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1.
Clin Cancer Res ; 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39012279

ABSTRACT

PURPOSE: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has continually increased during the past several decades. Using transoral robotic surgery (TORS) significantly improves functional outcomes relative to open surgery for OPSCC. However, TORS limits tactile feedback, which is often the most important element of cancer surgery. Fluorescence guided surgery (FGS) strategies to aid surgeon assessment of malignancy for resection are in various phases of clinical research but have the greatest potential impact for improving patient care when the surgeon has limited tactile feedback, such as during TORS. Here, we assessed the feasibility of intraoperative fluorescence imaging using panitumumab-IRDye800CW (PAN800) during TORS in OPSCC patients. PATIENTS AND METHODS: 12 consecutive patients with OPSCC were enrolled as part of a non-randomized, prospective, phase II FGS clinical trial using PAN800. TORS was performed with an integrated robot camera for surgeon assessment of fluorescence. Intraoperative and ex vivo fluorescence signals in tumors and normal tissue were quantified and correlated with histopathology. RESULTS: Intraoperative robot fluorescence views delineated OPSCC from normal tissue throughout the TORS procedure (10.7 mean tumor-to-background ratio), including in tumors with low expression of the molecular target. Tumor-specific fluorescence was consistent with surgeon-defined tumor borders requiring resection. Intraoperative robot fluorescence imaging revealed an OPSCC fragment initially overlooked during TORS based on brightfield views, further substantiating the clinical benefit of this FGS approach. CONCLUSIONS: Results from this OPSCC patient cohort support further clinical assessment of FGS during TORS to aid resection of solid tumors.

2.
Laryngoscope ; 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38895915

ABSTRACT

OBJECTIVE: To examine the impact of increased body mass index (BMI) on (1) tracheotomy timing and (2) short-term surgical complications requiring a return to the operating room and 30-day mortality utilizing data from the Multi-Institutional Study on Tracheotomy (MIST). METHODS: A retrospective analysis of patients from the MIST database who underwent surgical or percutaneous tracheotomy between 2013 and 2016 at eight institutions was completed. Unadjusted and adjusted logistic regression analyses were used to assess the impact of obesity on tracheotomy timing and complications. RESULTS: Among the 3369 patients who underwent tracheotomy, 41.0% were obese and 21.6% were morbidly obese. BMI was associated with higher rates of prolonged intubation prior to tracheotomy accounting for comorbidities, indication for tracheotomy, institution, and type of tracheostomy (p = 0.001). Morbidly obese patients (BMI ≥35 kg/m2) experienced a longer duration of intubation compared with patients with a normal BMI (median days intubated [IQR 25%-75%]: 11.0 days [7-17 days] versus 9.0 days [5-14 days]; p < 0.001) but did not have statistically higher rates of return to the operating room within 30 days (p = 0.12) or mortality (p = 0.90) on multivariable analysis. This same finding of prolonged intubation was not seen in overweight, nonobese patients when compared with normal BMI patients (median days intubated [IQR 25%-75%]: 10.0 days [6-15 days] versus 10.0 days [6-15 days]; p = 0.36). CONCLUSION: BMI was associated with increased duration of intubation prior to tracheotomy. Although morbidly obese patients had a longer duration of intubation, there were no differences in return to the operating room or mortality within 30 days. LEVEL OF EVIDENCE: III Laryngoscope, 2024.

3.
Laryngoscope ; 2024 May 18.
Article in English | MEDLINE | ID: mdl-38761157

ABSTRACT

OBJECTIVE: Confocal laser endomicroscopy (CLE) is an optical imaging technique that allows in vivo, real-time, microscope-like assessment of superficial lesions. Although there is substantial data on CLE use in the upper GI tract, there is limited information regarding its application in the nasal cavity and paranasal sinuses. This study aims to assess the feasibility and diagnostic metrics of CLE in the nasal cavity and paranasal sinuses regarding differentiation between healthy/benign and malignant tissue. These structures show, however, a wider variety of frequent and concomitant benign and malignant pathologies, which could pose an increased challenge for optical biopsy by CLE. METHODS: We performed CLE on a case series of six patients with various findings in the nose (three chronic rhinosinusitis, adenocarcinoma, meningoenzephalozele, esthesionneuroblastoma). Forty-two sequences (3792 images) from various structures in the nasal cavity and/or paranasal sinuses were acquired. Biopsies were taken at corresponding locations and analyzed in hematoxylin and eosin staining as a standard of reference. Three independent examiners blinded to the histopathology assessed the sequences. RESULTS: Healthy and inflamed mucosa could be distinguished from malignant lesions with an accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 84.1%, 85.4%, 83.1%, 72.5%, and 92.1%, respectively, with a substantial agreement between raters (Fleiss κ = 0.62). CONCLUSION: This technique shows, despite its limitations, potential as an adjunctive imaging technique during sinus surgery; however, the creation of a scoring system based on reproducible and defined characteristics in a larger more diverse population should be the focus of further research to improve its diagnostic value and clinical utility. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

