Eosinophilic Esophagitis: What the Otolaryngologist Needs to Know.

Eosinophilic esophagitis is a male-predominant disease with presentations ranging from nonspecific feeding issues to dysphagia and food impaction. The currently proposed pathophysiology is a combination of genetics, allergens, and epithelial barrier impairment. Diagnosis is reliant on history, endoscopic examination, and biopsy. Recent guidelines recognize the role of concurrent gastroesophageal reflux disease. Treatment is based on 3 paradigms: diet, drugs, and dilation. Drug therapy has historically focused on topical corticosteroids; as of 2022, dupilumab was approved for targeted biologic therapy. Dilation is reserved for symptomatic and anatomic management. As this clinical entity is better understood, additional therapies will hopefully be developed.

Navigating Pathways to Diagnosis in Idiopathic Subglottic Stenosis: A Qualitative Study.

OBJECTIVE: Idiopathic subglottic stenosis is a rare disease, and time to diagnosis is often prolonged. In the United States, some estimate it takes an average of 9 years for patients with similar rare disease to be diagnosed. Patient experience during this period is termed the diagnostic odyssey. The aim of this study is to use qualitative methods grounded in behavioral-ecological conceptual frameworks to identify drivers of diagnostic odyssey length that can help inform efforts to improve health care for iSGS patients. METHODS: Qualitative study using semi-structured interviews. Setting consisted of participants who were recruited from those enrolled in a large, prospective multicenter trial. We use directed content analysis to analyze qualitative semi-structured interviews with iSGS patients focusing on their pathways to diagnosis. RESULTS: Overall, 30 patients with iSGS underwent semi-structured interviews. The patient-reported median time to diagnosis was 21 months. On average, the participants visited four different health care providers. Specialists were most likely to make an appropriate referral to otolaryngology that ended in diagnosis. However, when primary care providers referred to otolaryngology, patients experienced a shorter diagnostic odyssey. The most important behavioral-ecological factors in accelerating diagnosis were strong social support for the patient and providers' willingness to refer. CONCLUSION: Several factors affected time to diagnosis for iSGS patients. Patient social capital was a catalyst in decreasing time to diagnosis. Patient-reported medical paternalism and gatekeeping limited specialty care referrals extended diagnostic odysseys. Additional research is needed to understand the effect of patient-provider and provider-provider relationships on time to diagnosis for patients with iSGS. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:815-824, 2024.

Association between Estrogen Exposure and Idiopathic Subglottic Stenosis.

OBJECTIVE: Idiopathic subglottic stenosis (iSGS) is a rare, recurrent, fibroinflammatory disease affecting the larynx and proximal trachea. Given it occurs primarily in adult females, estrogen is speculated to play a central pathophysiological role. This study aimed to evaluate relationships between estrogen exposure, disease progression, and recurrence. METHODS: North American Airway Collaborative (NoAAC) data of adults with iSGS obstructive airway lesions, who underwent index endoscopic airway dilation, were used to identify associations between estrogen exposure, disease characteristics, and time to recurrence (TTR), and interventions were analyzed using Kruskal-Wallis test and Pearson coefficient. Cox proportional hazards regression models compared hazard ratios by estrogen exposure. Kaplan-Meier curves were plotted for TTR based on menopausal status. RESULTS: In all, 533 females had complete estrogen data (33% premenopausal, 17% perimenopausal, 50% postmenopausal). Median estrogen exposure was 28 years. Overall, there was no dose-response relationship between estrogen exposure and disease recurrence. Premenopausal patients had significantly shorter time from symptom manifestation to diagnosis (1.17 vs. 1.42 years perimenopausal vs. 2.08 years postmenopausal, p < 0.001), shorter time from diagnosis to index endoscopic airway dilation (1.90 vs. 2.50 vs. 3.76 years, p = 0.005), and higher number of procedures (1.73 vs. 1.20 vs. 1.08 procedures, p < 0.001). CONCLUSIONS: We demonstrate premenopausal patients may have a more aggressive disease variant than their peri- and postmenopausal counterparts. However, it is unclear as to whether this is related to reduced estrogen in the peri- and postmenopausal states or the age-related physiology of wound healing and inflammation, regardless of estrogen. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:825-830, 2024.

