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Objective:To identify the prognostic significance of specific lymph node related characteristics for disease persistence and recurrence in patients with pre- or intra-operative evidence of neck metastases and no other risk factors.Method and resultsSixty-eight patients were identified; 50 per cent had persistent or recurrent disease. All underwent the same treatment strategy. There were no statistically significant differences in any of the patient- or tumour-related parameters when patients with and without persistence or recurrence were compared. Patients with recurrent or persistent disease had significantly larger (>3 cm) metastatic lymph nodes, but there were no differences regarding other lymph node related parameters (i.e. number, extracapsular extension, number of lymph nodes with extracapsular extension, and central vs lateral neck location). On multivariate analysis, however, none of the parameters were predictive of persistent or recurrent disease.Conclusion:In papillary thyroid carcinoma patients with no other risk factors, pre- or intra-operative evidence of cervical metastases was associated with a very high rate of disease persistence or recurrence. Specific lymph node characteristics were not shown to have prognostic significance. [ABSTRACT FROM PUBLISHER]

Purpose: To analyze recurrence patterns of chronic sinusitis with nasal polyposis (CRSwNP) in patients who underwent complete FESS and identify predisposing factors for different patterns of recurrence., Methods: Retrospective analysis of patients with CRSwNP who underwent complete FESS at our tertiary medical center. Recurrence patterns were classified into edema, polyp and normal endoscopy, as well as into early (within 6 months) and late recurrence. Statistical analysis to identify risk factors for recurrence included univariate, multivariate logistic regression and cox regression models., Results: 114 patients were included with an average follow-up of 27 months. 91% were categorized as type-2 inflammation. Recurrence was observed in 65.8% of patients within a mean of 12.9 months. 46.7% had polyp recurrence while 53.3% had edema recurrence. Early recurrence was observed in 41%. Serum eosinophilia > 500 cells/uL was found to be significantly associated with recurrence (RR = 1.62, p-value = 0.046), and particularly with polyp recurrence (RR = 3.9, p-value = 0.001). No predictive factors for early recurrence were identified. Edema recurrence was managed with intranasal corticosteroids while polyp recurrence required systemic therapy including biologic therapy., Conclusions: In this study, two thirds of patients experienced post operative recurrence, either mucosal edema or nasal polyps, with similar frequency during an average follow up of over 2 years. Early recurrence was noted in 41% of recurrent cases. Serum eosinophils > 500 cells/uL was the only risk factor for recurrence on multivariate analysis, more accurate markers are needed for improved treatment allocation to CRSwNP patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To estimate long-term prognosis of chemosensory dysfunctions among patients recovering from COVID-19 disease., Methods: Between April 2020 and July 2022, we conducted a prospective, observational study enrolling 48 patients who experienced smell and/or taste dysfunction during the acute-phase of COVID-19. Patients were evaluated for chemosensory function up to 24 months after disease onset., Results: During the acute-phase of COVID-19, 80% of patients reported anosmia, 15% hyposmia, 63% ageusia, and 33% hypogeusia. At two years' follow-up, 53% still experienced smell impairment, and 42% suffered from taste impairment. Moreover, 63% of patients who reported parosmia remained with olfactory disturbance. Interestingly, we found a negative correlation between visual analogue scale scores for smell and taste impairments during the acute-phase of COVID-19 and the likelihood of long-term recovery., Conclusion: Our study sheds light on the natural history and long-term follow-up of chemosensory dysfunction in patients recovering from COVID-19 disease. Most patients who initially suffered from smell and/or taste disturbance did not reach full recovery after 2 years follow-up. The severity of impairment may serve as a prognostic indicator for full recovery., (© 2024. The Author(s).)

Objective: The purpose of this study was to investigate whether patient, tumour and radiation therapy factors are associated with development of middle ear effusion (MEE) in nasopharyngeal carcinoma (NPC) patients., Deign, Settings, and Participants: A retrospective review of NPC patients treated between January 2000 and June 2018 at Rabin Medical Center. Patient factors, tumour factors, radiation doses, and radiation fields were collected and outlined if needed (middle ear, eustachian tube [ET], tensor veli palatini [TVP], and levator palatini [LVP] muscles), then analysed and compared between patients with MEE and those without and between sides in patients with unilateral MEE., Main Outcome Measures and Results: Seventy-three patients were enrolled. Most were males (71.2%) with advanced-stage diseases (78%). At the time of diagnosis 14 patients (19.2%) presented with MEE. Following radiation, 18 patients, with no evidence of MEE at presentation, developed MEE. Tumour stage, histology, and laterality were not associated with development of MEE. Comparison of mean radiation field dosages including-gross target volume, clinical target volume, and patient target volume showed no association with post-radiation MEE. In addition, no difference was found in the radiation doses to the middle ear, ET or the LVP nor the TVP between ears with and without MEE., Conclusions: Post-irradiation MEE remains a common adverse effect in NPC patients. Surprisingly, tumour stage, tumour laterality, and histology were not associated with MEE. Similar findings were observed for total radiation doses and specific doses to the middle ear, ET, and ET muscles., (© 2024 The Authors. Clinical Otolaryngology published by John Wiley & Sons Ltd.)

