RNA Sequencing of Idiopathic Subglottic Stenosis Tissues Uncovers Putative Profibrotic Mechanisms and Identifies a Prognostic Biomarker.

Idiopathic subglottic stenosis (iSGS) is a localized airway disease that almost exclusively affects females. Understanding the molecular mechanisms involved may provide insights leading to therapeutic interventions. Next-generation sequencing was performed on tissue sections from patients with iSGS (n = 22), antineutrophil cytoplasmic antibody-associated vasculitis (AAV; n = 5), and matched controls (n = 9) to explore candidate genes and mechanisms of disease. Gene expression changes were validated, and selected markers were identified by immunofluorescence staining. Epithelial-mesenchymal transition (EMT) and leukocyte extravasation pathways were the biological mechanisms most relevant to iSGS pathogenesis. Alternatively activated macrophages (M2) were abundant in the subepithelium and perisubmucosal glands of the airway in iSGS and AAV. Increased expression of the mesenchymal marker S100A4 and decreased expression of the epithelial marker epithelial cell adhesion molecule (EPCAM) further supported a role for EMT, but to different extents, in iSGS and antineutrophil cytoplasmic antibody-associated subglottic stenosis. In patients with iSGS, high expression of prostate transmembrane protein, androgen induced 1 (PMEPA1), an EMT regulator, was associated with a shorter recurrence interval (25 versus 116 months: hazard ratio = 4.16; P = 0.041; 95% CI, 1.056-15.60). Thus, EMT is a key pathogenetic mechanism of subglottic stenosis in iSGS and AAV. M2 macrophages contribute to the pathogenesis of both diseases, suggesting a shared profibrotic mechanism, and PMEPA1 may be a biomarker for predicting disease recurrence in iSGS.

Safety outcomes and patient convenience in outpatient parotidectomy.

BACKGROUND: Parotidectomies have historically been performed on an inpatient basis despite being well-tolerated surgeries with minimal postoperative wound care and low rates of complications at high-volume institutions. Past studies have supported the safety of outpatient surgery for parotidectomy but have been limited to superficial parotidectomy and have not addressed the patient experience surrounding the surgical intervention such as pre-operative and post-operative care and communication. PURPOSE: This study assesses the impact of outpatient superficial, deep, and partial parotid surgery on various parameters including surgical safety, distance traveled for care, utilization of telehealth, and patient-initiated communication. MATERIALS AND METHODS: Retrospective study from January 2020 to October 2021. Patients undergoing superficial lobe, deep lobe, and partial parotidectomies for benign and malignant pathologies were divided into inpatient and outpatient cohorts. A multivariable model examined the relationship between admission status and surgical complications, adjusted for age, sex, and tumor size. RESULTS: 159 patients total, 94 outpatient and 65 inpatients. No statistical difference in rates of surgical complications with the exception of salivary leak. There was an increased rate of salivary leak reported in the inpatient group (OR 5.4, 95 % CI 1.6 to 18.0, p = 0.01). Mean patient travel distance of 354 miles one-way. Post-operatively, 76 % were evaluated via video visit. Following discharge, >55 % of patients initiated communication with the surgical team, which was not statistically different between the groups. CONCLUSIONS: Outpatient parotidectomy is safe and can be more convenient, but telehealth communication must be balanced with rigorous attention to patient education.

Complications following laser wedge excision for idiopathic subglottic stenosis.

OBJECTIVES: Endoscopic laser wedge excision (LWE) is an effective treatment option for idiopathic subglottic stenosis (iSGS); however, data regarding complications following LWE are limited. The aim of the following analysis was to provide a review of frequency and type of complications that occur with LWE in patients with iSGS. STUDY DESIGN: Retrospective review. METHODS: Patients with iSGS undergoing LWE between January 2002 and September 2021 were performed. Demographic data were recorded. Complications were stratified into major and minor categories. The frequency of these complications and the respective treatment for them was analyzed. RESULTS: 212 patients within the study period underwent a total of 573 LWE procedures. All but two patients were female, with a median age of 54 years at time of LWE. Of these patients, 43 (20 %) patients experienced a complication. Of these, only 7 (15 %) of the reported complications were considered major while the rest were minor in nature. Major complications included 3 cases of post-operative hemoptysis, 1 case of tracheitis, and 3 cases of reduced vocal fold hypomobility with concurrent glottic stenosis. Minor complications consisted of 2 cases of tooth fracture and 34 cases of tongue paresthesia post-operatively that was self-limited. There were no mortalities. CONCLUSION: Major complications occur in <5 % of LWE procedures based off the analysis. All major complications were managed without significant long-term morbidity. Minor complications with the LWE are self-limited in nature. Our data supports the LWE as a safe treatment option for iSGS.

