Iatrogenic Cerebrospinal Fluid Leak in Endoscopic Sinus Surgery: Topographical Map and Influence of Skull Base Asymmetry.

BACKGROUND: Iatrogenic cerebrospinal fluid leak (iCSF-L) is a major complication of endonasal surgeries whose occurrence is always a potential adverse event due to anatomical variation/asymmetry of the skull base (SB). The aim of this manuscript is to provide a topographical map of iCSF-L and to investigate the role of SB asymmetry in iCSF-L occurrence. METHODS: In this retrospective study, the location of iCSF-L dural defect was studied and compared to patients affected by spontaneous and post-traumatic CSF-L. Considering only iCSF-L, after having collected the SB asymmetry data, the Keros, Gera, distance of the anterior ethmoidal artery from the SB, frontal sinus pneumatization, and Thailand-Malaysia-Singapore score classifications were compared to a control group of patients. RESULTS: A total of 153 CSF-Ls (103 spontaneous, 37 iatrogenic, and 13 traumatic) were included. A significant association was noted (p < 0.001) between the nature of the CSF-L and the areas involved. Considering iCSF-Ls, only the Gera classification was significantly different (p < 0.05) and the most reliable in predicting the risk of dural transgression (AUC = 0.719). CONCLUSIONS: ICSF-Ls present peculiar regional SB involvement with the cribriform plate, with the ethmoidal roof being the most involved. After having assessed the asymmetry of the SB, the Gera classification was the most reliable one.

Development of a reverse transcriptase digital droplet polymerase chain reaction-based approach for SARS-CoV-2 variant surveillance in wastewater.

An urgent need for effective surveillance strategies arose due to the global emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although vaccines and antivirals are available, concerns persist about the evolution of new variants with potentially increased infectivity, transmissibility, and immune evasion. Therefore, variant monitoring is crucial for public health decision-making. Wastewater-based surveillance has proven to be an effective tool to monitor SARS-CoV-2 variants within populations. Specific SARS-CoV-2 variants are detected and quantified in wastewater in this study using a reverse transcriptase digital droplet polymerase chain reaction (RT-ddPCR) approach. The 11 designed assays were first validated in silico using a substantial dataset of high-quality SARS-CoV-2 genomes to ensure comprehensive variant coverage. The assessment of the sensitivity and specificity with reference material showed the capability of the developed assays to reliably identify target mutations while minimizing false positives and false negatives. The applicability of the assays was evaluated using wastewater samples from a wastewater treatment plant in Ghent, Belgium. The quantification of the specific mutations linked to the variants of concern present in these samples was calculated using these assays based on the detection of single mutations, which confirms their use for real-world variant surveillance. In conclusion, this study provides an adaptable protocol to monitor SARS-CoV-2 variants in wastewater with high sensitivity and specificity. Its potential for broader application in other viral surveillance contexts highlights its added value for rapid response to emerging infectious diseases. PRACTITIONER POINTS: Robust RT-ddPCR methodology for specific SARS-CoV-2 variants of concern detection in wastewater. Rigorous validation that demonstrates high sensitivity and specificity. Demonstration of real-world applicability using wastewater samples. Valuable tool for rapid response to emerging infectious diseases.

Squamous cell carcinoma of the temporal bone: the impact of local control on survival.

BACKGROUND: Squamous cell carcinoma (SCC) of the temporal bone (TB) is a rare pathology originating from the external auditory canal (EAC). Surgery remains the gold standard to achieve local control.Aims/Objectives:The aim of this study was to evaluate overall survival (OS) and disease-free survival (DFS) after surgery of the SCC of EAC. MATERIAL AND METHODS: A retrospective chart review in a tertiary referral center included 26 patients: 23 were operated with lateral temporal bone resection (LTBR, n = 10) and extended temporal bone resection (ETBR, n = 13). The outcomes were OS and DFS. RESULTS: Adjuvant radiotherapy was performed in 91.3% (n = 21/23). Mean age was 60.8 and sex ratio was 1. Median follow-up was 43 months; The 5-years OS was 90% (± 9.5%) and 47.7% (± 12.9%) for stage I/II and III/IV respectively (p = .033). DFS was 67.6% (IC 95%, 51.4%-88.9%) without statistical difference between early advanced stage. Incomplete margins (p = .004) and Stage IV(p < .001) were associated with poorer DFS. Free margins significantly correlated with better OS (HR = 9.8, p = .04). CONCLUSION: En bloc surgical resection with free margins, coupled with postoperative radiotherapy, provides optimal local control. For stage IV tumors, where complete margins are achievable, ETBR is recommended to enhance local control.