4.
Laryngoscope ; 134(4): 1837-1841, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37860983

ABSTRACT

Transoral laser microsurgery represents the primary surgical modality for early laryngeal cancers with oncologic outcomes equivalent to radiotherapy. Accurate tumor mapping and margin assessment can be difficult, however, particularly during piecemeal or ablative resections, and for tumors with a wider geographic footprint. Tumor-targeted fluorescence-guided surgery in patients with head and neck cancer has empirically improved tumor and margin identification; this case details, for the first time, a fluorescence-guided surgical resection of a T2N0M0 transglottic tumor using panitumumab-IRDye800, an epidermal growth factor receptor monoclonal antibody covalently linked to near-infrared (NIR) dye. Laryngoscope, 134:1837-1841, 2024.


Subject(s)
Carcinoma, Squamous Cell , Indoles , Laryngeal Neoplasms , Laser Therapy , Humans , Laryngeal Neoplasms/pathology , Panitumumab , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/pathology , Microsurgery , Lasers , Glottis/surgery , Retrospective Studies , Neoplasm Staging
5.
Clin Geriatr Med ; 40(1): 91-116, 2024 02.
Article in English | MEDLINE | ID: mdl-38000864

ABSTRACT

Pruritus is the most common dermatologic complaint in the geriatric population. Its growing prevalence coincides with the rapid growth of the elderly population (>65 years of age) in the United States. According to the US Census Bureau, 16.9% of the population, or more than 56 million adults 65 years and older, lived in the United States in 2022. Pruritus is a condition that accompanies a diverse array of underlying etiologic factors. The mechanism of normal itch impulse transmission has been recently elucidated. The itch sensation originates from epidermal/dermal receptors connected to unmyelinated, afferent C-fibers that transmit the impulse from the periphery.


Subject(s)
Scabies , Aged , Humans , Scabies/complications , Scabies/diagnosis , Scabies/epidemiology , Pruritus/diagnosis , Pruritus/etiology , Pruritus/therapy
6.
JAMA Otolaryngol Head Neck Surg ; 149(12): 1066-1073, 2023 12 01.
Article in English | MEDLINE | ID: mdl-37796485

ABSTRACT

Importance: Tracheotomies are frequently performed by nonotolaryngology services. The factors that determine which specialty performs the procedure are not defined in the literature but may be influenced by tracheotomy approach (open vs percutaneous) and other clinicodemographic factors. Objective: To evaluate demographic and clinical characteristics associated with tracheotomies performed by otolaryngologists compared with other specialists and to differentiate those factors from factors associated with use of open vs percutaneous tracheotomy. Design, Setting, and Participants: This multicenter, retrospective cohort study included patients aged 18 years or older who underwent a tracheotomy for cardiopulmonary failure at 1 of 8 US academic institutions between January 1, 2013, and December 31, 2016. Data were analyzed from September 2022 to July 2023. Exposure: Tracheotomy. Main Outcomes and Measures: The primary outcome was factors associated with an otolaryngologist performing tracheotomy. The secondary outcome was factors associated with use of the open tracheotomy technique. Results: A total of 2929 patients (mean [SD] age, 57.2 [17.2] years; 1751 [59.8%] male) who received a tracheotomy for cardiopulmonary failure (652 [22.3%] performed by otolaryngologists and 2277 [77.7%] by another service) were analyzed. Although 1664 of all tracheotomies (56.8%) were performed by an open approach, only 602 open tracheotomies (36.2%) were performed by otolaryngologists. Most tracheotomies performed by otolaryngologists (602 of 652 [92.3%]) used the open technique. Multivariable regression analysis revealed that self-reported Black race (odds ratio [OR], 1.89; 95% CI, 1.52-2.35), history of neck surgery (OR, 2.71; 95% CI, 2.06-3.57), antiplatelet and/or anticoagulation therapy (OR, 1.74; 95% CI, 1.29-2.36), and morbid obesity (OR, 1.54; 95% CI, 1.24-1.92) were associated with greater odds of an otolaryngologist performing tracheotomy. In contrast, history of neck surgery (OR, 1.36; 95% CI, 0.96-1.92), antiplatelet and/or anticoagulation therapy (OR, 0.80; 95% CI, 0.56-1.14), and morbid obesity (OR, 0.94; 95% CI, 0.74-1.19) were not associated with undergoing open tracheotomy when performed by any service, and Black race (OR, 0.56; 95% CI, 0.44-0.71) was associated with lesser odds of an open approach being used. Age-adjusted Charlson Comorbidity Index score greater than 4 was associated with greater odds of both an otolaryngologist performing tracheotomy (OR, 1.26; 95% CI, 1.03-1.53) and use of the open tracheotomy technique (OR, 1.48, 95% CI, 1.21-1.82). Conclusions and Relevance: In this study, otolaryngologists were significantly more likely than other specialists to perform a tracheotomy for patients with history of neck surgery, morbid obesity, and ongoing anticoagulation therapy. These findings suggest that patients undergoing tracheotomy performed by an otolaryngologist are more likely to present with complex and challenging clinical characteristics.


