Morbidity and Long-Term Patient-Reported Outcomes Following Advanced Carotid Body Tumor Resection.

BACKGROUND: The reported risk of a cranial nerve (CN) injury is up to 1 in 4 patients in large registries of carotid body tumor (CBT) resection. Functional outcome for this population is unknown. METHODS: We evaluated consecutive patients who underwent CBT resection from November 2013 through October 2020. Demographics, intraoperative details, complications, and outcomes were recorded from the medical record. Permanent CN nerve injury was defined as deficits lasting >6 months. Frequency statistics, averages, chi-squared test, and multiple logistic regression were completed for primary end points of complications and disease-free survival. Patient-reported outcomes were gathered via telephone survey of patients conducted in September 2021. RESULTS: Fifty-one patients presented with CBTs and the following Shamblin classes: I (n = 7; 14%), II (n = 36; 69%), and III (n = 9; 17%). Head and neck oncology and vascular surgery jointly did 52% of CBT resections, including 6 of 9 Shamblin III cases. Eight patients (15.3%, all Shamblin II or III) suffered a total of 12 CN injuries - 8 CN XII (5 temporary and 3 permanent), 3 CN X (all permanent), and 1 CN XI (permanent). Seven of the CN injury subgroup had preoperative embolization and 5 were joint oncology/vascular cases. In addition, 4 separate carotid injuries required repair. Notably, all patients had disease-free survival postoperatively at a mean follow-up of 6 months. Patient-reported outcomes obtained in 70.6% of patients 1 year or more from index operation demonstrated that two-thirds of patients live without any permanent functional deficits, and the majority of those with continued deficits rate the symptoms as daily but mild in severity. CONCLUSIONS: In a series of complex CBT patients treated with preoperative embolization capabilities and multidisciplinary surgical approach, disease-free survival was achieved in all patients despite a high rate of iatrogenic CN injuries, most commonly CN XII. Patient-reported outcomes survey results indicate that injuries identified on clinical exam underreport patients' true postoperative CN deficits - especially branches of CN X. This data support the practice of aggressive primary resection of CBTs while providing guidance for expected functional outcomes due to CN injury risk.

Phase 1/2a, open-label, multicenter study of RM-1929 photoimmunotherapy in patients with locoregional, recurrent head and neck squamous cell carcinoma.

BACKGROUND: Recurrent head and neck squamous cell carcinoma (rHNSCC) represents a significant global health burden with an unmet medical need. In this study we determined the safety and efficacy of RM-1929 photoimmunotherapy in patients with heavily pretreated rHNSCC. METHODS: RM-1929 (anti-EGFR-IR700 dye conjugate) was infused, followed by tumor illumination. We evaluated safety, tumor response, and pharmacokinetics. RESULTS: Nine patients were enrolled in Part 1 (dose-finding) and 30 patients in Part 2 (safety and efficacy). No dose-limiting toxicities were experienced in Part 1; 640 mg/m2 with fixed light dose (50 J/cm2 or 100 J/cm) was recommended for Part 2. Adverse events (AEs) in Part 2 were mostly mild to moderate but 19 (63.3%) patients had AE ≥Grade 3, including 3 (10.0%) with serious AEs leading to death (not treatment related). Efficacy in Part 2: unconfirmed objective response rate (ORR) 43.3% (95% CI 25.46%-62.57%); confirmed ORR 26.7% (95% CI 12.28%-45.89%); median overall survival 9.30 months (95% CI 5.16-16.92 months). CONCLUSIONS: Treatment was well tolerated. Responses and survival following RM-1929 photoimmunotherapy in heavily pretreated patients with rHNSCC were clinically meaningful and warrant further investigation. CLINICAL TRIAL INFORMATION: NCT02422979.

Targeted hypoglossal nerve stimulation for the treatment of obstructive sleep apnea: Six-month results.

OBJECTIVES/HYPOTHESIS: This feasibility study was designed to show the preliminary safety and efficacy of targeted hypoglossal neurostimulation (THN), and to identify baseline predictors of successful therapy. STUDY DESIGN: Open-label, prospective, multicenter, single-arm cohort study, conducted at seven centers in the U.S.A. and Europe. METHODS: Forty-six participants with moderate to severe obstructive sleep apnea (OSA), failing or intolerant of continuous positive airway pressure, were implanted. Primary (Apnea-Hypopnea Index [AHI], Oxygen Desaturation Index [ODI]) and secondary (Arousal Index, Epworth Sleepiness Scale Index, Sleep Apnea Quality of Life Index) outcomes were measured at baseline and compared at 6 months. Data were analyzed to identify participant characteristics that would predict success with therapy. RESULTS: Sixty-seven adverse events (AEs) were observed among 36 participants; most of the AEs were related to the implant procedure and resolved without sequelae; one device replacement was necessary. Forty-three participants showed significant (P < .01) decreases in both AHI and ODI at 6 months; 35% (15 of 43) met criteria for AHI responders and 40% (17 of 43) for ODI responders. Significant improvement was observed in all the secondary endpoints. Predictors-of-success selection criteria were identified as baseline AHI < 65/hr, baseline apnea index ≤ 30, baseline body mass index < 35, and <15 events/hr of SpO2 decrease > 10%. Seven participants met these criteria; 86% (6 of 7) were AHI responders and 86% (6 of 7) were ODI responders, indicating that THN therapy can be efficacious in a carefully selected population of OSA patients. CONCLUSIONS: This feasibility study suggests that THN therapy is likely to be safe and effective in selected patients. LEVEL OF EVIDENCE: 2b Laryngoscope, 126:2618-2623, 2016.

