Cranial nerve V2 and Vidian nerve trauma secondary to lateral pterygoid recess encephalocele repair.

BACKGROUND: The incidence of adverse sequelae related to trauma of cranial nerve V2 (V2) and the Vidian nerve (VN) during endoscopic pterygoid recess repair (PRR) of lateral sphenoid encephalocele is insufficiently reported in the medical literature. As part of our quality assessment and improvement program we sought to analyze the incidence and severity of V2 and VN injury during a 9-year experience (2010-2018) with PRR. METHODS: Hypoesthesia, paresthesia, and dry eye and their impact on patient quality of life were sought through chart review and a self-reported 0 to 5 Likert scale for each symptom. RESULTS: Thirty-five patients underwent repair of spontaneous cerebrospinal-fluid (CSF) rhinorrhea, with 11 consecutive patients undergoing endoscopic PRR. Mean follow-up for PRR was 32.5 months (range, 2.4 to 103.3 months). Although definitive management resulted in 100% success, 1 required secondary treatment. Eight patients were available for long-term follow-up (72.7%) and completed a symptom severity questionnaire using a Likert-scale. All patients observed either hypoesthesia, paresthesia, or dry eye of varying gradation (scale, 0 to 5). None described disabling symptoms, and some reported gradual improvement. Numbness, paresthesia, and dry eye were reported by 6 of 8 (75%), 5 of 8 (62.5%), and 4 of 8 (50%) patients, respectively. The mean Likert score among the 8 patients who completed this questionnaire noticing hypoesthesia, paresthesia, and dry eye was 2.6, 1.3, and 1.8, respectively. CONCLUSION: Meticulous surgical technique is paramount for successful PRR and minimizing nerve injury, yet the anatomic variation of the lateral pterygoid recess can be challenging, and neural injury is a real risk. Preoperatively, patients should be counseled that although V2 or VN injury is common, most patients describe resulting symptoms to be rarely bothersome.

Isolated leptomeningeal progression from sinonasal carcinomas: Implications for staging workup and treatment.

PURPOSE: To evaluate the rate and risk factors of isolated leptomeningeal progression in sinonasal carcinomas. METHODS: We retrospectively reviewed imaging and clinical records to determine progression patterns, and estimated rates using the Kaplan-Meier method. We evaluated risk factors using proportional hazard regression. RESULTS: We analyzed 120 patients who received adjuvant or primary radiotherapy for sinonasal carcinomas. Most patients had T4 disease (68%) and underwent surgery (84%) and chemotherapy (72%). Twenty-seven (23%) patients developed distant metastases (DM), including 20 (17%) with isolated DMs. Leptomeningeal progression was the most common site of isolated DMs (n = 9; 45%) with an average disease-free interval of 1.2 years (0.1-4.3 years). High-grade histology (P = 0.0003), intracranial invasion (P < 0.0001), and neuroendocrine histology (P = 0.06) were associated with increased risk. CONCLUSIONS: Isolated leptomeningeal progression is a common pattern of DM in advanced sinonasal carcinomas. We recommend adding cerebrospinal fluid cytology and contrast-enhanced spine MRI to routine staging evaluations for high-risk patients.

Outcomes of Sinonasal Cancer Treated With Proton Therapy.