Objective: Treatment of sinonasal malignancies most often requires primary or postoperative radiation treatment. Post radiation sinonasal morbidity has been previously described; however, none addressed post-radiation sinus obstruction. Our objective was to investigate the long-term outcomes of post radiation complete isolated sinus opacification (CISO)., Methods: A retrospective analysis of sinonasal cancer patients treated with radiation therapy during the years 2002 to 2022. Clinical, imaging and treatment data were collected from patients' medical records. Only patients with at least 12 months of follow-up and available imaging for review were included., Results: Out of 109 patients, 37 patients were identified to meet the inclusion criteria. Mean follow-up was 58 months. 35% of patients were diagnosed with persistent post radiation CISO with a mean onset of 4 months. All these patients remained asymptomatic, and their imaging remained stable during follow-up with none developing an expanding mucocele. Ethmoid sinus tumor involvement was found to be more prevalent in the CISO group (62% vs. 25%, p-value = 0.048) as well as chemotherapy/immunotherapy (54% vs. 38%, p-value = 0.046). Multivariant analysis revealed that ethmoid sinus involvement (OR = 9.516, p-value = 0.047) and adjuvant therapy, either chemotherapy/immunotherapy (OR = 10.75, p-value = 0.036) were found to be a predictive factor for complete opacification., Conclusion: Our study revealed that a substantial number of post-radiation patients develop a stable and persistent CISO, often in the frontal and sphenoid sinuses. These patients remained asymptomatic, and none required surgical intervention during nearly 5 years of follow-up., Level of Evidence: 4 Laryngoscope, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose: To examine the long-term success rate of pediatric endoscopic DCR surgery via telephone questionnaires, as determined by patients and their parents., Methods: This is a retrospective cohort study of all patients who underwent DCR surgery at the Schneider Children's Medical Center of Israel between 2010 and 2020. We performed long-term follow-ups to assess the quality of life, surgical complications, and satisfaction with surgical outcomes., Results: Our study includes seventy-nine patients with a total of 108 eyes. The mean age at the time of DCR was 7.05 years (Std = 4, min = 0.3, max = 17.7) Mean follow-up time was 5.7 years (Std =2.5, min = 1.4, max = 11.1). Tubes were inserted for a mean of 129 days (Std = 101). Fifty-seven patients (72%) declared they had no complications after surgery, three patients (4%) reported pain after surgery, and 14 patients (17.7%) reported tube extrusion, which occurred 7-21 days after surgery. Forty-four patients (56%) reported no recurrence of symptoms, 29 (37%) complained of mild epiphora, and 18 (23%) reported some ocular discharge. Sixty-eight patients (86%) stated that they did not undergo additional surgery, while the remaining 11 (14%) reported undergoing a revision operation for symptom control. Satisfaction rate (1-7) mean score reported was 6.15 (Std = 1.6). Sixty-two (78%) reported improved quality of life, while 17 (22%) reported no improvement. Our questionnaire results have been compared with the TEARS scores with similar findings., Conclusion: Regardless of its etiology, endoscopic DCR surgery in the pediatric population is safe and efficient, with a high long-term patient satisfaction rate, as reported via a telephone questionnaire., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The long-term impact of rhinitis and chronic rhinosinusitis (CRS) on general health and medical services utilization in young adults have been limitedly studied., Methods: A case-control study in the Israeli Defense Forces, between the years 2005 and 2019, of all individuals with either rhinitis or CRS and a matched cohort of healthy individuals with a minimum of 5 years of consecutive follow-up., Results: The study groups included 617 patients with rhinitis and 296 patients with CRS and 2739 healthy controls with an average age of 28 years. During a mean follow-up of 8 years, a significant fraction of patients in both study groups were diagnosed with asthma compared to the control group, (26.1% and 23.3% vs. 3.7%, respectively; CI 95%: 12.1%-14.9%, p < 0.0001). 7.6% of patients with rhinitis developed CRS. Significantly increased loss of productivity and medical system utilization were noted in the study groups compared to controls (p < 0.0001). Moreover, deterioration in general health, manifested as loss of physical fitness for combative service was observed in a third of patients during follow-up., Conclusions: Rhinitis and CRS significantly impact productivity and medical service utilization in young adults, as well as general health associated with development of asthma and impairment of physical fitness. A minority of rhinitis patients develop CRS overtime, further affecting this patient group. These patients should be followed up and managed to improve disease control and associated outcomes., Level of Evidence: 3 Laryngoscope, 133:3299-3303, 2023., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose: To provide real-life data on azole treatment outcomes and the role of surgery in the current management of invasive fungal rhinosinusitis complicated by orbitocranial fungal infection (OCFI)., Methods: Data was collected retrospectively from a chart review from four participating centers and a systematic literature review. The study group included patients with OCFI treated with azole antifungals. The control cases were treated with other antifungal agents. The cranial and orbital involvement degree was staged based on the imaging. The extent of the surgical resection was also classified to allow for inter-group comparison., Results: There were 125 patients in the azole-treated group and 153 in the control group. Among the patients with OCFI cranial extension, 23% were operated on in the azole-treated group and 18% in the control group. However, meninges and brain resection were performed only in the controls (11% of patients) and never in the azole antifungals group. Orbital involvement required surgery in 26% of azole-treated cases and 39% of controls. Despite a more aggressive cranial involvement, azole-treated patients' mortality was significantly lower than in controls, with an OCFI-specific mortality rate of 21% vs. 52%. A similar, though not statistically significant, trend was found for the extent of the orbital disease and surgery., Conclusion: Despite less aggressive surgical intervention for cranial involvement, OCFI patients treated with azoles had a higher survival rate. This finding suggests we may improve morbidity with a more conservative surgical approach in conjunction with azole treatment. The same trend is emerging for orbital involvement.

Purpose: This study examines the impact of concomitant mucosal inflammation on clinical manifestations and long-term outcomes of Inverted Papilloma (IP)., Methods: This retrospective cohort study was conducted in five tertiary medical centers. The included patients underwent an attachment-oriented surgical resection for IP with a minimum follow-up of 3 years., Results: Of 185 patients with IP, 65 patients (35.1%) had synchronous mucosal inflammation with polypoid changes. The mean age was 56.7 years, and 69% were males. Most tumors originated from the maxillary sinus. Age, gender, Krouse stage, and tumor attachment site did not differ between the mucosal inflammation and IP-only groups. IP recurrence rate was twofold in the patients with mucosal inflammation (15.4% vs. 7.5%, p = 0.092). However, the difference was not significant, with a similar median time to recurrence between the two groups [15.5 (3-36) months vs. 16(6-96) months, p = 0.712]. In revision cases, IP recurred only in patients with mucosal inflammation (19% vs. 0%, p = 0.07). This group had a significantly worse 5-years recurrence-free survival than revision cases without mucosal inflammation (80.6% vs. 100%, p = 0.04)., Conclusions: IP in the setting of mucosal inflammation might be associated with a higher recurrence rate, predominantly after revision surgery. Otolaryngologists should consider this during these patients' diagnosis, surgical planning, and follow-up., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Orbital complications are the most common complication of acute rhinosinusitis, especially among pediatric patients. While most cases are treated with antibiotics alone, severe presentation may demand surgical intervention. Our goal was to determine which factors predict the need for surgery and to investigate the role of computerized tomography in the decision process., Methods: A retrospective review of all children hospitalized between 2001-2018 with orbital complications of acute rhinosinusitis in a university-affiliated children's hospital., Results: A total of 156 children were included. Mean age was 7.9 years (1-18 years). Twenty-three children (14.7%) were surgically treated, and the rest were conservatively treated. High fever, ophthalmoplegia and diplopia in association with minimal or no response to conservative treatment were predictive for surgical intervention, as well as higher inflammatory indices. Eighty-nine children (57%) underwent imaging during hospitalization. Presence of a subperiosteal abscess, as well as its size and its location were not found to be predictors for surgery., Conclusion: Clinical and laboratory findings in association with minimal or no response to conservative treatment predict the need for surgical intervention in cases of orbital complications of acute rhinosinusitis. As Computerized Tomography scans can have long-term implications in the pediatric population, caution and patience should be practiced when deciding on the timing of imaging in this population. Thus, close clinical and laboratory monitoring should lead the decision-making process in these cases and imaging should be reserved for when the decision for surgery has been made.

Objective: The aim of this study was to review the long-term complications associated with treatment of patients with sinonasal malignancies (SNMs) and risk factors for these complications., Methods: A retrospective analysis of all patients treated for SNMs at a tertiary care center between 2001 and 2018. A total of 77 patients were included. The primary outcome measure was post-treatment long-term complications., Results: Overall, long-term complications were identified in 41 patients (53%), and the most common were sinonasal (22 patients, 29%) and orbital/ocular-related (18 patients, 23%). In a multivariate regression analysis, irradiation was the only significant predictor of long-term complications (p = 0.001, OR = 18.86, CI = 3.31-107.6). No association was observed between long-term complications and tumour stage, surgical modality, or radiation dose/modality. Mean radiation dose ≥ 50 Gy to the optic nerve was associated with grade ≥ 3 visual acuity impairment (100% vs 3%; p = 0.006). Radiation therapy for disease recurrence was associated with additional long-term complications (56% vs 11%; p = 0.04)., Conclusions: Treatment of SNMs has substantial long-term complications, which are significantly associated with radiation therapy., (Copyright © 2023 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Background: Acute invasive fungal rhinosinusitis has been associated with high mortality rates., Objective: We aimed to explore the contribution of novel detection and treatment methods on the outcome of immunosuppressed children with acute invasive fungal rhinosinusitis., Methods: The records of all children with a hematologic or oncologic disease who developed acute invasive fungal rhinosinusitis between 2005-2020 were reviewed., Results: Thirty-four patients were included. Aspergillosis and mucormycosis were diagnosed in 20 patients (59%) and 12 patients (35%), respectively. Panfungal polymerase chain reaction (PCR) was associated with a change of treatment in 36% of patients. A more aggressive surgical approach as well as treatment with liposomal amphotericin B and novel antifungals were adopted in recent years. Overall, 26% of patients died of disease, however no disease-specific death occurred since 2012. Diagnosis using panfungal PCR ( p    =   .04) and treatment with novel antifungal medications ( p    =   .017) were significantly associated with disease-specific survival., Conclusion: Enhanced fungal detection using panfungal PCR and treatment with novel antifungal agents, combined with rapid diagnosis and treatment, aggressive surgical approach and better control over the underlying oncological disease, may significantly improve the outcome of immunosuppressed children with acute invasive fungal rhinosinusitis.