Subject(s)
Obesity, Morbid , Otolaryngology , Humans , Male , Middle Aged , Female , Tracheotomy , Otolaryngologists , Retrospective Studies , Anticoagulants
7.
Head Neck ; 45(11): 2851-2861, 2023 11.
Article in English | MEDLINE | ID: mdl-37682073

ABSTRACT

BACKGROUND: There is a paucity of data concerning molecular heterogeneity among glottic squamous cell carcinoma, and the clinical implications thereof. METHODS: Data corresponding to glottic squamous cell carcinoma were derived from The Cancer Genome Atlas. The Onco-GPS computational methodology was levied to derive four patterns of transcriptional activity and three functional subtypes of glottic cancer. RESULTS: Thirty glottic cancer samples stratified to three distinct oncogenic states (S0-S2) based on a Onco-GPS model containing four transcriptional components (F0-F3). Membership in S2 and association with transcriptional component F0 conveyed an invasive phenotype, with transcriptional activity strongly reflecting EMT programming (including TGF-B and NF-KB signaling). S2 membership also correlated with inferior disease-specific survival (HR 9.027, 95% CI 1.021-79.767), and higher incidences of extracapsular spread and perineural invasion. CONCLUSIONS: We present a functional taxonomy of glottic cancer, with subtypes demonstrating differential upregulation of canonical oncogenic networks and survival implications.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Laryngeal Neoplasms , Tongue Neoplasms , Humans , Laryngeal Neoplasms/pathology , Carcinoma, Squamous Cell/pathology , Neoplasm Staging , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/pathology , Tongue Neoplasms/pathology , Glottis/pathology , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/pathology
8.
Laryngoscope ; 133(11): 3094-3099, 2023 11.
Article in English | MEDLINE | ID: mdl-37194664

ABSTRACT

OBJECTIVE: The aim of this study was to gain quantitative insights into the role of daily voice use associated with mild phonotrauma via the Daily Phonotrauma Index (DPI), a measure derived from neck-surface acceleration magnitude (NSAM) and difference between the first two harmonic magnitudes (H1 - H2). METHODS: An ambulatory voice monitor recorded weeklong voice use for 151 female patients with phonotraumatic vocal hyperfunction (PVH) and 181 female vocally healthy controls. Three laryngologists rated phonotrauma severity from each patient's laryngoscopy. Mixed generalized linear models evaluated the accuracy, sensitivity, and specificity of the original DPI trained on all patients versus a mild DPI version trained on only patients rated with mild phonotrauma. Individual contribution of NSAM and H1 - H2 to each DPI model was also evaluated. RESULTS: Reliability across the laryngologists' phonotrauma ratings was moderate (Fleiss κ = 0.41). There were 70, 69, and 12 patients with mild, moderate, and severe phonotrauma, respectively. The mild DPI, compared to the original DPI, correctly classified more patients with mild phonotrauma (Cohen's d = 0.9) and less controls (d = -0.9) and did not change in overall accuracy. H1 - H2 contributed less to mild phonotrauma classification than NSAM for mild DPI. CONCLUSIONS: Compared with the original DPI, the mild DPI exhibited higher sensitivity to mild phonotrauma and lower specificity to controls, but the same overall classification accuracy. These results support the mild DPI as a promising detector of early phonotrauma and that NSAM may be associated with early phonotrauma, and H1 - H2 may be a biomarker associated with vocal fold vibration in the presence of lesions. LEVEL OF EVIDENCE: Level 4, case-control study Laryngoscope, 133:3094-3099, 2023.


Subject(s)
Voice Disorders , Voice , Humans , Female , Case-Control Studies , Reproducibility of Results , Vocal Cords/pathology
9.
Clin Case Rep ; 11(3): e7009, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36873066

ABSTRACT

Transoral robotic surgery (TORS) has evolved into a common surgical modality used to treat primarily oropharyngeal malignant and benign pathologies. The single port Intuitive Surgical da Vinci surgical robotics system facilitates access to the hypopharynx and cervical esophagus. We aim to describe our approach and advantages of the technique.