PURPOSE: To report disease outcomes after proton therapy (PT) for sinonasal cancer. METHODS AND MATERIALS: Eighty-four adult patients without metastases received primary (13%) or adjuvant (87%) PT for sinonasal cancers (excluding melanoma, sarcoma, and lymphoma). Common histologies were olfactory neuroblastoma (23%), squamous cell carcinoma (22%), and adenoid cystic carcinoma (17%). Advanced stage (T3 in 25% and T4 in 69%) and high-grade histology (51%) were common. Surgical procedures included endoscopic resection alone (45%), endoscopic resection with craniotomy (12%), or open resection (30%). Gross residual disease was present in 26% of patients. Most patients received hyperfractionated PT (1.2 Gy [relative biological effectiveness (RBE)] twice daily, 99%) and chemotherapy (75%). The median PT dose was 73.8 Gy (RBE), with 85% of patients receiving more than 70 Gy (RBE). Prognostic factors were analyzed using Kaplan-Meier analysis and proportional hazards regression for multiple regression. Dosimetric parameters were evaluated using logistic regression. Serious, late grade 3 or higher toxicity was reported using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4. The median follow-up was 2.4 years for all patients and 2.7 years among living patients. RESULTS: The local control (LC), neck control, freedom from distant metastasis, disease-free survival, cause-specific survival, and overall survival rates were 83%, 94%, 73%, 63%, 70%, and 68%, respectively, at 3 years. Gross total resection and PT resulted in a 90% 3-year LC rate. The 3-year LC rate was 61% for primary radiation therapy and 59% for patients with gross disease. Gross disease was the only significant factor for LC on multivariate analysis, whereas grade and continuous LC were prognostic for overall survival. Six of 12 local recurrences were marginal. Dural dissemination represented 26% of distant recurrences. Late toxicity occurred in 24% of patients (with grade 3 or higher unilateral vision loss in 2%). CONCLUSIONS: Dose-intensified, hyperfractionated PT with or without concurrent chemotherapy results in excellent LC after gross total resection, and results in patients with gross disease are encouraging. Patients with high-grade histology are at greater risk of death from distant dissemination. Continuous LC is a major determinant of survival justifying aggressive local therapy in nearly all cases.

International Consensus Statement on Allergy and Rhinology: Rhinosinusitis.

BACKGROUND: The body of knowledge regarding rhinosinusitis(RS) continues to expand, with rapid growth in number of publications, yet substantial variability in the quality of those presentations. In an effort to both consolidate and critically appraise this information, rhinologic experts from around the world have produced the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR:RS). METHODS: Evidence-based reviews with recommendations(EBRRs) were developed for scores of topics, using previously reported methodology. Where existing evidence was insufficient for an EBRR, an evidence-based review (EBR)was produced. The sections were then synthesized and the entire manuscript was then reviewed by all authors for consensus. RESULTS: The resulting ICAR:RS document addresses multiple topics in RS, including acute RS (ARS), chronic RS (CRS)with and without nasal polyps (CRSwNP and CRSsNP), recurrent acute RS (RARS), acute exacerbation of CRS (AECRS), and pediatric RS. CONCLUSION: As a critical review of the RS literature, ICAR:RS provides a thorough review of pathophysiology and evidence-based recommendations for medical and surgical treatment. It also demonstrates the significant gaps in our understanding of the pathophysiology and optimal management of RS. Too often the foundation upon which these recommendations are based is comprised of lower level evidence. It is our hope that this summary of the evidence in RS will point out where additional research efforts may be directed.

Recalcitrant rhinosinusitis, innate immunity, and mannose-binding lectin.

BACKGROUND: Mannose-binding lectin (MBL) is a protein produced by the liver that participates in innate immunity by tagging the surface of microbes for opsonization. Mannose-binding lectin deficiency is present in 7% of the population and has been implicated in recurrent respiratory tract infections in children. Mannose-binding lectin deficiency has not been explored in rhinosinusitis but is associated with increased mortality in adult pneumococcal infection. The purpose of this report is to describe a tertiary rhinology patient experience with MBL deficiency and recalcitrant rhinosinusitis. METHODS: This retrospective case series report characterizes predominantly adult patients with low MBL levels from January 2010 to June 2012. Indications for MBL testing, sinus culture data, immunological testing results, and treatments used to control rhinosinusitis are described. RESULTS: Mannose-binding lectin levels were deficient in 12 of 36 patients (33.3%) tested. IgG subclasses were abnormally low in 5 of 12 patients; IgA was normal in 11 of 12 patients; and IgM was normal in 11 of 12 patients. Staphylococcus aureus, coagulase-negative Staphylococcus species, and Pseudomonas aeruginosa, known to be "tagged" by MBL, were the most common organisms grown on culture. Treatments included culture directed systemic antimicrobial therapy and topical steroids/antibiotics. CONCLUSION: Mannose-binding lectin, an important component of the lectin complement pathway and innate immunity, is possibly associated with recalcitrant adult rhinosinusitis. Steroid/antibiotic irrigations appear to benefit patients with recalcitrant rhinosinusitis and possibly those with MBL deficiency. Given that the prevalence of MBL deficiency in this case series is 4 times that seen in the normal population, additional investigations are warranted to further elucidate the role of MBL deficiency in rhinosinusitis.

