Salvage surgery for recurrent or residual hypopharyngeal squamous cell carcinoma: A systematic review.

BACKGROUND: This systematic review aggregates the data of studies that include site-specific analyses of patients undergoing salvage surgery for residual or recurrent hypopharyngeal squamous cell carcinoma. METHODS: The primary outcomes are disease-free, disease-specific, and overall survival (DFS, DSS, and OS, respectively). Secondary outcomes include complications and postoperative feeding requirements. RESULTS: Fifteen studies met the inclusion criteria with a total of 442 patients. Two-year DFS is reported from 30.0 to 50.0% and 5-year DFS ranges from 15.0 to 57.1%. Five-year DSS ranges from 28.0 to 57.1%. Two-year OS ranges from 38.8 to 52.0% and 5-year OS ranges from 15.5 to 57.1%. Complications include pharyngocutaneous fistula (0.0-71.4%), carotid artery rupture (2.9-13.3%), and stomal stenosis (4.2-20.0%). Complete oral feeding achieved following surgery ranges from 61.9 to 100.0%, while complete gastrostomy tube dependence ranges from 0.0 to 28.6%. CONCLUSIONS: Salvage surgery for residual or recurrent hypopharyngeal squamous cell carcinoma has a relatively high complication rate and should be offered to patients with the understanding of a guarded prognosis.

Early Weight-Bearing After Fibula Free Flap Surgery.

Importance: Despite the widespread use of fibula free flap (FFF) surgery for head and neck reconstruction, there are no studies assessing if early weight-bearing (EWB) affects postoperative recovery, and the timing of weight-bearing initiation following FFF surgery varies considerably across institutions. Therefore, it is important to understand the effect of EWB in these patients and whether it could improve postoperative recovery. Objective: To assess the association of EWB after FFF surgery with donor-site complications, length of stay, and discharge to home status. Design, Setting, and Participants: This retrospective cohort study took place at Massachusetts Eye and Ear, a single tertiary care institution in Boston, Massachusetts. A total of 152 patients who received head and neck reconstruction with a fibula osteocutaneous free flap between January 11, 2010, and August 11, 2022, were included. Exposure: EWB on postoperative day 1 vs non-EWB on postoperative day 2 or later. Main Outcomes and Measures: Patient characteristics, including demographic characteristics and comorbidities, surgical characteristics, donor-site complications, length of stay, and discharge disposition, were recorded. Descriptive statistics and multivariate logistic regressions were used to compute effect sizes and 95% CIs to compare postoperative outcomes in EWB and non-EWB groups. Results: A total of 152 patients (median [IQR] age, 63 [55-70] years; 89 [58.6%] male) were included. The median (IQR) time to postoperative weight-bearing was 3 (1-5) days. Among all patients, 14 (9.2%) had donor-site complications. EWB on postoperative day 1 was associated with shorter length of stay (adjusted odds ratio [AOR], 0.10; 95% CI, 0.02-0.60), increased rate of discharge to home (AOR, 7.43; 95% CI, 2.23-24.80), and decreased donor-site complications (AOR, 0.11; 95% CI, 0.01-0.94). Conversely, weight-bearing 3 or more days postoperatively was associated with an increased risk of pneumonia (AOR, 6.82; 95% CI, 1.33-34.99). Conclusions and Relevance: In this cohort study, EWB after FFF surgery was associated with shorter length of stay, increased rate of discharge to home, and decreased donor-site complications. These findings support the role of early mobilization to optimize postoperative recovery after FFF surgery.

Predictors of multiple dilations and functional outcomes after total laryngectomy and laryngopharyngectomy.

BACKGROUND: Following total laryngectomy (TL) or laryngopharyngectomy (TLP), patients may develop strictures that require multiple dilations to treat. However, the risk factors associated with dysphagia refractory to a single dilation are unknown. METHODS: Single-institution retrospective review of patients who underwent at least one stricture dilation after TL/TLP between March 2013 and March 2022. RESULTS: A total of 49 patients underwent stricture dilation after TL/TLP. Thirty-five (71%) underwent multiple dilations. Pharyngocutaneous fistula, primary chemoradiation therapy, and a shorter time interval from TL/TLP to first dilation were independently associated with dysphagia requiring multiple dilations. Patients in the multiple dilations group had a higher rate of limited diet and G-tube dependence compared to patients in the single dilation group. CONCLUSIONS: Shorter time interval to stricture formation is a prognostic indicator of the need for multiple dilations following TL/TLP. Patients requiring multiple dilations are at increased risk of persistent dysphagia long-term.