10.
Otolaryngol Head Neck Surg ; 168(5): 1067-1078, 2023 05.
Article in English | MEDLINE | ID: mdl-36939401

ABSTRACT

OBJECTIVE: The role and extent of neck dissection in primary parotid cancer are controversial. Herein, we characterize patterns of lymph node metastasis in parotid cancer. STUDY DESIGN: Retrospective analysis. SETTING: National Cancer Database. METHODS: Patients with the 6 most common histologic subtypes of parotid cancer were selected. Primary outcomes were the distribution of positive lymph nodes by level and overall survival assessed by Cox analysis. Secondary outcomes included predictors of extended lymph node involvement (≥3 lymph nodes or Level IV/V involvement), via logistic regression. RESULTS: Six thousand nine hundred seventy-seven patients with acinic cell carcinoma, adenocarcinoma, adenoid cystic carcinoma, carcinoma ex pleomorphic adenoma (CExPA), mucoepidermoid carcinoma, and salivary duct carcinoma (SDC) were included. Among cN0 patients, 8.2% of low-grade tumor patients had occult nodal metastasis versus 30.9% in high-grade tumor patients. Elective neck dissection was not associated with an overall survival benefit (adjusted hazard ratio: 1.10; 0.94-1.30, p = .238). Among cN+ tumors, CExPA (odds ratio [OR]: 1.88, 1.05-3.39, p = .034) and high-grade pathology (OR: 3.03, 1.87-4.93, p < .001) were predictive of having ≥3 pathologic nodes. CExPA (OR: 2.13, 1.22-3.72, p = .008), adenocarcinoma (OR: 1.60, 1.11-2.31, p = .013), SDC (OR: 1.92, 1.17-3.14, p < .01), and high-grade pathology (OR: 3.61, 2.19-5.97, p < .001) were predictive of Level IV/V neck involvement. CONCLUSIONS: In parotid malignancy, nodal metastasis distribution is dependent on histology and grade. High-grade tumors and certain histologies (SDC and adenocarcinoma) had a higher incidence of occult nodes. Comprehensive neck dissection should also be considered for node-positive high-grade tumors, SDC, and adenocarcinoma.


Subject(s)
Adenocarcinoma , Parotid Neoplasms , Salivary Gland Neoplasms , Humans , Parotid Neoplasms/surgery , Parotid Neoplasms/pathology , Retrospective Studies , Lymphatic Metastasis/pathology , Neck Dissection , Adenocarcinoma/pathology , Adenocarcinoma/secondary , Adenocarcinoma/surgery , Salivary Gland Neoplasms/pathology , Lymph Nodes/pathology , Neoplasm Staging
11.
Life (Basel) ; 13(3)2023 Mar 09.
Article in English | MEDLINE | ID: mdl-36983895

ABSTRACT

Complete subglottic stenosis is often managed with surgical resection. However, involvement of the high subglottis can limit candidacy for open resection, and there are few treatment options for these patients. We refined an endoscopic approach that evolved into a tracheal rendezvous technique with T-tube placement as an alternative to open surgical resection. Here, we present our series, technique, and outcomes. A retrospective review was performed to identify patients who underwent endoscopic management of complete high subglottic stenosis at the University of California San Diego. The surgical technique was initially a two-step staged procedure and was subsequently revised to a single-stage procedure with stenosis ablation, dilation, and insertion of a T-tube, which was completed in one day. Patients were seen at regular follow-up intervals for reassessment. Five patients were identified with complete stenosis not amenable to surgical resection. The average age of the cohort was 44.8 years. The etiology of stenosis in all patients was related to prolonged intubation and tracheostomy, and the average length of stenosis was 19.6 mm. Stenosis resection was accomplished via laser ablation and balloon dilation, and the average T-tube length was 50.3 mm. All patients were discharged on postoperative day one. Two patients developed airway crusting within the T-tube and required emergency department visits. Decannulation was attempted in three patients, although failed in two. Tracheal rendezvous is a safe and effective procedure for patients with grade IV subglottic stenosis. This provides a feasible endoscopic alternative to patients who are not candidates for open surgical resection, ye are motivated to have phonatory capacity.

