTR from 16 preoperatively available radiological and procedural variables. Class imbalance adjustment, cross-validation, and random dropout were applied to prevent overfitting and ensure robustness of the predictive model. The authors subsequently compared the deep learning model to a conventional logistic regression model and to the Knosp classification as a gold standard.RESULTSOverall, 140 patients who underwent endoscopic transsphenoidal surgery were included. GTR was achieved in 95 patients (68%), with a mean extent of resection of 96.8% ± 10.6%. Intraoperative high-field MRI was used in 116 (83%) procedures. The deep learning model achieved excellent area under the curve (AUC; 0.96), accuracy (91%), sensitivity (94%), and specificity (89%). This represents an improvement in comparison with the Knosp classification (AUC: 0.87, accuracy: 81%, sensitivity: 92%, specificity: 70%) and a statistically significant improvement in comparison with logistic regression (AUC: 0.86, accuracy: 82%, sensitivity: 81%, specificity: 83%) (all p < 0.001).CONCLUSIONSIn this pilot study, the authors demonstrated the utility of applying deep learning to preoperatively predict the likelihood of GTR with excellent performance. Further training and validation in a prospective multicentric cohort will enable the development of an easy-to-use interface for use in clinical practice.

Background: The extent of resection (EOR) is a crucial outcome parameter in transsphenoidal pituitary surgery (TSS), and is linked to endocrinological outcome, postoperative morbidity, and mortality. We aimed to build a robust, quantitative, and easily reproducible imaging score able to predict EOR in TSS., Methods: The ratio (R) between the maximum horizontal adenoma diameter and intercarotid distance at the horizontal C4 segment was used to stratify our patient series in four classes: class I R ≤ 0.75, class II 0.75 < R ≤ 1.25, and class III R ≥ 1.25. Class IV included adenomas which completely encased the internal carotid artery. The resulting score was internally validated for robustness., Results: One hundred sixteen patients were included in the study, of which 96 (83%) for derivation and 20 (17%) for validation. EOR showed significant differences between grades (grade I, 100%; II, 97.9%; III, 94.2%; IV, 87.2%; all P < 0.05). The same applied to residual volume (RV) (grade I, 0 cm 3 ; II, 0.08 cm 3 ; III, 1.11 cm 3 ; IV, 1.63 cm 3 ; all P < 0.05). Differences in gross total resection (GTR) were statistically significant among classes I, II, and III (P < 0.05). The incidence of residual adenoma in the cavernous sinus increased also constantly from grade I up to grade IV although a significant difference was only found between grades III and II (P = 0.004). The score performed equally well in the validation cohort. Inter-observer agreement was high, with intraclass correlation coefficients > 0.89 for measurement of both the horizontal tumor diameter and the ICD among two independent raters (P < 0.001)., Conclusions: The proposed score is a simple and reproducible tool which reliably predicts surgical outcome including EOR, RV, and GTR of pituitary adenoma patients undergoing TSS.

Background: Aim was to analyse the role of PD-L1 in squamous cell carcinomas of the nasal vestibule. Advanced squamous cell carcinoma of the nasal vestibule is a highly aggressive tumour. The role of PD-L1 expression is unclear in this tumour type., Methodology: Forty-six patients diagnosed between 1995 and 2014 were analyzed. Baseline characteristics and outcome were correlated to immunohistochemical staining of PD-L1. PD-L1 positivity of tumour cells and tumour infiltrating immune cells (TIIC) was defined by any staining of more than 1% of the tumour cells., Results: PD-L1 expression was interpretable in 31 of 46 patients (67.4%). PD-L1 positivity was present in 14 (45.2%) patients tumour cells and 17 (54.8%) patients TIIC. PD-L1 positivity of tumour cells was associated with a favourable disease free survival (p=0.019)., Conclusions: Positivity for PD-L1 in tumour cells is a prognostic factor in squamous cell carcinoma of the nasal vestibule and might enable a patient-tailored treatment.