Evidence that human papillomavirus causes inverted papilloma is sparse.

BACKGROUND: Controversy exists regarding the pathogenesis of inverted papilloma as it relates to the involvement of human papillomavirus (HPV). The purpose of this report is to describe the prevalence of HPV in nondysplastic, "early inverted papilloma" and to summarize HPV detection rates in the general population and in other HPV related neoplasia. METHODS: This case series report characterizes consecutive inverted papilloma patients from January 2005 to August 2012 with regard to smoking history, dysplasia, and HPV detection rates. Presence or absence of low/high risk HPV was determined by standardized in situ hybridization DNA probes. Medline literature review was performed to determine the prevalence of HPV in inverted papilloma without moderate or severe dysplasia. RESULTS: Thirty-six consecutive patients were identified with an average age of 63.6 (range, 40-84) years; gender: 23 men, 13 women. More than half (55%) were active or former smokers (14% active and 41% former). High/low risk HPV was present in 1 in 36 (2.7%) patients and 1 in 36 (2.7%) had mild dysplasia. In the literature review: (1) HPV was detected in 16.4% of inverted papilloma without dysplasia; (2) oral cavity HPV detection was 4.2% to 11.4% in the normal population; and (3) HPV was normally detected in 85% to 95% of HPV-related neoplasia. CONCLUSION: Given histological features of inverted papilloma and comparatively low detection rates of HPV in inverted papilloma without dysplasia (2.7%), as well as the summary of the world literature, HPV is not related to the initial pathogenesis of inverted papilloma or inverted papilloma's tendency to persist or recur. It is postulated that since inverted papilloma is more an inflammatory polyp, it is susceptible to secondary HPV infection because of its metaplasia. Tobacco and other causes of respiratory epithelium remodeling are more plausible explanations for the initial tissue transformation to inverted papilloma.

Fungal rhinosinusitis: a retrospective microbiologic and pathologic review of 400 patients at a single university medical center.

Fungal Rhinosinusitis (FRS) is a well known entity, but only in more recent times have the types of FRS been more fully defined. In this study, we evaluate the diagnosis of FRS in a single medical center. Cases were divided into 2 main categories, non-invasive and invasive. Non-invasive FRS included fungus ball (FB) and allergic fungal rhinosinusitis (AFRS). Invasive FRS included acute invasive fungal rhinosinusitis (AIFRS), chronic invasive fungal rhinosinusitis (CIFRS), and chronic invasive granulomatous fungal rhinosinusitis (CGFRS). Fungal culture data, if available was reviewed. 400 patients with FRS were identified. 87.25% were non-invasive (45% AFRS, 40% FB, and 2% combined AFRS and FB and 12.5% were invasive 11% AIFRS 1.2% CIFRS 0.5% CGFRS. One patient (0.25%) had combined FB/CGFRS. Aspergillus sp. or dematiaceous species were the most common fungi isolated in AFS while Aspergillus sp. was most common in FB and AIFRS. In our experience, most FRS is non-invasive. In our patient population, invasive FRS is rare with AIFRS representing >90% of cases. Culture data supports that a variety of fungal agents are responsible for FRS, but Aspergillus sp. appears to be one of the most common organisms in patients with FRS.

Atypical mycobacterium detection in refractory chronic rhinosinusitis.

