Peri-operative management of endoscopic endonasal cerebrospinal fluid leak repair: an international survey.

PURPOSE: Peri-operative management of nasal cerebrospinal fluid (CSF) leaks is not consensual due to limited evidence. The main aim of this study was to identify key factors in peri-operative management of endoscopic endonasal CSF leak repair among international experts. METHODS: A 60-item survey questionnaire collected opinions of members of international learned societies of ENT surgeons and neurosurgeons on nasal packing, post-operative instructions, antibiotic prophylaxis, and CSF volume depletion. RESULTS: The survey had 153 respondents (124 otorhinolaryngologists and 29 neurosurgeons). A resting position was recommended by 85% (130/151) of respondents for extended CSF leak of the anterior skull base, mainly in Fowler's position (72% (110/153)). Nasal packing was used by 85% (130/153) of respondents; 33.3% (51/153) used it to stabilize the reconstruction, and 22.2% (34/153) to prevent bleeding. It was usually removed after 48 h in 44.4% of cases (68/153). CSF depletion was considered by 47.1% (72/153) of respondents in case of CSF leak recurrence and by 34.6% (53/153) in cases of increased intracranial pressure. All respondents gave specific postoperative instructions to patients including driving, running, swimming, diving restrictions and flighting restrictions. In subgroup analysis, ENT surgeons more often recommended a resting position than neurosurgeons (71% vs. 37.9% ; p = 0.0008) and prescribed more antibiotics (82.3% vs. 21.4% ; p < 0.0001). CONCLUSION: Although postoperative management after CSF closure remains challenging and not codified, this international survey revealed some points of consensus concerning resting position and restriction of post-operative activities. Prospective clinical studies must be undertaken to evaluate their efficiency.

How to perform prespecified subgroup analyses when using propensity score methods in the case of imbalanced subgroups.

BACKGROUND: Looking for treatment-by-subset interaction on a right-censored outcome based on observational data using propensity-score (PS) modeling is of interest. However, there are still issues regarding its implementation, notably when the subsets are very imbalanced in terms of prognostic features and treatment prevalence. METHODS: We conducted a simulation study to compare two main PS estimation strategies, performed either once on the whole sample ("across subset") or in each subset separately ("within subsets"). Several PS models and estimands are also investigated. We then illustrated those approaches on the motivating example, namely, evaluating the benefits of facial nerve resection in patients with parotid cancer in contact with the nerve, according to pretreatment facial palsy. RESULTS: Our simulation study demonstrated that both strategies provide close results in terms of bias and variance of the estimated treatment effect, with a slight advantage for the "across subsets" strategy in very small samples, provided that interaction terms between the subset variable and other covariates influencing the choice of treatment are incorporated. PS matching without replacement resulted in biased estimates and should be avoided in the case of very imbalanced subsets. CONCLUSIONS: When assessing heterogeneity in the treatment effect in small samples, the "across subsets" strategy of PS estimation is preferred. Then, either a PS matching with replacement or a weighting method must be used to estimate the average treatment effect in the treated or in the overlap population. In contrast, PS matching without replacement should be avoided in this setting.

Otitis media in severe asthma associated with chronic rhinosinusitis with nasal polyps: a new therapeutic target for biologics.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNPs) is associated with otitis media with effusion (OME) in about 25% of cases. The objective of this study was to assess the clinical efficacy of the 4 biologic agents currently available in France for severe asthma (omalizumab, mepolizumab, benralizumab and dupilumab) in 17 patients followed for both asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) and presenting otitis media with effusion (OME) on otoscopy. Methods: It was a multicenter retrospective study performed in 4 academic ENT and respiratory departments in Paris, France, with assessment of the clinical evolution of 17 patients with severe eosinophilic asthma and with chronic refractory OME and CRSwNPs treated by biologic agents. Global evaluation of treatment effectiveness (GETE) on asthma, CRSwNP and OME was classified on a 5-point scale as 1, excellent; 2, good; 3, moderate; 4, poor; or 5, symptoms worsening. Response was defined as an excellent/good score (1 or 2). Results: 17 patients were prescribed a total of 30 biologics. The evolution of OME did not follow that of asthma and CRSwNPs in 15 (88%) and 12 (70%) cases, respectively. Concerning OME, 19/30 (63%) patients were non-responders. Among the 10 patients who successively received ≥ 2 biologic agents, the OME response differed, depending on the considered agent Dupilumab had the highest response rate. Conclusions: Resistant OME, associated with asthma and chronic rhinosinusitis with nasal polyps, can present a disconnected evolution under biologics. CRSwNP-associated OME requires a specific evaluation to define the best treatment.