Objective: There is limited information regarding the recurrence patterns and efficacy of surveillance modalities in patients with sinonasal malignancies., Methods: A retrospective study was conducted between the years 2001-2018 at a tertiary care center. Included were all patients with sinonasal malignancies treated in our institution. Data regarding recurrence and survival were analyzed., Results: Eighty-one patients were included. Multimodal treatment was administered to the majority of patients. 24 (35.3%) patients recurred with a median time of 17 months (range, 4-180). Although the majority of recurrences occurred within the first 5 years (83.3%), 4 (16.6%) recurred later on (5-15 years). Recurrences were local in 83.3%, regional in 20.8% and distant in 16.6%. All local recurrences occurred within the radiation treatment field and all patients with distant failure had mucosal melanoma. The majority of recurrences (70.6%) were diagnosed clinically or endoscopically, mainly in patients with SCC during the first 2 years of follow up. MRI or PET-CT were crucial in detecting extra-sinus and distant failures. Salvage surgery was feasible in the majority of patients (58.3%). Overall, 5 years survival (OS) rate was 60.9%., Conclusions: Frequent clinic visits with nasal endoscopy combined with frequent imaging studies should be routinely practiced as part of a long-term surveillance plan. Longer follow up duration should be considered in these patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To explore the association between intraoperative surgical margin sampling by the frozen sections and recurrence in inverted papilloma surgery., Methods: A multicenter, retrospective study of patients who underwent attachment-oriented IP resection in four tertiary care medical centers with a minimal follow-up of 36 months., Results: The study included 220 surgeries with a mean follow-up period of 49 months (range 36-204). The endoscopic approach was used in all but 4 cases; 73% of procedures were primary. Overall recurrence was 10.45% (n = 23). Squamous cell carcinoma was found in 5 cases (2.2%). Intraoperative margin sampling was obtained in 145 cases. There was no difference in the recurrence rate between frozen section and no-frozen section groups (p = 0.44). Furthermore, margin sampling in various sites of tumor origin, in cases with concomitant nasal polyps (p = 0.53) and in revision cases (p = 0.08) showed no correlation with recurrence. In 26 cases when the surgery was extended following a positive frozen section, there was a significantly higher recurrence rate (OR = 6.94)., Conclusions: According to our results, intraoperative margin sampling did not affect the recurrence rate of IP, and therefore, its routine use should be questioned., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Surgeons are often faced with concerns regarding the risks versus benefits of endoscopic sinus surgery (ESS) in elderly patients., Objective: To analyze the risk for complications of ESS in the elderly (age ≥70 years) compared to younger patients, with emphasis on octogenarians., Methods: Retrospective review of medical charts of adult patients who underwent ESS at a tertiary referral center during the years 2014 to 2018., Results: We compared 128 elderly patients with 276 matched younger patients. In the elderly group mean age was 76 years (range, 70-91 years ). Thirty-one elderly patients were 80 years or older. Surgical complications in the elderly patients were 3.9%. Minor complications were 2.3% and major complications were 1.7%. The surgical complications rate was similar in the younger group (8%, P value: .127). Medical complications were observed in 2.3% comparing to 0.7% in younger patients. Interestingly, age, revision surgery, extent and duration of surgery, and modality of anesthesia were not identified as risk factors. Only ischemic heart disease (IHD) was identified as a risk factor for complications in a multivariate analysis in elderly patients. Comparison of elderly patients younger than 80 years with octogenarians revealed no difference in complication rate between these groups., Conclusions: Overall, ESS was found to be a safe procedure in elderly patients compared to younger patients. Octogenarian patients should not be denied upfront surgery. IHD is a risk factor for complications in elderly patients.

Background: Dacryocystorhinostomy is used to treat nasolacrimal duct obstruction when conservative measures fail. It may be performed via an external or endoscopic-endonasal approach. The aim of this study was to compare the outcomes of patients with nasolacrimal duct obstruction treated with simultaneous bilateral or unilateral dacryocystorhinostomy., Methods: The database of a tertiary medical center was retrospectively reviewed for all patients treated for nasolacrimal duct obstruction in 2012-2017. The study sample was divided into six groups by surgery type and approach: adults (>18 years) - external or endoscopic-endonasal sequential unilateral or simultaneous bilateral dacryocystorhinostomy (four subgroups); children (18 years) - endoscopic-endonasal unilateral or simultaneous bilateral dacryocystorhinostomy (two subgroups). Data were collected on patient age and sex, surgery and anesthesia type and duration, and complications., Results: The cohort included 95 adults and 27 children who underwent 111 and 41 surgical procedures, respectively. Among the adults, the durations of anesthesia and surgery were significantly longer in the external bilateral dacryocystorhinostomy group than the others, but no such differences were found between simultaneous bilateral endonasal dacryocystorhinostomy and unilateral dacryocystorhinostomy by either approach. Among the children, there was no significant between-group difference in surgery duration.In neither age population was bilateral endoscopic surgery associated with an excess of intraoperative or postoperative complications of hemorrhage, infection, and epiphora., Conclusion: The lack of intergroup differences in clinical, surgical, and outcome parameters suggests that in cases of bilateral nasolacrimal duct obstruction in adults and children, simultaneous bilateral endoscopic-endonasal dacryocystorhinostomy may yield excellent therapeutic results.

Objective/hypothesis: Anticoagulant and antiplatelet medications (ACAP) are known to be associated with an increased risk for epistaxis. There are conflicting results regarding the impact of Novel Oral Anticoagulants (NOAC) on epistaxis and its severity., Study Design: Retrospective chart review of patients who were admitted to the ED in our tertiary level hospital with a diagnosis of epistaxis during the years 2012 to 2018., Methods: Retrospective analysis of patients presenting to tertiary level emergency otolaryngological care during the years 2012 to 2018. The impact of various ACAP medications on epistaxis severity, hospital admission, and recurrence was analyzed., Results: A total of 470 patients were identified. Two hundred and twenty-nine patients (49%), were not on any anticoagulant/antiplatelet (ACAP) medications (controls) and 241 patients (51%) were taking at least one ACAP medication (ACAP group). Patients in the ACAP group were at a higher risk for severe epistaxis (OR = 1.8, P < .05) and were more likely to be hospitalized (OR = 2.17, P < .05). Surprisingly, the risk for recurrence was similar in the ACAP and control groups (15%, P > .05). Compared to controls, Warfarin and Enoxaparin increased the overall risk for severe epistaxis (OR = 4.4, P < .05) and for hospital admission (OR = 2.1, P < .05). Specifically, an increased risk for posterior tamponade (OR = 19, P < .001), significant blood loss (OR = 4.4, P = .032), and blood transfusion (OR = 4.7, P = .007) were identified as well. Interestingly, NOACs were not associated with increased risk for severe epistaxis, hospital admission, tamponade, and significant blood loss or blood transfusion compared to controls., Conclusions: Compared to older generation anticoagulants and antiplatelet medications, NOACs demonstrated an improved safety profile, in terms of epistaxis severity, need for hospital admission and outcomes. These results may suggest a more conservative approach and less hospitalization when treating epistaxis in patients receiving NOACs., Level of Evidence: 4 Laryngoscope, 131:1946-1951, 2021., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose: To report the authors' experience with endoscopic unpowered dacryocystorhinostomy in the treatment of pediatric nasolacrimal duct obstruction, and to evaluate whether surgical site reassessment (after the appropriate healing period) affects clinical outcomes., Methods: This retrospective study included 47 children aged between 1.5 and 17.0 years (mean age: 6.9 years) who underwent endoscopic unpowered dacryocystorhinostomy between 2014 and 2019 at one tertiary care hospital. Twenty-six patients required unilateral and 21 required bilateral endoscopic dacryocystorhinostomy. The main outcome measures were duct patency on lacrimal irrigation ("anatomical success") and resolution of symptoms ("clinical success") over 6 months of postoperative follow-up., Results: Sixty-eight dacryocystorhinostomy procedures were performed. Surgical site reassessment during tube removal was performed in 52 of 68 cases. Five cases (9.6%) required treatment of local pathologies, only after which was symptomatic relief achieved. Overall anatomical success was observed in 49 (94.2%) of the 52 cases in which nasal endoscopy was performed, including the 5 cases treated during reevaluation. Clinical success was observed in 63 (92.6%) cases., Conclusions: Pediatric endoscopic dacryocystorhinostomy is an effective surgical procedure used to correct nasolacrimal system obstruction resistant to conservative measures. The unpowered endoscopic dacryocystorhinostomy technique is practical and safe in the pediatric population. Surgical site reassessment allows treating local pathologies threatening ostium patency and increases clinical success rates. [ J Pediatr Ophthalmol Strabismus . 2021;58(3):168-173.] .