AI Model Versus Clinician Otoscopy in the Operative Setting for Otitis Media Diagnosis.

Prior work has demonstrated improved accuracy in otitis media diagnosis based on otoscopy using artificial intelligence (AI)-based approaches compared to clinician evaluation. However, this difference in accuracy has not been shown in a setting resembling the point-of-care. In this study, we compare the diagnostic accuracy of a machine-learning model to that of pediatricians using standard handheld otoscopes. We find that the model is more accurate than clinicians (90.6% vs 59.4%, P = .01). This is a step towards validation of AI-based diagnosis under more real-world conditions. With further validation, for example on different patient populations and in deployment, this technology could be a useful addition to the clinician's toolbox in accurately diagnosing otitis media.

Robotic Thyroidectomy via Posterior Neck Approach Using the Da Vinci Single Port System.

We describe a remote access thyroidectomy technique: robotic thyroidectomy via posterior neck approach using the Da Vinci single port (Sp) robotic system. This approach is feasible and safe in the Western population. Laryngoscope, 2023.

Development and Content Validity of a Novel Patient-Reported Outcome Measure for Total Laryngectomy: The LARY-Q.

OBJECTIVES: To develop a patient-reported outcomes measure (PROM) for total laryngectomy. STUDY DESIGN: Qualitative interviews with a purposive sample of patients with total laryngectomy, followed by cognitive debriefing interviews with patients and expert feedback. METHODS: Concept elicitation was performed using in-depth qualitative interviews with a purposive sample of patients who had undergone total laryngectomy. Patients were recruited from head and neck surgery and speech-language pathology clinics as well as via laryngectomy support groups. Interviews were conducted, recorded, transcribed, and coded, resulting in a conceptual framework and item pool. Using the item pool, preliminary scales were drafted. The scales were revised iteratively over 5 rounds using feedback from cognitive interviews with patients and multi-institutional and multi-disciplinary expert feedback. RESULTS: A total of 15 patients with total laryngectomy (mean age 68 years, range 57-79) were interviewed resulting in 1555 codes. The codes were used to form a conceptual framework grouped into top-level domains of stoma, function, health-related quality of life, devices, and experience of care. Items were used to form 15 preliminary scales that were revised over five rounds of cognitive debriefing interviews (n = 9 patients) and expert feedback (n = 17 experts). The field-test version of the LARY-Q has 18 scales and 277 items in total. CONCLUSIONS: The LARY-Q is a novel PROM designed to assess outcomes associated with total laryngectomy. The next step involves a field test study with a heterogenous sample of patients to assess the psychometric properties of the LARY-Q and perform item reduction.

Online Searches Related to Total Laryngectomy.

OBJECTIVE: To identify the most frequently asked questions regarding "laryngectomy" through an assessment of online search data. METHODS: Google Search data based on the search term "laryngectomy" were analyzed using Google Trends and Search Response. The most common People Also Ask (PAA) questions were identified and classified by the concept. Each website linked to its respective PAA question was rated for understandability, ease of reading, and reading grade level. RESULTS: Search popularity for the term "laryngectomy" remained stable between 2017 and 2022. The most popular PAA themes were post-laryngectomy speech, laryngectomy comparison to tracheostomy, stoma and stoma care, survival/recurrence, and post-laryngectomy eating. Of the 32 websites linked to the top 50 PAA's, eleven (34%) were at or below an 8th grade reading level. CONCLUSION: Post-laryngectomy speech, eating, survival, the stoma, and the difference between laryngectomy and tracheostomy are the most common topics searched online in relation to "laryngectomy." These are important areas for both patient and healthcare provider education. LEVEL OF EVIDENCE: N/A Laryngoscope, 133:2971-2976, 2023.

Predicting Progression of Oral Lesions to Malignancy Using Machine Learning.