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.

Venous sinus stenting after repair of skull base spontaneous cerebrospinal fluid leaks: A single-center retrospective cohort series with case-control analysis.

BACKGROUND: Management of idiopathic intracranial hypertension (IIH) is recommended after surgical repair of spontaneous cerebrospinal fluid leaks (sCSF-leaks) of the skull base for prevention of recurrence. PURPOSE: To assess the feasibility of venous sinus stenting, a treatment commonly used for the treatment of IIH associated with intracranial venous sinus stenosis (VSS), after sCSF-leaks closure. MATERIALS AND METHODS: A single-center cohort series of consecutive patients who underwent sCSF-leak closure was retrospectively analyzed. Stenting was considered either for leak recurrence or in prophylactic manner after repair in patients with VSS as confirmed by cerebral venous imaging. Leak recurrence, need for new repair or adjunctive treatment of IIH, meningitis, and stenting complications were determined at the last follow-up. Cases who had prophylactic stenting were compared to historical controls before stenting option. RESULTS: Twenty-two patients had intracranial venous stenting after sCSF-leak closure. Their median age was 58 years (Q1=45; Q3=68), BMI=31 kg.m-2 (Q1=27; Q3=36), and female rate=85%. The overall rate of successful repair after stenting was 95% (95% CI = 87-100%) at a median follow-up of 2.4 years (Q1=1.2; Q3=3.3). Adjunctive treatment for IIH was needed in 4 patients (4/22, 18%) including 2 patients without leak recurrence. No meningitis, permanent morbidity or mortality was observed after stenting. Compared to 18 controls, cases had significantly less recurrence (P = 0.03), and a trend for less adjunctive treatment for IIH (P = 0.06). CONCLUSIONS: Our study suggests that stenting might be a valid option for prevention of sCSF-leak recurrences after repair in patients with intracranial venous sinus stenosis.

Different repartition of the cryptic species of black aspergilli according to the anatomical sites in human infections, in a French University hospital.

Black aspergilli of the section Nigri are rarely differentiated at the species level when originating from human specimens. We wondered whether some cryptic species could be more frequently observed in some clinical entities. We analyzed the 198 black isolates consecutively collected from the external ear canal (EEC; n = 66), respiratory specimens (n = 99), and environment (n = 33). DNA was extracted and species identification was performed upon the partial calmodulin gene. We identified by decreasing frequency: Aspergillus welwitschiae (35.3%), Aspergillus tubingensis (34.3%), Aspergillus niger (17.2%), Aspergillus luchuensis (4%), Aspergillus aff. welwitschiae (3%), Aspergillus neoniger (2%), Aspergillus piperis (1.5%), Aspergillus japonicus (1.0%), Aspergillus vadensis (0.5%), and two Aspergillus tubingensis clade (1%). The distribution of the three main cryptic species was different between EEC and respiratory samples (P < 0.001) but not different between respiratory and environment samples (P = 0.264). Aspergillus welwitschiae was more often associated with EEC (54.5%), whereas A. tubingensis and A. niger were predominant in respiratory samples (39.4 and 26.3%, respectively). Among the 99 respiratory isolates, only 10 were deemed responsible for probable invasive aspergillosis, of which six were mixed with other pathogenic moulds. This study shows the interest to pursue the identification of clinical isolates in the Aspergillus section Nigri to unravel some specific associations with clinical entities. The association of A. welwitschiae with otomycosis suggests a better fitness to infect/colonize the ear canal. Also, members of the Aspergillus section Nigri alone are rarely responsible for invasive aspergillosis. LAY SUMMARY: We analyzed 198 black aspergilli isolates collected from different samples type to determine their species identification. We observe a different distribution of species between ear canal and respiratory samples (P < 0.001), suggesting a better fitness of A. welwitschiae to infect the ear canal.

Functional treatment of temporal bone chondroblastoma: retrospective analysis of 3 cases.

PURPOSE: To describe and analyse functional treatment of temporal bone chondroblastoma (TBCh). METHODS: From January 2000 to June 2019, at the Department of Otorhinolaryngology, Hôpital Lariboisière, Paris, France, patients with TBCh were enrolled in this study. All cases routinely performed pre-operatory work-up including evaluation of performance status, audio-vestibular function test, ear endoscopy, contrasted CT scan and MRI of head and neck region; in one case we also performed an angio-CT scan. All patients underwent resection of the tumour with a "functional" approach RESULTS: Three male patients (mean age 46,6 years)-two primary tumours and one recurrence-were treated. In all three cases the tumour invaded the middle ear with a variable degree of hearing loss and infiltration of temporal bone structures. All surgeries were performed with a microscopic approach associated with open/endoscopic approach when necessary. Inner ear and facial nerve were speared in all cases and the TMJ was partially resected in 2 cases due to its moderate involvement. At present, after a mean follow-up of 103 months (range 40-225 months), only one case presented recurrence which has been successfully treated with radiotherapy. CONCLUSIONS: Our results of treatment suggest that functional surgery can be relevant in the management of TBCh since it is focused on both treatment of this pathology and maintenance of a good quality of life.

