Update in the classification and the role of intra-arterial stenting in the management of carotid body paragangliomas.

BACKGROUND: To review the Shamblin classification of carotid body paragangliomas (CBPs) and the role of intra-arterial stenting in their surgical management. METHODS: Retrospective case series of 20 patients with 28 CBPs that were surgically resected at our center. Intra-arterial stenting was performed in Shamblin II and II classes. RESULTS: The mean follow-up was 47.8 months. Five (17.9%) tumors were Shamblin class I, 15 (53.6%) were class II, and 8 (28.6%) were class III. Thirteen (68.4%) CBPs were associated with other paragangliomas. The internal carotid artery (ICA) was stented preoperatively in eight (28.6%) cases and occluded in four (14.3%) cases. The tumor extended to the jugular foramen in six cases (21.4%). Intraoperatively, there was an ICA injury in one case of Shamblin II CBP in the present era. CONCLUSIONS: The proposed classification enables the clinician to plan the management of the ICA and the right approach. Stenting of the ICA gives a chance for complete tumor removal with arterial preservation.

Facial Nerve Outcomes Following Total Excision of Vestibular Schwannoma by the Enlarged Translabyrinthine Approach.

OBJECTIVE: To study the early and late facial nerve (FN) outcomes in different tumor classes in addition to determining the predictive factors for the same. STUDY DESIGN: A retrospective clinical study. SETTING: A quaternary referral otology and skull base center. PATIENTS AND METHODS: A retrospective study of 1983 cases of vestibular schwannomas (VSs) with preoperative normal FN function, undergoing total excision with anatomical preservation of the nerve by enlarged translabyrinthine approach (ETLA) were included. FN status was recorded postoperatively at day 1, at discharge, and at 1-year follow-up and were analyzed in different tumor sizes. RESULTS: At 1 year, 988 patients with House-Brackmann (H-B) grade I and II FN at day 1 after surgery, 958 (96.9%) maintained their status up-to 1 year. Of the 216 patients with H-B grade III at day 1 after surgery, 113 (52.3%) improved to H-B grade I and II. Similarly, of the 779 patients with H-B grade IV and VI FN function at day 1 after surgery, improvement to H-B III and H-B I and II were noted in 442 (56.7%) and 80 (10.3%) of patients, respectively. Intrameatal and extrameatal tumors upto 2 cm showed better recovery from H-B grade III to H-B I and II and from H-B grade IV and VI to H-B I and III when compared with extrameatal tumors >2 cm (p = 0.001). CONCLUSION: Tumors of smaller sizes have good immediate postoperative FN results and recover well at the end of 1 year while more than 3 cm have poor outcomes and recover poorly at the end of 1 year. When the VSs reaches more than 1 cm, the HB I and II outcomes drop significantly.

Temporal Bone Meningo-Encephalic-Herniation: Etiological Categorization and Surgical Strategy.

OBJECTIVE: To study the clinical presentation, intraoperative findings and surgical management in meningo-encephalic-herniation (MEH) based on the etiology. STUDY DESIGN: A retrospective clinical study and is a follow-up on the previously published report in 2009. SETTING: A quaternary referral otology and skull base center PATIENTS AND METHODS:: The inclusion criteria were intraoperatively verified MEH in patients with a minimum follow-up of 12 months, which yielded 262 operated ears. The data were extracted regarding demographics, laterality, clinical presentation, past surgeries, contralateral-ear condition, intraoperative findings, complications, recurrences, revision-surgeries, audiometric-data, and follow-up. RESULTS: The mean age at surgery was 49.7 years with the involvement of right-ear in 53.8% of patients. Lesions were categorized based on the etiology as chronic-otitis-media with/without cholesteatoma-MEH (COM/CHOL-MEH)-47.7%, iatrogenic-MEHs -20.9%; traumatic-MEHs -8% and spontaneous-MEHs -23.3%. At presentation, hearing loss (100 and 98.2%) and otorrhea (65.6 and 49.1%) were predominant in COM/CHOL-MEHs and iatrogenic-MEHs, respectively. On the other hand, meningitis (23.9 and 14.3%) and cerebrospinal fluid-leak (52.4 and 42.8%) were more pronounced in spontaneous and traumatic MEHs, respectively. Surgical approaches included 1) transmastoid, 2) middle-cranial-fossa-approach, 3) combined, and 4) middle-ear-obliteration (MEO) techniques. A total of 52.8% of COM/CHOL-MEHs and 49.1% of iatrogenic-MEHs underwent MEO. Middle-cranial-fossa approach was predominantly used in spontaneous-MEHs (52.5%) and traumatic-MEHs (38.1%). The defect was mostly single (75.2%). Smaller, multiple, bilateral lesions were more common in spontaneous-MEHs with tegmen-tympani involvement (57.4%). CONCLUSION: Incorporating etiology into MEHs is a key-step that can be used as a guidance in choosing the right surgery. MEO is a part of armamentarium, and should be used whenever needed, if the objective is performing a definitive surgery.