OBJECTIVE: To use large-scale electronic health record (EHR) data to develop machine learning models predicting malignant transformation of oral lesions. METHODS: A multi-institutional health system database was used to identify a retrospective cohort of patients with biopsied oral lesions. The primary outcome was malignant transformation. Chart review and automated system database queries were used to identify a range of demographic, clinical, and pathologic variables. Machine learning was used to develop predictive models for progression to malignancy. RESULTS: There were 2192 patients with a biopsied oral lesion, of whom 1232 had biopsy proven oral dysplasia. There was malignant transformation in 34% of patients in the oral lesions dataset, and in 54% of patients in the dysplasia subset. Multiple machine learning-based models were trained on the data in two experiments, (a) including all patients with biopsied oral lesions and (b) including only patients with biopsy-proven dysplasia. In the first experiment, the best machine learning models predicted malignant transformation among the biopsied oral lesions with an area under the curve (AUC) of 86%. In the second experiment, the random forest model predicted malignant transformation among lesions with dysplasia with an AUC of 0.75. The most influential features were dysplasia grade and the presence of multiple lesions, with smaller influences from other features including anemia, histopathologic description of atypia, and other prior cancer history. CONCLUSION: With diverse features from EHR data, machine learning approaches are feasible and allow for generation of models that predict which oral lesions are likely to progress to malignancy. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1156-1162, 2023.

Clinical Perineural Invasion and Immunotherapy for Head and Neck Cutaneous Squamous Cell Carcinoma.

OBJECTIVES/HYPOTHESIS: To describe outcomes of advanced head and neck cutaneous squamous cell carcinoma (cSCC) with clinical perineural invasion (cPNI) treated with immune checkpoint inhibitor (ICI) therapy, and to describe post-treatment radiographic findings in the context of clinical response to treatment using a new grading system. STUDY DESIGN: Retrospective chart review. METHODS: Retrospective chart review was performed for 11 patients treated with ICI for head and neck cSCC with cPNI of large named nerves. The primary outcome was response to treatment as defined by radiographic and clinical evidence. Clinical responses were defined as improvement in symptoms of neuropathic pain, hypoesthesia, nerve weakness, or decrease in visible tumor. Imaging studies were graded based on a new classification system for perineural invasion and reviewed by two neuroradiologists since RECISTv1.1 is inadequate to adjudicate response in these patients. RESULTS: Nine (82%) patients had radiographic perineural disease control on ICI. Eight patients had improved radiographic perineural disease and one had stable disease. Of these, complete resolution of radiographic evidence of perineural disease was seen in only one patient. Seven (64%) patients had clinical responses, with either improved or stable radiographic disease. CONCLUSIONS: ICI therapy is a viable treatment option for head and neck cSCC with cPNI. Radiographic and clinical evidence of response correlate well, with improvement in neuropathic pain being the most sensitive clinical marker of response. Even with favorable findings on repeat imaging and stable clinical course, complete resolution of perineural thickening and enhancement is rare. A grading system for classifying changes in perineural disease over time is proposed. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:1213-1218, 2022.

Risk Factors for Laryngectomy for Dysfunctional Larynx After Organ Preservation Protocols: A Case-Control Analysis.

OBJECTIVE: (1) To identify factors associated with severe dysfunctional larynx leading to total laryngectomy after curative treatment of head and neck squamous cell carcinoma and (2) to describe swallowing and voice outcomes. STUDY DESIGN: Retrospective single-institution case-control study. SETTING: Tertiary care referral center. METHODS: A 10-year chart review was performed for patients who had previously undergone radiation or chemoradiation for head and neck mucosal squamous cell carcinoma and planned to undergo total laryngectomy for dysfunctional larynx, as well as a control group of matched patients. Controls were patients who had undergone radiation or chemoradiation for mucosal squamous cell carcinoma but did not have severe dysfunction warranting laryngectomy; these were matched to cases by tumor subsite, T stage, and time from last treatment to video swallow study. Main outcomes assessed were postoperative diet, alaryngeal voice, pharyngeal dilations, and complications. RESULTS: Twenty-six patients were scheduled for laryngectomy for dysfunctional larynx, of which 23 underwent surgery. Originally treated tumor subsites included the larynx, oropharynx, hypopharynx, oral cavity, and a tumor of unknown origin. The median time from end of cancer treatment to laryngectomy was 11.5 years. All cases were feeding tube or tracheostomy dependent or both prior to laryngectomy. As compared with matched controls, cases were significantly less likely to have undergone IMRT (intensity-modified radiotherapy) and more likely to have pulmonary comorbidities. Eighty-nine percent of cases with follow-up achieved functional alaryngeal voice, and all were able to have oral intake. CONCLUSION: Non-IMRT approaches and pulmonary comorbidities are associated with laryngectomy for dysfunction after radiation or chemoradiation.

