Disease Endotypes Predict the Severity of Mucous Membrane Pemphigoid.

Mucous membrane pemphigoid is an autoimmune disease with variable clinical presentation and multiple autoantigens. To determine whether disease endotypes could be identified on the basis of the pattern of serum reactivity, the clinical and diagnostic information of 70 patients with mucous membrane pemphigoid was collected, and reactivity to dermal or epidermal antigens, using indirect immunofluorescence, and specific reactivity to bullous pemphigoid (BP) autoantigens BP180 and BP230, collagen VII, and laminin 332 were evaluated. Most patients had lesions at multiple mucosae, with the most prevalent being oropharyngeal (mouth, gingiva, pharynx; 98.6%), followed by ocular (38.6%), nasal (32.9%), genital or anal (31.4%), laryngeal (20%), and esophageal (2.9%) sites and skin (45.7%). Autoantigen profiling identified BP180 (71%) as the most common autoantigen, followed by laminin 332 (21.7%), collagen VII (13%), and BP230 IgG (11.6%). Reactivity to dermal antigens predicted a more severe disease characterized by a higher number of total sites involved, especially high-risk sites, and a decreased response to rituximab. In most cases, identification of dermal indirect immunofluorescence reactivity is an accurate predictor of disease course; however, confirmation of laminin 332 reactivity is important, with dermal indirect immunofluorescence positivity because of an increased risk of solid tumors. In addition, the ocular mucosae should be monitored in patients with IgA on direct immunofluorescence.

Post-operative Complication Rate Comparison Between Airway Surgery and Upper Airway Stimulation Using NSQIP and ADHERE.

OBJECTIVE: Postoperative complication rates were compared between obstructive sleep apnea surgery (OSAS) and hypoglossal nerve upper airway stimulation (UAS). STUDY DESIGN: Cohort. SETTING: Multi-institutional international databases. METHODS: OSAS data were collected from the NSQIP database (2014; American College of Surgeons National Surgery Quality Improvement Program). UAS data were obtained from the ADHERE registry (Adherence and Outcome of Upper Airway Stimulation for OSA International Registry; 2016-December 2019). ADHERE comorbidities and complications were categorized to match NSQIP definitions. A chi-square test was used for proportion P values. RESULTS: There were 1623 UAS procedures in ADHERE and 310 in NSQIP. The UAS group was older than the OSAS group (mean ± SD, 60 ± 11 vs 42 ± 13 years) but similarly male (75% vs 77%) and overweight (body mass index, 29 ± 4 vs 29 ± 3 kg/m2). There was a higher proportion of hypertension, diabetes, and heart disease in the UAS cohort. Palatopharyngoplasty was the most common surgical procedure (71%), followed by tonsillectomy (25%). UAS operative time was longer (132 ± 47 vs 54 ± 33 minutes). Postoperative length of stay was not normally distributed, as 71% of UAS stays were <1 day as opposed to 40% of OSA stays (P < .0001). Thirty-day return to the operating room related to the procedure was 0.1% for UAS and 4.8% for OSAS (P < .0001). Surgical site infections were 0.13% for UAS and 0.9% for OSAS (P = .046). CONCLUSION: The UAS cohort was older and more likely to have comorbid hypertension, diabetes, and heart disease. Despite baseline differences, the postoperative complication rate was lower with UAS than with OSAS.

Esophageal Manometry, pH Testing, Endoscopy, and Videofluoroscopy in Patients With Globus Sensation.