Correction to: Paragangliomas arise through an autonomous vasculo-angio-neurogenic program inhibited by imatinib.

The given and family names of two co-authors were incorrect in the published article. The correct spelling should read as: Sampath Chandra Prasad and Vinagolu K Rajasekhar.

Paragangliomas arise through an autonomous vasculo-angio-neurogenic program inhibited by imatinib.

Tumours can be viewed as aberrant tissues or organs sustained by tumorigenic stem-like cells that engage into dysregulated histo/organogenetic processes. Paragangliomas, prototypical organoid tumours constituted by dysmorphic variants of the vascular and neural tissues found in normal paraganglia, provide a model to test this hypothesis. To understand the origin of paragangliomas, we built a biobank comprising 77 cases, 18 primary cultures, 4 derived cell lines, 80 patient-derived xenografts and 11 cell-derived xenografts. We comparatively investigated these unique complementary materials using morphofunctional, ultrastructural and flow cytometric assays accompanied by microRNA studies. We found that paragangliomas contain stem-like cells with hybrid mesenchymal/vasculoneural phenotype, stabilized and expanded in the derived cultures. The viability and growth of such cultures depended on the downregulation of the miR-200 and miR-34 families, which allowed high PDGFRA and ZEB1 protein expression levels. Both tumour tissue- and cell culture-derived xenografts recapitulated the vasculoneural paraganglioma structure and arose from mesenchymal-like cells through a fixed developmental sequence. First, vasculoangiogenesis organized the microenvironment, building a perivascular niche which in turn supported neurogenesis. Neuroepithelial differentiation was associated with severe mitochondrial dysfunction, not present in cultured paraganglioma cells, but acquired in vivo during xenograft formation. Vasculogenesis was the Achilles' heel of xenograft development. In fact, imatinib, that targets endothelial-mural signalling, blocked paraganglioma xenograft formation (11 xenografts from 12 cell transplants in the control group versus 2 out of 10 in the treated group, P = 0.0015). Overall our key results were unaffected by the SDHx gene carrier status of the patient, characterized for 70 out of 77 cases. In conclusion, we explain the biphasic vasculoneural structure of paragangliomas and identify an early and pharmacologically actionable phase of paraganglioma organization.

Surgical technique and results of cable graft interpositioning of the facial nerve in lateral skull base surgeries: experience with 213 consecutive cases.