Objective: To evaluate the correlation between the ability to predict the attachment site of sinonasal inverted papilloma by computed tomography and the long-term surgical outcome., Study Design: Retrospective cohort study., Setting: Five tertiary medical centers., Methods: Study patients underwent attachment-oriented resection of inverted papilloma. The primary outcome was tumor recurrence., Results: Among 195 patients eligible for the study, focal hyperostosis was recognized on computed tomography in 65% (n = 127), in 71% of primary cases (n = 101), and in 50% of revision procedures (n = 26). There was a trend for a higher incidence of squamous cell carcinoma among the patients without detectable hyperostosis ( P = .051). Location of hyperostosis coincided with the actual tumor attachment site in 114 patients (90%). Discordance between these parameters did not differ significantly ( P = .463) between 11 primary and 2 revision cases. The overall rate of recurrence was 9.7% (n = 19), with a mean time to recurrence of 20 months (range, 7-96 months). The rate of recurrence did not correlate with any of the following: tumor stage, surgical approach, presence of squamous cell carcinoma, whether the surgery was primary or revision, and the presence or location of focal hyperostosis on computed tomography. Inverted papilloma recurred significantly more often (38.5%) when the intraoperative findings of the tumor attachment site did not match the location of hyperostosis observed on computed tomography (odds ratio, 6.5; 95% CI, 1.78-23.66)., Conclusion: Detectability of focal hyperostosis on preoperative computed tomography does not affect the long-term outcome of inverted papilloma resection.

Purpose: The purpose of this study was to describe the microbiology of recurrent acute exacerbations of chronic rhinosinusitis over time., Methods: Retrospective review of patients with recurrent acute exacerbations of chronic rhinosinusitis who underwent endoscopic-guided cultures during acute exacerbations of chronic rhinosinusitis., Results: 386 cultures were obtained from 112 patients during recurrent acute exacerbations of CRS. A change of bacterial isolates during the course of recurrent exacerbations was observed in 68% (76/112) of patients, necessitating a change of treatment in 40% (45/112). The main risk factor for the subsequent change in cultures was polymicrobial growth. Sinus surgery was not associated with subsequent change in cultured isolates. Resistant strains developed in 11.6% (13/112) of patients, of whom those with abnormal mucociliary clearance being at the highest risk., Conclusion: Repeated middle meatal cultures should be considered in patients with recurrent exacerbations of CRS, particularly in cases not responding to standard therapy.

Epistaxis is a common debilitating manifestation in hereditary hemorrhagic telangiectasia (HHT), due to mucocutaneous telangiectases. The epistaxis can be difficult to control despite available treatments. Dysregulated angiogenesis has been shown to be associated with telangiectases formation. Topical propranolol has demonstrated antiangiogenic properties. We performed a two-phase study, i.e., a double-blind placebo-controlled phase, followed by an open-label phase. The aim of the study was assessment of safety and efficacy of nasal propranolol gel in HHT-related epistaxis. Twenty participants with moderate-severe HHT-related epistaxis were randomized to eight weeks of propranolol gel 1.5%, or placebo 0.5 cc, applied to each nostril twice daily; and continued propranolol for eight weeks in an open-label study. For the propranolol group, the epistaxis severity score (ESS) improved significantly (-2.03 ± 1.7 as compared with -0.35 ± 0.68 for the placebo group, p = 0.009); hemoglobin levels improved significantly (10.5 ± 2.6 to 11.4 ± 2.02 g/dL, p = 0.009); and intravenous iron and blood transfusion requirement decreased. The change in nasal endoscopy findings was not significant. During the open-label period, the ESS score improved significantly in the former placebo group (-1.99 ± 1.41, p = 0.005). The most common adverse event was nasal mucosa burning sensation. No cardiovascular events were reported. Our results suggest that topical propranolol gel is safe and effective in HHT-related epistaxis.

Background: Chordomas are locally invasive neoplasms, arising from notochordal remnants and can appear anywhere along the axial skeleton. Local recurrences are common, and distant metastases may occur years after the initial presentation., Methods: Literature review of current treatment strategies for chordomas of the skull base., Results: Surgery is the mainstay of treatment and complete resection has paramount importance for prognosis.When complete resection is not achieved recurrent disease is common. The anatomical complexity of the skull base makes resection complex. Endonasal endoscopic approaches to the clivus has become increasingly favored in recent years although addressing reconstruction of the skull base to prevent CSF leak may be challenging.Evidence suggests that radiotherapy should not be considered as a primary single modality when trying to achieve cure of the disease. Nonetheless, immediate post-operative radiotherapy improves survival. Many strategies have been suggested to preserve sensitive vital structures in the skull base during treatment but as for survival there is no evidence of advantage when comparing adjuvant therapy with photon radiotherapy, gamma knife surgery, proton beam therapy, and carbon ion radiation therapy.There is no evidence to support cytotoxic chemotherapy in the treatment of chordomas but targeted therapies have started to show promise. Several optional molecular targets exist. Brachyury is overexpressed in 95% of chordomas but not in other mesenchymal neoplasms. However, its precise role in chordoma pathogenesis is currently unclear, and its cellular location in the nucleus makes it difficult to target. The inhibition of brachyury in chordoma cell lines induces growth arrest and apoptosis. This does not have clinical application to date. There are retrospective results with different molecular targeted therapies for advanced chordomas with some effectiveness., Conclusion: Despite improvements made in the past 10 years in our knowledge of chordoma biology, available therapies still offer a limited benefit. There is an unmet need for new therapeutic options for patients with advanced disease. Therefore, patients with advanced disease should be encouraged to participate in clinical trials when and where available., Competing Interests: None., (© 2020 The Authors.)

Objectives: Preoperative maxillary sinus imaging findings have been suggested to be associated with complications and outcomes of sinus lift and dental implant procedures; nonetheless the evidence is controversial. The aim of this study was to examine the association between preoperative maxillary sinus imaging findings and outcomes of sinus lift and dental implant procedures in asymptomatic patients., Methods: We included all patients who underwent maxillary sinus lift and dental implant procedures between 2014 and 2017. Maxillary sinus imaging findings were extracted from pre-procedural dental computed tomography scans, and outcomes of the procedures were assessed., Results: A total of 145 procedures were included. No sinonasal symptoms were reported preoperatively. In 46% of cases maxillary sinus imaging was abnormal. The most common imaging finding was peripheral mucosal thickening (38%). Sinus floor cyst/polyp was identified in 13% of the cases, of which 47% occupied more than 50% of the sinus volume. Partial or complete opacification of the maxillary sinus was documented in 3% of cases. The sinus ostium and ostiomeatal complex were obstructed in 7% and 1%, respectively. Mucosal perforation was documented in 22% of cases and was inversely related to mucosal thickening ( P  = 0.011). Other minor post-operative complications did not correlate with radiological findings. Post-surgical sinusitis was not observed in any of the patients regardless of pre-surgical imaging findings., Conclusions: Incidental maxillary sinus imaging findings such as mucosal swelling, cysts or polyps, regardless of their severity or size, and maxillary ostial obstruction may not need to be addressed prior to sinus augmentation and dental implant procedures in asymptomatic patients. Patients with complete sinus opacification should be referred to an otolaryngologist prior to surgery. Further controlled trials, in larger cohorts, are needed to corroborate our findings.