OBJECTIVES/HYPOTHESIS: Combine techniques commonly employed in the clinical workup of patients with isolated globus sensation to identify the most common pharyngoesophageal abnormality. The primary aim was to retrospectively review high-resolution manometry, pH probe testing, contrast videofluoroscopy, and endoscopy studies in patients with a primary complaint of globus sensation. The specific hypothesis was esophageal high-resolution manometry identifies the most significant proportion of abnormalities compared to all other modalities. STUDY DESIGN: Retrospective cohort study. METHODS: An inclusive retrospective chart review was performed for patients evaluated between 2009 and 2016 with the primary complaint of globus sensation. Age at testing, self-identified gender, associated diagnoses, and results from each modality were collected. Descriptive statistics and pairwise comparisons were performed as well as sensitivity and specificity calculations. RESULTS: One hundred seventy-two patients met inclusion criteria. The cohort had an age range of 22.7 to 88.5 years and was predominantly female. Esophageal manometry identified abnormalities in 62.8% of patients, and pH testing identified abnormal acidification in approximately 20%. The esophagram identified abnormalities in 24% of patients, and esophagogastroduodenoscopy identified abnormalities in 22%. Modified barium swallows were normal in 93% of patients. Measures of sensitivity and specificity of other modalities were poor compared to esophageal manometry and pH testing. CONCLUSIONS: Patients with isolated globus sensation have evidence of esophageal dysmotility and laryngopharyngeal and gastroesophageal reflux disease in high proportions. Esophageal high-resolution manometry testing identifies the greatest proportion of abnormalities of the investigated modalities. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:2120-2125, 2020.

The impact of time after radiation treatment on dysphagia in patients with head and neck cancer enrolled in a swallowing therapy program.

BACKGROUND: Swallowing dysfunction after radiotherapy (RT) for head and neck cancer can be devastating. A randomized control trial compared swallow exercises versus exercise plus neuromuscular electrical stimulation therapy and found no overall difference in outcomes. METHODS: Quality of life (QOL), diet, and swallowing variables collected at discrete intervals on 117 patients were reanalyzed to test the hypothesis that shorter time between the completion of radiotherapy and beginning of the swallowing therapy program yielded improved outcomes. RESULTS: At baseline, subjects < 1 year post radiation had significantly better function than subjects >2 years post RT in several measures. Over the therapy program, the early group showed significant improvement in diet and QOL. Swallowing physiologic variables showed no difference between groups. CONCLUSION: Beginning a swallowing therapy program within 1 year of completion of radiotherapy demonstrates more consistent improvement in QOL and diet performance compared to later periods.

Nf2 Mutation in Schwann Cells Delays Functional Neural Recovery Following Injury.

Merlin is the protein product of the NF2 tumor suppressor gene. Germline NF2 mutation leads to neurofibromatosis type 2 (NF2), characterized by multiple intracranial and spinal schwannomas. Patients with NF2 also frequently develop peripheral neuropathies. While the role of merlin in SC neoplasia is well established, its role in SC homeostasis is less defined. Here we explore the role of merlin in SC responses to nerve injury and their ability to support axon regeneration. We performed sciatic nerve crush in wild-type (WT) and in P0SchΔ39-121 transgenic mice that express a dominant negative Nf2 isoform in SCs. Recovery of nerve function was assessed by measuring mean contact paw area on a pressure pad 7, 21, 60, and 90 days following nerve injury and by nerve conduction assays at 90 days following injury. After 90 days, the nerves were harvested and axon regeneration was quantified stereologically. Myelin ultrastructure was analyzed by electron microscopy. Functional studies showed delayed nerve regeneration in Nf2 mutant mice compared to the WT mice. Delayed neural recovery correlated with a reduced density of regenerated axons and increased endoneurial space in mutants compared to WT mice. Nevertheless, functional and nerve conduction measures ultimately recovered to similar levels in WT and Nf2 mutant mice, while there was a small (∼17%) reduction in the percent of regenerated axons in the Nf2 mutant mice. The data suggest that merlin function in SCs regulates neural ultrastructure and facilitates neural regeneration, in addition to its role in SC neoplasia.

Impact of Compliance on Dysphagia Rehabilitation in Head and Neck Cancer Patients: Results from a Multi-center Clinical Trial.