OBJECTIVE The aim in this study was to review the technique and outcomes of cable graft interpositioning of the facial nerve (FN) in lateral skull base surgeries. METHODS The authors retrospectively evaluated data from patients who had undergone cable graft interpositioning after nerve sacrifice during skull base tumor removal between June 1987 and May 2015. All patients had undergone lateral skull base approaches to remove tumors at a quaternary referral center in Italy. Facial nerve function was evaluated before and after surgery using the House-Brackmann (HB) grading system. RESULTS Two hundred thirteen patients were eligible for study. The mean follow-up was 44.3 months. The most common pathology was vestibular schwannoma (83 cases [39%]), followed by FN tumor (67 cases [31%]). Facial nerve tumors had the highest incidence of nerve interruption (67 [66%] of 102 cases). Preoperative FN function was normal (HB Grade I) in 105 patients (49.3%) and mild (HB Grade II) in 19 (8.9%). At the last postoperative follow-up, 108 (50.7%) of the 213 patients had recovered to Grade III nerve function. Preoperative HB grading of the FN was found to have a significant effect on outcome (p = 0.002). CONCLUSIONS Cable graft interpositioning is a convenient and well-accepted procedure for immediate restoration of the FN. The study results, over a large number of patients, showed that the stitch-less fibrin glue-aided coaptation technique yields good results. The best possible postoperative result achieved was an HB Grade III. The chances of a good postoperative result increase when FN function is normal preoperatively. Slow-growing tumors of the cerebellopontine angle had a favorable outcome after grafting.

Rapidly growing cystic vestibular schwannoma with sudden onset facial palsy, ten years after subtotal excision.

An elderly male patient diagnosed with a right-sided cystic vestibular schwannoma (CVS) at our center underwent a translabyrinthine approach with a subtotal excision to preserve the facial nerve (FN). The tumor grew slowly for the first 9 years but in the subsequent 2 years grew rapidly, with the patient developing a FN paralysis. Using the previous approach, a second surgery was done and the tumor was excised, leaving behind a sheath of tumor on the facial and lower cranial nerves. This case demonstrates that CVSs show unpredictable growth patterns and need to be followed up for a longer period of time. Laryngoscope, 128:1649-1652, 2018.

Cochlear Implantation in Chronic Otitis Media With Cholesteatoma and Open Cavities: Long-term Surgical Outcomes.

OBJECTIVES: To evaluate the long-term surgical outcomes of cochlear implantation (CI) in chronic otitis media (COM) with cholesteatoma and open cavities using subtotal petrosectomy (STP). To review device explantation (DE) patients and reimplantation considerations. STUDY DESIGN: Retrospective review. SETTING: Otology and skull base center. PATIENTS AND METHODS: Charts of 35 patients (36 ears) with COM with cholesteatoma, including open cavities, who underwent CI were reviewed for surgical outcomes and DE. Patient demographics, pathologies, previous surgeries, staging of implantation, salient intraoperative findings at the time of implantation and follow-up were evaluated. Details of patients with DE were evaluated for cause, operative findings, and reimplantation considerations. RESULTS: Mean age of patients was 65.94 years. Nineteen open cavities, 11 primary cholesteatomas, 3 petrous bone cholesteatomas, and 3 atelectatic middle ears represented the pathologies with 31 patients of CI with concurrent STP and 5 patients where implantation was staged. The mean follow-up was 7.16 years ranging from 2 to 13 years. Four patients (11%) had DE due to extrusion and cavity infection with three reimplanted in same or contralateral ear. All explantations occurred within 24 months of primary implantation. No residual or recurrent cholesteatoma was observed in any of the patients during follow-up. CONCLUSION: CI is feasible in COM with cholesteatoma and open cavities with the use of STP and single-stage implantation can be performed in the absence of purulence. Despite low risk of residual cholesteatoma post meticulous disease removal, risk of DE remains, particularly in open cavity patients, and is higher than standard implantation. Reimplantation is often possible with careful considerations.

Cochlear Implantation in Cochlear Ossification: Retrospective Review of Etiologies, Surgical Considerations, and Auditory Outcomes.