Objectives: Intranasal septal splints are often used in nasal septal surgeries. Routine use of postoperative antibiotics is an accepted practice, although data regarding its efficacy in preventing postsurgical complications are limited. This study aimed to examine bacterial colonization on septal splints following prophylactic antibiotic therapy and the association with postoperative infections., Methods: Fifty-five patients underwent septoplasty by a single surgeon between March 2015 and April 2016. All had intranasal septal splints and were given antibiotic prophylaxis for 7 days until removal of splints. Nasal cultures were taken before surgery, and septal splints were examined for bacterial colonization following their removal., Results: Thirty-six patients (65%) had positive nasal culture prior to surgery. The most common isolates were Staphylococcus aureus (30%) and Enterobacteriaceae species (66%). All these patients had postoperative bacterial colonization on septal splints. In 15 patients with negative preoperative cultures, bacteria were isolated postoperatively. An increased resistance profile was documented postoperatively in 9 patients (16%), including two with multidrug resistance. In two of these patients preoperative wild-type strains acquired antibiotic resistance postoperatively. No adverse drug reactions to antibiotics were reported., Conclusions: Increased bacterial growth and emergence of resistant strains were observed on intranasal septal splints despite prophylactic antibiotic treatment. Nonetheless, this did not translate into clinical infection. Thus, considering antibiotics overuse and increasing bacterial resistance, further research is needed to determine the role of antibiotic prophylaxis in the setting of intranasal splints.

Purpose: To carry out a pilot study to evaluate the efficacy of a novel, drivable endoscope (the Peregrine™ Drivable ENT Scope), compared to standard rigid endoscopes in the access, visualization, and irrigation of the paranasal sinus anatomy., Methods: A prospective, multi-center, feasibility study was conducted on seventeen subjects who underwent primary functional endoscopic sinus surgery and were evaluated with the drivable endoscope and standard, rigid endoscopes (0°, 30° and 70°, as applicable). A CT scan was available for image guidance, as needed. The primary efficacy endpoint was the ability to access and visualize sinonasal anatomic landmarks. Secondary endpoints included device usability, as measured by a usability questionnaire given to surgeons postoperatively; the device's ability to irrigate the sinuses and patient reports of tolerability and pain during postoperative procedures., Results: The drivable endoscope success rate in visualizing all paranasal sinus anatomic landmarks was 55.6% better than the standard rigid endoscopes: 98.3% (178/181) versus 42.7% (76/178); p < 0.001. Surgeons rated scores of over 4 (on a 1-5 scale) for the usability of the drivable endoscope to enter the maxillary, frontal and sphenoid sinuses. The ability to irrigate the sinuses using the drivable endoscope was given a mean score of 4.3, and image quality was given a mean score of 3.4. The three patients evaluated postoperatively reported low pain and high tolerability scores with the drivable endoscope., Conclusions: These preliminary results indicate that the drivable endoscope is effective, easy to use and highly tolerable in sinonasal endoscopy.

Background: The impact on quality of life (QoL) of bilateral inferior turbinate reduction (BITR) performed in the setting of endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) has been a point of controversy. The aim of this study was to determine whether addition of BITR to ESS is associated with improved QoL when compared with ESS alone., Methods: This study presented findings a multi-institutional, retrospective analysis of a prospective open cohort of patients electing ESS for failed medical management of CRS. QoL parameters were compared between patients who underwent ESS alone vs those who underwent ESS with BITR., Results: A total of 571 patients with CRS who elected to undergo ESS were identified. Sixty-one of these patients also underwent concurrent BITR, whereas 510 patients underwent ESS without BITR. Mean length of follow-up was 15.1 months. Comparison between baseline and last postoperative QoL, olfaction, and endoscopic scores revealed significant improvement in both groups. Overall, BITR surgery was not significantly associated with clinically significant incremental improvement in QoL in either the polyp or non-polyp group. Nevertheless, statistically significant improvement was noted for the nasal congestion/blockage symptom in polyp patients (p = 0.006) and in primary surgery patients (p = 0.027) who underwent BITR., Conclusion: BITR in the setting of ESS for CRS is not associated with significant incremental improvement in overall QoL vs ESS alone. However, BITR in polyp and primary surgery patients undergoing ESS appears to offer a significant incremental improvement in nasal congestion/blockage symptoms compared with ESS alone. Future studies are warranted to better corroborate these findings., (© 2019 ARS-AAOA, LLC.)

Background: Recurrent periorbital cellulitis (RPOC) associated with rhinosinusitis is rarely noted and scarcely discussed in the literature. The aim of our study was to analyze the characteristics and disease course of a group of pediatric patients with RPOC., Methods: The medical records of all pediatric patients with a diagnosis of RPOC treated in a tertiary children's hospital were retrieved. Included were patients with a history of two or more episode of RPOC., Results: A total of 14 children were included. Mean follow up was 3 years (SD ± 2.5). Median age of first POC episode was 12 months (range 5 months-12 years). Overall, 75 events of RPOCs were documented. A median of 3 events per patient was noted (range 2-16). Preseptal cellulitis was diagnosed in all but five patients, in whom orbital cellulitis or subperiosteal abscess were identified, one following failure of conservative treatment, and the remaining at first presentation or recurrence. Rhinorrhea was present in only five patients (35%). The majority of patients were treated with intra-venous antibiotics. Imaging studies were performed in all patients revealing ethmoidal sinusitis in all patients, with lamina papyracea dehiscence in two patients. Immune deficiency was diagnosed in one patient. Endoscopic sinus surgery was performed in seven patients, in four as preventive procedure and in three during an acute phase. Post-operative recurrent disease was noted in two patients that were operated during the acute phase., Conclusions: RPOC is a rare entity. Rhinosinusitis should be suspected in events of recurrent preseptal cellulitis even in the absence of nasal symptoms. CT scan is diagnostic for sinus origin of disease and possible anatomical abnormalities. In the majority of patients no evident etiology was identified. Elective Surgery or prophylactic antibiotic treatment should be strongly considered in this subgroup of patients as it seems beneficial., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Orbital complications of rhinosinusitis in adults are scarcely discussed in the literature., Objective: To review our experience with the management of orbital complications of rhinosinusitis in the adult patient population and identify key factors in the characteristics and management of these patients., Design: Retrospective case series during the years 2004 to 2016 in a tertiary referral center including all patients with rhinosinusitis and orbital complications., Main Outcomes and Measures: Severity of complications, risk factors, clinical, imaging and microbiological data, treatment outcomes., Results: Seventy patients were identified. Median age at diagnosis was 38 years. In 57%, complications were associated with acute rhinosinusitis and in 43% with chronic rhinosinusitis, most of whom had a history of previous sinus surgery. Thirty-five percent of patients received antibiotics prior to admission. The majority of the previously operated patients (61%) had some form of orbital wall dehiscence noted on imaging. Preseptal cellulitis was the most common complication (61.5%) encountered, followed by orbital cellulitis (23%), sub-periosteal abscess (11.5%), orbital abscess (3%), and cavernous sinus thrombosis (1.5%). Gram-positive bacteria were more commonly isolated from acute rhinosinusitis patients and gram-negative bacteria from chronic rhinosinusitis (CRS) patients. Complete recovery was noted in all patients, of whom 85% were managed conservatively. All, but 1 patient, with an abscess or cavernous sinus thrombosis required surgical drainage. Older age was the only risk factor identified for severe complications., Conclusions: In contrast to the pediatric population, CRS is very common in adults with orbital complications of rhinosinusitis, with previous sinus surgery and orbital wall dehiscence being noticeably common. Older patients are at risk for more severe complications. Conservative treatment suffices in patients with preseptal and orbital cellulitis. In more advanced stages, surgical drainage is advocated with excellent results. Larger cohort studies are needed to further investigate this patient group.