12.
Ann Surg ; 277(5): e1138-e1142, 2023 05 01.
Article in English | MEDLINE | ID: mdl-35001037

ABSTRACT

OBJECTIVE: We aimed to discern clinico-demographic predictors of large (≥8) tracheostomy tube size placement, and, secondarily, to assess the effect of large tracheostomy tube size and other parameters on odds of decannulation before hospital discharge. SUMMARY OF BACKGROUND DATA: Factors determining choice of tracheostomy tube size are not well-characterized in the current literature, despite evidence linking large tracheostomy tube size with posttracheotomy tracheal stenosis. The effect of tracheostomy tube size on timing of decannulation is also unknown, an important consideration given reported associations between endotracheal tube size and probability of failed extubation. METHODS: We collected information pertaining to patients who underwent tracheotomy at 1 of 10 U.S. health care institutions between 2010 and 2019. Tracheostomy tube size was dichotomized (≥8 and <8). Multivariable logistic regression models were fit to identify predictors of (1) large tracheostomy tube size, and (2) decannulation before hospital discharge. RESULTS: The study included 5307 patients, including 2797 (52.7%) in the large tracheostomy cohort. Patient height (odds ratio [OR] = 1.060 per inch; 95% confidence interval [CI] 1.041-1.070) and obesity (1.37; 95% CI 1.1891.579) were associated with greater odds of large tracheostomy tube; otolaryngology performing the tracheotomy was associated with significantly lower odds of large tracheostomy tube (OR = 0.155; 95% CI 0.131-0.184). Large tracheostomy tube size (OR = 1.036; 95% CI 0.885-1.213) did not affect odds of decannulation. CONCLUSIONS: Obesity was linked with increased likelihood of large tracheostomy tube size, independent of patient height. Probability of decannulation before hospital discharge is influenced by multiple patient-centric factors, but not by size of tracheostomy tube.


Subject(s)
Tracheostomy , Tracheotomy , Humans , Retrospective Studies , Device Removal , Obesity
13.
Laryngoscope ; 133(3): 601-606, 2023 03.
Article in English | MEDLINE | ID: mdl-35562187

ABSTRACT

OBJECTIVES: To compare overall survival outcomes associated with transoral laser microsurgery (TLM) with neck dissection versus definitive radiotherapy in the management of T2N0 supraglottic squamous cell carcinoma. METHODS: Data were extracted from the National Cancer Database concerning patients with cT2N0M0 supraglottic cancer treated with either TLM and neck dissection with minimum lymph node yield of 10 or definitive radiotherapy. Predictors of overall survival were assessed via Cox proportional hazards regression. RESULTS: Seventy-six cT2N0 supraglottic squamous cell carcinoma patients who underwent TLM with neck dissection (+/- adjuvant therapy) versus 991 patients who underwent radiotherapy. TLM was associated with an overall survival benefit (OR = 0.574; 95% CI 0.383-0.860) compared with radiotherapy. There was no difference in survival between TLM patients receiving adjuvant treatment and those receiving definitive radiotherapy. CONCLUSIONS: An up-front, TLM-based surgical approach to cT2N0 supraglottic cancer may offer an overall survival benefit compared with definitive radiotherapy, and should receive more frequent consideration as a primary approach to this disease process. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:601-606, 2023.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Laryngeal Neoplasms , Laser Therapy , Humans , Neck Dissection , Microsurgery , Treatment Outcome , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/surgery , Retrospective Studies , Laryngeal Neoplasms/radiotherapy , Laryngeal Neoplasms/surgery , Laryngeal Neoplasms/pathology , Squamous Cell Carcinoma of Head and Neck/radiotherapy , Squamous Cell Carcinoma of Head and Neck/surgery , Head and Neck Neoplasms/surgery , Lasers
14.
Otolaryngol Head Neck Surg ; 167(2): 274-285, 2022 08.
Article in English | MEDLINE | ID: mdl-34609937

ABSTRACT

OBJECTIVE: Recurrence is known to predict laryngeal squamous cell cancer (LSCC) survival. Recurrence patterns in T4a LSCC are poorly characterized and represent a possible explanation for observed survival discrepancies by treatment rendered. STUDY DESIGN: Retrospective database review. SETTING: Veterans Affairs national database. METHODS: Patients with T4a LSCC between 2000 and 2017 were identified and stratified by treatment (chemoradiotherapy [CRT] vs total laryngectomy + neck dissection + adjuvant therapy [surgical]). Primary outcomes were locoregional and distant recurrence. Secondary outcomes of overall mortality, larynx cancer mortality, and noncancer mortality were evaluated in Cox and Fine-Gray models. RESULTS: A total of 1043 patients had comparable baseline demographics: 438 in the CRT group and 605 in the surgical group. Patients undergoing CRT had higher proportions of node positivity (64.6% vs 53.1%, P < .001). Locoregional and distant recurrence were less common in the surgical group (23.0% vs 37.2%, P < .001; 6.8% vs 13.3%, P < .001, respectively); however, distant metastatic rates did not differ within the N0 subgroup (P = .722). On multivariable regression, surgery demonstrated favorable locoregional recurrence (hazard ratio [HR], 0.49; 95% CI, 0.39-0.62; P < .001), distant recurrence (HR, 0.47; 95% CI, 0.31-0.71; P < .001), overall mortality (HR, 0.75; 95% CI, 0.64-0.87; P < .001), and larynx cancer mortality (HR, 0.69; 95% CI, 0.56-0.85; P < .001). CONCLUSION: T4a LSCC survival discrepancies between surgical and nonsurgical treatment are influenced by varying recurrence behaviors. Surgery was associated with superior disease control and improved survival. Beyond the known benefit in locoregional control with surgery, there may be a protective effect on distant recurrence that depends on regional disease burden.