Side-door temporoparietal fascia flap: First experience with a novel technique for anterior skull base reconstruction.

BACKGROUND: Modern achievements in transnasal endoscopic skull base (SB) surgery have led to complex resections that render reconstruction a challenge. Temporoparietal fascia flap (TPFF) is a suitable option for SB reconstruction. The side-door TPFF technique for anterior SB reconstruction is described here for the first time in a real-life surgical setting. METHODS: Patients affected by a SB malignancy who underwent cranioendoscopic resection were included. For reconstruction, a multilayer reconstruction technique including side-door TPFF transposition was employed. RESULTS: TPFF transposition was performed in five patients. The TPFF could be easily transposed via a side-door approach. It adequately covered the edges of the defect and supported optimal healing of the surgical site. During follow-up, vitality and integration of the TPFF were assessed endoscopically and radiologically. CONCLUSIONS: The TPFF side-door transposition technique is a valuable option in anterior SB reconstruction that can provide fast and effective healing, especially in patients needing adjuvant radiotherapy.

Nasoseptal flap with extended pedicle dissection based on the maxillary artery: Clinical series of 55 cases.

KEY POINTS: Nasoseptal flap with extended pedicle dissection is a low morbidity and high success rate flap. It is a flap that can be applied to reconstruct a wide range of ipsilateral skull base defects.

Curative high-dose reirradiation for patients with recurrent head and neck adenoid cystic carcinomas: outcomes and analysis of patterns of failure.

BACKGROUND: To investigate the outcomes of patients who underwent curative reirradiation (reRT), with intensity-modulated radiation therapy (IMRT) or proton therapy (PT) for unresectable recurrent or second primary head and neck adenoid cystic carcinoma (HNACC). METHODS: Ten patients, mostly KPS 90%, were reirradiated (3/10 with IMRT and 7/10 with PT) at a median maximum dose to the CTV of 64.2 Gy from July 2011 to November 2021. Locations at the time of reRT were mainly the sinus (4/10) and the salivary glands (including the parotid and submandibular gland, 3/10). CTCAEv5 was used to assess acute and late toxicities. Follow-up was the time between the end of reRT and the date of last news. RESULTS: The median time between the two irradiations was 53.5 months (IQR: 18-84). After a median follow-up of 26 months (range, 12.5-51.8 months), six patients had developed a locoregional recurrence (LR), of which four occurred within the previously irradiated volume. Two and three-year locoregional failure-free survival (LFFS) and overall survival (OS) were 55.6% [95%CI: 31-99.7%], and 41% [18.5-94%] and 66.7% [42-100%] and 44.4% [21.4-92.3%], respectively. LFFS and OS were significantly better in the subgroup of sinus tumors (p = .013) and the subgroup of patients re-irradiated more than two years after the first course of irradiation (p = .01). Seven patients had impairments before the start of reRT, including hearing impairment (3/10) and facial nerve impairment (3/10). The most severe late toxicities were brain necrosis (2/10), osteoradionecrosis (1/10) and vision decreased (1/10). CONCLUSION: Curative reRT for HNACC is possible for selected cases, but the LR rate in the irradiated field and the risk of severe toxicity remain high. Improved selection criteria and more carefully defined target volumes may improve outcome in these patients. A further study including larger cohort of patients would be useful to confirm these results.

The "Gift Wrap" Technique - A Method that Simplifies the Placement of Fascia Lata in the Reconstruction of the Skull Base Following Endoscopic Endonasal Surgery: A Technical Note.