The role of total parotidectomy in high-grade parotid malignancy: A multisurgeon retrospective review.

PURPOSE: Determine rates of intra-parotid and neck nodal metastasis, identify risk factors for recurrence, and report outcomes in patients with primary high-grade parotid malignancy who undergo total parotidectomy and neck dissection. MATERIALS & METHODS: Retrospective review of patients undergoing total parotidectomy and neck dissection for high-grade parotid malignancy between 2005 and 2015. The presence and number of parotid lymph nodes, superficial and deep, as well as cervical lymph nodes involved with metastatic disease were assessed. Risk factors associated with metastatic spread to the parotid deep lobe were identified and recurrence rates reported. RESULTS: 75 patients with median follow-up time of 47 months. 35 patients (46.7%) had parotid lymph node metastasis. Seven patients (9.3%) had deep lobe nodal metastasis without metastasis to the superficial lobe nodes. Nine patients (12%) had positive intra-parotid nodes without positive cervical nodes. Cervical nodal disease was identified in 49.3% patients (37/75). Local, parotid-bed recurrence rate was 5.3% (4/75). Regional lymph node recurrence rate was also 5.3% (4/75). Rate of distant metastasis was 30.6% (23/75). The overall disease free survival rate for all patients at 2 and 5 years were 71% and 60% respectively. CONCLUSION: Parotid lymph node metastasis occurred at a similar rate to cervical lymph node metastasis (46.7% and 49.3%, respectively). Deep lobe parotid nodal metastasis occurred in nearly a quarter of patients and can occur without superficial parotid nodal metastasis. Rate of recurrence in the parotid bed, which may represent local or regional recurrence, was similar to regional cervical lymph node recurrence. Total parotidectomy and neck dissection should be considered high-grade parotid malignancy regardless of clinical nodal status.

Mandibular Defect Reconstitution: A Contaminated Caprine Model of Bone Regeneration.

PURPOSE: Mandibular reconstitution with bioabsorbable scaffolds seems feasible with the application of 3-dimensional printing combined with bioactive proteins. As yet, previous studies have been limited in number of animals and have avoided a contaminated defect. We present a caprine model of mandibular defect bone regeneration with a 3-dimensionally printed bioabsorbable scaffold contaminated with oral secretions and explore the impact of bone morphogenic protein in mandibular bone reconstitution. METHODS: A 3-cm, contaminated mandibular defect was generated in 18 goats and stabilized with 2 mandibular reconstruction plates. An uncoated scaffold was placed in 6 goats, and in the final 6 goats, the scaffold was coated with bone morphogenic protein-2. In 6 goats, the defect was left empty. After 12 weeks, the operative site, scaffold, and adjacent mandible were plasticized, sectioned, and evaluated histologically to assess for bone regeneration. RESULTS: The specimens revealed only focal (average of 5.8% of the scaffold pores) and early bone formation in the scaffold-only group. In the scaffold + bone morphogenic protein-2 group, there was more (average of 51.4% of the pores) bone formation. In the periosteum-only group, the ratio of the bone thickness of the defect to that of the normal bone ranged from 0.16 to 0.78. No major infections occurred. CONCLUSIONS: This caprine model serves as an excellent method to assess reconstructive options for contaminated mandibular deficits. Bone regeneration was documented in a 3-cm contaminated caprine mandibular defect reconstructed with a 3-dimensionally printed synthetic scaffold with or without the addition of bone morphogenic protein-2. Bone morphogenic protein-2 significantly augments bone generation in the synthetic scaffold. Residual mandibular periosteum generated bone. Future studies will focus on optimizing vascularization.

Tumor-specific prognosis of mutation-positive patients with head and neck paragangliomas.