A Rare Complication of Fine-Needle Aspiration of Neck Structures.

Fine-needle aspiration (FNA) is a generally accepted tool for safe diagnostic evaluation in the workup of lesions and masses. Aside from the commonly discussed risks of infection and minor bleeding related to skin puncture, other more serious complications have been reported sparingly. We present two cases of pneumothorax from FNA of neck structures, which have been theorized but not previously reported to our knowledge. Discussion of cases of this complication rather than solely a theoretical understanding of it will aid in diagnosis and management of this complication.

Pre-tracheotomy for Potentially Emergent Airway Scenarios: Indications and Outcomes.

OBJECTIVES/HYPOTHESIS: Airway access in the setting of unsuccessful ventilation and intubation typically involves emergent cricothyrotomy or tracheotomy, procedures with associated significant risk. The potential for such emergent scenarios can often be predicted based on patient and disease factors. Planned tracheotomy can be performed in these cases but is not without its own risks. We previously described a technique of pre-tracheotomy or exposing the tracheal framework without entering the trachea, as an alternative to planned tracheostomy in such cases. In this way, a tracheotomy can be easily completed if needed, or the wound can be closed if it is not needed. This procedure has since been used in an array of indications. We describe the clinical situations where pre-tracheotomy was performed as well as subsequent patient outcomes. METHODS: Retrospective series of patients undergoing a pre-tracheotomy from 2015 to 2020. Records were reviewed for patient characteristics, indication, whether the procedure was converted to tracheotomy or closed at the bedside, and any post-procedural complications. RESULTS: Pre-tracheotomy was performed in 18 patients. Indications included failed extubation after head and neck reconstruction, subglottic stenosis, laryngeal masses, laryngeal edema, thyroid masses, and an oropharyngeal bleed requiring operative intervention. Tracheotomy was avoided in 10 patients with wound closed at the bedside; procedure was converted to tracheotomy in the remaining eight. There were no complications. Indications for conversion included failed extubation, intraoperative hemorrhage, significant stridor with dyspnea, and inability to ventilate. CONCLUSION: Pre-tracheotomy offers simplified airway access and provides a valuable option in scenarios where tracheotomy may, but not necessarily, be needed. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E2802-E2809, 2021.

An unwitnessed case of foreign body aspiration of barium from an unknown source.

Foreign body (FB) aspiration is potentially life-threatening in children. A variety of sources and objects have been noted in aspiration events with possible complications ranging from mild to life-threatening. While rare, barium aspiration can cause severe complications, and removal is particularly challenging. Complications of retained barium include acute respiratory distress syndrome, pneumonitis, sepsis, even death. Regardless of the foreign body's identity, substance removal is critical in management. Resourcefulness of removal techniques and an interdisciplinary approach may allow for maximally effective management. We present a case of a pediatric barium aspiration from an unknown source and review evaluation and management strategies.

Drug Induced Sleep Endoscopy Identification of Adenoid Regrowth in Pediatric Obstructive Sleep Apnea.

OBJECTIVE: To establish the incidence and possible contributing factors leading to adenoid regrowth in children with pediatric sleep apnea using drug induced sleep endoscopy (DISE). METHODS: Children treated for obstructive sleep apnea following previous adenoidectomy were evaluated using DISE. Adenoid regrowth was scored by the same attending physician using a 5-point grading scale. Age, sex, body mass index (BMI) percent for age, polysomnogram results, initial adenoid size before adenoidectomy, and postoperative complications were evaluated. RESULTS: Fifty-six patients (age range 22 months to 16 years) met inclusion criteria. Twenty-five children (44.6%) had Grade 2 adenoid or larger. Mean age at the time of DISE was 7.11 years, with an average of 1.75 years since initial adenoidectomy. Mean preadenoidectomy size based on intraoperative nasopharyngeal mirror assessment was Grade 2.55 (95% CI 2.30-2.79). Adenoid size at time of sleep endoscopy was Grade 1.64 (95% CI 1.30-1.98). Characteristics associated with adenoid regrowth were higher body mass index for age percentile at time of endoscopy (P < 0.05), initial adenoid size (P < 0.01), and time between initial adenoidectomy and endoscopy (P = 0.05). CONCLUSIONS: Body mass index for age percentile, initial adenoid size, and time between initial adenoidectomy and drug induced sleep endoscopy correlate with regrowth in childhood obstructive sleep apnea.