BACKGROUND: With the advancement of endoscopic endonasal surgery in the treatment of anterior skull base (ASB) pathologies, extended, watertight reconstructions are needed to prevent cerebrospinal fluid (CSF) leakage. This often involves the use of multilayers closure, with free fascia lata (FL) graft frequently used as an in- and/or outlay. However, positioning the FL properly can be challenging and time-consuming, particularly on wider defects. In this technical note, we present an easier and faster way to position FL using a silicone sheet. METHODS: FL graft is harvested using a standard technique. The required dimensions are evaluated depending on the extent of the dural defect taking in consideration that FL graft should exceed the edges of the dural defect especially laterally. It is then wrapped around a semi rigid pattern (Silastic sheet) and secured with several monofilament 5/0 sutures. The "package" is transferred through the endonasal corridor to the defect. The sutures are divided and taken out; the fascia is unfolded, and its edges are inserted into the subdural space without any twisting or folding of the flap. Finally, the silicone sheet is withdrawn from the nasal cavity, leaving the FL well-stretched in perfect position. RESULTS: We illustrate this technique in the management of a large anterior skull base chondrosarcoma, which necessitated significant bone and dural resection. CONCLUSIONS: The "Gift wrap" technique offers an alternative approach for positioning the FL, which is less time-consuming compared to the traditional technique. Moreover, it enables improved placement of the FL, enhancing its efficacy.

An Endoscopic Procedure for the Simultaneous Treatment of both Otosclerosis and Malleus Fixation.

To report the case of the simultaneous treatment of otosclerosis and malleus fixation through an entirely endoscopic transcanal approach. A targeted transcanalar epitympanotomy with annular bony ridge conservation was planned preoperatively, with 3D CT localization of the fixed part of the malleus head. The upper part of the malleus head and the superior ossified ligament of the malleus were drilled. A 0.6 mm stapedotomy was performed and a piston inserted. The patient's recovery was uneventful, with closure of the air-bone gap on her postoperative audiogram, associated with an overclosure in 500Hz, 1kHz, 2 kHz and 4 kHz. Laryngoscope, 2023.

Septal Nasopharyngeal "Kite Flap" for Long-Term Patency of Petrous Apex Cholesterol Granuloma.

Medial petrous apex cholesterol granuloma is a benign lesion which treatment is generally based on a trans-nasal marsupialization. When the artificial ostium is created, it is usually kept open with local flaps, like the septal nasopharyngeal "kite flap", a reliable local vascularized flap. Laryngoscope, 2023.

Local budesonide therapy in the management of persistent hyposmia in suspected non-severe COVID-19 patients: Results of a randomized controlled trial.

OBJECTIVES: Consequences of COVID-19 on olfactory functions remained unclear during the pandemic. We assessed the efficacy of local budesonide in addition to olfactory rehabilitation when managing non-severe COVID-19 patients with persistent hyposmia. METHODS: A multicentric, randomized, superiority trial was conducted (ClinicalTrials.gov NCT04361474). The experimental group (EG) received budesonide and physiological saline nasal irrigations administered via three syringes of 20 ml in each nasal cavity in the morning and evening for 30 days. The control group (CG) received a similar protocol without budesonide. Patients were included if they were >18 years old, with a SARS-CoV-2 infection and presenting an isolated hyposmia persisting 30 days after symptom onset. The primary endpoint was the percentage of patients with improvement of more than two points on the ODORATEST score after 30 days of treatment. RESULTS: In total, 123 patients were included and randomized (EG: 62 vs CG: 61). Two patients from the EG met the primary endpoint with no statistical difference between the two groups (P = 0.5). CONCLUSION: To our knowledge, this is the first study evaluating local budesonide for COVID-19 related hyposmia treatment even though previous trials were performed with other local corticosteroids. Local budesonide efficacy was not demonstrated for persistent hyposmia related to COVID-19.

Extended sphenoidotomy combined with transpterygoid approach for sphenoidal sinus inverted papilloma.

PURPOSE: Inverted papilloma of the sphenoid sinus (IPSS) is a rare tumor with debated surgical management due to its proximity to vital structures. The aim of this manuscript is to highlight the role of a transpterygoid approach (TPA) and pedicle-orientated strategy in case of involvement of critical structures in IPSS and compare it with data from the literature. METHODS: Patients with primary IPSS between January 2000 and June 2021 were included. Pre-operative CT/MRI were analyzed to classify the pneumatization of the SS and predict the insertion point of the inverted papilloma. All patients were treated with a trans-sphenoidal approach which was combined with a TPA in case of lateral insertion point. A systematic search was also performed to summarize the available literature. RESULTS: Twenty-two patients were treated for IPSS. By CT, the SS was categorized with type III pneumatization in 72.8% of cases. Eleven patients (50%) were treated with a TPA with a statistical association with the insertion point on the SS lateral wall (p = 0.01), rather than a SS pneumatization (p = 0.63). The overall success was 95.5% after a mean follow-up of 35.9 months. For the literature, 26 publications were included on 97 patients and described a trans-sphenoidal approach with a success rate of 84.6% after a mean follow-up of 24.5 months. CONCLUSION: IPSS is generally treated with a sphenoidotomy approach, although in selected cases, a TPA should be preferred to expose the whole SS lateral wall though allowing a complete pedicled oriented resection of the tumor.