Objective: To compare the mortality rate of a large epistaxis cohort with the fatalities of the general Swiss population and to evaluate significant risk factors for impending early death., Methods: 568 patients out of an epistaxis cohort from a former study were contacted by mail to answer a questionnaire. Deceased patients were identified from March, 2007 through April, 2014. Death rates were compared to the general Swiss population. Different potential risk factors were evaluated by multivariate analysis., Results: Thirty-four percent of the included patients (61 of total n=181) died during the observation period. The mean number of deaths per year was 8.7. Binary logistic regression identified anterior localization (p=0.027), comorbid endogenous bleeding predisposition including hemorrhagic hereditary telangiectasia (p=0.017) and age (p<0.01) as independent and significant risk factors for early death in epistaxis patients. A significantly higher mortality was found within our epistaxis cohort compared to the Swiss general population., Conclusion: With the present data a trivial event such as epistaxis, especially when anteriorly located, needs to be seen in a new light. Emergency consultation because of nose bleeding might be an unexpected bad predictor for mortality. Although conclusions need to be considered with caution due to the retrospective character of the study, we regard epistaxis as an independent alarm-signal. After an acute nose bleed requiring emergency consultation, active collaboration with the patient's general practitioner and additional efforts to check for the patient's general health might be more useful than so far assumed., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To determine the incidence of occult cerebrospinal fluid leaks (CSF) after functional endoscopic sinus surgery (FESS) and to evaluate the diagnostic performance of beta2-transferrin in blood-contaminated conditions., Study Design: Prospective cohort study., Methods: An analysis of 57 intraoperative samples using hydrogel 6 beta2-transferrin assay after FESS was undertaken. In case of CSF positive samples and continuing rhinorrhea, reanalysis after more than 1 year was conducted. In-vivo analysis of a primary spontaneous CSF leak sample took place to verify difficulties in detecting beta2-transferrin in blood-contaminated settings. Own titrations were performed to evaluate detection limits of CSF by beta2-transferrin and beta-trace protein assays in these settings., Results: An incidence of 13% for occult CSF leaks after FESS was found. In blood-contaminated conditions, routine beta2-transferrin assays showed low sensitivity. In over 1 year follow-up, all samples were negative for CSF and none of them developed clinical relevant CSF leaks or meningitis., Conclusion: Occult and clinically irrelevant CSF leaks do occur in a significant proportion of patients during and shortly after FESS. Intra- and postoperatively, routine beta2-transferrin assays show low sensitivity. They should not be used in these settings. The clinical course of patients with occult CSF leaks indicated possibility of an uneventful follow-up.

Background: Rhinoplasty represents one of the most challenging and frequently performed procedures in plastic surgery and non-surgical rhinoplasty is rarely considered. The aim of this study was to investigate whether the Nasella Nose Former (NNF), a newly developed non-surgical rhinoplasty device, could improve objective and subjective results following surgical rhinoplasty and even correct the shape of the nose without any surgery at all., Methodology: In this prospective, monocentric, two-armed, non-blinded randomized, controlled clinical trial, a total of 43 participants were included. In the Surgical group, 22 patients undergoing open or closed rhinoplasty with osteotomies were randomised based on their birth year; 15 of them got to wear the NNF over 8 weeks postoperatively and 7 patients getting surgery without the NNF formed the control group. In the Cosmetic group, 21 participants wore the NNF without surgery over 14 months. At every follow-up exam, angles for crookedness, nasal hump and width were measured, the investigator assessed the patients nose and asked for patient satisfaction using a Likert-scale., Results: Patients in the Surgical group wearing the NNF did not show any significant difference concerning objective measurements, investigator assessments and patient satisfaction compared to those not wearing the NNF. In the Cosmetic group, participants did not show objective improvements in measurements and investigator assessment. However, participants were significantly more satisfied after 14 months with their nasal back, nasal axis and outer nose in general., Conclusions: Considering the results of this study, we conclude that this perfectly customised external device to enhance surgical rhinoplasty outcomes or correct the shape of the nose without surgery does not seem to be effective and that further investigations in this field are not meaningful.