OBJECTIVES: 1) To review the surgical and auditory outcomes and complications of cochlear implantation in cases with cochlear ossification. 2) To evaluate association between the extent and etiology of ossification to outcomes. STUDY DESIGN: Retrospective study. SETTING: Otology and skull base surgery center. SUBJECTS AND METHODS: Charts of 40 patients (42 ears) with cochlear ossification undergoing cochlear implantation were reviewed. Demographic features, operative findings, auditory outcomes, and complications were analyzed. Operative findings included extent of cochlear ossification, extent of drilling required to obtain patent cochlear lumen, approach (posterior tympanotomy/subtotal petrosectomy), electrode insertion (partial/complete, scala tympani/vestibuli), and complications. Auditory outcomes were assessed over a 4-year follow-up period using vowel, word, sentence, and comprehension scores. Patients were divided into groups (otosclerotic/non-otosclerotic and round window/basal turn ossification) for comparison of auditory outcomes. Outcomes were compared with 60 randomly identified controls (adults with postlingual deafness) who underwent implantation with no cochlear ossification. RESULTS: The median age and duration of deafness of patients was 54.39 and 27.15 years, respectively. Etiology of cochlear ossification was otosclerosis in 23 of 42 ears and mixed in 19 of 42 ears (chronic otitis media, temporal bone fractures, idiopathic, meningitis, Cogan's syndrome) with exclusive round window involvement in 54.7% of cases and the rest having partial or complete basal turn ossification. 59.5% ears underwent subtotal petrosectomy for implantation. Three patients underwent scala vestibuli insertion and five had incomplete electrode insertion. Auditory outcomes were comparable in otosclerotic and non-otosclerotic cases and in round window and basal turn ossification cases. No significant differences were observed in auditory scores when compared with controls with no ossification. CONCLUSIONS: Cochlear implantation in cochlear ossification is feasible despite surgical challenges and modifications. Auditory outcomes in basal turn ossification appear to be comparable to cases with no ossification with extent of ossification having no significant association with outcomes.

Surgical Management of Intrinsic Tumors of the Facial Nerve.

BACKGROUND: Intrinsic tumors of the facial nerve are a rare entity. Dealing with this subset of tumors is challenging both in terms of decision making and surgical intervention. OBJECTIVE: To review the outcomes of surgical management of facial nerve tumors and cable nerve graft interpositioning. METHODS: A retrospective analysis was performed at a referral center for skull base pathology. One hundred fifteen patients who were surgically treated for facial nerve tumors were included. In case of nerve interruption during surgery, the cable nerve interpositioning technique was employed wherein the facial nerve palsy lasted for less than 1-yr duration. In cases of facial nerve palsy lasting for greater than 1 yr, the nerve was restituted by a hypoglossal facial coaptation. RESULTS: Various degrees of progressive paralysis were seen in 84 (73%) cases. Sixty nine (60%) of the tumors involved multiple segments of the facial nerve. Sixty-two (53.9%) tumors involved the geniculate ganglion. Seventy four (64.3%) of the cases were schwannomas. Hearing preservation surgeries were performed in 60 (52.1%). Ninety one (79.1%) of the nerves that were sectioned in association with tumor removal were restituted primarily by interposition cable grafting. The mean preoperative House-Brackmann grading of the facial nerve was 3.6. The mean immediate postoperative grading was 5.4, which recovered to a mean of 3.4 at the end of 1 yr. CONCLUSION: In patients with good facial nerve function (House-Brackmann grade I-II), a wait-and-scan approach is recommended. In cases where the facial nerve has been interrupted during surgery, the cable nerve interpositioning technique is a convenient and well-accepted procedure for immediate restitution of the nerve.

Decision Making in the Wait-and-Scan Approach for Vestibular Schwannomas: Is There a Price to Pay in Terms of Hearing, Facial Nerve, and Overall Outcomes?

BACKGROUND: The wait-and-scan modality has emerged as an important strategy in the management of vestibular schwannoma (VS) as it has been demonstrated that many tumors grow slowly or do not show any growth over long periods. OBJECTIVE: To analyze long-term outcomes of wait-and-scan in the treatment of patients with VS, discuss the factors contributing to the decision making, determine the inherent risks of the policy, and compare our results with literature. METHODS: In total, 576 patients with sporadic unilateral VS who were managed with wait-and-scan were reviewed retrospectively. Of these, a subset of 154 patients with 5-yr follow-up was separately analyzed. The tumor characteristics including patterns of growth, rate of growth, hearing outcomes, and likely factors affecting the above parameters were analyzed. RESULTS: The mean period of follow-up was 36.9 ± 30.2 mo. The mean age was 59.2 ± 11.6 yr. Thirteen different patterns of tumor growth were observed. Eighty-four (54.5%) of 154 tumors with 5-yr follow-up showed no growth throughout 5 yr. Fifty-six (36.4%) tumors showed mixed growth rates. Only 57 (37%) patients had serviceable hearing at the start of follow-up, but 32 (56.1%) maintained it at the end of follow-up. One hundred fifty (26%) of the 576 patients who failed wait-and-scan had to be taken up for surgery. CONCLUSION: While there may be no price to pay in wait-and-scan as far as hearing is concerned, this may not be the case for facial nerve outcomes, wherein the results may be better if the patients are taken earlier for surgery.