Outcomes of Cartilage-Sparing Wide Local Excision for Primary Melanoma of the External Ear.

OBJECTIVE: To describe outcomes after cartilage-sparing wide local excision for primary melanoma of the external ear. STUDY DESIGN: Retrospective analysis of patients undergoing external ear melanoma excision using a cartilage-sparing approach at a university-based tertiary care center between 2010 and 2018. SETTING: University-based tertiary care center. SUBJECT AND METHODS: Chart review was performed for all patients over age 18 who were treated for melanoma of the external ear at Massachusetts Eye and Ear between 2010 and 2018. Patients with melanoma in situ or with melanomas in noncartilaginous areas of the ear (eg, lobule) were excluded. RESULTS: A total of 8 patients underwent cartilage-sparing excision. Sentinel lymph node biopsy was performed in 7 patients, with positive lymph nodes in 1 of 7 cases. Positive margins and local recurrence occurred in 1 of 8 (12.5%) patients during a mean (SD) follow-up time of 22.5 (15.1) months (SE, 5.3 months). No distant metastasis or death was observed. CONCLUSION: Cartilage-sparing wide local excision for melanoma of the external ear is a surgical approach that enables surgeons to follow guideline-recommended oncologic excision margins but has the added benefit of improved postoperative aesthetic outcomes as well as reconstructive options through preservation of the auricular cartilage framework.

Sentinel lymph node biopsy for high-risk cutaneous squamous cell carcinoma of the head and neck.

OBJECTIVES/HYPOTHESIS: To describe outcomes of a single institution experience with sentinel lymph node biopsy (SLNB) for high-risk cutaneous squamous cell carcinoma of the head and neck. STUDY DESIGN: Retrospective case series. METHODS: Chart review was performed for patients who presented with clinically node negative cutaneous squamous cell carcinoma of the head and neck between December 2007 and May 2018. Patients who met high-risk criteria underwent SLNB and excision, with or without adjuvant therapy. Patients who underwent prior neck dissection were excluded. The main outcomes were SLNB result, lymph node spread, recurrence-free survival, disease-specific survival, and overall survival. RESULTS: Eighty-three patients underwent successful SLNB, and one patient underwent selective neck dissection for intraoperatively identified occult lymph node metastasis. Five patients (6%) had a sentinel node positive for tumor, of whom 4/5 received further treatment (neck dissection, radiation, and/or systemic therapy) with no further recurrence at the time of last follow-up. SLNB had a negative predictive value of 95% to 100%. Recurrent tumor at presentation, tumor arising from an area of chronic inflammation, and immunosuppression were significantly associated with increased risk of subsequent recurrence, with a mean follow-up of 19.9 months. CONCLUSIONS: SLNB can be used to identify regional lymph node metastases in cutaneous squamous cell carcinoma of the head and neck with a high negative predictive value (95%-100%). Factors associated with recurrence were tumor being locally recurrent at presentation, arising from an area of chronic inflammation, and immunosuppression. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:108-114, 2020.

Activity of caffeic acid phenethyl ester in Caenorhabditis elegans.

AIM: Caffeic acid (3,4-dihydroxycinnamic acid) phenethyl ester (CAPE), the major constituent of propolis, is able to increase the survival of the nematode Caenorhabditis elegans after infection with the fungal pathogen Candida albicans. RESULTS: CAPE increases the expression of several antimicrobial proteins involved in the immune response to C. albicans. Structural derivatives of CAPE were synthesized to identify structure-activity relationships and decrease metabolic liability, ultimately leading to a compound that has similar efficacy, but increased in vivo stability. The CED-10(Rac-1)/PAK1 pathway was essential for immunomodulation by CAPE and was a critical component involved in the immune response to fungal pathogens. CONCLUSION: Caenorhabditis elegans is an efficient heterologous host to evaluate immunomodulatory compounds and identify components of the pathway(s) involved in the mode of action of compounds.