Radiation-induced dedifferentiated chondrosarcoma with orbital invasion.

PURPOSE: To report 2 interventional cases of dedifferentiated chondrosarcoma with orbital involvement after radiotherapy performed in childhood and to review the literature on chondrosarcoma in the orbit following radiation treatment. METHODS: Retrospective analysis of medical records of 2 patients with chondrosarcoma of the orbits with review of the literature. RESULTS: The first patient developed chondrosarcoma of the orbital and maxillary sinus 36 years after external beam radiation therapy to the OS to treat retinoblastoma. The second patient developed a large orbital chondrosarcoma 35 years after external beam radiation therapy in the treatment of craniofacial fibrous dysplasia. CONCLUSIONS: These cases highlight the risk of secondary chondrosarcoma in patients following radiotherapy and the importance of lifetime monitoring.

Posterior septal resection: a simple surgical option for management of nasal septal perforation.

IMPORTANCE: Large and complex nasal septal perforations may cause considerable patient discomfort and are challenging to repair. Posterior septal resection (PSR) is a simple procedure and can be incorporated into the surgical management algorithm for this patient population. OBJECTIVE: To evaluate PSR for the treatment of symptomatic complex and large nasal septal perforations. DESIGN, SETTING, AND PARTICIPANTS: Retrospective medical chart review from 1995 through 2007 of patients who underwent PSR. Medical charts were reviewed, and a follow-up telephone questionnaire was performed. INTERVENTIONS: Posterior septal resection. MAIN OUTCOMES AND MEASURES: Improvement of selected symptoms after PSR. RESULTS: Twenty-one patients were identified, 16 patients had thorough documentation of perioperative information contained in their medical charts, and 12 patients were available for follow-up survey. All patients tolerated the procedure well without long-term sequelae from surgery. Overall nasal discomfort was significantly improved in 12 of 12 patients (P < .001). All nasal symptom scores of obstruction, pain, whistling, drainage, crusting, and epistaxis showed statistically significant (P < .05) improvement from preoperative values. Nasal obstruction and crusting were symptoms that improved with high statistical significance (P < .001). Patients reported on average a 79% improvement (range, 45%-100% improvement) in nasal airway, with only 1 patient reporting no improvement. All patients were satisfied with their surgery and would undergo the procedure again and recommend it to others. CONCLUSIONS AND RELEVANCE: Posterior septal resection provides overall patient satisfaction and improvement in subjective nasal symptom scores when used for large and complex septal perforations. This simple procedure may be included in the treatment algorithm of large and complex symptomatic septal perforations.

Improved skin paddle survival in pectoralis major myocutaneous flap reconstruction of head and neck defects.

OBJECTIVE: To examine our outcomes with skin paddle survival using pectoralis myocutaneous flaps in reconstruction of the head and neck. The pectoralis major myocutaneous flap has been associated with a notable incidence of distal skin necrosis and flap loss. Our experience has been favorable compared with that reported in the literature. METHODS: Retrospective medical record review of 81 cases of pectoralis major muscle flap reconstruction performed in 78 patients from 1995 to 2008 using a flap harvest technique that is slightly different from the classic descriptions. Data were obtained regarding coexisting health conditions and perioperative complications, which were divided into major and minor categories. Major complications were defined as total flap failure or greater than 25% skin paddle loss. Minor complications and donor site complications included fistulas that were managed conservatively, wound dehiscence not requiring additional surgery, local infections, seromas, and hematomas. RESULTS: Of the 81 flaps performed, 22 complications were encountered. Total flap loss was not encountered in any patient. The overall major complication rate in myocutaneous flaps was 3 of 76 (4%), with these cases consisting of significant skin paddle loss. Minor complications occurred in 14 of 81 myofascial and myocutaneous flaps (17%). Donor site complications of the chest wall occurred in 5 of 81 flaps (6%). CONCLUSIONS: Skin paddle necrosis may be minimized with modifications of the classic technique. We believe that extension of the skin flap over the rectus sheath is the cause of distal skin flap necrosis. The pectoralis major myocutaneous flap remains a valuable reconstructive option in the head and neck.