Cochlear Implantation in Otosclerosis: Surgical and Auditory Outcomes With a Brief on Facial Nerve Stimulation.

OBJECTIVES: 1) To review the surgical and auditory outcomes in patients of cochlear implantation in otosclerosis. 2) To review complications and postimplantation facial nerve stimulation (FNS). 3) To compare the auditory outcomes between patients displaying cochlear ossification to the nonossified ones. STUDY DESIGN: Retrospective study. SETTING: Quaternary Otology and Skull base surgery center. SUBJECTS AND METHODS: Charts of 36 patients (38 ears) with otosclerosis undergoing cochlear implantation were reviewed from the cochlear implant database. Demographic features, operative findings, auditory outcomes, and postimplantation FNS were analyzed. Operative findings included extent of cochlear ossification, approach (posterior tympantomy/subtotal petrosectomy), electrode insertion (partial/complete, scala tympani/vestibuli), and complications. All the patients underwent implantation using straight electrodes. Auditory outcomes were assessed over a 4-year follow-up period using vowel, word, sentence, and comprehension scores. Patients were divided into two groups (with and without cochlear ossification) for comparison of auditory outcomes. RESULTS: The mean age and duration of deafness of patients was 59.72 and 28.9 years respectively. Twenty-three of 38 ears had cochlear ossification, with exclusive round window involvement in 60% of the patients, with the rest having partial or complete basal turn ossification. 36.8% ears underwent subtotal petrosectomy for cochlear ossification. One patient underwent scala vestibuli insertion and two had incomplete electrode insertion. Patients with no ossification had no intra or postoperative complications. One patient had bilateral FNS managed by alterations in programming strategy. Auditory outcomes in patients without any ossification were better than in patients with ossification, though statistically insignificant in most parameters. CONCLUSION: Cochlear implantation in otosclerosis provides good auditory outcomes, despite high incidence of cochlear ossification. Patients of FNS can be managed by alterations in programming strategy, without affecting auditory outcomes.

Effects of PPARα inhibition in head and neck paraganglioma cells.

Head and neck paragangliomas (HNPGLs) are rare tumors that may cause important morbidity, because of their tendency to infiltrate the skull base. At present, surgery is the only therapeutic option, but radical removal may be difficult or impossible. Thus, effective targets and molecules for HNPGL treatment need to be identified. However, the lack of cellular models for this rare tumor hampers this task. PPARα receptor activation was reported in several tumors and this receptor appears to be a promising therapeutic target in different malignancies. Considering that the role of PPARα in HNPGLs was never studied before, we analyzed the potential of modulating PPARα in a unique model of HNPGL cells. We observed an intense immunoreactivity for PPARα in HNPGL tumors, suggesting that this receptor has an important role in HNPGL. A pronounced nuclear expression of PPARα was also confirmed in HNPGL-derived cells. The specific PPARα agonist WY14643 had no effect on HNPGL cell viability, whereas the specific PPARα antagonist GW6471 reduced HNPGL cell viability and growth by inducing cell cycle arrest and caspase-dependent apoptosis. GW6471 treatment was associated with a marked decrease of CDK4, cyclin D3 and cyclin B1 protein expression, along with an increased expression of p21 in HNPGL cells. Moreover, GW6471 drastically impaired clonogenic activity of HNPGL cells, with a less marked effect on cell migration. Notably, the effects of GW6471 on HNPGL cells were associated with the inhibition of the PI3K/GSK3ß/ß-catenin signaling pathway. In conclusion, the PPARα antagonist GW6471 reduces HNPGL cell viability, interfering with cell cycle and inducing apoptosis. The mechanisms affecting HNPGL cell viability involve repression of the PI3K/GSK3ß/ß-catenin pathway. Therefore, PPARα could represent a novel therapeutic target for HNPGL.