Infliximab for the Treatment of Inflammatory Labyrinthitis: A Retrospective Cohort Study.

Inflammatory labyrinthitis is defined as a fluctuant vestibulo-cochlear syndrome associated with an impairment of the blood-labyrinthine barrier (BLB) on delayed FLAIR MRI sequences. Systemic and intratympanic corticosteroids are the gold standard treatment but their effect is frequently insufficient. The objective is here to determine whether infliximab could be of value in the treatment of bilateral inflammatory labyrinthitis. A retrospective monocentric study was conducted between January 2013 and December 2021. All patients included in the study were affected with a bilateral vestibulo-cochlear syndrome associated with bilateral blood-labyrinthine barrier impairment. Patients were administered infliximab at the dose of 5 mg/kg every 6 weeks for 6 months. Audiometry, MRI with delayed FLAIR sequences on the labyrinth, and corticosteroid doses still required were assessed both before and after treatment with infliximab was completed. Pure-tone average (PTA) was the primary outcome. The secondary outcomes were the speech recognition threshold (SRT), the Dizziness Handicap Inventory (DHI) score, and the corticosteroid (CS) dose. A total of nine patients including five men and four women were enrolled in the study. Thirteen ears were analyzed. After a 6-month period of treatment, the mean PTA (54 ± 24 db versus 66 ± 22 db; p = 0.027), SRT (54 ± 37 db versus 66 ± 32 db; p = 0.041) and DHI score (27 ± 15 versus 9 ± 2; p = 0.032) significantly improved. After the 6-month treatment period, the mean CS dose decreased from 38 ± 33 to 6 ± 5 mg/day (p = 0.003). We conclude that infliximab substantially improves the vestibulo-cochlear function in patients with bilateral inflammatory labyrinthitis and could be of value in corticosteroid-dependent cases.

Expression, Prognostic Value and Correlation with HPV Status of Hypoxia-Induced Markers in Sinonasal Squamous Cell Carcinoma.

(1) Background: In head and neck squamous cell carcinoma, tumor hypoxia has been associated with radio/chemoresistance and poor prognosis, whereas human papillomavirus (HPV)-positive status has a positive impact on treatment response and survival outcomes. The aim of this study was to evaluate the expression and the potential prognostic value of hypoxia-induced endogenous markers in patients treated for squamous cell carcinoma of the nasal cavity and paranasal sinuses (SNSCC), and their correlation with HPV status. (2) Methods: In this monocentric study, patients treated in a curative intent for a SNSCC were screened retrospectively. Protein expression of CA-IX, GLUT-1, VEGF, VEGF-R1, and HIF-1α was determined by immunohistochemical staining, scored, and then correlated with overall survival (OS) and locoregional recurrence free survival (LRRFS). HPV status was assessed and correlated with hypoxic markers. (3) Results: 40 patients were included. A strong expression of CA-IX, GLUT-1, VEGF, and VEGF-R1 was detected in 30%, 32.5%, 50%, and 37.5% of cases, respectively. HIF-1α was detected in 27.5% of cases. High CA-IX expression was associated in univariate analysis with poor OS (p = 0.035), but there was no significant association between GLUT-1, VEGF, VEGF-R1, and HIF-1α expression, and OS/LRRFS. There was no correlation found between HPV status and hypoxia-induced endogenous markers (all p > 0.05). (4) Conclusions: This study provides data on the expression of hypoxia-induced endogenous markers in patients treated for SNSCC and underlines the potential role of CA-IX as a prognostic biomarker for SNSCC.

Proton therapy and/or helical tomotherapy for locally advanced sinonasal skull base adenoid cystic carcinoma: Focus on experience of the Institut Curie and review of literature.