BACKGROUND: Genetic testing to identify succinate dehydrogenase (SDH) mutations in patients with head and neck paraganglioma (HNP) has been in clinical practice for more than a decade. However, the recurrence and metachronous tumor occurrence risks in surgically treated mutation-positive patients are not well studied. METHODS: Clinical and procedural details of consecutive patients who underwent excision for HNP from January 1996 to October 2016 were retrospectively reviewed. End points included recurrence, metachronous tumor detection, and mortality. Germline DNA was tested to identify mutations in SDHx genes. Patients were divided into three groups on the basis of genetic testing: group I, positive; group II, negative; and group III, unknown or offered but not tested. RESULTS: HNP was diagnosed in 268 patients, 214 (147 female; mean age, 47 years) included in this study. Directed genetic testing was performed in 68; mutations were detected in SDH in 47 (69%), a majority SDHD. In group I, 47 patients had 64 procedures for 81 tumors (52 carotid body tumors [CBTs]); 17 (36%) were bilateral, 7 (15%) multiple, 3 (6%) functional, and 7 (15%) malignant. Residual tumor in 10 was significant in 2, managed by radiation therapy and reoperation. Local recurrence was detected in 12 patients (25%) at a median of 8 years; 11 metachronous mediastinal and retroperitoneal paragangliomas were detected in 8 (17%) at a median of 13 years. Systemic metastases occurred in five (10%). Six patients (13%) had more than one recurrence. In group II, 21 patients had 22 procedures for 23 tumors, 17 CBTs. Two (9%) were bilateral and two (9%) malignant. Excision was complete in all with no recurrence or systemic metastasis at last follow-up. For group III, 146 patients underwent 153 procedures for 156 tumors, 95 CBTs; 7 (5%) were bilateral, 2 (1%) multiple, 8 (5%) functional, and 1 (0.6%) malignant. Local recurrence was detected in nine (6%) at a median of 9 years and metachronous HNP in three (2%) at a median of 5 years. Systemic metastases occurred in two (1%). Mortality was 4% in group I and 3% in group III, none procedure or tumor related. Group I (mutation positive) had 10-year overall, recurrence-free, and metachronous tumor-free survival rates of 93%, 69.4%, and 73%, respectively, lower than the other groups (P < .001). CONCLUSIONS: Bilateral, functional, malignant, recurrent, and metachronous tumors are more common in SDH mutation-positive patients with HNP. Overall survival in patients with HNP is high. Metachronous tumors or local recurrences occur late, and long-term follow-up is necessary.

Recurrent pleomorphic adenoma of the parotid gland: A comparison of radiographic and pathologic tumor burden.

PURPOSE: To compare recurrent pleomorphic adenoma tumor burden as detected on magnetic resonance and computerized tomography imaging with postoperative histopathology. MATERIALS AND METHODS: 44 patients were identified at a tertiary medical center between 2000 and 2015. Patients were included if they had viewable preoperative imaging and a postoperative diagnosis of recurrent pleomorphic adenoma. Primary outcomes were differences in the number and size of lesions detected on imaging and pathology. RESULTS: The size in greatest dimension between pathology and imaging was not significant on aggregate MRI + CT (p = 0.78), MRI (p = 0.41), or CT (p = 0.69). There were more lesions found on pathology compared to both aggregate MRI + CT (p = 0.003) and CT alone (p = 0.014). The number of lesions between MRI and pathology failed to reach significance (p = 0.06). On univariate analysis, the interval between imaging and pathology (recurrent surgery) did not significantly affect the number of lesions detected (p = 0.18). On multivariable analysis, CT as the primary imaging modality and >1 recurrence was independently associated with greater inaccuracy with respect to number of lesions detected (p = 0.006; p = 0.008). CONCLUSION: The size of the largest lesion on pathology can be accurately determined with imaging. Compared to MRI, CT scans significantly underpredict the number of lesions found on pathology. MRI should be prioritized unless contraindications exist. These findings will help guide imaging choice, preoperative planning, and patient counseling.

Whole genome sequencing reveals complexity in both HPV sequences present and HPV integrations in HPV-positive oropharyngeal squamous cell carcinomas.