Decreased FOXJ1 expression and its ciliogenesis programme in aggressive ependymoma and choroid plexus tumours.

Well-differentiated human cancers share transcriptional programmes with the normal tissue counterparts from which they arise. These programmes broadly influence cell behaviour and function and are integral modulators of malignancy. Here, we show that the master regulator of motile ciliogenesis, FOXJ1, is highly expressed in cells along the ventricular surface of the human brain. Strong expression is present in cells of the ependyma and the choroid plexus as well as in a subset of cells residing in the subventricular zone. Expression of FOXJ1 and its transcriptional programme is maintained in many well-differentiated human tumours that arise along the ventricle, including low-grade ependymal tumours and choroid plexus papillomas. Anaplastic ependymomas as well as choroid plexus carcinomas show decreased FOXJ1 expression and its associated ciliogenesis programme genes. In ependymomas and choroid plexus tumours, reduced expression of FOXJ1 and its ciliogenesis programme are markers of poor outcome and are therefore useful biomarkers for assessing these tumours. Transitions in ciliogenesis define distinct differentiation states in ependymal and choroid plexus tumours with important implications for patient care. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The role of mycelium production and a MAPK-mediated immune response in the C. elegans-Fusarium model system.

Fusariosis is an emerging infectious complication of immune deficiency, but models to study this infection are lacking. The use of the soil nematode Caenorhabditis elegans as a model host to study the pathogenesis of Fusarium spp. was investigated. We observed that Fusarium conidia consumed by C. elegans can cause a lethal infection and result in more than 90% killing of the host within 120 hours, and the nematode had a significantly longer survival when challenged with Fusarium proliferatum compared to other species. Interestingly, mycelium production appears to be a major contributor in nematode killing in this model system, and C. elegans mutant strains with the immune response genes, tir-1 (encoding a protein containing a TIR domain that functions upstream of PMK-1) and pmk-1 (the homolog of the mammalian p38 MAPK) lived significantly shorter when challenged with Fusarium compared to the wild type strain. Furthermore, we used the C. elegans model to assess the efficacy and toxicity of various compounds against Fusarium. We demonstrated that amphotericin B, voriconazole, mancozeb, and phenyl mercury acetate significantly prolonged the survival of Fusarium-infected C. elegans, although mancozeb was toxic at higher concentrations. In conclusion, we describe a new model system for the study of Fusarium pathogenesis and evolutionarily preserved host responses to this important fungal pathogen.

Occupational kidney cancer: exposure to industrial solvents.

We report seven cases of renal cell carcinoma in workers diagnosed with occupational exposure via skin contact and inhalation to industrial solvents containing benzene. The clinical significance of these cases are: (a) all seven patients diagnosed with kidney cancer were seen by private physicians who missed addressing occupational history to industrial solvents; (b) emphasize the importance of taking an in-depth history including occupational history in any patient presented to the clinician, especially like in these cases, kidney cancer; and (c) demonstrate the importance of educating workers. We believe that there exist more patients with renal cancer whose diagnosis has been rendered "idiopathic" due to the lack of detailed occupational, environmental, personal, and family history.

Chronic ammonia inhalation and interstitial pulmonary fibrosis: a case report and review of the literature.

Ammonia is an irritant gas with a characteristic pungent odor, which is widely used in industry. Inasmuch as ammonia is highly soluble in water and, upon inhalation, is deposited in the upper airways, occupational exposures to ammonia have commonly been associated with sinusitis, upper airway irritation, and eye irritation. Acute exposures to high levels of ammonia have also been associated with diseases of the lower airways and interstitial lung. In this study, the authors report on a patient with long-term, repetitive occupational exposure to ammonia at levels at or above odor recognition who developed interstitial lung disease. The scientific literature on inhaled ammonia exposure is reviewed and discussed. The authors conclude that the taking of a careful occupational exposure history for patients presenting with shortness of breath associated with ammonia exposure may assist with an early diagnosis, thus allowing for treatment early in the disease process and prevention of further exposure.