Objective: Sinonasal undifferentiated carcinoma (SNUC) is an aggressive malignancy first described by Frierson et al. in 1986. As the tumor is very rare, current treatment recommendations are based on institutional case reports. We thus felt the need to perform a comprehensive systematic review and meta-analysis to investigate how treatment modalities are associated with survival., Design: Case-series, systematic review and meta-analysis METHODS: We searched the OvidMedline, OvidEmbase, Web of Science, Biosis, Scopus and the Cochrane Library database libraries. We extracted aggregate and individual patient data for statistical analysis. To study the association between treatment modalities and survival, we used random-effects meta-regression for the aggregate- and cox mixed-effects models., Results: 379 citations were found; 29 case series could be included in the final analysis, including a total number of 390 single patients (34.6% female). Median age at diagnosis was 52 years. 80.9% of patients presented with a T4 tumor and 16.0% with nodal metastasis at diagnosis. In individual patient data (IPD) meta-analysis, single modality (surgery alone or radiation alone) treatment was associated with reduced survival compared to double modality (surgery & radiation or chemoradiation) treatment (adjusted Hazard Ratio [aHR] 2.97, 95% ConfidenceInterval [1.41-6.27]) and compared to triple modality (surgery & radiation & chemotherapy) treatment (aHR 2.80 95%-CI 1.29-6.05 for triple vs. single modality). Triple modality treatment was not superior to double modality treatment. (aHR 1.06, 95%-CI 0.59-1.92)., Conclusion: Double and triple modality treatment are associated with improved survival over single modality but there is no evidence that triple modality is superior to double modality treatment., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: Injuries to the internal carotid artery (ICA) are potentially lethal complications in transsphenoidal surgery (TSS) for pituitary lesions. The intercarotid distance (ICD) is thus a major parameter, determining the width of the surgical corridor in TSS. The purpose of the study is to investigate changes in ICD at different levels of the ICA during and after TSS using high definition intraoperative MRI (3T-iMRI)., Methods: Pre-, intra- and 3 months postoperative MRI images of 85 TSS patients were reviewed. ICD was measured at the horizontal (ICDC4h) and vertical (ICDC4v) intracavernous C4 segment as well as at the C6 segment (ICDC6). Association between ICD change at different levels and time points were compared and potential factors predicting ICD reduction were analyzed., Results: ICD decreased intraoperatively at all three segments of ICA by -3% (median decreases: ICDC4h: -0.5 mm, ICDC4v: -0.7 mm ICDC6: -0.4 mm). At 3 months postoperative MRI, ICD reduced by a further -4%, -2% and -4% respectively (median decreases ICDC4h: -0.7, ICDC4v: -0.4 mm, ICDC6: -0.5 mm). Postoperative narrowing in ICD occurred independent of further resection after 3T-iMRI. ICD change correlated between different levels of the ICA indicating a uniform shift perioperatively. Preoperative ICD was significantly associated with the intraoperative reduction in ICDC4v and ICDC6., Conclusions: We have demonstrated a uniform narrowing in ICD at different levels of the ICA during and after TSS adenoma resection. Surgeons should be aware of this change since it determines the width of the surgical corridor and can thus influence the ease of surgery.

Background: The nasoseptal flap (NSF) is a universally used surgical technique to cover defects of the skull base after extended sinonasal surgery. Long-term follow-up of complications, sequelae, and smell function is largely unknown., Objective: The main objective of this study was to investigate monorhinal olfaction after transsphenoidal skull base surgery., Methods: Patients who underwent skull base surgery for midline lesions (craniopharyngioma and pituitary tumors) by using a NSF, also referred to as the Haddad flap, were assessed for their long-term outcome. Endoscopic examination was conducted and the bilateral "Sniffin' Sticks" test was performed before surgery. Each side was tested separately in the postoperative follow-up consultation., Results: Twenty patients were included in the study. No flap failures were observed. One anterior perforation and one small posterior septal perforation were found during long-term follow-up. None of the patients had nasal breathing impairment, whereas two patients had nose bleeds. A significant decrease in olfactory function was observed on the flap donor side in four patients (20%) compared with that observed in one patient (5%) on the opposite side., Conclusion: NSF reconstructions for midline lesions were efficient and safe in the long term. Olfactory impairment on the donor side was frequently encountered. Although subclinical, these findings justified a monorhinal smell testing before surgery, which possibly prevented bilateral smell impairment in patient with preexisting single-sided olfactory loss.

