How far are we off? Analyzing the accuracy of surgical margin relocation in the head and neck.

BACKGROUND: Positive surgical margin rates remain high in head and neck cancer surgery. Relocation is challenging given the complex, three-dimensional (3D) anatomy. METHODS: Prospective, multi-institutional study to determine accuracy of head and neck surgeons and pathologists relocating margins on virtual 3D specimen models using written descriptions from pathology reports. Using 3D models of 10 head and neck surgical specimens, each participant relocated 20 mucosal margins (10 perpendicular, 10 shave). RESULTS: A total of 32 participants, 23 surgeons and 9 pathologists, marked 640 margins. Of the 320 marked perpendicular margins, 49.7% were greater than 1 centimeter from the true margin with a mean relocation error of 10.2 mm. Marked shave margins overlapped with the true margin a mean 54% of the time, with no overlap in 44 of 320 (13.8%) shave margins. CONCLUSIONS: Surgical margin relocation is imprecise and challenging even for experienced surgeons and pathologists. New communication technologies are needed.

Top advances of the year: Head and neck cancer.

Advances in treatment deintensification for human papillomavirus-associated oropharyngeal cancer include use of transoral surgery to permit reduction in pathologic risk-based postoperative therapy after transoral resection. The E3311 cooperative group trial demonstrated 3-year progression-free survival (PFS) of 95% for intermediate risk patients treated with 50 Gy radiation alone, with no decrement for those with a smoking history. Favorable risk patients could be observed, with a 3-year PFS of 93%. Reduction in radiation dose is also feasible for favorable risk patients (low or no smoking history and low stage) treated with chemoradiation on the NRG HN002 trial, where 2-year PFS was 90.7%. For those favorable risk patients treated with radiation alone, 2-year PFS was 87.7% and this arm did not meet criteria for further testing. Important phase 3 trials of immunotherapy in first-line treatment of recurrent and/or metastatic head and neck cancer were also reported in 2022. For patients with nonnasopharyngeal sites of disease, the combination of the programmed death-1-directed antibody nivolumab plus the anti-CTLA-4 agent ipilimumab was not superior to chemotherapy plus cetuximab in the Checkmate 651 trial. However, in an important breakthrough for patients with nasopharyngeal cancer, the JUPITER-02 trial, conducted in China, Singapore, and Taiwan among patients with predominantly Epstein-Barr virus-related cancers, demonstrated a significant improvement in PFS (hazard ratio, 0.52) when toripalimab was added to gemcitabine/cisplatin chemotherapy. Immature survival data indicate overall survival will likely also be impacted.

Indications and outcomes of superselective neck dissection: A review and analysis of the literature.

Superselective neck dissection, defined as dissection of two or less contiguous neck levels, has recently been introduced to reduce surgical morbidity of neck dissection while maintaining favorable oncologic outcomes. The purpose of this review is to report the results of superselective neck dissection when applied to specific settings: the management of regional disease after chemoradiation, head and neck squamous cell carcinoma with clinical N0 necks, and high risk papillary thyroid carcinoma.

The effects of concurrent chemoradiation therapy to the base of tongue in a preclinical model.