Phase I trial of gefitinib in combination with radiation or chemoradiation for patients with locally advanced squamous cell head and neck cancer.

PURPOSE: To establish the safety and toxicity profile of daily gefitinib with radiation alone or with concurrent chemoradiotherapy in previously untreated patients with locally advanced squamous cell head and neck cancer (LAHNC). PATIENTS AND METHODS: Patients with intermediate-stage LAHNC were treated with concomitant boost radiation (RT) alone with escalating doses of daily gefitinib (250 or 500 mg; cohort I). Once a safety profile was determined with RT alone, patients with high-risk disease were then treated with daily gefitinib (250 or 500 mg), weekly cisplatin (CDDP; 30 mg/m2), and once-daily RT (cohort II). Patients also received post-RT gefitinib at 250 mg daily for a period of up to 2 years. RESULTS: Twenty-three patients were enrolled and assessable for toxicity. No dose-limiting toxicities (DLTs) were observed in patients treated in cohort I at either 250 or 500 mg of gefitinib daily with concomitant boost RT to 72 Gy. In patients receiving chemoradiotherapy and gefitinib (cohort II), DLTs included one grade 4 diarrhea and one grade 4 neutropenic fever. Fifteen patients started maintenance gefitinib, and eight (53%) experienced grade 1 to 2 acne-like skin rash and diarrhea, but no grade 3 or 4 toxicity occurred. CONCLUSION: Gefitinib (250 or 500 mg daily) was well tolerated with concomitant boost RT or concurrent chemoradiotherapy with weekly CDDP. Protracted administration of gefitinib for up to 2 years at 250 mg daily was also tolerated well.

The surgical management of oral cancer.

Oral cavity cancers represent an area of head and neck oncology with some unique and interesting management themes. In spite of a significant paradigm shift in the treatment of many head and neck cancers toward us-ing primary chemoradiation, this treatment is not frequently applied to the oral cavity. Small cancers of the oral cavity are usually managed by surgery alone. Larger cancers are usually treated with primary surgery followed by chemoradiation. Neck treatment is offered to patients who have a greater than 20% chance of having lymph node metastasis or who have neck disease at the time of presentation. Neck treatment may involve surgery, radiation therapy, or both. Reconstruction of surgical defects of the oral cavity runs the gamut of techniques from the most simple to the most complex three-dimensional microvascular composite flaps. A multidisciplinary setting with a tumor board and multiple supportive services provides the best care for patients who have advanced-stage cancers.

Myoepithelial carcinoma ex pleomorphic adenoma of salivary glands: a problematic diagnosis.

We report the case of a 77-year-old woman who presented with a 6-year history of pleomorphic adenoma with multiple recurrences. Despite the clinical suspicion of a malignant process, the detection of myoepithelial carcinoma ex pleomorphic adenoma was not achieved by means of a preoperative biopsy or a frozen section removed intraoperatively, as the lesion only showed mild cytological atypia with no frank malignant features. Only a thorough evaluation of the resected tumor enabled the diagnosis of a malignancy. We discuss the difficulties that may be encountered in attempting to diagnose these rare myoepithelial lesions by means of small biopsy specimens.

Detection of occult cervical micrometastases in patients with head and neck squamous cell cancer.

OBJECTIVE: The incidence of occult nodal metastases associated with head and neck squamous cell carcinoma (HNSCC) and the clinical significance of nodal micrometastases by cytokeratin immunohistochemical analysis are examined. STUDY DESIGN: In all, 1012 lymph nodes from 50 patients treated between 1992 and 2001 at the University of Colorado Health Sciences Center (Denver, CO) were evaluated retrospectively for micrometastases. METHODS: Serial sectioning in 5-to 6-microm interval specimens stained either with hematoxylin and eosin (H&E) or immunostaining for cytokeratins using the monoclonal antibody cocktail AE1/AE3 was performed in 21 N0, 11 N1, and 14 N2 patient cases. Cases that showed scattered cells with suspect staining qualities but without morphological features consistent with HNSCC were further evaluated by epithelial membrane antigen (EMA) immunohistochemical analysis. RESULTS: H&E-stained and cytokeratin-stained sections revealed occult nodal micrometastases in 3.8% of N0 and 5% of N1 cases. Overall, 26 micrometastases were identified in N0 and N1 patients, causing 29% of N0 patients and 45% of N1 patients to be upstaged. Cytokeratin immunostaining detected micrometastases in eight cases that were negative on H&E serial sectioning. Serial sectioning by H&E alone identified three additional micrometastases. Negative EMA immunostaining confirmed the absence of malignant cells in lymph node sections that were equivocal on cytokeratin staining. CONCLUSIONS: The use of serial sectioning with H&E and cytokeratin immunohistochemical analysis increases the detection of micrometastases that are often elusive by routine processing in patients with HNSCC. Improved methods of detecting micrometastases may provide a basis for improved planning of postoperative therapy for patients already at risk for tumor recurrence.