BACKGROUND: High risk human papillomaviruses (HPV) plays important roles in the development of cervical cancer, a number of other anogenital cancer and they are increasingly found in oropharyngeal squamous cell carcinoma (OPSCC), however there has not been comprehensive analysis about the role how these viruses play in the development of OPSCC. METHODS: To characterize the physical status of HPV within OPSCC and to determine the effect this has throughout the host genome, we have performed 30-40X whole genome sequencing (WGS) on the BGI sequencing platform on 34 OPSCCs: 28 of which were HPV positive. We then examined the sequencing data to characterize the HPV copy number and HPV physical status to determine what effect they have on both HPV and human genome structural changes. RESULTS: WGS determined the HPV copy number across the viral genome. HPV copy number ranged from 1 copy to as high as 150 copies in each individual OPSCC. Independent of HPV copy number, most tumors had either a small or a very large deletion in the viral genome. We discovered that these deletions were the result of either HPV integration into the human genome or HPV-HPV sequence junctions. WGS revealed that ~ 70% of these tumors had HPV integrations within the human genome and HPV integration occurred independent of HPV copy number. Individual HPV integrations were found to be highly disruptive resulting in structural variations and copy number changes at or around the integration sites. CONCLUSIONS: WGS reveals that there is a great complexity in both HPV sequences present and the HPV integrations events in HPV positive OPSCCs tumors. Thus HPV may be playing different roles in the development of different OPSCCs and this further challenge the HPV-driven carcinogenesis model first proposed for cervical cancer.

Common fragile sites (CFS) and extremely large CFS genes are targets for human papillomavirus integrations and chromosome rearrangements in oropharyngeal squamous cell carcinoma.

Common fragile sites (CFS) are chromosome regions that are prone to form gaps or breaks in response to DNA replication stress. They are often found as hotspots for sister chromatid exchanges, deletions, and amplifications in different cancers. Many of the CFS regions are found to span genes whose genomic sequence is greater than 1 Mb, some of which have been demonstrated to function as important tumor suppressors. CFS regions are also hotspots for human papillomavirus (HPV) integrations in cervical cancer. We used mate-pair sequencing to examine HPV integration events and chromosomal structural variations in 34 oropharyngeal squamous cell carcinoma (OPSCC). We used endpoint PCR and Sanger sequencing to validate each HPV integration event and found HPV integrations preferentially occurred within CFS regions similar to what is observed in cervical cancer. We also found that many of the chromosomal alterations detected also occurred at or near the cytogenetic location of CFSs. Several large genes were also found to be recurrent targets of rearrangements, independent of HPV integrations, including CSMD1 (2.1Mb), LRP1B (1.9Mb), and LARGE1 (0.7Mb). Sanger sequencing revealed that the nucleotide sequences near to identified junction sites contained repetitive and AT-rich sequences that were shown to have the potential to form stem-loop DNA secondary structures that might stall DNA replication fork progression during replication stress. This could then cause increased instability in these regions which could lead to cancer development in human cells. Our findings suggest that CFSs and some specific large genes appear to play important roles in OPSCC. © 2016 Wiley Periodicals, Inc.

Melanoma of the external ear: A population-based study.

BACKGROUND: Primary melanoma of the external ear (PMEE) is rare and therefore well-suited for large population-based registry analysis. The objective of this study was to utilize the Surveillance, Epidemiology, and End Results (SEER) set of cancer registries to determine the incidence, treatment, and survival characteristics of PMEE. METHODS: A retrospective cohort analysis of SEER data from 2004 to 2013 identified all cases of PMEE stage I-IV by AJCC 7th edition guidelines. Population-based incidence was calculated. Cancer-specific survival data by stage was assessed using Kaplan-Meier analysis and the relative effects of tumor characteristics were analyzed with Cox regression models. RESULTS: A total of 5481 patients were analyzed (mean age 66.7years, 86.5% male, 93.6% non-Hispanic white). The incidence of PMEE was 1.91 per 100,000 persons-per-year. At diagnosis, 68.1% were stage I, 15.2% were stage II, 4.7% were stage III, 1.5% were stage IV, and 10.8% were unknown. The five-year overall and cancer-specific survival was 78.8% and 90.0%, and, according to AJCC stage, was 85.7% and 95.3% for stage I (n=2287), 64.6% and 81.1% for stage II (n=453), 50.8% and 57.0% for stage III (n=154), 17.2% and 20.5% for stage IV (n=34), and 71.0% and 87.1% for unknown stage (n=330), respectively. The multivariable Cox model identified tumor characteristics that were independently associated with survival. CONCLUSIONS: This is the first study to characterize the epidemiology, presentation and outcome of PMEE using the SEER registries. Older age, increasing Breslow thickness, stage, presence of ulceration, positive lymph nodes and distant metastasis each independently predicted time to cancer-specific death.