A 5-year, 16-site, randomized controlled trial enrolled 170 HNC survivors into active (estim + swallow exercise) or control (sham estim + swallowing exercise) arms. Primary analyses showed that estim did not enhance swallowing exercises. This secondary analysis determined if/how patient compliance impacted outcomes. A home program, performed 2 times/day, 6 days/week, for 12 weeks included stretches and 60 swallows paired with real or sham estim. Regular clinic visits ensured proper exercise execution, and detailed therapy checklists tracked patient compliance which was defined by mean number of sessions performed per week (0-12 times) over the 12-week intervention period. "Compliant" was defined as performing 10-12 sessions/week. Outcomes were changes in PAS, HNCI, PSS, OPSE, and hyoid excursion. ANCOVA analyses determined if outcomes differed between real/sham and compliant/noncompliant groups after 12 weeks of therapy. Of the 170 patients enrolled, 153 patients had compliance data. The mean number of sessions performed was 8.57/week (median = 10.25). Fifty-four percent of patients (n = 83) were considered "compliant." After 12 weeks of therapy, compliant patients in the sham estim group realized significantly better PAS scores than compliant patients in the active estim group (p = 0.0074). When pooling all patients together, there were no significant differences in outcomes between compliant and non-compliant patients. The addition of estim to swallowing exercises resulted in worse swallowing outcomes than exercises alone, which was more pronounced in compliant patients. Since neither compliant nor non-compliant patients benefitted from swallowing exercises, the proper dose and/or efficacy of swallowing exercises must also be questioned in this patient population.

Celecoxib Versus Placebo in Tonsillectomy: A Prospective, Randomized, Double-Blind Placebo-Controlled Trial.

OBJECTIVES: Celecoxib is a cyclooxygenase-2-specific inhibitor indicated to treat acute pain and pain secondary to osteoarthritis and rheumatoid arthritis. Surgical models of acute pain have demonstrated superior pain relief to placebo. The objective of this study was to test the safety and efficacy of celecoxib for pain relief after tonsillectomy compared to placebo. METHODS: Adult subjects were randomized to 200 mg celecoxib versus placebo with a loading dose the night before surgery then twice daily for 10 days. Subjects were instructed to supplement the study drug with hydrocodone/acetaminophen liquid or acetaminophen for pain as needed. Subjects completed a daily diary regarding their pain, nausea, vomiting, diet, and activity. RESULTS: Seventeen subjects enrolled. Intraoperative blood loss was similar between groups, and no subject had postoperative bleeding. Three patients returned to the emergency department for treatment, and 2 patients could not complete the diaries, all in the placebo group. Subjects in the placebo group required statistically significant (P < .05) higher doses of narcotic and acetaminophen to control pain. Pain and diet rating scores were slightly better in the celecoxib group compared to placebo. CONCLUSIONS: In this small cohort, celecoxib reduced postoperative narcotic and acetaminophen requirements compared to placebo without complications.

Efficacy of electrical stimulation and exercise for dysphagia in patients with head and neck cancer: A randomized clinical trial.

BACKGROUND: Neuromuscular electrical stimulation (NMES) is a highly sought after but poorly studied treatment for dysphagia among patients with head and neck cancer with dysphagia. This study investigated the efficacy of NMES in this patient population. METHODS: In this double-blinded, randomized controlled trial, 170 patients with head and neck cancer experiencing posttreatment dysphagia were randomized into active NMES + swallow exercise versus sham NMES + swallow exercise groups. Outcomes after a 12-week program included changes in fluoroscopy measures, diet, and quality of life. RESULTS: After the 12-week program, the active NMES group had significantly worse Penetration Aspiration Scale scores than the sham group. Both groups reported significantly better diet and quality of life. No other measures were significant. CONCLUSION: NMES did not add benefit to traditional swallow exercises. Unfortunately, swallow exercises were not effective by themselves either. For patients with head and neck cancer with moderate to severe dysphagia caused by radiation therapy, current behavioral therapies are of limited help in reversing long-term dysphagia. © 2015 Wiley Periodicals, Head Neck 38: E1221-E1231, 2016.