Objectives: Fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) has been increasingly used in the past decade. Incidental FDG-avid findings are encountered in these studies, several of which with clinical significance. However, the significance of incidental FDG-avid sinonasal findings has not been studied to date., Study Design: Retrospective cohort study., Setting: A single tertiary medical center., Materials and Methods: The medical records were reviewed of patients with incidental sinonasal positive FDG uptake between 2007 and 2016 who referred for further otolaryngological diagnostic workup., Results: A total of 26 patients were identified, all of whom underwent a diagnostic surgical procedure. Histopathology revealed chronic inflammation (n = 12, 46.1%), malignancy (n = 7, 26.9%), inverted papilloma (n = 4, 15.5%), and fungal infections (n = 3, 11.5%). A unilateral maxillary sinus with FDG uptake was documented for 16 (61.5%) patients. CT evidence of bilateral disease and mucosal or sinus wall thickening correlated with inflammatory disease., Conclusions: Incidental lesions with positive FDG uptake in the sinonasal cavities are at a high risk (40%) of being neoplastic. A diagnostic biopsy is advocated in these cases.

Introduction: Survival rates of solid organ transplant recipients are steadily increasing. Chronic immunosuppression is a key to sustain the transplanted organ. Thus, these patients are at a higher risk for fulminant disease and severe complications of rhinosinusitis (RS). Surprisingly, this has been scarcely discussed in the literature., Objective: To analyze the characteristics and disease course of RS in solid organ transplant recipients., Materials and Methods: Retrospective study. Medical records of all solid organ transplant recipients with a diagnosis RS treated at a national transplant center between the years 2001 and 2016 were reviewed., Results: Of 4562 solid organ transplant recipients, a documented diagnosis of RS was identified only in 61 (1.3%) patients. Sixty-four patients presented with posttransplantation RS; of them, 54.5% had chronic RS (CRS) and the remaining 45.5% patients were diagnosed with acute RS. Microbial cultures grew almost exclusively bacterial pathogens. A documented invasive fungal infection was noted in only 2 patients. A total of 24 (40%) patients underwent endoscopic sinus surgery, the majority (22) for CRS. On subgroup analysis, surgical intervention was more frequent in lung transplant recipients ( P = .005). Neither specific disease nor surgical complications were found., Conclusions: Interestingly, acute fulminant infection or sinusitis complications in solid organ transplant patients were much lower than expected. CRS in this patient group was less frequent than expected as well. Whether chronic immunosuppression minimizes the likelihood for CRS deserves further investigation. A more surgically oriented approach in CRS patients may be favored early in the management course of medically refractory patients in light of patients excellent outcomes.

Background: Endoscopic sinus surgery (ESS) is often recommended for symptomatic patients with recurrent acute or chronic rhinosinusitis who have failed conservative treatment. Postoperative care has been felt to be critical for both maintaining the surgical patency of the operated sinuses and improving patient symptoms. Debridement of the sinonasal cavities is one such postoperative care measure that has frequently been studied in the literature, often with conflicting conclusions., Objectives: To assess the effects of postoperative sinonasal debridement versus no debridement following endoscopic sinus surgery., Search Methods: The Cochrane ENT Information Specialist searched the ENT Trials Register; Central Register of Controlled Trials (CENTRAL, via the Cochrane Register of Studies); PubMed; EMBASE; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 21 May 2018., Selection Criteria: Randomised controlled trials comparing postoperative nasal debridement versus no debridement in adult patients with recurrent acute or chronic rhinosinusitis undergoing endoscopic sinus surgery. We included studies in which the patients acted as self-controls (i.e. one side of the nose underwent debridement and the other side did not) only for the secondary endoscopy outcomes., Data Collection and Analysis: We used the standard methodological procedures expected by Cochrane. Our primary outcome measures were: health-related quality of life, disease severity (patient-reported symptom scores) and significant adverse effects (bleeding requiring intervention, severe pain, iatrogenic injury). Secondary outcomes were: postoperative endoscopic appearance of the sinonasal surgical cavities (endoscopic scores), recorded use of postoperative medical treatment and rate of revision surgery. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics., Main Results: We included four studies (152 participants), with a follow-up duration ranging from three months to 12 months. In two studies patients acted as self-controls, i.e. one side of the nose underwent debridement and the other side did not ('split-nose' studies). The risk of bias in all studies was high, mostly due to the inability to blind the patients to the debridement procedure.Primary outcomesDisease-specific health-related quality of life scoresOnly one study (58 participants) provided data for disease-specific health-related quality of life. At six months follow-up, lower disease-specific health-related quality of life scores, measured using the Sino-Nasal Outcome Test-22 (SNOT-22, range 0 to 110), were noted in the debridement group but the difference was not statistically significant (9.7 in the debridement group versus 10.3 in the control group, P = 0.47) (low-quality evidence).Disease severity (patient-reported symptom score)Only one study (60 participants) provided data for disease severity measured by visual analogue scale (VAS) score. No significant differences in total symptom score were observed between groups postoperatively (low-quality evidence).Significant adverse effectsSignificant adverse effects related to the debridement procedure were not reported in any of the included studies, however it is not clear whether data regarding adverse effects were not collected or if none were indeed observed in any of the included studies.Secondary outcomesAll four studies assessed thepostoperative endoscopic appearance of the sinonasal cavities using the Lund-Kennedy score (range 0 to 10). A pooled analysis of endoscopic scores in the two non 'split-nose' studies revealed better endoscopic scores in the debridement group, however this was not a statistically significant difference (mean difference -0.31, 95% confidence interval (CI) -1.35 to 0.72; I² = 0%; two studies; 118 participants) (low-quality evidence). A sub-analysis of the adhesion formation component of the endoscopic score was available for all four studies and revealed a significantly lower adhesion rate in the debridement group (risk ratio 0.43, 95% CI 0.28 to 0.68; I² = 29%; four studies; 152 participants). Analysis of the number needed to treat to benefit revealed that for every three patients undergoing debridement, the endoscopic score would be decreased by one point in one patient. For every five patients undergoing debridement adhesion formation would be prevented in one patient.Use of postoperative medical treatment was reported in all studies, all of which recommended nasal douching. Steroids (systemic or nasal) were administered in two studies. However, the data were very limited and heterogeneous, therefore we could not analyse the impact of concomitant postoperative medical treatment.The rate of revision surgery was not reported in any of the included studies, however it is not clear whether these data were not recorded or if there were no revision surgeries in any of the included studies., Authors' Conclusions: We are uncertain about the effects of postoperative sinonasal debridement due to high risk of bias in the included studies and the low quality of the evidence. Sinonasal debridement may make little or no difference to disease-specific health-related quality of life or disease severity. Low-quality evidence suggests that postoperative debridement is associated with a significantly lower risk of adhesions at three months follow-up. Whether this has any impact on longer-term outcomes is unknown.