BACKGROUND: Sinonasal adenoid cystic carcinomas (SNACC) have high propensity for skull base (SB) infiltration. Unresectability or incomplete surgical resection in such cases make radiotherapy treatment paramount. Curative dose escalation is challenging because of adjacent organs at risk, especially in locally advanced cases. METHODS: Eighteen patients that had locally advanced SB SNACC with unresectable or incomplete surgical resection treated by proton therapy and/or helical tomotherapy at Institut Curie between 3/2010 and 8/2020 were retrospectively included. RESULTS: After median follow-up of 52 months, 5-year OS, LRRFS, DMFS, DFS rates were, respectively, 47% (95%CI: 26-83), 50% (95%CI: 36-88), 39% (95%CI: 26-81), 33% (95%CI: 22-73). One patient had grade 4 late optic nerve disorder. Eight patients had grade 3 late toxicity including mainly hearing impairments. CONCLUSION: Proton therapy and helical tomotherapy are effective and safe methods for curative dose escalation of locally advanced SB SNACC, which are a poor prognosis subgroup. Available literature suggests carbon-ion therapy could be an efficient alternative.

Development of a Droplet Digital PCR to Monitor SARS-CoV-2 Omicron Variant BA.2 in Wastewater Samples.

Wastewater-based surveillance can be used as a complementary method to other SARS-CoV-2 surveillance systems. It allows the emergence and spread of infections and SARS-CoV-2 variants to be monitored in time and place. This study presents an RT-ddPCR method that targets the T19I amino acid mutation in the spike protein of the SARS-CoV-2 genomes, which is specific to the BA.2 variant (omicron). The T19I assay was evaluated both in silico and in vitro for its inclusivity, sensitivity, and specificity. Moreover, wastewater samples were used as a proof of concept to monitor and quantify the emergence of the BA.2 variant from January until May 2022 in the Brussels-Capital Region which covers a population of more than 1.2 million inhabitants. The in silico analysis showed that more than 99% of the BA.2 genomes could be characterized using the T19I assay. Subsequently, the sensitivity and specificity of the T19I assay were successfully experimentally evaluated. Thanks to our specific method design, the positive signal from the mutant probe and wild-type probe of the T19I assay was measured and the proportion of genomes with the T19I mutation, characteristic of the BA.2 mutant, compared to the entire SARS-CoV-2 population was calculated. The applicability of the proposed RT-ddPCR method was evaluated to monitor and quantify the emergence of the BA.2 variant over time. To validate this assay as a proof of concept, the measurement of the proportion of a specific circulating variant with genomes containing the T19I mutation in comparison to the total viral population was carried out in wastewater samples from wastewater treatment plants in the Brussels-Capital Region in the winter and spring of 2022. This emergence and proportional increase in BA.2 genomes correspond to what was observed in the surveillance using respiratory samples; however, the emergence was observed slightly earlier, which suggests that wastewater sampling could be an early warning system and could be an interesting alternative to extensive human testing.

Otosclerosis: audiometric results and quality of life after stapedectomy with interposition or CO2 laser-calibrated stapedotomy without interposition.

BACKGROUND: The surgical treatment of otosclerosis consists of the replacement of the stapes using a piston. AIMS/OBJECTIVES: The objective of this study is to assess the audiometric results and quality of life (QOL) of patients who underwent surgery for otosclerosis by stapedectomy with fascia interposition (STIP) or by stapedotomy using CO2 laser (SLaser) without fascia interposition. MATERIAL AND METHODS: Ninety-one patients operated on for otosclerosis by STIP (40 patients) and by SLaser (51 patients) were included. Audiometric results were graphically displayed using the Amsterdam Hearing Evaluation Plot and were compared to the Common Otology Database (COD) comprising 660 patients. The patients' QOL was assessed with an otological validated survey. The significance level was p < .05. RESULTS: There was no significant difference in hearing improvement between SLaser and STIP-operated patients. There was no significant difference between our results and that of COD. QOL was significantly improved (+3.5/10) postoperatively for both STIP and SLaser in both social and professional fields. CONCLUSIONS AND SIGNIFICANCE: By comparing QOL and hearing gain of STIP and SLaser, our results suggest that both surgical techniques are a safe and successful treatment for otosclerotic stapes fixation. Further studies aiming at comparing larger series may confirm and refine these results.