Ketorolac after free tissue transfer: a comparative effectiveness study.

OBJECTIVE: We sought to compare postoperative pain and complications in patients undergoing free tissue transfer for reconstruction of head and neck defects with and without ketorolac. METHODS: In this retrospective cohort study, we identified patients who underwent head and neck free tissue transfer procedures at the University of Iowa between July 2010 and December 2012. A subset of patients received ketorolac as an anti-platelet agent. Main outcome measures include postoperative analgesic use, pain scores, and bleeding complications. RESULTS: We identified 138 free tissue transfers, with 42 procedures in the ketorolac cohort. In the first 7 postoperative days, patients in the ketorolac and non-ketorolac cohorts received equivalent narcotic doses (morphine equivalents, 48.9 mg/day vs 46.6 mg/day, P = .72). The ketorolac group reported higher mean pain scores (3.1 vs 2.4, P = .004). Ketorolac use was not associated with need for transfusion (P = .86) or number of days with neck drains (P = .79). CONCLUSION: Ketorolac did not demonstrate a significant analgesic effect in this group of patients in terms of pain scores and opioid requirements. However, there also was no evidence to suggest a higher likelihood of bleeding complications. Ketorolac may be safely used as an anti-platelet agent, with narcotic requirements unchanged.

Endoscopic transnasal resection of ameloblastoma with intracranial extension.

Ameloblastoma is a rare odontogenic tumor with characteristics of epithelial tissue that produces enamel for the developing tooth. This lesion is generally considered benign, but has malignant forms that invade locally and metastasize. We present a 60-year-old man with maxillary ameloblastoma that after multiple recurrences developed intracranial extension with dural involvement of the middle cranial fossa and was treated by endoscopic transnasal resection followed by radiation therapy. Our technique and intraoperative findings are described with a review of the literature on intracranial ameloblastoma. This patient represents a unique account of endoscopic transnasal resection being utilized in the treatment of intracranial extension of ameloblastoma and demonstrates potential for application in similar cases.

Accuracy of fine-needle aspiration and imaging in the preoperative workup of salivary gland mass lesions treated surgically.

OBJECTIVES/HYPOTHESIS: Fine-needle aspiration (FNA) biopsy and imaging are commonly used in the preoperative assessment of salivary gland mass lesions. The goal of this retrospective study was to clarify the role of FNA and imaging in the workup of salivary gland masses. STUDY DESIGN: Retrospective cohort study. METHODS: A computer search identified patients with an FNA of a salivary gland lesion with subsequent excision during a 10-year study period. Chart review of study patients was performed, and information on site of lesion, age, gender, radiologic diagnosis, pain in the tumor area, and facial paralysis was recorded and analyzed. RESULTS: There were 543 patients who had an FNA and subsequent histopathology. The majority of the tumors were in the parotid gland (n = 492, 90.9%), followed by submandibular gland (n = 45, 8.3%). The incidence of malignancy across all sites was 29.7%. The mean patient age was 54.1 years, and 54.1% were female. The sensitivity and specificity of FNA were 85.7% and 99.5%, respectively. Positive predictive value (PPV) was 98.6%, and negative predictive value (NPV) was 94.3%. A total of 464 patients had available radiologic studies. For the radiological diagnoses, sensitivity was 81.8% and specificity was 67.3%, whereas PPV and NPV were 52.7% and 89.3%, respectively. CONCLUSIONS: FNA is a reliable method of preoperatively assessing both benign and malignant salivary gland lesions. Preoperative imaging has a lower sensitivity and specificity than FNA in differentiating malignant from benign tumors. Older age, pain, and facial paralysis are clinical features independently associated with malignancy.

Association between severity of dysphagia and survival in patients with head and neck cancer.

