Spencer C. Payne

Endoscopic Transsphenoidal Surgery for Acromegaly: Remission Using Modern Criteria, Complications, and Predictors of Outcome

CONTEXT Despite the growing application of endoscopic transsphenoidal surgery (ETSS), outcomes for GH adenomas are not clearly defined. OBJECTIVE We reviewed our experience with ETSS with specific interest in remission rates using the 2010 consensus criteria, predictors of remission, and associated complications. DESIGN AND SETTING This was a retrospective single institution study. PATIENTS, INTERVENTIONS, AND OUTCOME MEASURES: Sixty acromegalic patients who underwent ETSS were identified. Remission was defined as a normal IGF-I and either a suppressed GH less than 0.4 ng/ml during an oral glucose tolerance test or a random GH less than 1.0 ng/ml. RESULTS Remission was achieved in all 14 microadenomas and 28 of 46 macroadenomas (61%). Tumor size, age, gender, and history of prior surgery were not predictive on multivariant analysis. In hospital postoperative morning GH levels less than 2.5 ng/ml provided the best prediction of remission (P < 0.001). Preoperative variables predictive of remission included Knosp score (P = 0.017), IGF-I (P = 0.030), and GH (P = 0.042) levels. New endocrinopathy consisted of diabetes insipidus in 5%, adrenal insufficiency in 5.4%, and new hypogonadism in 29% of men and 17% of women. However, 41% of hypogonadal men had normal postoperative testosterone levels and 83% of amenorrheic women regained menses. The most common complaints after surgery were sinonasal (36 of 60, 60%) resolving in all but two. CONCLUSIONS ETSS for GH adenomas is associated with high rates of remission and a low incidence of new endocrinopathy. Despite the panoramic views offered by the endoscope, invasive tumors continue to have lower rates of remission.

Endoscopic vs Microsurgical Transsphenoidal Surgery for Acromegaly: Outcomes in a Concurrent Series of Patients Using Modern Criteria For Remission

CONTEXT It is unclear whether endoscopic transsphenoidal surgery (ETSS) or microsurgical transsphenoidal surgery (MTS) is a superior surgical approach for pituitary adenomas. OBJECTIVE The objective of the study was to compare the outcome of surgery with ETSS and MTS by experienced pituitary surgeons using criteria of remission using current consensus criteria for acromegaly. DESIGN AND SETTING This was a retrospective review of prospectively recorded outcomes. The study was conducted at a tertiary referral center. Patients, Interventions, and Outcome Measures: Remission was defined as a normal IGF-I level and either suppressed GH less than 0.4 ng/mL during an oral glucose tolerance test or random GH less than 1.0 ng/mL. The Youden indices were calculated to determine the optimal cutoffs for using immediate postoperative GH levels to predict the results of later testing for remission. RESULTS Preoperative demographics and tumor characteristics were not significantly different between patients undergoing ETSS (72 patients) or MTS (41 patients). Overall, postoperative remission was achieved in 20 of 23 microadenomas (87%) and 59 of 90 macroadenomas (66%). Remission rates and perioperative complications were not significantly different between ETSS and MTS groups, except for self-reported sinusitis and alterations in taste or smell, which were significantly higher in patients treated with ETSS. Preoperative variables predicting remission in multivariate analysis included GH less than 45 ng/mL [odds ratio (OR) 6.4, P = .010)] and Knosp score of 0-2 (OR 6.8, P < .001). Postoperative in-hospital GH less than 1.15 ng/mL provided the best predictor of remission (OR 7.7, P < .001; sensitivity of 73%, specificity of 85%) defined by follow-up testing. CONCLUSIONS Outcomes of transsphenoidal surgery for acromegaly by experienced pituitary surgeons do not differ between endoscopic and microscopic techniques. Regardless of the mode of resection, patients with high preoperative GH levels and Knosp scores are less likely to achieve remission. An immediate postoperative GH level of less than 1.15 ng/mL provides the best immediate predictor of remission, but long-term outcomes are indicated.