Survival outcomes, prognostic factors, and effect of adjuvant radiotherapy and prophylactic neck dissection in salivary acinic cell carcinoma: A prospective multicenter REFCOR study of 187 patients.

BACKGROUND: Acinic cell carcinomas (AciCCs) are malignant tumours of the salivary glands. The aim of this work was to analyse data from the national REFCOR multicenter cohort (i) to investigate the prognostic factors influencing survival outcomes in AciCC, (ii) to assess the impact on survival of postoperative radiotherapy (RT) in patients treated for AciCC without high-grade transformation and (iii) to explore the prognostic impact of prophylactic neck dissection (ND) in patients treated for AciCC of the major salivary glands. PATIENTS AND METHODS: Data from all the patients treated for salivary AciCC between 2009 and 2020 were extracted from the REFCOR database. Survival outcomes and prognostic factors influencing Disease-Free Survival (DFS) and Overall Survival (OS) were investigated using univariate and multivariate analyses. Propensity score matching was used to assess the impact of postoperative RT and prophylactic ND on DFS. RESULTS: A total of 187 patients were included. After a median follow-up of 53 months, their 5-year OS and DFS rates were 92.8% and 76.2%, respectively. In multivariate analysis, male sex, older age, higher T and N status, and high grade were independently associated with a worse DFS. In the subpopulation analysed after propensity score matching, patients with cN0 AciCC without high-grade transformation who were treated by surgery and RT did not have an improved DFS compared to patients who were treated by surgery alone (hazard ratio (HR) = 0.87, p = 0.8). Factors associated with nodal invasion were T3-T4 status and intermediate/high histological grade. After propensity score matching, prophylactic ND was associated with a trend toward a better DFS (HR = 0.46, p = 0.16). CONCLUSIONS: These results suggest that (i) long-term follow-up (>5 years) should be considered in patients with AciCC, (ii) treatment by surgery alone could be an option in selected cN0 patients with AciCC without high-grade transformation and (iii) prophylactic ND may be considered preferentially in patients with T3-T4 status and/or intermediate/high histological grade.

Extended Endoscopic Pre-Lacrimal Medial Maxillectomy To the Anterior Maxillary Sinus Wall.

Endoscopic pre-lacrimal medial maxillectomy involving the resection of the antero-medial maxillary sinus wall is a novel expanded procedure that allows the management of far lateral or antero-medial benign pathologies of the maxillary sinus, without increasing peri-operative morbidity. Laryngoscope, 133:2874-2877, 2023.

Long-Term Outcomes in Head and Neck Paragangliomas Managed with Intensity-Modulated Radiotherapy.

OBJECTIVES: Head & Neck Paragangliomas have been historically relying on surgery mostly, with worsened quality of life and major sequelae. Conventional external radiation therapy seems to offer an equivalent control rate with a low toxicity profile. The aim of this study was to assess the safety and efficiency of intensity-modulated radiation therapy in Head & Neck paragangliomas. METHODS: This is a retrospective monocentric study conducted in a referral center, including all patients treated with IMRT, whether as an exclusive or post-operative treatment for a tympanic and jugular, carotid, or vagal paraganglioma. Data collection was performed through the manuscript and computerized medical files, including consultation, operative, imaging, pathological analyses, delineation, and treatment planning reports. Success was defined as the complete or partial regression or stabilization without progression, or relapse in accordance with the RECIST criteria. Acute toxicities and long-term sequelae were assessed. RESULTS: Our cohort included 39 patients included between 2011 and 2021: 18 patients treated for a TJ PG (45.9%), 11 patients for a carotid PG (28.4%), and 9 for a vagal PG (23.1%). Twenty-nine patients had IMRT as an exclusive treatment (74.4%), whereas 10 patients had a post-operative complementary treatment (25.6%). Median follow-up in our cohort was 2318 days (average = 2200 days, 237-5690, sd = 1281.9). Among 39 patients, 37 were successfully controlled with IMRT (94.8%), and the toxicity profile was low without any major toxicity. CONCLUSION: IMRT seems an ideal treatment, whether exclusive or post-operative for Head & Neck paragangliomas. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:607-614, 2023.