The aim of this study was to analyze the role of Ki-67, p53, and the "aberrant p53 pattern" in squamous cell carcinomas of the nasal vestibule. Patients between 1995 and 2014 were included. Baseline characteristics and outcome were analyzed with respect to immunohistochemical staining of Ki-67 and p53. "Aberrant p53 pattern" was represented by a moderate or strong staining of at least 60% of the tumor cells or a complete absence of immunoreactivity. Forty-six patients were included of whom 31 (67.4%) were available for Ki-67 and 32 (69.9%) for p53 immunohistochemistry. The "aberrant pattern" of p53 was present in 50% of the patients. While immunoreactivity for both Ki-67 and p53 was not related to each other or outcome, the "aberrant p53 pattern" was associated with a worse disease-free survival (p = 0.014). The "aberrant p53 pattern" is a negative prognostic factor in squamous cell carcinoma of the nasal vestibule and might enable a patient-tailored treatment.

Objectives: To determine the rate of surgical-site infections (SSI) in neurosurgical procedures involving a shared-resource intraoperative magnetic resonance imaging (ioMRI) scanner at a single institution derived from a prospective clinical quality management database., Methods: All consecutive neurosurgical procedures that were performed with a high-field, 2-room ioMRI between April 2013 and June 2016 were included (N = 195; 109 craniotomies and 86 endoscopic transsphenoidal procedures). The incidence of SSIs within 3 months after surgery was assessed for both operative groups (craniotomies vs. transsphenoidal approach)., Results: Of the 109 craniotomies, 6 patients developed an SSI (5.5%, 95% confidence interval [CI] 1.2-9.8%), including 1 superficial SSI, 2 cases of bone flap osteitis, 1 intracranial abscess, and 2 cases of meningitis/ventriculitis. Wound revision surgery due to infection was necessary in 4 patients (4%). Of the 86 transsphenoidal skull base surgeries, 6 patients (7.0%, 95% CI 1.5-12.4%) developed an infection, including 2 non-central nervous system intranasal SSIs (3%) and 4 cases of meningitis (5%). Logistic regression analysis revealed that the likelihood of infection significantly decreased with the number of operations in the new operational setting (odds ratio 0.982, 95% CI 0.969-0.995, P = 0.008)., Conclusions: The use of a shared-resource ioMRI in neurosurgery did not demonstrate increased rates of infection compared with the current available literature. The likelihood of infection decreased with the accumulating number of operations, underlining the importance of surgical staff training after the introduction of a shared-resource ioMRI., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to analyze the role of p16 INK4a and the prevalence of human papillomavirus (HPV) in squamous cell carcinoma (SCC) of the nasal vestibule., Methods: Patients diagnosed from 1995 to 2014 were included in this study. Assessment of p16 INK4a and HPV-DNA polymerase chain reaction (PCR) was performed and analyzed with respect to baseline, clinicopathological, and outcome parameters. The p16 INK4a positivity was defined as unequivocal nuclear and cytoplasmic staining of ≥70% of the cells, whereas 50%-69% was considered to be a "borderline" result., Results: There were 46 patients with SCCs of the nasal vestibule, of whom 31 (67.4%) were available for p16 INK4a and 30 (65.2%) for analysis of HPV. Expression of p16 INK4a was present in 19.4% and showed coincidence with high-risk HPV (P < .001). Neither p16 INK4a nor HPV-DNA had significant impact on outcome., Conclusion: Significant immunoreactivity for p16 INK4a was present in about one-fifth of the samples and figured as a surrogate marker of high-risk HPV infection. There was no influence on outcome., (© 2017 Wiley Periodicals, Inc.)