Clinical Practice Guideline Otitis Media with Effusion (Update)

Objective This update of a 2004 guideline codeveloped by the American Academy of Otolaryngology—Head and Neck Surgery Foundation, the American Academy of Pediatrics, and the American Academy of Family Physicians, provides evidence-based recommendations to manage otitis media with effusion (OME), defined as the presence of fluid in the middle ear without signs or symptoms of acute ear infection. Changes from the prior guideline include consumer advocates added to the update group, evidence from 4 new clinical practice guidelines, 20 new systematic reviews, and 49 randomized control trials, enhanced emphasis on patient education and shared decision making, a new algorithm to clarify action statement relationships, and new and expanded recommendations for the diagnosis and management of OME. Purpose The purpose of this multidisciplinary guideline is to identify quality improvement opportunities in managing OME and to create explicit and actionable recommendations to implement these opportunities in clinical practice. Specifically, the goals are to improve diagnostic accuracy, identify children who are most susceptible to developmental sequelae from OME, and educate clinicians and patients regarding the favorable natural history of most OME and the clinical benefits for medical therapy (eg, steroids, antihistamines, decongestants). Additional goals relate to OME surveillance, hearing and language evaluation, and management of OME detected by newborn screening. The target patient for the guideline is a child aged 2 months through 12 years with OME, with or without developmental disabilities or underlying conditions that predispose to OME and its sequelae. The guideline is intended for all clinicians who are likely to diagnose and manage children with OME, and it applies to any setting in which OME would be identified, monitored, or managed. This guideline, however, does not apply to patients <2 months or >12 years old. Action Statements The update group made strong recommendations that clinicians (1) should document the presence of middle ear effusion with pneumatic otoscopy when diagnosing OME in a child; (2) should perform pneumatic otoscopy to assess for OME in a child with otalgia, hearing loss, or both; (3) should obtain tympanometry in children with suspected OME for whom the diagnosis is uncertain after performing (or attempting) pneumatic otoscopy; (4) should manage the child with OME who is not at risk with watchful waiting for 3 months from the date of effusion onset (if known) or 3 months from the date of diagnosis (if onset is unknown); (5) should recommend against using intranasal or systemic steroids for treating OME; (6) should recommend against using systemic antibiotics for treating OME; and (7) should recommend against using antihistamines, decongestants, or both for treating OME. The update group made recommendations that clinicians (1) should document in the medical record counseling of parents of infants with OME who fail a newborn screening regarding the importance of follow-up to ensure that hearing is normal when OME resolves and to exclude an underlying sensorineural hearing loss; (2) should determine if a child with OME is at increased risk for speech, language, or learning problems from middle ear effusion because of baseline sensory, physical, cognitive, or behavioral factors; (3) should evaluate at-risk children for OME at the time of diagnosis of an at-risk condition and at 12 to 18 months of age (if diagnosed as being at risk prior to this time); (4) should not routinely screen children for OME who are not at risk and do not have symptoms that may be attributable to OME, such as hearing difficulties, balance (vestibular) problems, poor school performance, behavioral problems, or ear discomfort; (5) should educate children with OME and their families regarding the natural history of OME, need for follow-up, and the possible sequelae; (6) should obtain an age-appropriate hearing test if OME persists for 3 months or longer OR for OME of any duration in an at-risk child; (7) should counsel families of children with bilateral OME and documented hearing loss about the potential impact on speech and language development; (8) should reevaluate, at 3- to 6-month intervals, children with chronic OME until the effusion is no longer present, significant hearing loss is identified, or structural abnormalities of the eardrum or middle ear are suspected; (9) should recommend tympanostomy tubes when surgery is performed for OME in a child <4 years old; adenoidectomy should not be performed unless a distinct indication exists (nasal obstruction, chronic adenoiditis); (10) should recommend tympanostomy tubes, adenoidectomy, or both when surgery is performed for OME in a child ≥4 years old; and (11) should document resolution of OME, improved hearing, or improved quality of life when managing a child with OME.

Evidence for distinct histologic profile of nasal polyps with and without eosinophilia

To evaluate the histology, RNA, and protein signatures of nasal polyps (NPs) in order to demonstrate specific subtypes of disease and differentiate “idiopathic” NPs based on tissue eosinophilia.

Early outcomes of endoscopic transsphenoidal surgery for adult craniopharyngiomas

OBJECT Although the transsphenoidal approach for subdiaphragmatic craniopharyngiomas has been performed for many years, there are few reports describing the role of the endoscopic transsphenoidal technique for suprasellar craniopharyngiomas. The purpose of this study was to report the outcomes of the endoscopic transsphenoidal approach for adults with craniopharyngiomas in whom the goal was gross-total resection. METHODS Twelve patients were identified who were older than 18 years at the time of their pure endoscopic transsphenoidal surgery. Their medical records and imaging studies were retrospectively reviewed. RESULTS Gross-total resection was achieved in 42% of cases when assessed by intraoperative impression alone and in 75% when assessed by the first postoperative MR imaging study. However, 83% of patients achieved at least a 95% resection when assessed by both intraoperative impression and the first postoperative MR imaging study. Permanent diabetes insipidus occurred postoperatively in 44% of patients. Six (67%) of 9 patients who had a functioning hypothalamic-pituitary axis preoperatively developed panhypopituitarism after surgery. Visual improvement or normalization occurred in 78% of patients with preoperative visual deficits. Although no patient experienced a postoperative CSF leak, 1 patient was treated for meningitis. CONCLUSIONS The authors have achieved a high rate of radical resection and symptomatic improvement with the endoscopic transsphenoidal technique for both subdiaphragmatic (sellar/suprasellar) and supradiaphragmatic (suprasellar) craniopharyngiomas. However, this is also associated with a high incidence of new endocrinopathy. Endoscopic assessment of tumor resection may be more sensitive for residual tumor than the first postoperative MR imaging study.