Background: Packing of the middle meatus and ethmoid cavities is a common practice in endoscopic sinus surgery (ESS), but its necessity recently has been challenged. The aim of this study was to formulate a decision-analysis model to determine the need for packing in ESS and identify variables affecting the decision., Methods: A systematic review of the literature was conducted for all randomized control trials comparing packing to no packing in ESS, and a decision-analysis model was generated. Probabilities and utilities were derived from the literature. Sensitivity analysis was used to determine which variables most affected the model., Results: No packing was associated with better expected utilities than packing. On sensitivity analysis, packing was preferred when the disutility of no packing outweighed the disutility of packing, and when the probability for synechiae was greater than 35% without packing or lower than 2% with packing. When the component of packing removal was subtracted from the overall disutility simulating absorbable packing, the results favored packing., Conclusion: Our decision-analysis model indicates that middle meatal packing is not advantageous for patients undergoing ESS. Absorbable packing materials have a less adverse effect on quality of life than nonabsorbable materials., Level of Evidence: 1a. Laryngoscope, 127:1506-1512, 2017., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

Clinically useful molecular tools to triage gastric cancer patients are not currently available. We aimed to develop a molecular tool to predict gastric cancer risk in endoscopy-driven biopsies obtained from high-risk gastric cancer clinics in low resource settings.We discovered and validated a DNA methylation biomarker panel in endoscopic samples obtained from 362 patients seen between 2004 and 2009 in three high-risk gastric cancer clinics in Lima, Perú, and validated it in 306 samples from the Cancer Genome Atlas project ("TCGA"). Global, epigenome wide and gene-specific DNA methylation analyses were used in a Phase I Biomarker Development Trial to identify a continuous biomarker panel that combines a Global DNA Methylation Index (GDMI) and promoter DNA methylation levels of IRF4, ELMO1, CLIP4 and MSC.We observed an inverse association between the GDMI and histological progression to gastric cancer, when comparing gastritis patients without metaplasia (mean = 5.74, 95% CI, 4.97-6.50), gastritis patients with metaplasia (mean = 4.81, 95% CI, 3.77-5.84), and gastric cancer cases (mean = 3.38, 95% CI, 2.82-3.94), respectively (p < 0.0001). Promoter methylation of IRF4 (p < 0.0001), ELMO1 (p < 0.0001), CLIP4 (p < 0.0001), and MSC (p < 0.0001), is also associated with increasing severity from gastritis with no metaplasia to gastritis with metaplasia and gastric cancer.Our findings suggest that IRF4, ELMO1, CLIP4 and MSC promoter methylation coupled with a GDMI>4 are useful molecular tools for gastric cancer risk stratification in endoscopic biopsies.

Severe forms of chronic rhinosinusitis (CRS), a common upper airway inflammatory disorder, are associated with nasal polyps (NPs). NP disease is ameliorated by glucocorticoid (GC) treatment, whose cellular effects are poorly understood. We therefore assessed the influence of GC therapy on NPs in CRS patients, focusing on regulatory T (T reg ) cells. T reg cell populations were analyzed by flow cytometry in NPs and control tissues from GC-treated CRS patients and controls. After GC exposure, selective expansion of T reg cells was seen within NPs, and not blood or adjacent ethmoid tissues. To confirm direct GC effects, NPs from the same patients were biopsied prior to, and following, 1week of oral GC exposure. Direct expansion of Tregs into the same NP bed was detected in 4/4 CRS patients following GC exposure. T reg cell spikes into NPs were secondary to cellular recruitment given limited Ki67 expression within these regulatory cells. Chemokine gene expression profiling identified several chemokines, notably CCL4, induced within NPs upon GC treatment. Neutralization of chemokine receptor/ligand interactions using CCR4 small molecule antagonists reduced T reg migration towards GC-treated NPs in an ex vivo migration assay. Our findings suggest that the common use of GCs in the treatment of NP disease leads to recruitment of T reg cells from peripheral sites into NP tissues, which may be critical to the anti-inflammatory effect of GCs. Mechanistically T reg expansion appears to be conferred, in part, by chemokine receptor/ligand interactions induced following corticosteroid therapy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Immunosuppressive therapy places pediatric patients at risk of developing life-threatening sinonasal infections. Diagnosis and treatment are challenging owing to nonspecific signs and symptoms. The aim of this study was to present our department's experience with the surgical management of acute rhinosinusitis in immunosuppressed children., Methods: The records of all children with a hematologic or oncologic disease who underwent endoscopic sinus surgery (ESS) for acute rhinosinusitis from January 2005 to May 2014 were reviewed. Data were retrospectively collected on demographics, clinical and imaging characteristics, microbiology, pathology, treatment and outcome., Results: Thirty-four-immunosuppressed children underwent ESS for acute rhinosinusitis. Most patients had a fungal infection. Nineteen patients died at the end of follow-up; 10 deaths were infection-related. Facial swelling was the only symptom that correlated with death of infection. Relapse of the underlying disease, bone marrow transplantation, and long duration of neutropenia correlated with infection-related mortality. Fungal infection, and specifically Aspergillus, correlated with death from infection., Conclusions: ESS is a safe and efficient procedure for diagnosing and treating immunosuppressed pediatric patients with acute rhinosinusitis. Early detection and aggressive medical and surgical treatment, with control of underlying risk factors, are crucial to improve outcome.

Objective: The clinical presentation of sphenoid sinusitis can be highly variable. Rarely, sphenoid sinusitis may present with cranial nerve complications due to the proximity of these structures to the sphenoid sinus., Method: A case series from Rabin Medical Center and all cases of cranial nerves palsies secondary to sphenoid sinusitis that have been reported in the literature were reviewed., Results: Seventeen patients were identified. The abducent nerve was the most common cranial nerve affected (76%), followed by the oculomotor nerve (18%). One patient had combined oculomotor, trochlear and abducent palsies. The most common pathology was isolated purulent sphenoid sinusitis in 64% followed by allergic fungal sinusitis (AFS) in 18%, and fungal infection in 18%. 94% had an acute presentation. The majority (85%) received a combined intravenous antibiotics and surgical treatment. The remainder received conservative treatment alone. Complete recovery of cranial nerve palsy was noted in 82% during follow up., Conclusion: Sphenoid sinusitis presenting as diplopia and headaches is rare. A neoplastic process must be ruled out and early surgical intervention with intravenous antimicrobial therapy carry an excellent outcome with complete resolution of symptoms.

Background: Medullary thyroid carcinoma management consists mainly of surgical resection and is largely chemoresistant. There is ongoing effort to discover novel therapies for medullary thyroid carcinoma. Increased levels of heat shock proteins have been associated with multiple cancers and are being studied as potential therapeutic targets. The purpose of this study was to determine the expression levels of heat shock proteins 90 and 70 and of glucose related protein 78 in medullary thyroid carcinoma tissues compared with normal thyroid tissues., Methods: 20 tissue specimens of medullary thyroid carcinoma and 10 specimens of thyroids without malignancy were analyzed by immunohistochemistry., Results: Medullary thyroid carcinoma specimens showed 27% higher expression level of heat shock protein 90 immunostaining, and a 43% higher expression level of heat shock protein 70 immunostaining versus normal controls. These differences, however, were not statistically significant. A significantly higher expression level was noted for glucose related protein 78 in the medullary thyroid carcinoma specimens than in the controls., Conclusion: This study indicates increased expression levels of heat shock proteins 90 and 70 and glucose related protein 78 levels in medullary thyroid carcinoma. These findings, though preliminary imply that these proteins may have a role in medullary thyroid carcinoma's tumor biology and may have and future therapeutic options. Larger cohorts are needed to corroborate these results., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We investigated if prenatal exposures to tobacco smoke lead to changes in mitochondrial DNA content (mtDNA) in cord serum and adversely affect newborns' health. Umbilical cord serum cotinine levels were used to determine in utero exposure to smoking. Cord serum mtDNA was measured by quantitative polymerase chain reaction analysis of the genes coding for cytochrome c oxidase1 (MT-CO1) and cytochrome c oxidase2 (MT-CO2). Log transformed levels of mtDNA coding for MT-CO1 and MT-CO2 were significantly higher among infants of active smokers with higher serum level of cotinine (p < 0.05) and inversely associated with gestational age (p = 0.08; p = 0.02). Structural equation modeling results confirmed a positive association between cotinine and MT-CO1 and2 (p < 0.01) and inverse associations with gestational age (p = 0.02) and IGF-1 (p < 0.01). We identified a dose-dependent increase in the level of MT-CO1 and MT-CO2 associated to increased cord serum cotinine and decreased gestational age.