Head and neck desmoplastic melanoma: Utility of sentinel node biopsy.

PURPOSE: The utility of sentinel lymph node biopsy in desmoplastic melanoma has been questioned due to multiple reports of a low rate of occult nodal metastasis in this variant of melanoma. We describe a single institution experience with management of desmoplastic melanoma of the head and neck and discuss the utility of sentinel lymph node biopsy. MATERIALS AND METHODS: A retrospective review was performed of 49 patients with desmoplastic melanoma of the head and neck at a tertiary care center from 1994 to 2014. RESULTS: Sentinel lymph node biopsy was performed in 15 patients. Only 1 (6.7%) of these patients was found to have a positive sentinel node. Of the 46 patients without evidence of neck disease at presentation, 3 (6.5%) were found to have occult nodal disease or developed neck recurrences. When looking at the entire cohort, there were a total of 16 recurrences in 14 patients (28.6%). The majority (85.7%) of recurrences were either local or distant metastasis with only 2 (14.3%) recurrences being in regional lymph node basins. The overall rates of local, regional, and distant recurrences were 14.2%, 4.1%, and 10.2% respectively. The mixed pathologic subtype was not associated with a higher rate of nodal metastasis. CONCLUSIONS: Desmoplastic melanoma has a low rate of occult nodal metastasis and a high propensity to recur locally or as a distant metastasis, regardless of regional node status. Our experience combined with the uncertain impact that sentinel node status has on survival raises the question of the utility of routine sentinel node biopsy in this specific variant of melanoma.

Treatment of oropharyngeal dysphagia secondary to idiopathic cricopharyngeal bar: Surgical cricopharyngeal muscle myotomy versus dilation.

OBJECTIVE: To compare swallowing outcomes following cricopharyngeal (CP) dilation versus surgical myotomy in patients with dysphagia secondary to idiopathic CP bar. METHODS: All patients had an idiopathic CP bar without a history of Zenker's diverticulum, head and neck cancer, or systemic neurologic disease treated between 2000 and 2013. The Functional Outcome Swallowing Scale (FOSS) was utilized to assess dysphagia symptoms. RESULTS: Twenty-three patients underwent 46 dilations and 20 patients had a myotomy. Nineteen of 23 (83%) patients in the dilation group and all patients in the myotomy group reported improved swallow function. The median difference in pre- versus post-intervention FOSS scores was not statistically significant (p=0.07) between the dilation and myotomy groups with mean reductions of 1.3 and 1.8, respectively. Seventeen of 23 (74%) dilation patients had persistent or recurrent dysphagia with 13 (57%) requiring repeat dilation and 4 (17%) undergoing CP myotomy. The median time to first reintervention in the dilation group was 13.6months. Nineteen of 20 (95%) surgical myotomy patients did not experience recurrent dysphagia. CONCLUSION: Both endoscopic CP dilation and myotomy led to similar initial improvement in swallow function for patients with primary idiopathic CP bar; however, dilation is more likely to provide temporary benefit.

Myhre-LAPs syndrome and intubation related airway stenosis: keys to diagnosis and critical therapeutic interventions.