Tracheocutaneous Sinus following Tracheocutaneous Fistula Repair: Management Strategies in a Pediatric Patient.

OBJECTIVE: To present a rare case of a pediatric tracheocutaneous sinus years after repair of a tracheocutaneous fistula and to review management strategies. BACKGROUND: A tracheocutaneous fistula is a common sequela of pediatric tracheostomy and can occur in as many as one in three pediatric patients. There is debate in the literature regarding optimal surgical management. CASE PRESENTATION: An 8-year-old girl presented to the emergency department with swelling and erythema over the anterior neck. Clinical exam and diagnostic imaging revealed an underlying tracheocutaneous sinus. DISCUSSION: Complications following pediatric tracheostomy are common and range in complexity from stomal granulation to tracheocutaneous fistula. There is some debate regarding the optimal surgical management of children with tracheocutaneous fistula following tracheostomy. This report discusses the management of a pediatric child with an unusual tracheocutaneous sinus and reviews the various surgical techniques which have been described for definitive repair.

Negative-Pressure Wound Therapy for Ludwig's Angina: A Case Series.

Negative-pressure wound therapy (NPWT) is a well-established therapeutic approach for various complex wound classes. There is currently limited information on the use of NPWT for the scope of head and neck wounds. However, NPWT has been used successfully in some cases, including malignancy, infection, and trauma. In West Virginia, the incidence of dental-related infections leading to Ludwig's Angina is high due to lack of access to dental care. Our case series describes the application of vacuum-based therapy in conjunction with antibiotic therapy for quick, effective closure of deep tissue infections before definitive complex wound repair via graft and flap reconstructions. Over a period of 3 months, 2 patients with submental infections extending to the lateral neck demonstrated clean, efficient wound closure with NPWT for less than 14 days while hospitalized at West Virginia University Medicine. Outpatient follow-up with these patients demonstrated excellent cosmetic outcomes with minimal contracture or hypertrophy of healing tissue. NPWT promotes wound healing through decreased edema, improved perfusion, and increased granulation of tissue based on our findings. Our series encourages the use of NPWT for initial closure of complex wounds secondary to deep neck infections.

Epigenetic therapy in gastrointestinal cancer: the right combination.

Epigenetics is a relatively recent field of molecular biology that has arisen over the past 25 years. Cancer is now understood to be a disease of widespread epigenetic dysregulation that interacts extensively with underlying genetic mutations. The development of drugs targeting these processes has rapidly progressed; with several drugs already FDA approved as first-line therapy in hematological malignancies. Gastrointestinal (GI) cancers possess high degrees of epigenetic dysregulation, exemplified by subtypes such as CpG island methylator phenotype (CIMP), and the potential benefit of epigenetic therapy in these cancers is evident. The application of epigenetic drugs in solid tumors, including GI cancers, is just emerging, with increased understanding of the cancer epigenome. In this review, we provide a brief overview of cancer epigenetics and the epigenetic targets of therapy including deoxyribonucleic acid (DNA) methylation, histone modifications, and chromatin remodeling. We discuss the epigenetic drugs currently in use, with a focus on DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors, and explain the pharmacokinetic and mechanistic challenges in their application. We present the strategies employed in incorporating these drugs into the treatment of GI cancers, and explain the concept of the cancer stem cell in epigenetic reprogramming and reversal of chemo resistance. We discuss the most promising combination strategies in GI cancers including: (1) epigenetic sensitization to radiotherapy, (2) epigenetic sensitization to cytotoxic chemotherapy, and (3) epigenetic immune modulation and priming for immune therapy. Finally, we present preclinical and clinical trial data employing these strategies thus far in various GI cancers including colorectal, esophageal, gastric, and pancreatic cancer.