A 70-year-old patient with known hereditary haemorrhagictelangiectasia (HHT) was seen regularly in our outpatient clinic. He underwent multiple therapeutical interventions, including both surgical and medical, for the treatment of recurrent epistaxis without sustained success. Due to a concurrent diagnosis of idiopathic pulmonary fibrosis, treatment with the tyrosine kinase inhibitor nintedanib was initiated, after which point the patient reported a dramatic and unanticipated improvement in his epistaxis and skin telangiectasia. On the basis of this case report, we propose that nintedanib may be a potential treatment option for refractory epistaxis in HHT., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Septal perforation closure is still often invasive and complex, with relatively low closure rates., Objectives: We aimed to provide the first results of a case series of 20 patients with nasal septal perforations who underwent septal perforation repair by both an open and a minimally invasive technique by using a graft that consisted of temporoparietal fascia and a polydioxanone (PDS) plate without mucosal flaps. Between 2014 and 2016, we tested, for the first time, the feasibility of the insertion of this graft via a hemitransfixion incision at our institution. The rationale for the closed approach was to avoid any visible nasal scars. We reported our results of both approaches., Methods: The septal perforations were closed by insertion of a graft, which consisted of a 0.25-mm PDS flexible plate enveloped by temporoparietal fascia, into the perforation. The insertion of the graft was performed either via a columellar incision (open approach) or via a cosmetically advantageous hemitransfixion incision (closed approach) in an underlay technique. No attempts were made to close the perforation by mucosal flap rotation and/or advancement. Protective silastic sheeting to both sides of the perforation provided fixation to the graft while natural mucosal healing occurred over the perforation in the course of 3 to 8 weeks., Results: Eighteen of 20 perforations were closed by mucosa at the last follow-up. The mean follow-up was 8.7 months. Thirteen patients had surgery via the closed approach., Conclusion: We showed, for the first time, that the insertion of a graft that consisted of a PDS flexible plate enveloped in temporoparietal fascia via a hemitransfixion incision was feasible and resulted in complete mucosal closure of nasal septal perforations in most patients. By performing the hemitransfixion incision, we avoided any visible nasal scars.

Objective: This study aims to evaluate local control and intermediate-term cosmetic outcome in patients with cancer of the nose treated with intensity-modulated radiotherapy (IMRT)., Methods: From June 2008 to September 2015, 36 consecutive patients presenting with nasal cavity, ala of the nose, or nasal vestibule tumors were treated at the Department of Radiation Oncology, University Hospital Zurich either postoperatively (n = 14; 3/14 with nasal ablation) or with definitive IMRT (n = 22). Of these 36 patients, 8 presented with recurrent disease after surgery only and 1/36 with N1 disease. Concurrent systemic therapy was administered in 18/36 patients (50%). Nasal follow-up (FU) imaging documentation of 13 patients with preserved organ and >6 months FU offers a pre/post IMRT FU comparison. In addition, these patients' subjective evaluation of cosmesis was assessed., Results: Mean/median FU was 41/33 months (range 5-92 months). Salvage ablation with curative intent was undergone by 3 patients with local relapse after definitive (n = 2) and postoperative (n = 1) IMRT. The 3‑year local control, ultimate local control, and overall survival rates were 90, 97, and 90 %, respectively. Subjective and objective cosmetic outcome after IMRT is very satisfying so far., Conclusion: IMRT for nasal tumors was found to be effective and well tolerated. Intermediate-term cosmetic results are good. Radical surgical procedures may be saved for curative salvage treatment.

The objective of this study is to analyze the presenting symptoms, the time to correct diagnosis and outcome of a European patient cohort with sinonasal lymphoma focusing on unilateral vs. bilateral sinonasal involvement. In a retrospective setting in a European tertiary referral center, eleven patients (9 males, 2 females) with sinonasal lymphoma diagnosed between 2002 and 2015 were identified and divided into a unilateral and bilateral group according to their CT finding. Clinical findings on first presentation, the presence of B symptoms, the radiologic findings, overall survival and disease-specific survival were assessed. 55 % of the patients suffered from bilateral manifestation, which was associated with a delayed diagnosis (10 vs. 1.5 months, p < 0.05). B symptoms (67 vs. 0 %) and death of disease (50 vs. 0 %) were observed only in the bilateral group. Nasal NK/T-cell lymphoma was the most frequent diagnosis, followed by diffuse large B-cell lymphoma. Bilateral mucosal manifestation with B symptoms was shown to be common within the rare entity of sinonasal lymphomas and patients with bilateral sinonasal manifestation are at risk for a delayed diagnosis with worse outcome.