BACKGROUND: This study examined risk factors for dysphagia, a common and serious condition in patients with head and neck cancer, and the association between severity of dysphagia and survival. METHODS: Chart reviews were performed on patients diagnosed with head and neck cancer between January 2001 and April 2003, who had dysphagia diagnoses or swallowing evaluations. Regression analyses determined factors associated with dysphagia and the association between observed survival and severity of dysphagia. RESULTS: Almost 50% of the 407 patients had dysphagia. Risk factors included advanced stage, older age, female sex, and hypopharyngeal tumors. The most severe dysphagia ([L.] nil per os or "nothing by mouth" status), which was associated with lower survival rates, was the strongest independent predictor of survival. CONCLUSIONS: Swallowing problems should be considered when determining appropriate cancer-directed treatment and posttreatment care. Because of dysphagia's high incidence rate and association with survival, a speech-language pathologist should be involved to ensure routine diagnostic and therapeutic swallowing interventions.

Outcomes after the use of gastrostomy tubes in patients whose head and neck cancer was managed with radiation therapy.

BACKGROUND: The purpose of this study was to examine the effect of continued oral intake and duration of gastrostomy tube placement on posttreatment nutritional outcomes in patients being irradiated for head and neck cancer. METHODS: Factors associated with continued oral intake and its association with posttreatment outcomes were analyzed. RESULTS: Patients with no oral intake (39.6% of 91) were more likely to have laryngeal tumors, advanced disease, and pretreatment gastrostomy tube placement. Of the 55 patients whose gastrostomy tubes had been removed, those with continued oral intake and shorter gastrostomy tube placement were more likely to maintain their weight and report eating scores in the higher-functioning category, but have more restricted diets. Observed survival was significantly better for the continued-oral-intake group (p = .001). CONCLUSION: The beneficial effects of continued oral intake and shorter gastrostomy tube placement on posttreatment outcomes shown in this study suggest that clinicians involved in these patients' care should emphasize oral intake during treatment.

Quantitative PCR analysis of laryngeal muscle fiber types.

UNLABELLED: Voice and swallowing dysfunction as a result of recurrent laryngeal nerve paralysis can be improved with vocal fold injections or laryngeal framework surgery. However, denervation atrophy can cause late-term clinical failure. A major determinant of skeletal muscle physiology is myosin heavy chain (MyHC) expression, and previous protein analyses have shown changes in laryngeal muscle fiber MyHC isoform with denervation. RNA analyses in this setting have not been performed, and understanding RNA levels will allow interventions better designed to reverse processes such as denervation in the future. Total RNA was extracted from bilateral rat thyroarytenoid (TA), posterior cricoarytenoid (PCA), and cricothyroid (CT) muscles in rats. Primers were designed using published MyHC isoform sequences. SYBR Green real-time reverse transcription-polymerase chain reaction (SYBR-RT-PCR) was used for quantification. The electropherogram showed a clear separation of total RNA to 28S and 18S subunits. Melting curves illustrated single peaks for all type MyHC primers. All MyHC isoforms were identified in all muscles with various degrees of expression. Quantitative PCR is a sensitive method to detect MyHC isoforms in laryngeal muscle. Isoform expression using mRNA analysis was similar to previous analyses but showed some important differences. This technique can be used to quantitatively assess response to interventions targeted to maintain muscle bulk after denervation. LEARNING OUTCOMES: (1) Readers will be able to describe the relationship between myosin heavy chain expression and muscle contractile properties. (2) Readers will be able to separate myosin heavy chain isoforms into slow and fast twitch phenotypes. (3) Readers will be able to describe differential muscle isoform expression between different laryngeal muscles. (4) Readers will be able to compare this study to other modalities of determining muscle fiber type.

Epiglottis is not essential for successful swallowing in humans.