OBJECTIVES: Atypical mycobacterium (AM) involvement in refractory chronic rhinosinusitis (CRS) is sought by some surgeons with customary acid-fast bacilli cultures (AFBC) in the operating room (OR). We evaluate our experience with AM in CRS by describing (1) associated risk factors, (2) species identified, and (3) frequency of positive cultures in clinic versus OR. STUDY DESIGN: Case series with chart review. SETTING: Tertiary rhinology practice. SUBJECTS AND METHODS: AFBC taken between 2005 and 2011 were identified from a microbiology laboratory database. Charts were reviewed for gender, age, medical history, risk factors for AM, pathogen types, and treatments, with statistical comparison using Pearson χ(2). The benefit of "targeted AFBC" for cases with high clinical suspicion was compared with "customary AFBC" in the OR. RESULTS: Thirty-seven patients were identified with AM, of which 10 had one or more risk factors for AM including foreign body (n = 4), non-HIV immune dysfunction (n = 4), and previous chemoradiation (n = 4). Six different AM species were identified: most frequently Mycobacterium abscessus (57.1%), followed by Mycobacterium avium-intracellulare complex (14.3%) and Mycobacterium chelonae (14.3%). "Targeted AFBC" from the outpatient setting were positive in 10 of 190 (5.3%) patients, whereas 10 of 373 (2.6%) patients of "customary AFBC" in the OR were positive (P = .12). Macrolide therapy was employed in 23 of 37 (62%) patients with AM-associated CRS but was not prescribed in patients with positive "customary AFBC" alone. CONCLUSION: AM-associated CRS is an uncommon condition that can occur in the absence of foreign body or overtly altered innate/adaptive immunity. Indications and efficacy of macrolide therapy, as well as the potential relationships between existence of AM in tap water, AM biofilms, and frequent use of nasal irrigations warrant further investigation in refractory CRS.

Oral antifungal therapy for Fusarium-associated chronic rhinosinusitis.

BACKGROUND: Fusarium is commonly reported as an organism found in fungus-associated chronic rhinosinusitis (CRS) yet it is known to be resistant to commonly used antifungal therapies. The goals of this work are to report the incidence of Fusarium-associated CRS in fungal cultures and to describe the treatment experience with oral antifungal agent aimed at this problem. METHODS: Patients with sinus cultures obtained from 2005 through 2008 were retrospectively identified and their medical records were evaluated. Cultures were obtained in patients with recalcitrant rhinosinusitis when purulent discharge was observed. Patient response to the therapy was measured upon the basis of self reported symptom improvements and endoscopic examination. RESULTS: In this 4-year period 2,570 outpatient fungal cultures were obtained and 194 (7.5%) were positive for Fusarium. These 194 positive cultures appeared in 94 individuals. Thirty-four tested positive multiple times. Twenty-three (24.5%) had severe recalcitrant CRS poorly responsive to standard therapies warranting antifungal therapy aimed at Fusarium. Fifteen individuals were treated with voriconazole, 5 with posaconazole, and 3 with both at separate times. Endoscopic evidence of initial improvement on therapy was evident in 16 of 23 patients (69.6%). Of 18 patients who could comment on their experience with the antifungal treatments, nearly 90% of them reported substantial improvement with the therapy. Nine (9/23; 39.1%) were forced to discontinue oral antifungal therapy due to untoward effects. CONCLUSION: Fusarium appears in 7.55% of outpatient cultures of CRS. Of the patients testing positive for Fusarium, 25% received oral antifungal therapy. A positive response was seen in 16 of 23 (69.6%) while receiving other standard therapies. Since Fusarium is not routinely sensitive to commonly used antifungal agents, it warrants special attention.

Rapid In-situ hybridization for dematiaceous fungi using a broad-spectrum oligonucleotide DNA probe.

Dematiaceous fungi are a diverse group of "darkly" pigmented fungi, which contain melanin in their cell walls and are commonly found in soil worldwide. Although morphology and histochemical stains may aid identification in tissue sections, these means for species identification are not specific. In-situ hybridization (ISH) for abundant fungal rRNA sequences may provide a means for detecting dematiaceous fungi. In this study, a 24-base synthetic biotin-labeled oligonucleotide probe targeting rRNA sequences of a variety of dematiaceous fungi was developed. This probe was tested on a cohort of 29 patients with culture-proven cases of dematiaceous fungal-associated rhinosinusitis (26 allergic fungal sinusitis, 2 fungal ball, and 1 acute invasive fungal sinusitis). Fungal cultures were positive for Alternaria species (10), Bipolaris species (5), Curvularia species (10), Cladosporium species (1), Scedosporium prolificans (1), Scopulariopsis species (1), and dematiaceous species, not otherwise specific (1). ISH showed positivity in fungal organisms in 24 of 29 specimens. ISH was negative in culture-proven examples of Rhizopus species, Aspergillus species, Fusarium species, Paecilomyces species, Histoplasmosis capsulatum, Candida species, and Blastomyces dermatitidis. ISH with a dematiaceous-specific fungal probe may be useful for differentiating dematiaceous fungi from other filamentous fungi in tissues, particularly those responsible for fungal rhinosinusitis.