Unlabelled: The goal of this study was to evaluate independent risk factors for long-term epistaxis recurrences and their severity. Individual retrospective cohort study-2b level of evidence. The medical information of 603 emergency epistaxis patients was acquired during a former study. This cohort has been contacted 6 years later by conventional mail and asked to answer a specific paper questionnaire. The following parameters were evaluated: recurrent epistaxis episodes, need for a surgical intervention to stop the recurrent bleeding, patient's history for hypertension and diabetes, intake of hemostasis impairing medication now and in the past. One hundred and six (106) patients were included in the study (35.8 % response rate). The mean observation period was 76.58 months. Almost half of the patients (41.5 % = 44/106) reported at least one recurrent epistaxis episode. Patients with exposure to VKA (vitamin K antagonists) showed significantly more frequently a recurrent epistaxis episode. The binary logistic regression confirmed the intake of VKA as an independent and significant risk factor with an odds ratio of 11.6. Every single patient who had to undergo a surgical intervention to stop a recurrent bleeding stated ASA (Acetylsalicylic Acid) intake. We provide evidence that the intake of a vitamin K antagonist is an independent long-term risk factor for recurrent epistaxis episodes. The intake of ASA is a risk factor for the severity of recurrent epistaxis with the increased need for a surgical intervention not only in a short- but also in a long-term perspective., Level of Evidence: This prognostic investigation, designed as a combined prospective and retrospective cohort study, reaches level 2b level of evidence as it includes retrospective aspects.

Objective: Epistaxis is the most frequent rhinologic emergency with a high treatment morbidity. This study assessed the long-term outcome after epistaxis treatment with regard to patient comfort during the treatment, long-term complications and rate of recurrences., Methods: A questionnaire cohort study was performed at the ENT department of the University Hospital Zurich. In April 2014, 363 patients were contacted, who were treated between March 2007 and April 2008 for the reason of epistaxis using a written questionnaire to elucidate the patients' condition after the treatment. The type of treatment, subjective discomfort as well as degree of pain, complications, permanent sequelae and recurrences were assessed., Results: 109 questionnaires were analyzed (response rate of 36%). The overall same-sided recurrence rate after successful treatment during the 6.4-year follow-up was 22%. Discomfort was reported in 48% after cautery, 86% after packing and in 11% after surgery. Strong or very strong pain was perceived in 8% after cautery, 26% after packing and in 0% after surgery alone. Complications consisted of nasal crusting in 15% after cautery and nasal breathing impairment in 24% after packing. Permanent harm was reported in 4% after cautery versus 20% after packing plus surgery., Conclusions: The data confirm the high rate of recurrences despite adequate treatment in the long-term analysis. The rate of post-treatment complications is considerably high with nasal crusting being the main inconvenience. It further shows that patients keep a vivid memory of the treatment even many years later and that packing is extremely uncomfortable to patients., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Particles trapped in the evanescent field of an ultrathin optical fibre interact over very long distances via multiple scattering of the fibre-guided fields. In ultrathin fibres that support higher order modes, these interactions are stronger and exhibit qualitatively new behaviour due to the coupling of different fibre modes, which have different propagation wave-vectors, by the particles. Here, we study one dimensional longitudinal optical binding interactions of chains of 3 μm polystyrene spheres under the influence of the evanescent fields of a two-mode microfibre. The observation of long-range interactions, self-ordering and speed variation of particle chains reveals strong optical binding effects between the particles that can be modelled well by a tritter scattering-matrix approach. The optical forces, optical binding interactions and the velocity of bounded particle chains are calculated using this method. Results show good agreement with finite element numerical simulations. Experimental data and theoretical analysis show that higher order modes in a microfibre offer a promising method to not only obtain stable, multiple particle trapping or faster particle propulsion speeds, but that they also allow for better control over each individual trapped object in particle ensembles near the microfibre surface.