OBJECTIVES: Myhre-LAPS syndrome is a recently recognized disease caused by a mutation in the SMAD4 gene. This results in a range of pathology including laryngotracheal stenosis, arthropathy, prognathism and short stature, or LAPS syndrome. We aim to delineate the role of intubation in development of airway stenosis in these patients as well as provide insight into diagnosis and management of this syndrome. Herein we present four patients with Myhre-LAPS syndrome complicated by airway stenosis and perform a systematic review of all cases of Myhre-LAPS syndrome with reported airway pathology. STUDY DESIGN: Retrospective review METHODS: All patients diagnosed with Myhre-LAPS syndrome and airway stenosis at a single institution from 1981 to 2014 were reviewed. RESULTS: Four patients (4F, median age 42) were identified that met inclusion criteria. Initial presenting signs included progressive shortness of breath, dyspnea on exertion and respiratory distress. All four (100%) patients had multi-level airway stenosis most commonly in the subglottic and glottic regions and all patients had undergone at least one endotracheal intubation prior to presentation. One patient with a history of nasal tracheal intubation presented with nasal obstruction and was found to have choanal as well as subglottic stenosis. Two of the four (50%) patients are tracheostomy tube dependent, 1/4 (25%) died of a fatal cardiac arrhythmia and 1/4 (25%) has had 6 endoscopic treatments for subglottic stenosis in 4 years with rapid symptom recurrence. CONCLUSIONS: Myhre-LAPS syndrome is characterized by progressive systemic fibrosis and patients are diagnosed by characteristic findings of prognathism, short stature, abnormal facies, and thick skin among other abnormalities. Airway management is complicated by recurrent, refractory subglottic stenosis often preceded by elective intubation as well as maxillary hypoplasia, trismus, and limited neck extension. Endotracheal intubation and surgical intervention should be approached with caution in these patients and multidisciplinary care teams are necessary to address all manifestations of this syndrome.

A selected group of large common fragile site genes have decreased expression in oropharyngeal squamous cell carcinomas.

The common fragile sites (CFSs) are large regions of profound genomic instability found in all individuals. The frequent deletions and other alterations in these regions in multiple cancers has led to the discovery of a number of extremely large genes contained within these regions and several of the large CFS genes have already been demonstrated to function as tumor suppressors involved in the formation of many different cancers. To study the large CFS genes in oropharyngeal squamous cell carcinoma (OPSCC), we did RNA seq analysis from 11 head and neck cancer patients. This revealed that there are six large CFS genes which consistently had decreased expression in the tumor samples compared to their matched normal tissues. These six genes are PARK2, DLG2, NBEA, CTNNA3, DMD, and FHIT. PARK2 and FHIT are located within the two most frequently expressed CFSs and both have been demonstrated to function as tumor suppressors, while the other large genes are found to have frequent alterations in multiple cancers. Validation experiments using real time PCR indicated that over 60% of OPSCC tumors showed decreased expression for all six genes. Both HPV-positive and HPV-negative OPSCCs had similar proportions with loss of expression of these genes. Our results suggest that this selected group of large genes might serve as potential tumor suppressors involved in the development of OPSCCs. Further studies are needed to investigate whether the decreased expression observed is due to genomic instability within the CFS regions or the selection for alterations of specific large CFS genes.

Reoperative experience with papillary thyroid cancer.

BACKGROUND: Intense postoperative monitoring has resulted in increasing detection of patients with recurrent papillary thyroid cancer (PTC). Our goals included quantifying successful reoperation, and analyzing surgical complications and reasons for relapse. METHODS: From 1999 to 2008, a total of 410 patients underwent reoperation for PTC relapse. We analyzed post-reoperative disease outcomes, reasons for relapse, and complications. RESULTS: Bilateral reoperative thyroidectomy was performed in 13 (3 %) patients; lobectomy, 34 (8 %); central neck (VI) soft tissue local recurrence excision, 47 (11.5 %); bilateral VI node dissection, 107 (26 %); unilateral VI dissection, 112 (27 %); levels II-V dissection, 93 (23 %); levels III-V, 86 (21 %); lateral single- or two-compartment dissection, 51 (12 %); and node picking, 20 (5 %) of level VI and 53 (13 %) lateral neck. Complications occurred in 6 %; including hypoparathyroidism, 3 %; unintentional recurrent laryngeal nerve (RLN) paralysis, 3 %; phrenic nerve injury, 0.5 %; spinal accessory nerve injury, 0.5 %; and chyle leak in 1.6 %. Of 380 (93 %) patients with follow-up (mean 5.2 years); 274 (72 %) patients are alive with no structural evidence of disease, 38 % developed disease relapse (mean 2.1 years), 42 (11 %) died from PTC, and 55 (14 %) are alive with disease. The reason for relapse was a false negative pre-reoperative ultrasound (US) in 18 (5 %), nodal recurrence in the operative field in 37 (10 %), a combination of these two reasons in 10 (3 %), and disease virulence (local or systemic recurrence) in 81 (21 %). CONCLUSIONS: Although 72 % of patients were rendered structurally disease free after reoperation, nearly 40 % suffered additional relapse. Improved surgical technique or preoperative localization might positively affect 15-20 %; at least 20 % reflect the biologic aggressiveness of the disease.