MRI contribution for the detection of endolymphatic hydrops in patients with superior canal dehiscence syndrome.

PURPOSE: Patients with superior semicircular canal dehiscence syndrome, which can only be treated by surgery, present cochleo-vestibular symptoms related to a third-mobile window but also endolymphatic hydrops. Since cVEMP and oVEMP are disturbed by the presence of the dehiscence, the aim of the study is to assess the value of MRI for the diagnosis of endolymphatic hydrops in patients with superior semicircular canal dehiscence syndrome in comparison with cVEMP and oVEMP. METHODS: In this retrospective cohort study we enrolled 33 ears in 24 patients with superior semicircular dehiscence syndrome who underwent a 4-h delayed intravenous Gd-enhanced 3D-FLAIR MRI and pure tone audiometry, cVEMP and oVEMP. For each patient MRI images were evaluated by two radiologists who used a compartmental endolymphatic hydrops grading system in comparison with cVEMP and oVEMP. RESULTS: Endolymphatic hydrops was found on MRI in 9 out of 33 SCDS ears (27.3%). We found no significant correlation between the presence of endolymphatic hydrops on MRI and cVEMP and oVEMP (p = 0.36 and p = 0.7, respectively). However, there was a significant correlation between the presence of endolymphatic hydrops on MRI and the degree of sensorineural hearing loss, Air Conduction-Pure Tone Average level (p = 0.012) and Bone Conduction-Pure Tone Average level (p = 0.09), respectively. CONCLUSION: We demonstrated that EH might be observed in 27.3% of superior semicircular dehiscence syndrome ears. The role of inner ear MRI is important to detect endolymphatic hydrops, since cVEMP and oVEMP are disturbed by the presence of the dehiscence, because these patients could benefit from a medical treatment. LEVEL OF EVIDENCE: Level 3.

Aspergillus flavus malignant external otitis in a diabetic patient: case report and literature review.

PURPOSE: Malignant external otitis is an aggressive and potentially life-threatening infection. This rare disorder is typically caused by Pseudomonas aeruginosa and affects almost exclusively elderly diabetic patients. However, fungal malignant external otitis have been identified, especially in immunocompromised hosts. METHODS: We report a rare case of invasive malignant external otitis caused by Aspergillus flavus in a diabetic patient without other underlying immunosuppression. A review of Aspergillus spp. malignant external otitis since voriconazole became the first line for invasive aspergillosis was performed. RESULTS: A 72-year-old man with diabetes mellitus developed invasive malignant external otitis with a vascular involvement. The patient was treated with empiric courses of antibiotics until a fungal infection was diagnosed. Proven Apsergillus infection was based on histopathological examination and isolation of A. flavus from culture of osteo-meningeal biopsies. Despite optimal antimicrobial therapy with voriconazole, the patient presented with cerebral infarction in the setting of an angioinvasive fungal infection leading to a fatal outcome. From a review of the literature, we found 39 previously published cases of proven Aspergillus spp. malignant external otitis treated with new triazoles. CONCLUSION: Given our experience and the literature review, a fungal etiology should be considered early in the course of malignant external otitis unresponsive to a conventional broad spectrum antibiotic therapy, with the need for a tissue biopsy to confirm the diagnosis.

Evaluating the prognostic potential of the Ki67 proliferation index and tumour-infiltrating lymphocytes in olfactory neuroblastoma.