The aim of this systematic review was to synthesize the results of original studies assessing antibiotic efficacy at different time points after initiating treatment in patients with a moderate probability of acute bacterial rhinosinusitis. We searched the Cochrane library for systematic reviews on the efficacy of antibiotic treatment in patients with acute rhinosinusitis (ARS). Only randomized controlled trials (RCTs) that compared treatment of any antibiotic with placebo were included. The synthesis of the results of six RCTs showed a benefit of antibiotic treatment compared to placebo for the rate of improvement after 3 [pooled odds ratio (OR) 2.78 (95 % confidence interval (CI) 1.39-5.58)] and 7 [OR 2.29 (95 % CI 1.19-4.41)] days after initiation in patients with symptoms and signs of ARS lasting for 7 or more days. After 10 days [pooled OR 1.36 (95 % CI 0.66-2.90)], improvement rates did not differ significantly between patients treated with or without antibiotics. Compared to placebo, antibiotic treatment relieves symptoms in a significantly higher proportion of patients within the first days of treatment. Reporting an overall average treatment efficacy may underestimate treatment benefits in patients with a self-limiting illness.

Objective: The aim of this study was to quantitatively assess the role of intraoperative high-field 3-T MRI (3T-iMRI) in improving the gross-total resection (GTR) rate and the extent of resection (EOR) in endoscopic transsphenoidal surgery (TSS) for pituitary adenomas., Methods: Radiological and clinical data from a prospective database were retrospectively analyzed. Volumetric measurements of adenoma volumes pre-, intraoperatively, and 3 months postoperatively were performed in a consecutive series of patients who had undergone endoscopic TSS. The quantitative contribution of 3T-iMRI was measured as a percentage of the additional rate of GTR and of the EOR achieved after 3T-iMRI., Results: The cohort consisted of 50 patients (51 operations) harboring 33 nonfunctioning and 18 functioning pituitary adenomas. Mean adenoma diameter and volume were 21.1 mm (range 5-47 mm) and 5.23 cm(3) (range 0.09-22.14 cm(3)), respectively. According to Knosp's classification, 10 cases were Grade 0; 8, Grade 1; 17, Grade 2; 12, Grade 3; and 4, Grade 4. Gross-total resection was the surgical goal (targeted [t]GTR) in 34 of 51 operations and was initially achieved in 16 (47%) of 34 at 3T-iMRI and in 30 (88%) of 34 cases after further resection. In this subgroup, the EOR increased from 91% at 3T-iMRI to 99% at the 3-month MRI (p < 0.05). In the 17 cases in which subtotal resection (STR) had been planned (tSTR), the EOR increased from 79% to 86% (p < 0.05) and GTR could be achieved in 1 case. Intrasellar remnants were present in 20 of 51 procedures at 3T-iMRI and in only 5 (10%) of 51 procedures after further resection (median volume 0.15 cm(3)). Overall, the use of 3T-iMRI led to further resection in 27 (53%) of 51 procedures and permitted GTR in 15 (56%) of these 27 procedures; thus, the GTR rate in the entire cohort increased from 31% (16 of 51) to 61% (31 of 51) and the EOR increased from 87% to 95% (p < 0.05)., Conclusions: The use of high-definition 3T-iMRI allowed precise visualization and quantification of adenoma remnant volume. It helped to increase GTR and EOR rates in both tGTR and tSTR patient groups. Moreover, it helped to achieve low rates of intrasellar remnants. These data support the use of 3T-iMRI to achieve maximal, safe adenoma resection.