In situ hybridization for specific fungal organisms in acute invasive fungal rhinosinusitis.

Acute invasive fungal rhinosinusitis (AIFRS) most commonly occurs in immunosuppressed patients. The identification of fungal subtypes is important for management, and cultures can be negative. We studied 55 specimens from 23 patients with AIFRS (Rhizopus sp, 6; Aspergillus sp, 8; Fusarium sp, 1; Alternaria sp, 1; and culture negative, 7) using in situ hybridization (ISH) with biotin-labeled oligonucleotide probes targeting Aspergillus sp, Fusarium sp, Rhizopus sp, and a sequence identified in dematiaceous fungi. Ribosomal RNA preservation was established by using a pan-fungal probe. Nucleic acid preservation was seen in 18 patients (33 specimens [60%]). ISH using the specific fungal probes highlighted the respective fungal organisms in all culture-positive cases with adequate negative controls. Of the 7 culture-negative AIFRS cases, 4 had preserved fungal sequences. Of these cases, 2 additional cases of Aspergillus and 1 additional case of dematiaceous species were identified. In our study, 60% of AIFRS cases had fungal nucleic acid preservation. ISH can effectively identify fungi in AIFRS. ISH for specific fungal pathogens may aid in species identification in specimens with negative cultures.

Proton pump inhibitor therapy improves symptoms in postnasal drainage.

BACKGROUND & AIMS: Gastroesophageal reflux is common among patients with postnasal drainage. We investigated whether proton pump inhibitor therapy improved symptoms in patients with postnasal drainage without sinusitis or allergies. METHODS: In a parallel-group, double-blind, multi-specialty trial, we randomly assigned 75 participants with continued symptoms of chronic postnasal drainage to groups that were given 30 mg of lansoprazole twice daily or placebo. Participants were followed up for 16 weeks. Symptoms were assessed at baseline and after 8 and 16 weeks. Ambulatory pH and impedance monitoring assessed presence of baseline reflux. The primary objective of the study was to determine if acid suppressive therapy improved postnasal drainage symptoms. The secondary objective was to assess if pH and impedance monitoring at baseline predicted response to treatment. RESULTS: Postnasal drainage symptoms improved significantly among patients given lansoprazole compared with placebo. After 8 and 16 weeks, participants given lansoprazole were 3.12-fold (1.28-7.59) and 3.50-fold (1.41-8.67) more likely to respond, respectively, than participants given placebo. After 16 weeks, median (interquartile) percent symptom improvements were 50.0% (10.0%-72.0%) for participants given lansoprazole and 5.0% (0.0%-40.0%) for participants given placebo (P = .006). Neither baseline presence of typical reflux symptoms nor esophageal physiologic parameters predicted response to therapy. CONCLUSIONS: Among participants with chronic postnasal drainage without evidence of sinusitis and allergies, twice-daily therapy with proton pump inhibitors significantly improved symptoms after 8 and 16 weeks. The presence of heartburn, regurgitation, abnormal levels of esophageal acid, or nonacid reflux did not predict response to therapy.

Outcomes of minimally invasive endoscopic resection of anterior skull base neoplasms.

OBJECTIVES/HYPOTHESIS: The objective of this study was to review clinical outcomes of minimally invasive endoscopic resection (MIER) for anterior skull base (ASB) neoplasms. STUDY DESIGN: Retrospective data review. METHODS: Data analysis was performed on all patients undergoing MIER from October 2000 to December 2008. RESULTS: Thirty-one patients with mean age of 58 years underwent MIER. Malignant and benign tumors were managed in 25 (80.6%) and six (19.4%) cases, respectively. Most common histopathologies were squamous cell carcinoma (six), esthesioneuroblastoma (five), mucosal melanoma (five), and sinonasal undifferentiated carcinoma (four). American Joint Committee on Cancer tumor staging was T3N0M0 and T4N0M0 in 14 (56%) and 11 (44%) of the malignant cases, respectively. Surgical resection with curative intent was performed in 28 cases (90.3%). Multilayered skull base reconstruction was performed in most patients; lumbar drains were used in eight cases (25.8%). Twenty-one patients (67.7%) were disease free, five patients (16.1%) were dead from disease, three patients (9.7%) were alive with disease, and two patients (6.5%) died from unrelated causes at mean follow-up of 31.7 months. CONCLUSIONS: This study validated technical feasibility of MIER for diversity of benign and malignant ASB histopathology. Majority of patients were able to avoid adjunct craniotomy, whereas lumbar drainage was utilized in selective cases. This surgical strategy resulted in low complication rate and acceptable disease-free survival in patients with advanced T3 and T4 malignant lesions. Future studies should focus on multicenter trials to facilitate more robust survival analysis and comparison to open surgical approaches.