Subject(s)
Head and Neck Neoplasms , Laryngeal Neoplasms , Head and Neck Neoplasms/surgery , Humans , Laryngeal Neoplasms/pathology , Laryngectomy , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck/pathology
15.
Clin Cancer Res ; 27(24): 6772-6786, 2021 12 15.
Article in English | MEDLINE | ID: mdl-34548317

ABSTRACT

PURPOSE: Human papillomavirus (HPV) plays a major role in oncogenesis and circular extrachromosomal DNA (ecDNA) is found in many cancers. However, the relationship between HPV and circular ecDNA in human cancer is not understood. EXPERIMENTAL DESIGN: Forty-four primary tumor tissue samples were obtained from a cohort of patients with HPV-positive oropharynx squamous cell carcinoma (OPSCC). Twenty-eight additional HPV oropharyngeal cancer (HPVOPC) tumors from The Cancer Genome Atlas (TCGA) project were analyzed as a separate validation cohort. Genomic, transcriptomic, proteomic, computational, and functional analyses of HPVOPC were applied to these datasets. RESULTS: Our analysis revealed circular, oncogenic DNA in nearly all HPVOPC, with circular human and human-viral hybrid ecDNA present in over a third of HPVOPC and viral circular DNA in remaining tumors. Hybrid ecDNA highly express fusion transcripts from HPV promoters and HPV oncogenes linked to downstream human transcripts that drive oncogenic transformation and immune evasion, and splice multiple, diverse human acceptors to a canonical SA880 viral donor site. HPVOPC have high E6*I expression with specific viral oncogene expression pattern related to viral or hybrid ecDNA composition. CONCLUSIONS: Nonchromosomal circular oncogenic DNA is a dominant feature of HPVOPC, revealing an unanticipated link between HPV and ecDNA that leverages the power of extrachromosomal inheritance to drive HPV and somatic oncogene expression.


Subject(s)
Alphapapillomavirus , Head and Neck Neoplasms , Oncogene Proteins, Viral , Oropharyngeal Neoplasms , Papillomavirus Infections , DNA, Circular , DNA, Viral/genetics , Head and Neck Neoplasms/genetics , Humans , Oncogene Proteins, Viral/genetics , Oncogenes/genetics , Oropharyngeal Neoplasms/genetics , Papillomaviridae/genetics , Papillomavirus Infections/complications , Papillomavirus Infections/genetics , Proteomics
16.
Laryngoscope ; 131(12): 2766-2772, 2021 12.
Article in English | MEDLINE | ID: mdl-34296772

ABSTRACT

OBJECTIVES: Transoral laser microsurgery (TLM) is commonly utilized for early glottic cancer and offers favorable oncologic and functional outcomes. However, the survival implications of salvage therapy for recurrent or persistent disease have not been definitively characterized. STUDY DESIGN: Retrospective, national database cohort study. METHODS: Data were extracted from Veterans Health Affairs (VHA) Informatics and Computing Infrastructure (VINCI) concerning the TLM-based management of T1-T2 glottic squamous cell carcinoma patients between 2000 and 2017. Patients were characterized as either requiring TLM-only, or in cases of persistent or recurrent local disease, TLM plus change in treatment modality (radiotherapy, chemoradiotherapy, or open surgery). Predictors of overall survival (OS), cancer-specific survival (CSS), and salvage-free survival were evaluated via Cox and Fine-Gray models. RESULTS: About 553 patients (70.9% T1a, 13.4% T1b, 15.7% T2) were included, with a median follow-up time of 74.5 months. The need for non-TLM salvage increased along with more advanced disease (11.7% T1a, 29.7% T1b, 32.2% T2). Compared to patients with T1a disease, those with T1b and T2 tumors initially treated with TLM had a significantly higher probability of receiving non-TLM salvage (T1b: HR 2.70, 95% CI: 1.61-4.54; T2: HR 3.02, 95% CI: 1.88-4.84). In a multivariable model, receipt of non-TLM salvage was not a significant predictor of either OS (HR = 0.91, 95% CI: 0.62-1.33, P = .624) or CSS (HR 1.21 95% CI 0.51-2.86, P = .667). CONCLUSION: The majority of patients with early glottic cancer that are managed with TLM do not require additional salvage therapy. When non-TLM salvage was required, there was no decrement in OS or CSS. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2766-2772, 2021.