Objective: Malignant external otitis (MEO) is an aggressive infection, primarily affecting elderly diabetic patients. It begins in the external ear canal and spreads to adjacent structures. This study investigated the clinical characteristics of patients diagnosed and treated for MEO and analyzed factors affecting patient outcomes., Study Design: Historical cohort., Setting: Tertiary medical center., Methods: Medical records of all patients diagnosed and treated for MEO from 1990 to 2013, were retrospectively reviewed. Clinical features, laboratory, imaging and outcomes were analyzed., Results: 88 patients were included, mean age was 73±11.5years, 61 (69%) were male. Of these, 75% had diabetes. Mean follow-up was 60months. The most common presenting symptoms were otalgia (89%), external ear canal edema (86%) and otorrhea (84%). Pseudomonas aeruginosa was isolated in 61% of ear cultures. All patients were treated with antibiotics, 22% had surgery and 8% hyperbaric oxygen. Overall survival rate was 38% in 5years, with disease specific mortality 14%. DM, facial nerve palsy, positive CT scan and age above 70 were found to correlate and predict disease-specific mortality., Conclusions: MEO carries a grave prognosis. The presence of two or more of the following features, DM, facial nerve palsy, positive CT scan and age above 70, predicts poor outcome, and highlights the need for prolonged, vigorous treatment., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Although the safety of topical nasal steroids is well established for nasal spray forms, data regarding the safety of steroid irrigations is limited. We studied the effect of long-term budesonide nasal irrigations (>6 months) on hypothalamic-pituitary-adrenal axis (HPAA) function and intraocular pressure (IOP) in patients post-endoscopic sinus surgery., Methods: This was retrospective case series. Adrenal function was assessed by using the high-dose cosyntropin stimulation test., Results: A total of 48 patients were assessed, with a mean duration of budesonide irrigations of 22 months. Stimulated cortisol levels were abnormally low in 11 patients (23%). None reported to have symptoms of adrenal suppression. Three of 4 patients who repeated the study being off budesonide for at least 1 month returned to near normal levels. Logistic regression analysis revealed that concomitant use of both nasal steroid sprays and pulmonary steroid inhalers was significantly associated with HPAA suppression (p = 0.024). Patients with low stimulated cortisol levels were able to continue budesonide irrigations under the supervision of an endocrinologist without frank clinical manifestations of adrenal insufficiency. IOP was within normal limits in all patients., Conclusion: Long-term use of budesonide nasal irrigations is generally safe, but asymptomatic HPAA suppression may occur in selected patients. Concomitant use of both nasal steroid sprays and pulmonary steroid inhalers while using daily budesonide nasal irrigations is associated with an increased risk. Rhinologists should be alerted to the potential risks of long-term use of budesonide nasal irrigations, and monitoring for HPAA suppression may be warranted in patients receiving long-term budesonide irrigation therapy., (© 2016 ARS-AAOA, LLC.)

There are only limited data in the literature, and none specifically from the Middle East, on the pathogenic bacteria in chronic rhinosinusitis (CRS) as opposed to healthy nasal cavities and their association with disease severity. The present study was conducted in the department of head and neck surgery of a tertiary medical center. Middle meatal swabs were taken preoperatively from patients with CRS with nasal polyposis (CRSwNP) (n = 60), CRS without nasal polyposis (CRSsNP) (n = 50), and control patients with septal deviation (n = 26) or no nasal abnormalities (n = 27). Culture findings were compared among the groups and correlated with CRS severity. Positive pathogenic culture rates were 78% in the CRSwNP group and 64% in the CRSsNP group. Twenty pathogenic bacterial species were identified; the most common was Staphylococcus aureus (27%). The most common Gram-negative isolate was Citrobacter spp. (17%). Gram-negative species were significantly more prevalent in the CRSwNP group than the others. Mean Lund-Mackay scores were 12.8 in the CRSwNP group and 6.9 in the CRSsNP group, and were unrelated to the culture findings. Positive culture rates were significantly higher in the septal deviation (54%) than the nasal healthy group (26%), although both values were significantly lower than in the CRS groups. In conclusion, patients with CRS have higher rates of bacterial isolates than patients without CRS. CRSwNP is associated with more Gram-negative bacteria than CRSsNP, regardless of disease severity. The relatively high positive culture rate in patients with septal deviation merits investigation., (© 2016 S. Karger AG, Basel.)

We examined the relationship between the O(6)-methylguanine-methyltransferase (MGMT) methylation status and clinical outcomes in newly diagnosed glioblastoma multiforme (GBM) patients who were treated with Gliadel wafers (Eisai, Tokyo, Japan). MGMT promoter methylation has been associated with increased survival among patients with GBM who are treated with various alkylating agents. MGMT promoter methylation, in DNA from 122 of 160 newly diagnosed GBM patients treated with Gliadel, was determined by a quantitative methylation-specific polymerase chain reaction, and was correlated with overall survival (OS) and recurrence-free survival (RFS). The MGMT promoter was methylated in 40 (32.7%) of 122 patients. The median OS was 13.5 months (95% confidence interval [CI] 11.0-14.5) and RFS was 9.4 months (95% CI 7.8-10.2). After adjusting for age, Karnofsky performance score, extent of resection, temozolomide (TMZ) and radiation therapy (RT), the newly diagnosed GBM patients with MGMT methylation had a 15% reduced mortality risk, compared to patients with unmethylated MGMT (hazard ratio 0.85; 95% CI 0.56-1.31; p=0.46). The patients aged over 70 years with MGMT methylation had a significantly longer median OS of 13.5 months, compared to 7.6 months in patients with unmethylated MGMT (p=0.027). A significant difference was also found in older patients, with a median RFS of 13.1 versus 7.6 months for methylated and unmethylated MGMT groups, respectively (p=0.01). Methylation of the MGMT promoter in newly diagnosed GBM patients treated with Gliadel, RT and TMZ, was associated with significantly improved OS compared to the unmethylated population. In elderly patients, methylation of the MGMT promoter was associated with significantly better OS and RFS., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objectives/hypothesis: To analyze complications associated with nasoseptal flap elevation and reconstruction in endoscopic skull base surgery., Study Design: Case series., Methods: Retrospective chart review of all patients who underwent nasoseptal flap procedure in our institution between 2008 and 2013., Results: A total of 121 patients were identified with a mean follow-up time of 10.4 months. Complications associated with this procedure occurred in 33 patients (27%). The majority of complications were related to the septal donor site and included septal perforation, cartilage necrosis, and prolonged crusting. Other complications included intraoperative injury to the flap pedicle (n = 4) or recurrent/persistent cerebrospinal fluid leak occurring in the early postoperative period (n = 7). Long-term quality-of-life data assessed via Sinonasal Outcome Test-22 questionnaires did not reveal notable differences when compared to preoperative scores., Conclusion: The complication rate associated with nasoseptal flap elevation and inset is higher than previously described. The majority of complications became manifest beyond the immediate postoperative period and were associated with the septal donor site, including septal perforation, prolonged crusting, and cartilage necrosis. We hypothesize that donor site morbidity may be related to compromise of the contralateral septal vascular supply during the procedure. The range and frequency of complications of nasal septal flap surgery should be considered in counseling patients who may receive a nasoseptal flap for skull base reconstruction., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

Spontaneous meningoencephalocele (SME) of the sphenoid wing is a rare cause of cerebrospinal fluid (CSF) leakage. Surgical closure of the fistula is usually required. The approach taken depends on the location of the defect and the extension of the meningoencephalocele. The endoscopic transpterygoid approach may be useful. We prospectively analyzed the three cases of SME of the sphenoid wing with lateral sphenoid sinus extension treated endoscopically at Stanford over the last 3 years with regard to imaging findings, operative technique, and operative morbidity. In our three cases, the extent of pterygopalatine fossa (PPF) exposure undertaken, complete in one and partial in two, depended on the defect site. Follow-up ranged from 17 to 25 months. The fistula was completely closed in all three cases. Extant literature reports a 97% rate of successful closure (N = 65 of 67, with a mean follow-up of 25 months) and no major complications. Endoscopic transpterygoid repair is a useful, safe alternative to traditional approaches for repair of SME of the sphenoid wing. Its feasibility depends on the site of the defect, which can be identified by preoperative imaging. Larger PPF exposure and postoperative lumbar drainage of CSF can be useful and have a low risk of morbidity.