OBJECTIVES/HYPOTHESIS: To develop a clinically relevant model of oropharyngeal concurrent chemoradiation therapy (CCRT) in order to quantify the effects of CCRT on tongue function and structure. CCRT for advanced oropharyngeal cancer commonly leads to tongue base dysfunction and dysphagia. However, no preclinical models currently exist to study the pathophysiology of CCRT-related morbidity, thereby inhibiting the development of targeted therapeutics. STUDY DESIGN: Animal model. METHODS: Twenty-one male Sprague-Dawley rats were randomized into three groups: 2 week (2W), 5 month (5M), and control (C). The 2W and 5M animals received cisplatin, 5-fluorouracil, and five fractions of 7 Gy to the tongue base; the C animals received no intervention. In vivo tongue strength and displacement, as well as hyoglossus muscle collagen content, were assessed. Analyses were conducted 2 weeks or 5 months following completion of CCRT in the 2W and 5M groups, respectively. RESULTS: Peak tetanic and twitch tongue forces were significantly reduced in both 2W and 5M animals compared to controls (tetanic: P = .0041, P = .0089, respectively; twitch: P = .0201, P = .0020, respectively). Twitch half-decay time was prolonged in 2W animals compared to controls (P = .0247). Tongue displacement was significantly reduced across all testing parameters in 5M animals compared to both the C and 2W groups. No differences in collagen content were observed between experimental groups. CONCLUSIONS: The current study is the first to describe a preclinical model of CCRT to the head and neck with an emphasis on clinical relevance. Tongue strength decreased at 2 weeks and 5 months post-CCRT. Tongue displacement increased only at 5 months post-CCRT. Fibrosis was not detected, implicating alternative causative factors for these findings. LEVEL OF EVIDENCE: NA Laryngoscope, 1783-1790, 2018.

Orthognathic Considerations of Vascular Malformations.

Vascular malformations affect the craniofacial skeleton in many ways, depending on the type of the lesion and its location. The lesions may exert a mass effect and cause thinning or thickening of the bone or cause expansion from direct bony infiltration. Orthognathic surgery can be used to correct any malocclusion or open bite deformities after the soft tissues are addressed.

Laryngeal distribution of recurrent respiratory papillomatosis in a previously untreated cohort.

OBJECTIVES/HYPOTHESIS: To describe the distribution of recurrent respiratory papillomatosis (RRP) lesions across 21 laryngeal anatomic regions in previously untreated patients at initial presentation to provide insight regarding the natural history of RRP. STUDY DESIGN: Multi-institutional, retrospective case series. METHODS: Initial laryngoscopic examination videos of 83 previously untreated patients with adult-onset RRP were reviewed. Papilloma locations were recorded using a 21-region laryngeal schematic. Multivariate analyses by anatomic subsite were conducted for the entire population and for subgroups stratified by sex, age, and proton pump inhibitor (PPI) usage. Heat maps were generated, hierarchically color coding the anatomic distribution of disease. RESULTS: In this cohort, RRP was most likely to occur on the true vocal folds (TVFs) and anterior commissure (P < .0001, odds ratio [OR]: 7.02); within the TVFs, the membranous vocal folds (MVFs) were most likely to be affected (P < .0001, OR: 3.56). The cohort was predominantly male (80.7%); males had a higher average number of affected sites (P = .005) and were more likely to have lesions in any laryngeal subsite (P < .0001, OR: 2.88,) compared to females. PPI users were more likely than nonusers to have disease in any laryngeal subsite (P = .0037, OR: 1.62), particularly in the posterior and subglottic regions (P = .0061, OR: 2.53). Age was not correlated with lesion prevalence or distribution. CONCLUSIONS: In untreated patients presenting to three laryngology clinics, the MVFs were most likely to be affected by RRP. Males had more anatomic sites affected by papilloma than females. The influence of PPI use on RRP distribution warrants further investigation. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:138-143, 2018.

The Safety of Antithrombotic Therapy During In-office Laryngeal Procedures-A Preliminary Study.

INTRODUCTION: In-office laryngeal procedures present an alternative to the risks and costs associated with general anesthesia. However, the inherent control afforded by the operative theater is decreased potentially increasing the risk of complications. Many patients undergoing these procedures have traditional surgical risk factors, such as antithrombotic (AT) medical therapy. We sought to quantify complication rates for in-office procedures as a function of AT therapy. METHODS: A retrospective review of 127 diverse, in-office laryngeal procedures was performed and patients were then stratified based on AT medication status and type of procedure. The primary dependent variables were intraoperative and postoperative complications. Additionally, in those patients undergoing procedures with the goal of voice improvement, Voice Handicap Index (VHI)-10 scores were used to quantify the success of the procedure as a function of AT therapy. RESULTS: Of the 127 procedures, 27 procedures (21.2%) involved patients on some form of AT agent that was not ceased for the procedure. Across all patients, no intraoperative complications were encountered, irrespective of therapeutic status. Three postoperative complications were noted; all in patients not on AT therapy. A statistically significant improvement in VHI-10 scores was noted across all patients, irrespective of AT status. CONCLUSIONS: AT medications do not appear to increase the risk of complications associated with in-office laryngeal procedures. Furthermore, AT therapy seemed to have no negative impact on the voice outcomes of patients undergoing procedures for voice improvement.