Transnasal odontoid resection: is there an anatomic explanation for differing swallowing outcomes?

OBJECT: Swallowing dysfunction is common following transoral (TO) odontoidectomy. Preliminary experience with newer endoscopic transnasal (TN) approaches suggests that dysphagia may be reduced with this alternative. However, the reasons for this are unclear. The authors hypothesized that the TN approach results in less disruption of the pharyngeal plexus and anatomical structures associated with swallowing. The authors investigate the histological and gross surgical anatomical relationship between pharyngeal plexus innervation of the upper aerodigestive tract and the surgical approaches used (TN and TO). They also review the TN literature to evaluate swallowing outcomes following this approach. METHODS: Seven cadaveric specimens were used for histological (n = 3) and gross anatomical (n = 4) examination of the pharyngeal plexus with the TO and TN surgical approaches. Particular attention was given to identifying the location of cranial nerves (CNs) IX and X and the sympathetic chain and their contributions to the pharyngeal plexus. S100 staining was performed to assess for the presence of neural tissue in proximity to the midline, and fiber density counts were performed within 1 cm of midline. The relationship between the pharyngeal plexus, clivus, and upper cervical spine (C1-3) was defined. RESULTS: Histological analysis revealed the presence of pharyngeal plexus fibers in the midline and a significant reduction in paramedian fiber density from C-2 to the lower clivus (p < 0.001). None of these paramedian fibers, however, could be visualized with gross inspection or layer-by-layer dissection. Laterally based primary pharyngeal plexus nerves were identified by tracing their origins from CNs IX and X and the sympathetic chain at the skull base and following them to the pharyngeal musculature. In addition, the authors found 15 studies presenting 52 patients undergoing TN odontoidectomy. Of these patients, only 48 had been swallowing preoperatively. When looking only at this population, 83% (40 of 48) were swallowing by Day 3 and 92% (44 of 48) were swallowing by Day 7. CONCLUSIONS: Despite the midline approach, both TO and TN approaches may injure a portion of the pharyngeal plexus. By limiting the TN incision to above the palatal plane, the surgeon avoids the high-density neural plexus found in the oropharyngeal wall and limits injury to oropharyngeal musculature involved in swallowing. This may explain the decreased incidence of postoperative dysphagia seen in TN approaches. However, further clinical investigation is warranted.

Symptom-Free Intervals Following Laser Wedge Excision for Recurrent Idiopathic Subglottic Stenosis.

OBJECTIVE: Analyze the duration of symptom-free intervals following laser wedge excision (LWE) for recurrent idiopathic subglottic stenosis (iSGS). Secondary aim includes evaluating the influence of patient-related or disease factors. STUDY DESIGN: Retrospective review. SETTING: Tertiary center. METHODS: Review of iSGS patients who underwent LWE between 2002 and 2021. LWE patients without prior airway surgery were labeled LWE primary (LWEP) and those with prior history of dilation were labeled LWE secondary (LWES). A conditional frailty repeated events model was used to analyze the median time to recurrence (MTR) for each nth recurrence. Secondary analysis included stratification by use of medical therapy and initial preoperative characteristics of scar (Myer-Cotton grade, distance between the glottis and superior-most aspect of scar, DGS; length of scar, DL). RESULTS: Two hundred and ten iSGS patients underwent LWE (131 LWEP, 79 LWES). The proportion of patients experiencing at least 1, 3, 6, and 12 recurrences, respectively, was 68.0% (n = 143), 40.7% (n = 85), 20.0% (n = 42), and 5.2% (n = 11). There was exponential time-shortening from the 1st to 12th recurrence (P < .0001). While MTR was 4.1 years after the first LWE, this fell to 2.8, 1.7, 1.0, and 0.7 years for the 2nd, 3rd, 6th, and 12th recurrences. Furthermore, LWEP patients experienced longer MTR than LWES counterparts within the first 6 recurrences (P < .01). There was no significant relationship between intersurgical interval and medication adherence, DL, DGS, or grade for recurrences beyond the first (P = .207, P = .20, P = .43, P = .16). CONCLUSION: Symptom-free intervals in iSGS shorten with each subsequent recurrence and LWE. The difference in MTR between LWEP and LWES groups was significant within the first 6 recurrences with LWEP having longer MTR.