Controversy has continued for well over 100 years regarding the role of the epiglottis in deglutition. We describe the effect of isolated epiglottectomy on swallowing success in a case series of 3 adult human subjects with isolated epiglottectomy due to trauma, surgery, or cancerous erosion. The patients were 42, 51, and 70 years of age, and swallowing was analyzed objectively with videofluoroscopy. All subjects exhibited successful swallowing with all food types: thin liquid, puree, and solid food. Specifically, the patient with traumatic epiglottectomy exhibited rapid swallowing success, the patient with surgical epiglottectomy exhibited a short period of dysphagia due to postoperative edema, followed by swallowing success, and the patient with epiglottectomy due to cancerous erosion of the entire epiglottis exhibited long-term adaptation, with successful swallowing maintained. We conclude that the epiglottis is not essential for successful swallowing in humans, because individuals can readily adapt to isolated epiglottectomy and avoid tracheal aspiration.

Multifactorial dysphagia: diffuse idiopathic skeletal hyperostosis and eosinophilic esophagitis.

Swallowing is a complex, multistage event with oral, pharyngeal, and esophageal phases. A thorough clinical examination for swallowing complaints begins to differentiate whether the problem is due to anatomic, mechanical, or neurologic etiologies. Based on the clinical suspicion, additional tests may be beneficial, including fluoroscopic and direct imaging methods, and electrophysiologic measurements. A multidisciplinary approach may also be advantageous, as in this case of dysphagia from diffuse idiopathic skeletal hyperostosis and eosinophilic esophagitis, which incorporated care from otolaryngology, speech pathology, orthopedic surgery, and gastroenterology.

Insular thyroid carcinoma in a patient with Cowden syndrome.

Cowden syndrome is an autosomal dominant disorder characterized by benign and malignant hamartomatous lesions that can develop from all three germ cell derivatives. This disorder predisposes patients to develop malignant tumors of the breast, endometrium, and thyroid. We present a patient with clinically relevant manifestations of Cowden syndrome, with genetic verification, impacting by way of airway compromise due to hamartomas, urinary tract abnormalities, and insular thyroid cancer. This case illustrates the value of recognizing Cowden syndrome at an earlier stage when the patient could have received appropriate management to decrease the morbidity of untreated hamartomatous growths, and an elective thyroidectomy would have been a viable option to manage his malignancy. Through this case report, we provide further insight into management of this disorder.

Adverse events associated with concurrent chemoradiation therapy in patients with head and neck cancer.

OBJECTIVE: To assess toxicities, functional outcomes, and health-related quality of life associated with concurrent chemoradiation therapy (CRT) in patients with head and neck cancer. DESIGN: Prospective and retrospective outcomes study. SETTING: Tertiary care institution. PATIENTS: Participants in the longitudinal Outcomes Assessment Project whose head and neck cancer was treated with CRT between February 1, 2000, and March 1, 2007 (n = 104). INTERVENTIONS: Patients prospectively provided functional and health-related quality of life information, including data from the 1-year and most current follow-up visits. Medical records were reviewed to determine toxicity and survival rates. MAIN OUTCOME MEASURES: Well-defined acute and late toxicities; functional outcomes (diet, dentition, tracheostomies); head and neck cancer-specific, general health, and depression outcomes; and survival rates. RESULTS: Most patients had oropharyngeal or laryngeal tumors (87.5%) and advanced-stage disease (75.0%). Approximately one-half had hematologic toxicities and toxicity-related treatment delays. Approximately one-quarter had neurotoxicities and/or ototoxicites, moist desquamation, pneumonia, nausea and vomiting requiring hospitalization or intravenous fluids, dehydration or malnutrition requiring hospitalization, and mild or moderate fever. Although patients receiving the current intensity-modulated radiation therapy (IMRT) protocol using the Pinnacle(3) planning system had more toxicity-related treatment delays, they had fewer toxicities and better functional and health-related quality of life outcomes compared with those receiving conventional lateral opposing-field radiation or the initial IMRT protocol using the Best nomos PEACOCK planning system. CONCLUSIONS: Patients receiving CRT experience a substantial number of treatment-related adverse events, primarily affecting oropharyngeal and laryngeal function, with improvement noted for the current IMRT protocol. Improving dental prosthetic rehabilitation and including evaluations with speech and swallowing pathologists before and during treatment may enhance patient outcomes.