Subject(s)
Laryngeal Neoplasms/surgery , Natural Orifice Endoscopic Surgery/adverse effects , Neoplasm Recurrence, Local/therapy , Salvage Therapy/statistics & numerical data , Squamous Cell Carcinoma of Head and Neck/surgery , Aged , Aged, 80 and over , Chemoradiotherapy, Adjuvant/statistics & numerical data , Databases, Factual/statistics & numerical data , Female , Glottis/pathology , Humans , Laryngeal Neoplasms/diagnosis , Laryngeal Neoplasms/mortality , Male , Microsurgery/adverse effects , Microsurgery/methods , Middle Aged , Natural Orifice Endoscopic Surgery/methods , Neoplasm Recurrence, Local/epidemiology , Neoplasm Staging , Radiotherapy, Adjuvant/statistics & numerical data , Retrospective Studies , Salvage Therapy/methods , Squamous Cell Carcinoma of Head and Neck/diagnosis , Squamous Cell Carcinoma of Head and Neck/mortality , United States/epidemiology , United States Department of Veterans Affairs/statistics & numerical data
17.
Oral Oncol ; 121: 105440, 2021 10.
Article in English | MEDLINE | ID: mdl-34329867

ABSTRACT

BACKGROUND: Hypopharyngeal cancer is associated with poor survival. Robotic surgery is emerging as a treatment for hypopharyngeal tumors, but no rigorous data are available to assess its effect on survival. METHODS: The National Cancer Database (NCDB) was used to identify patients with T1 and T2 hypopharyngeal tumors undergoing robotic surgery, laser surgery, and primary radiation with or without chemotherapy from 2010 to 2016. All adult patients with available staging and no distant metastasis were included. RESULTS: We compared 57 patients undergoing robotic surgery, 236 undergoing laser surgery, and 5,742 undergoing primary radiation. Compared to laser surgery, patients undergoing robotic surgery were significantly more likely to have negative margins, neck dissection, lower incomes, and care at an academic center. Rates of robotic surgery also significantly increased from 2010 to 2015. After multivariate regression, robotic surgery was associated with significantly improved overall survival compared to laser surgery and primary radiation. CONCLUSION: Robotic surgery improves overall survival for T1 and T2 hypopharyngeal tumors compared to laser surgery and primary radiation in this NCDB cohort. This effect may be mediated by decreased positive margin rates relative to laser surgery. Rates of hypopharyngeal robotic surgery are expected to increase with wider adoption of robotic platforms and may improve overall survival rates for hypopharyngeal cancer.


Subject(s)
Hypopharyngeal Neoplasms , Robotic Surgical Procedures , Adult , Humans , Hypopharyngeal Neoplasms/radiotherapy , Hypopharyngeal Neoplasms/surgery , Hypopharynx/pathology , Hypopharynx/surgery , Margins of Excision , Retrospective Studies , Treatment Outcome
18.
Cancer ; 127(15): 2705-2713, 2021 08 01.
Article in English | MEDLINE | ID: mdl-33799314

ABSTRACT

BACKGROUND: Black patients with laryngeal squamous cell carcinoma (LSCC) historically have inferior outcomes in comparison with White patients. The authors investigated these racial disparities within the Veterans Health Administration (VHA), an equal-access system, and within the Surveillance, Epidemiology, and End Results (SEER) program, which is representative of the US hybrid-payer system. METHODS: Patients with invasive (T1 or greater) LSCC were included from SEER (2004-2015) and the VHA (2000-2017). The primary outcomes of overall survival (OS) and larynx cancer-specific survival (LCS) were evaluated in Cox and Fine-Gray models. RESULTS: In the SEER cohort (7122 patients: 82.6% White and 17.4% Black), Black patients were more likely to present with advanced disease and had inferior OS (hazard ratio [HR], 1.37; 95% CI, 1.26-1.50; P < .0001) in a multivariable analysis. Black LCS was worse in a univariable analysis (HR, 1.42; 95% CI, 1.27-1.58; P < .0001), but this effect was attenuated by 83% when the authors controlled for the TNM category and was found to be insignificant in a multivariable analysis (HR, 1.05; 95% CI, 0.93-1.18; P = .42). In the VHA cohort (9248 patients: 79.7% White and 20.3% Black), the 2 racial cohorts presented with similar tumor characteristics and similar OS (HR, 0.95; 95% CI, 0.89-1.02; P = .14). Black LCS was similar in univariable (HR, 1.10; 95% CI, 1.00-1.22; P = .05) and multivariable analyses (HR, 1.02; 95% CI, 0.92-1.14; P = .67). CONCLUSIONS: Black patients with LSCC had a tumor burden at diagnosis and survival outcomes comparable to those of White patients within the VHA; this was counter to what was observed in the SEER analysis and prior national trends. This study's findings point toward the notable role of health care access in contributing to racial health disparities in the realm of larynx cancer.