AIMS: Olfactory neuroblastomas (ONBs) are rare malignant tumours that arise in the nasal vault. To date, the Hyams grade remains the only widely used histological grading system. However, it is based only on morphological criteria, and has not been updated since 1988. The objective of this study was to explore the prognostic potential of the Ki67 proliferation index (PI) and tumour-infiltrating lymphocytes (TILs) in ONB. METHODS AND RESULTS: A retrospective study was conducted on a bicentric series of 45 cases. The Ki67 PI was determined by counting at least 1000 nuclei on whole slides. TILs were evaluated with CD20, CD4 and CD8 immunohistochemical markers on whole slides. In this series, Hyams grades I, II, III and IV accounted for 13.4%, 44.4%, 20% and 22.2% of all cases, respectively. The Ki67 PI ranged from 1 to 93; the Ki67 PI was significantly higher in Hyams grade III-IV ONBs than in Hyams grade I-II ONBs (P < 0.0001). A Ki67 PI of ≥25 was associated with poorer survival (P = 0.02). TILs were present in both stromal and intratumoral compartments, but were located predominantly in the stromal component of the tumour. The numbers of intratumoral CD8+ cells/mm2 and CD4+ cells/mm2 were greater in high-grade ONBs than in low-grade ONBs (P = 0.0015 and P = 0.043, respectively). The numbers of T cells/mm2 and B cells/mm2 were not associated with survival, but a CD4/CD8 ratio of >2 was significantly associated with shorter survival (P = 0.04). CONCLUSION: Our findings suggest that the Ki67 PI and TILs could be used as prognostic markers, as a potential alternative to the Hyams grade.

Establishment of a nasopharyngeal carcinoma cell line capable of undergoing lytic Epstein-Barr virus reactivation.

Epstein-Barr virus (EBV) infects more than 90% of the adult human population. Undifferentiated nasopharyngeal carcinoma (NPC) is common in Southeast Asia, with a particularly high incidence among southern Chinese. The EBV genome can be detected in practically all cancer cells in undifferentiated NPC. The role of EBV in pathogenesis of undifferentiated NPC remains elusive. NPC cell lines are known to be difficult to establish in culture. The EBV+ve NPC cell lines, even if established in culture, rapidly lost their EBV episomes upon prolonged propagation. At present, the C666-1 NPC cell line, which is defective in lytic EBV reactivation, is the only EBV+ve NPC cell line available for NPC and EBV research. The need to establish new and representative NPC cell lines is eminent for NPC and EBV research. In this study, we report the use of the Rho-associated kinase inhibitor (Y-27632) has facilitated the establishment of a new EBV+ve NPC cell line from an earlier established NPC xenograft, C17. The C17 cell line was tumorigenic in immune-deficient mice (NOD/SCID). It retained the EBV episomes and could be induced to undergo productive lytic reactivation of EBV to generate infectious virus particles. The C17 cell line represents a new investigative tool for NPC and EBV studies. The ability of C17 to undergo lytic reactivation is unique and opens up the opportunity to examine regulation of latent and lytic infection of EBV and their contributions to NPC pathogenesis.

Toll-like receptor 3 stimulation triggers metabolic reprogramming in pharyngeal cancer cell line through Myc, MAPK, and HIF.

Toll-like receptor 3 (TLR3) has a dual role in cancer; its activation can trigger apoptosis as well as stimulate cancer cell survival, proliferation, and progression. We have shown here that TLR3 activation can induce metabolic reprogramming in a pharyngeal cancer cell line, leading to increased aerobic glycolysis, cell migration, elevated levels of reactive oxidative species (ROS), and decreased anti-oxidative response. Key proteins in these signaling pathways are heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), pyruvate kinase M2 (PKM2), and CD44 variants, which were over-expressed after TLR3 stimulation. TLR3 activation also induced upregulation of different genes involved in cancer progression (VEGF, MMP9, uPAR) and enzymes involved in glycolytic pathway. Most of the observed effects were Myc-dependent; however, some of them were also connected with MAPK and HIF signaling pathways. Since TLR3 agonists are being investigated as potential novel cancer therapy adjuvants and apoptosis inducers, alone or in combination with other therapeutic options, data presented here suggest extreme caution before their introduction into clinical practice. The fact that TLR3 ligands [poly(I:C) and poly(A:U)] can also aid cancer survival and progression, through induction of metabolic reprogramming, emphasizes the need to investigate this particular topic. Our data suggest that the combination of TLR3 ligands with Myc or MAPK inhibitors may be a way to neutralize their undesirable effects while enhancing their anti-tumor effect. © 2016 Wiley Periodicals, Inc.

How I do it. The pedicled temporoparietal fascia flap for skull base reconstruction after endonasal endoscopic approaches.