Treatment of glomus jugulare tumors with gamma knife radiosurgery.

Surgical resection, preoperative embolization, radiation therapy, and stereotactic radiosurgery have been used to treat glomus jugulare tumors (GJT). However, the optimal treatment of these tumors remains unclear. The authors report their data on treatment of GJTs with gamma knife radiosurgery (GKS).

Prominent role of IFN-γ in patients with aspirin-exacerbated respiratory disease.

BACKGROUND Aspirin-exacerbated respiratory disease (AERD) is distinguished from aspirin-tolerant asthma/chronic sinusitis in large part by an exuberant infiltration of eosinophils that are characterized by their overexpression of metabolic pathways that drive the constitutive and aspirin-induced secretion of cysteinyl leukotrienes (CysLTs). OBJECTIVE We defined the inflammatory milieu that in part drives CysLT overproduction and, in particular, the role of IFN-γ in the differentiation of eosinophils. METHODS Quantitative real-time PCR was performed for TH1 and TH2 signature cytokines on tissue from control subjects, patients with chronic hyperplastic eosinophilic sinusitis, and patients with AERD, and their cellular source was determined. The influence of IFN-γ on maturation, differentiation, and functionality of eosinophils derived from hematopoietic stem cells was determined. RESULTS Gene expression analysis revealed that tissue from both aspirin-tolerant subjects and patients with AERD display a TH2 cytokine signature; however, AERD was distinguished from chronic hyperplastic eosinophilic sinusitis by the prominent expression of IFN-γ. Intracellular and immunohistochemical cytokine staining revealed that the major sources of these cytokines were the eosinophils themselves. IFN-γ promoted the maturation of eosinophil progenitors, as measured by increased mRNA and surface expression of CCR3 and sialic acid-binding immunoglobulin-like lectin 8 (Siglec-8). Additionally, IFN-γ increased the expression of genes involved in leukotriene synthesis that led to increased secretion of CysLTs. IFN-γ-matured eosinophil progenitors were also primed, as demonstrated by their enhanced degranulation. CONCLUSIONS High IFN-γ levels distinguish AERD from aspirin-tolerant asthma and underlie the robust constitutive and aspirin-induced secretion of CysLTs that characterize this disorder.

Genetics and phenotyping in chronic sinusitis

Chronic sinusitis with nasal polyposis historically has been treated as a single monolithic clinical disorder. Just as asthma is now accepted as numerous heterogeneous diseases, chronic sinusitis should also be viewed as comprising several diseases with varying causes, with each one characterized by distinct histologic and gene and protein expression patterns. This includes recognition of the need to define these diseases based on the presence or absence of an eosinophilic infiltrate but also on additional distinctions based on unique agents that drive their development and perpetuation. As a collection of heterogeneous diseases, proper differential diagnosis is required to delineate appropriate therapeutic intervention. This review will focus on recognized distinct presentations of chronic sinus disease, including distinguishing the clinical presentations, cellular and molecular characteristics, genetic differences, and current treatment options for each.

Retrospective analysis of a concurrent series of microscopic versus endoscopic transsphenoidal surgeries for Knosp Grades 0–2 nonfunctioning pituitary macroadenomas at a single institution