Subtotal petrosectomy: Surgical technique, indications, outcomes, and comprehensive review of literature.

OBJECTIVES/HYPOTHESIS: To describe the technique of subtotal petrosectomy (STP), to analyze the outcomes, and to review the literature STUDY DESIGN: A retrospective review. METHODS: Four hundred sixty cases of STP performed for various indications were included in the study, which was conducted at a quaternary referral center for otology and skull base surgery. Surgical and audiological parameters, and complications were evaluated. Our results were compared with the existing literature on the subject. RESULTS: Two hundred ninety-seven (64.6%) patients had been subjected to multiple surgeries before an STP was performed. The most common indication for STP was recurrent chronic otitis with or without cholesteatoma, with 165 (35.9%) patients. Difficult cases of cochlear implantation, temporal bone fractures, and class B3 tympanomastoid paragangliomas were the next most common indications, with 91 (19.8%), 43 (9.4%), and 38 (8.3%) cases, respectively. The median follow-up of the patient pool was 36 ± 19 months. Recidivism and postauricular wound fistula were the most common complications, seen in five (1.1%) patients each. This series of STP is the largest reported in the literature CONCLUSIONS: STP is a very useful and safe surgical tool in the management of a variety of problematic situations in otology, as it offers the possibility of a definitive cure by offering radical clearance. This procedure can be combined safely with hearing implantation procedures. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:2833-2842, 2017.

Lateral skull base surgery in a pediatric population: A 25-year experience in a referral skull base center.

OBJECTIVE: To analyze the pathology and surgical outcomes of lateral skull base (LSB) procedures in a pediatric population. STUDY DESIGN: Retrospective case review in a referral skull base center. METHODS: Charts of pediatric patients who underwent defined LSB procedures from 1983 to 2015 for various pathologies were evaluated at our center. A systematic review of literature was performed and our results were compared with the literature. RESULTS: 63 patients presented with 65 diseased ears. The mean age was 13 years. 29 (44.6%) presented with hearing loss and 28 (44.4%) and chronic otorrhea. The most common pathology was petrous bone cholesteatoma (27, 42.5%) followed by vestibular schwannoma (10, 15.8%). Subtotal petrosectomy (24, 35.8%) was the most common surgical procedure followed by, transotic (18, 26.8%). The facial nerve function was preserved in 45 (67.1%) and the hearing in 28 (41.7%) cases respectively. No major complications, including mortality was encountered in our series. CONCLUSION: In rare and extensive pathologies involving the skull base in a pediatric population, the surgeon is posed with the dilemma of trying to achieve facial and hearing preservation while dealing with total tumor clearance. Mastery over LSB procedures can ensure complete disease clearance with optimal functional outcomes. LEVEL OF EVIDENCE: 2b.

Vestibular Schwannoma Resection with Ipsilateral Simultaneous Cochlear Implantation in Patients with Normal Contralateral Hearing.

OBJECTIVE: To report the hearing results of cochlear implantation simultaneous to vestibular schwannoma (VS) resection by means of a translabyrinthine approach in patients with normal contralateral hearing. METHODS: This was a prospective study including adults with sporadic VS. Tumors were resected by means of a modified translabyrinthine approach with preservation of the cochlear nerve. RESULTS: A total of 13 patients underwent cochlear implantation. At 14 months, the mean pure-tone audiogram was 56 dB. The mean speech recognition was 80%. Cochlear implantation provides monaural and binaural benefits in all the conditions tested, including sound localization. CONCLUSIONS: Cochlear implantation can be safely performed simultaneously to VS resection with satisfactory hearing results provided that the cochlear nerve is anatomically intact.