Subject(s)
Laryngeal Neoplasms , Veterans , Black People , Health Services Accessibility , Humans , Laryngeal Neoplasms/therapy , Proportional Hazards Models , SEER Program , United States/epidemiology
19.
Laryngoscope ; 131(9): 2006-2010, 2021 09.
Article in English | MEDLINE | ID: mdl-33734447

ABSTRACT

OBJECTIVES/HYPOTHESIS: To conduct longitudinal postoperative follow-up and discern health-related quality-of-life (HR-QoL) changes using a validated questionnaire among patients undergoing head and neck surgeries during a short-term, global surgical trip in a resource-limited setting. To identify clinicodemographic predictors of post-operative HR-QoL improvements in this setting. STUDY DESIGN: Retrospective observational study with prospective follow-up. METHODS: Patients undergoing surgery at Moi Teaching and Referral Hospital in Eldoret, Kenya through the authors' short-term surgical trip (STST) between 2016 and 2019 were asked to complete preoperative Short Form-36 (SF-36) HR-QoL questionnaires, and postoperative SF-36 questionnaires during subsequent follow-up. Preoperative and postoperative SF-36 domain scores, and two composite scores (mental component summary [MCS] and physical component summary [PCS]) were compared. Linear regression models were fit to identify clinicodemographic factors predictors of general health (GH), MCS, and PCS scores. RESULTS: Among the 26 participating patients, significant improvements were seen in post-operative GH (mean change = 19.8) and MCS (mean change = 11.2) scores. Lower pre-operative GH, MCS, and PCS scores were predictive of greater improvement in the corresponding post-operative scores. Longer time to follow-up was associated with greater improvement in GH score. Mean follow-up interval was 23.1 months (SD = 1.8 months). CONCLUSIONS: Utilizing the SF-36 questionnaire, we found that patients' perception of their general and psychosocial health improved after undergoing head and neck surgeries through a global STST. This study provides important, preliminary evidence that that elective surgeries performed in low-resource settings convey substantial benefit to patient QoL. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2006-2010, 2021.


Subject(s)
Head and Neck Neoplasms/surgery , Medically Underserved Area , Otorhinolaryngologic Diseases/surgery , Quality of Life/psychology , Surveys and Questionnaires/statistics & numerical data , Adult , Cost-Benefit Analysis , Female , Follow-Up Studies , Humans , Kenya/epidemiology , Linear Models , Male , Otolaryngologists/statistics & numerical data , Postoperative Complications/epidemiology , Postoperative Complications/psychology , Predictive Value of Tests , Prospective Studies , Retrospective Studies , Safety
20.
Head Neck ; 43(1): 137-144, 2021 01.
Article in English | MEDLINE | ID: mdl-32945595

ABSTRACT

BACKGROUND: The clinical impact of Medicaid expansion in otolaryngology is uncertain. Herein, we evaluate the impact of Medicaid expansion on treatment patterns (primary radiotherapy vs surgery) in the early glottic cancer population. METHODS: Data regarding adults with Tis-T2N0M0 glottic cancer that were treated with either surgery or radiotherapy between January 2010 and December 2016 were obtained from the Surveillance, Epidemiology, and End Results (SEER) cancer database. Changes in treatment trends and survival in the Medicaid expansion setting were discerned. RESULTS: The proportion of patients undergoing radiotherapy decreased from 64.8% to 59% after the Patient Protection and Affordable Care Act (PPACA) was implemented. State Medicaid expansion status was associated with reduced odds of radiation therapy (odds ratio [OR] = 0.66). Patients were diagnosed more often with earlier stage disease (20.6% vs 17.0% T2 diagnoses) in the Medicaid expansion cohort. CONCLUSION: The implementation of the PPACA was associated with a significant increase in surgical therapy for and earlier diagnosis of glottic cancer.


Subject(s)
Laryngeal Neoplasms , Tongue Neoplasms , Adult , Humans , Insurance Coverage , Laryngeal Neoplasms/radiotherapy , Medicaid , Patient Protection and Affordable Care Act , United States/epidemiology
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