Surgical Outcomes in Zenker Diverticula: A Multicenter, Prospective, Longitudinal Study.

OBJECTIVE: To compare improvement in patient-reported outcomes (PROM) in persons undergoing endoscopic and open surgical management of Zenker diverticula (ZD). METHODOLOGY: Prospective, multicenter cohort study of all individuals enrolled in the Prospective OUtcomes of Cricopharyngeus Hypertonicity (POUCH) Collaborative who underwent surgery for ZD. Patient survey, radiography reports, and the 10-item Eating Assessment Tool (EAT-10) pre- and post-procedure were abstracted from a REDCap database, which summarized means, medians, percentages, and frequencies of. Outcome based on operative intervention (endoscopic vs. open) was compared using t-test, Wilcoxon rank sum test or chi-square test, as appropriate. RESULTS: One hundred and forty-seven persons were prospectively followed. The mean age (SD) of the cohort was 68.7 (11.0). Overall, 66% of patients reported 100% improvement in EAT-10; 81% of patients had greater than 75% improvement; and 88% had greater than 50% improvement. Endoscopic was used for n = 109 patients, and open surgical intervention was used for n = 38. The median [interquartile range, IQR] EAT-10 percent improvement for endoscopic treatment was 93.3% [72, 100], and open was 100% [92.3, 100] (p = 0.05). The incidence of intraoperative complications was 3.7% for endoscopic and 7.9% for open surgical management. The median [IQR] in follow-up was 86 and 97.5 days, respectively. CONCLUSION: Both endoscopic and open surgical management of ZD provide significant improvement in patient-reported outcomes. The data suggest that open diverticulectomy may provide a modest advantage in symptomatic improvement compared to endoscopic management. The data suggest that the postoperative complication rate is higher in the open surgical group. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:97-102, 2024.

Surgical Nonresponders in Zenker Diverticulum and Lower Esophageal Pathology (POUCH Collaborative).

OBJECTIVE: To identify characteristics of patients who have poor improvement in symptoms following surgical management of Zenker Diverticulum (ZD). METHODS: Prospective, multicenter cohort study of all individuals enrolled in the Prospective OUtcomes of Cricopharyngeus Hypertonicity (POUCH) Collaborative who underwent surgical repair of ZD between August 2017 and January 2024. Patient demographics, esophagrams, and the 10-item Eating Assessment Tool (EAT-10) pre- and post-procedure were obtained from a REDCap database. t-tests, Wilcoxon rank sum tests, Chi-square or Fisher's exact tests were used to compare the characteristics. Patients with <50% improvement in their EAT-10 scores were deemed surgical nonresponders (SNRs). Those with ≥50% improvement in their EAT-10 scores were deemed surgical responders (SRs). RESULTS: A total of 184 patients were prospectively followed after undergoing either open or endoscopic surgical management. Twenty-two patients (12%) were deemed SNRs. Preoperative presence of a hiatal hernia was statistically significant characteristic between the SNRs (63.6%) and SRs (32.1%) (p = 0.004). Size of the ZD and history of previous ZD surgery was not a significant characteristic. The length of stay and complication rate were not statistically different between the groups. CONCLUSION: Coexistent esophageal pathology may lead to poor symptomatic improvement following ZD surgery. Preoperative workup of other esophageal disorders is recommended to detect likely SNRs. For SNRs, further esophageal workup may be necessary to evaluate for other esophageal causes related to poor symptomatic improvement following ZD surgery. LEVEL OF EVIDENCE: Level 3 Laryngoscope, 2024.