Feeding soy protein isolate and n-3 PUFA affects polycystic liver disease progression in a PCK rat model of autosomal polycystic kidney disease.

OBJECTIVE: In polycystic liver disease (PCLD), multiple cysts cause liver enlargement, structural damage, and loss of function. Soy protein and dietary ω-3 polyunsaturated fatty acids (n-3 PUFAs) have been found to decrease cyst proliferation and inflammation in polycystic kidney disease. Therefore, the aim of the study was to investigate whether soy protein and n-3 PUFA supplementation attenuates PCLD. METHODS: Young (age 28 days) female PCK rats were fed (n = 12 per group) either casein + corn oil (casein + CO), casein + soybean oil (casein + SO), soy protein isolate + soybean oil (SPI + SO), or SPI + 1:1 soybean/salmon oil blend (SPI + SB) diet for 12 weeks. Liver histology, gene expression by real-time quantitative polymerase chain reaction, and serum markers of liver injury were determined. RESULTS: Diet had no effect on PCLD progression as indicated by no significant differences in liver weight and hepatic proliferation gene expression between diet groups. PCK rats fed SPI + SB diet, however, had the greatest (P < 0.05) histological evidence of hepatic cyst obstruction, portal inflammation, steatosis, and upregulation (P = 0.03) of fibrosis-related genes. Rats fed SPI + SB diet also had the lowest (P < 0.001) serum cholesterol and higher (P < 0.05) serum alkaline phosphatase and bilirubin concentrations. CONCLUSIONS: Feeding young female PCK rats SPI and n-3 PUFA failed to attenuate PCLD progression. Furthermore, feeding SPI + SB diet resulted in complications of hepatic steatosis attributable to cysts obstruction of bile duct and hepatic vein. Based on the results, it was concluded that diet intervention alone was not effective at attenuating PCLD associated with autosomal recessive polycystic kidney disease.

Dietary n-3 polyunsaturated fatty acids or soy protein isolate did not attenuate disease progression in a female rat model of autosomal recessive polycystic kidney disease.

Polycystic kidney disease (PKD) is an incurable genetic disorder that is characterized by multiple benign cysts. As PKD advances, cyst growth increases kidney volume, decreases renal function, and may lead to end-stage renal disease; however, in a PKD rat model, feeding soy protein isolate (SPI) reduced cyst proliferation and growth. The n-3 polyunsaturated fatty acids (PUFAs) are noted for their anti-inflammatory actions. Therefore, diet therapy could offer a potentially efficacious, safe, and cost-effective strategy for treating PKD. The objective of this study was to investigate the role of soy protein and/or n-3 PUFAs on PKD progression and severity in the rat model of autosomal recessive PKD. We hypothesized that the antiproliferative and anti-inflammatory actions associated with soy protein and n-3 PUFA supplementation will attenuate PKD progression in female PCK rats. For 12 weeks, young (age, 28 days) female PCK rats were randomly assigned (n=12/group) to 4 different diets: casein±corn oil, casein±soybean oil, SPI±soybean oil, or SPI±1:1 soybean/salmon oil (SPI±SB). The feeding of the different protein and lipid sources had no significant effect on relative kidney weight. Histologic evaluation showed no significant differences in cortical or medullary cyst size, interstitial inflammation, and fibrosis among diet groups. However, rats fed SPI±SB diet had cortical cyst obstruction and the highest (P<.01) serum blood urea nitrogen concentration. Rats fed SPI±SB diet had the highest (P<.001) renal docosahexaeonic acid, but there were no significant differences in renal tissue inflammation and proliferation gene expression among the diet groups. Based on these results, dietary soy protein and/or n-3 PUFAs did not attenuate disease progression or severity in the female PCK rat model of autosomal recessive PKD.