OBJECT The object of this study was to compare surgical outcomes and complications in a contemporaneous series of patients undergoing either microscopic or endoscopic transsphenoidal surgery for nonfunctioning pituitary macroadenomas without imaging evidence of cavernous sinus invasion. METHODS This is a retrospective analysis of a prospectively collected database from a single institution. Data were collected from patients whose surgery had occurred in the period from June 2010 to January 2013. Patients who underwent microscopic or endoscopic surgery for Knosp Grade 0, 1, or 2 nonfunctioning pituitary macroadenomas were included in the study. Patients who had clinically secreting or Knosp Grade 3 or 4 tumors and patients who were undergoing revision surgery were excluded from analysis. Eligible patient records were analyzed for outcomes and complications. Statistical analyses were performed on tumor volume, intraoperative factors, postoperative complications, and degree of resection on 1-year postoperative MRI. The results were used to compare the outcomes after microscopic and endoscopic approaches. RESULTS Forty-three patients underwent microscopic transsphenoidal surgery, and 56 underwent endoscopic transsphenoidal surgery. There were no statistical differences in the intraoperative extent of resection or endocrinological complications. There were significantly more intraoperative CSF leaks in the endoscopic group (58% vs 16%); however, there was no difference in the incidence of postoperative CSF rhinorrhea (12% microscopic vs 7% endoscopic). Length of hospitalization was significantly shorter in patients undergoing an endoscopic approach (3.0 days vs 2.4 days). Two-month follow-up imaging was available in 95% of patients, and 75% of patients had 1-year follow-up imaging. At 2 months postprocedure, there was no evidence of residual tumor in 79% (31 of 39) and 85% (47 of 55) of patients in the microscopic and endoscopic groups, respectively. At 1 year postprocedure, 83% (25 of 30) of patients in the microscopic group had no evidence of residual tumor and 82% (36 of 44) of those in the endoscopic group had no evidence of residual tumor. CONCLUSIONS The microscopic and endoscopic techniques provide similar outcomes in the surgical treatment of Knosp Grades 0-2 nonfunctioning pituitary macroadenomas.

Pilot study of budesonide inhalant suspension irrigations for chronic eosinophilic sinusitis

nary function testing have been implemented to optimize asthma control. It has not been uncommon for a subject taking a daily OIT dose without eating a meal or snack in the 2 hours before dosing to have symptoms with a dose that had been previously tolerated; taking the same dose with a substantial meal or snack the next day and thereafter prevents further reactions. Additionally, several subjects have experienced allergic symptoms with exercise after OIT dosing, and we advise these subjects to avoid exertion for 2 hours after dosing. Finally, 1 subject had several systemic reactions when menses was coupled with exercise despite no symptoms with daily dosing in the interval between episodes and was eventually withdrawn from the study. She was not taking other medications (eg, nonsteroidal anti-inflammatory drugs). Of note, she did not have systemic reactions each time she exercised during menses. At this time, the role of menses is unclear, and further study is needed. In the studies to date, peanut and food OIT have a good safety profile, and home dosing is infrequently associated with adverse reactions. However, allergic symptoms should be expected, and subjects and their families should be counseled about circumstances associated with an increased possibility of reacting to previously tolerated OIT doses. As OIT for food allergy becomes increasingly studied in research settings, implementing these recommendations and modifications can improve the safety of these experimental protocols. Pooja Varshney, MD Pamela H. Steele, CPNP Brian P. Vickery, MD J. Andrew Bird, MD Ananth Thyagarajan, MD Amy M. Scurlock, MD Tamara T. Perry, MD Stacie M. Jones, MD A. Wesley Burks, MD From Pediatric Allergy and Immunology, Department of Pediatrics, Duke University Medical Center, Durham, NC, and Pediatric Allergy and Immunology, Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children’s Hospital, Little Rock, Ark. E-mail: wesley.burks@duke.edu. Disclosure of potential conflict of interest: P. Varshney received the National Institutes of Health T32 Training Grant. B. P. Vickery has received research support from the Thrasher Research Foundation. J. A. Bird has received research support from the Food Allergy Initiative. A. M. Scurlock has received research support from the National Institutes of Health. T. T. Perry has received research support from the National Institutes of Health and the Robert Wood Johnson Foundation. S. M. Jones is a consultant for and board member of the Food Allergy & Anaphylaxis Network and has received research support from the National Institutes of Health and DYAX Corporation. A. W. Burks is a Consultant for ActoGeniX NV, Intelliject, McNeil Nutritionals, and Novartis; is a minority stockholder of Allertein and MastCell, Inc; is on the Advisory Board for Dannon Co. Probiotics; is on the Expert Panel for Nutricia; has received research support from the National Institutes of Health, the Food Allergy & Anaphylaxis Network, and the Wallace Research Foundation; has served as an expert witness on the topic of food allergies; is on the Medical Board of Directors for the Food Allergy & Anaphylaxis Network and the Dermatological Allergy Committee for the American College of Allergy, Asthma & Immunology; is a member for the National Institutes of Health Hypersensitivity, Autoimmune and Immunemediated Disease Study Section; and is on the Journal of Allergy and Clinical Immunology reviewer board. The rest of the authors have declared they have no conflict of interest.