Proton therapy for maxillary sinus carcinoma.

OBJECTIVES: To compare the dose-volume data of three-dimensional conformal proton therapy (3DCPT) versus intensity-modulated radiotherapy (IMRT) for a paranasal sinus malignancy. METHODS: 3DCPT and IMRT plans were created for a T4N0 maxillary sinus carcinoma. RESULTS: The target volume dose distributions were comparable for 3DCPT and IMRT. The mean and integral doses for all normal tissues were lower for 3DCPT. The maximum doses for both plans to the ipsilateral optic nerve/retina/lens, temporal lobe, pituitary, and brain exceeded tolerance doses. The contralateral parotid, lacrimal gland, and lens were avoided with 3DCPT. Neither 3DCPT nor IMRT exceeded the maximal tolerated dose for the brainstem, optic chiasm, contralateral temporal lobe, parotid, or lacrimal gland. CONCLUSIONS: Both 3DCPT and IMRT sufficiently covered the target volume(s). Although 3DCPT reduced the mean and integral dose to all of the normal tissues, both 3DCPT and IMRT irradiated the ipsilateral optic structures beyond acceptable tolerance doses.

Prospective analysis of epicutaneous testing for inhalant allergy: comparison of arm and back subsites with mRAST.

OBJECTIVES: 1) To compare epicutaneous testing (ET) from four skin subsites (forearm, upper arm, upper back, lower back) and 2) to compare ET to modified RAST (mRAST) for inhalant allergens. STUDY DESIGN: Prospective clinical trial. SUBJECTS AND METHODS: Fifty one patients underwent ET at four skin subsites and mRAST to six antigens and positive and negative controls. RESULTS: The forearm and upper back showed best sensitivity to positive controls and all subsites demonstrated similar specificity to negative controls. The forearm and upper back demonstrated best sensitivity and specificity for most antigens. No statistically significant differences were noted for antigen sensitivity and specificity for the four subsites. ET and mRAST agreed best on D. farinae and timothy grass and least on short ragweed and dog epithelium. CONCLUSION: This study confirms that forearm and upper back demonstrate very good sensitivity and specificity for positive and negative controls and most tested antigens. This has important diagnostic implications for clinical practice of inhalant allergy.

Esthesioneuroblastoma: 25-year experience at a single institution.

OBJECTIVES: To evaluate outcomes for patients with esthesioneuroblastoma treated at a single institution during a 25-year period. DESIGN: Eighteen patients with pathologic diagnosis of esthesioneuroblastoma between 1980 and 2004 were retrospectively identified. RESULTS: Two patients had Kadish A, seven had Kadish B, and nine had Kadish C disease. The mean follow-up was 71 months. Treatment regimens consisted of surgery alone (four patients), surgery followed by postoperative radiation (six patients), surgery followed by postoperative chemoradiotherapy (three patients), preoperative radiotherapy (two patients), preoperative chemoradiotherapy (one patient), chemoradiotherapy (one patient), and surgery plus chemotherapy (one patient). Surgical approaches (n = 17) consisted of 13 traditional craniofacial resections, one endoscopic-assisted cranionasal resection, and three minimally invasive endoscopic resections. The 10-year disease-specific survival was 80%. The overall recurrence-free survival at five and 10 years was 62% and 46%, respectively. Positive surgical margins and TNM staging predicted survival. CONCLUSION: Both endoscopic and open surgical approaches have been successful in treating a small number of esthesioneuroblastoma patients with high survival and low rate of surgical complications.