Background: The optimal treatment algorithm for noncutaneous melanomas must yet be established., Objective: To compare systemic treatment-relevant mutational status, metastatic pattern and response to systemic treatment in noncutaneous melanoma., Methods: Retrospective single-center study analyzing 64 noncutaneous melanoma patients treated between January 2006 and September 2013., Results: c-KIT mutations were found exclusively in vulvovaginal melanoma (4/7). Overall status for NRAS and BRAF mutations was low (1/7 and 0/21 detected mutations, respectively). Seven out of 7 vulvovaginal and 6/13 sinonasal melanomas first metastasized to lymph nodes, whereas 18/22 ocular melanomas first metastasized to the liver. Response to systemic treatment in vulvovaginal melanomas was best for imatinib with a disease control rate of 3/3 and overall for ipilimumab with a disease control rate of 3/10. Sorafenib was associated with adverse drug reactions (6/13) and poor results., Conclusion: Noncutaneous melanomas show few tumor-signaling pathway mutations and distinct metastasization patterns. Immunotherapy induces response rates in mucosal melanoma similar to those in cutaneous melanoma., (© 2015 S. Karger AG, Basel.)

Epistaxis is a very common emergency in otorhinolaryngology. Anterior ethmoidal artery ligation using an external approach is one of the surgical options in posterior epistaxis. We present, to the best of our knowledge, the first reported case of an intracerebral abscess after epistaxis treatment with ligation of the anterior ethmoidal artery using an endoscopic-assisted external approach in a 56-year-old patient. The patient presented 4 days postoperatively with an orbital cellulitis. A CT was performed and a frontobasal hypodensity was found. An additional MR tomography the next day showed a lesion suspicious for an intracerebral abscess. Despite intravenous antibiotic therapy, the lesion increased and was successfully treated by the neurosurgeons, with abscess resection over a craniotomy and frontobasal repair using a pedicled periosteal flap. Surgeons have to be aware of this rare but possibly lethal severe complication and should consider early imaging studies, especially if a periorbital cellulitis appears., (2015 BMJ Publishing Group Ltd.)

Collective coherent scattering of laser light induces strong light forces between polarizable point particles. These dipole forces are strongly enhanced in magnitude and distance within the field of an optical waveguide so that at low temperature the particles self-order in strongly bound regular patterns. The stationary configurations typically exhibit super-radiant scattering with strong particle and light confinement. Here we study collective excitations of such self-consistent crystalline particle-light structures as function of particle number and pump strength. Multiple scattering and absorption modify the collective particle-field eigenfrequencies and create eigenmodes of surprisingly complex nature. For larger arrays this often leads to dynamical instabilities and disintegration of the structures even if additional damping is present.

It is key for successful auricular (AUR) cartilage tissue-engineering (TE) to ensure that the engineered cartilage mimics the mechanics of the native tissue. This study provides a spatial map of the mechanical and biochemical properties of human auricular cartilage, thus establishing a benchmark for the evaluation of functional competency in AUR cartilage TE. Stress-relaxation indentation (instantaneous modulus, Ein; maximum stress, σmax; equilibrium modulus, Eeq; relaxation half-life time, t1/2; thickness, h) and biochemical parameters (content of DNA; sulfated-glycosaminoglycan, sGAG; hydroxyproline, HYP; elastin, ELN) of fresh human AUR cartilage were evaluated. Samples were categorized into age groups and according to their harvesting region in the human auricle (for AUR cartilage only). AUR cartilage displayed significantly lower Ein, σmax, Eeq, sGAG content; and significantly higher t1/2, and DNA content than NAS cartilage. Large amounts of ELN were measured in AUR cartilage (>15% ELN content per sample wet mass). No effect of gender was observed for either auricular or nasoseptal samples. For auricular samples, significant differences between age groups for h, sGAG and HYP, and significant regional variations for Ein, σmax, Eeq, t1/2, h, DNA and sGAG were measured. However, only low correlations between mechanical and biochemical parameters were seen (R<0.44). In conclusion, this study established the first comprehensive mechanical and biochemical map of human auricular cartilage. Regional variations in mechanical and biochemical properties were demonstrated in the auricle. This finding highlights the importance of focusing future research on efforts to produce cartilage grafts with spatially tunable mechanics., (Copyright © 2015 Elsevier Ltd. All rights reserved.)