BACKGROUND: Endoscopic endonasal approaches (EEA) are an alternative for removing challenging nasopharyngeal or skull base lesions. In some cases, a nasoseptal flap (NSF) is not always available and such complex procedures may lead to carotid arteries exposition and/or dura mater (DM) wide opening. Meticulous carotid coverage and DM reconstruction are crucial for preventing early and delayed complications. METHOD: We propose a step-by-step description of the pedicled temporoparietal fascia flap (TPFF) technique, with a focus on its pitfalls, advantages and limits. CONCLUSION: The TPFF is a reliable flap for skull base reconstruction when other pedicled flaps are not available. KEY POINTS: 1. Reliable flap even for irradiated patients 2. CT angiography with 3D reconstruction as pre-operative imaging 3. Doppler ultrasound probe to draw the artery's trajectory on skin 4. TPFF elevation concomitantly to the endoscopic procedure 5. Hemicoronal incision sufficient to harvest the TPFF 6. Superficial dissection in a plane just beneath the hair follicles 7. Dissection plane deep to the fad pad to preserve the frontal branch of the facial nerve 8. Surgical corridor wide enough to avoid any compression of the pedicle 9. Double visualization to avoid any twist and Doppler control of the STA patency 10. Close follow-up, toilet in clinics.

Value of systematic analysis of the olfactory cleft in case of cerebrospinal rhinorrhea: incidence of olfactory arachnoid dilatation.

To report on the presence of olfactory arachnoid dilatations (OAD), a previously undescribed radiologic feature of spontaneous cerebrospinal fluid (CSF) rhinorrhea originating from the cribriform plate of the ethmoid bone. The medical records of all patients treated between 2001 and 2011 at a tertiary care center for a spontaneous CSF rhinorrhea originating from the cribriform plate were retrospectively reviewed. The radiological work-up included high-resolution computed tomography and magnetic resonance imaging with at least the following sequences: T1, T2, and T2 with fast imaging employing steady state acquisition (FIESTA). Thirty cases were identified. The mean age at diagnosis was 49. Fourteen patients (47 %) had a body mass index (BMI) of 30 or more and 3 patients (10 %) had a BMI between 25 and 29.9. Five patients had a history of meningitis. The imaging work-up revealed a bone defect of the cribriform plate in 6 cases (20 %), associated to a typical meningocele in 14 cases (47 %). In ten patients (33 %), there was no defect of the cribriform plate, but ultrathin coronal T2-FIESTA sequences revealed an OAD, i.e. a dilatation of the arachnoid sheath of the olfactory fibers, in nine cases (30 %), or a "pseudo-polyp" outlined by a thin layer of arachnoid (1 patient, 3 %). Preoperative imaging should be carefully analyzed for the presence of OAD or "pseudo-polyp" in patients presenting with a CSF rhinorrhea without bony defect of the cribriform plate.

Minimally invasive video-assisted thyroidectomy: tips and pearls for the surgical technique.

BACKGROUND: The objectives of this study were first to show principles of the minimally invasive video-assisted thyroidectomy (MIVAT), based on a video highlighting critical steps, and second to discuss tips and pearls to assist surgical teams that would like to start using this technique. METHODS: Based on a video, we described tips and pearls of a MIVAT. RESULTS: MIVAT includes 5 main steps: (1) skin incision and identification of the common carotid artery, (2) dissection and ligation of the upper pedicle, (3) identification of the inferior laryngeal nerve and parathyroid glands, (4) isthmectomy and lobe extraction, and (5) closure. DISCUSSION: Coordination between the surgeon and the 2 assistants is of paramount importance for the performance of MIVAT. Appropriate material is also required. The magnification and tissue contrast emphasizes the identification of the vessels, the superior and inferior laryngeal nerves, and parathyroid glands, on a large-view screen.

Critical analysis of recurrences of esthesioneuroblastomas: can we prevent them?

Esthesioneuroblastoma (ENB) involving the anterior skull base is a rare malignant tumour derived from the olfactory epithelium. The gold standard of surgical treatment is currently craniofacial resection (CFR), which allows efficient removal of the tumour but entails significant morbidity. To reduce morbidity combined with good visualization of tumour limits removal, endonasal endoscopy resection (EER) has developed. The objective of this work was (1) to describe the EER surgical procedure, the morbidity, and the limitations of this endoscopic approach as compared with CFR, (2) analyse recurrences to define risk factors of recurrences and (3) to discuss a therapeutic decision algorithm. Retrospective series of 18 patients with ENB endoscopically treated in a university tertiary referral centre over 13 years. Fifteen of those underwent radiotherapy. Epidemiological data, clinical and imaging findings, histology, treatment modalities and outcome of patients were studied. Mean follow-up was 31 months. Morbidity was mainly related to radiotherapy. Three recurrences were detected: one bone and one sylvian metastasis, and a local recurrence in a patient not irradiated. One recurrence spread through leptomeningeal propagation. Dural extension and frontal invasion were significantly associated with recurrences (p = 0.001 and p = 0.019, respectively). Patients with dural extension or frontal invasion should receive aggressive treatment. With a low rate of perioperative morbidity and efficient local control, EER seems to be a promising approach for selected cases of ENB.