Concurrent oral human papilloma virus infection in patients with recurrent respiratory papillomatosis: a preliminary study.

OBJECTIVES/HYPOTHESIS: To determine oral human papilloma virus (HPV) colonization in patients with adult-onset recurrent respiratory papillomatosis (AO-RRP) and their long-term partners. STUDY DESIGN: Prospective, cohort study METHODS: Patients with pathology-confirmed AO-RRP and a small cohort of their long-term partners were subjected to a standardized oral rinse and swab protocol to obtain oral epithelial cells. DNA from these samples was extracted and subjected to both qualitative analyses via multiplex polymerase chain reaction as well as to a commercially available linear array assay for the determination of specific HPV subtypes. RESULTS: Samples were collected from 27 patients with AO-RRP and six long-term sexual partners. Qualitative analysis of agarose gel products using a multiple genotype primer cocktail suggested the presence of HPV DNA in oral rinse or swabs in 26 patients (96%) and four partner samples (67%). A subset of these positive patient samples was then subjected to genotyping; a spectrum of HPV subtypes was observed. Interestingly, HPV81 was identified in many samples. CONCLUSION: Recent data suggest that less than 7% of the general population is HPV positive in the oral cavity. Our data suggest that the oral colonization rate is much higher in patients with AO-RRP. Additionally, long-term sexual partners of patients with RRP had a much higher rate of HPV positivity. These preliminary data may have implications for viral transmission and provide a framework for enhanced patient education as well as further investigation. LEVEL OF EVIDENCE: 4.

Magnetic resonance imaging of the effortful swallow.

OBJECTIVE: The effortful swallow was designed to improve posterior mobility of the tongue base and increase intraoral pressures. We characterized the effects of this maneuver via dynamic magnetic resonance imaging (dMRI) in healthy patients. METHODS: A 3-T scanner was used to obtain dMRI images of patients swallowing pudding using normal as well as effortful swallows. Ninety sequential images were acquired at the level of the oropharynx in the axial plane for each swallow; 3 series were obtained for each swallow type for each patient. Images were acquired every 113 ms during swallowing. The images were analyzed with respect to oropharyngeal closure duration, anteroposterior and transverse distance between the oropharyngeal walls, and oropharyngeal area before and after closure. RESULTS: Preswallow reduced pharyngeal area was observed (P = .02; mean = 212.61 mm² for effortful, mean = 261.92 mm² for normal) as well as prolonged pharyngeal closure during the swallow (P < .0001; mean = 742.18 ms for effortful, mean = 437.31 ms for normal). No other differences were noted between swallow types. Interrater and intrarater reliability of all measurements was excellent. CONCLUSION: This preliminary investigation is the first to evaluate the effects of effortful swallows via dMRI. In our cohort, consistent physiologic changes were elicited, consistent with clinical dogma regarding this maneuver.

Risk factors for adult-onset recurrent respiratory papillomatosis.

OBJECTIVES/HYPOTHESIS: To evaluate risk factors strongly associated with adult-onset recurrent respiratory papillomatosis (AO-RRP). STUDY DESIGN: Prospective, age- and sex-matched, case control. METHODS: Patients with AO-RRP and controls completed a computer-based, 89-item questionnaire across three academic institutions. RESULTS: Forty-eight AO-RRP patients were compared to 73 controls; 43 of the 48 AO-RRP patients were male (89.5%). The difference in the median number of lifetime sexual partners between AO-RRP (15) and controls (10) was significant (P = 0.0387). Additionally, an increased number of lifetime sexual partners (≥ 26) was associated with AO-RRP. No significant difference for the number of lifetime oral sex partners was observed between groups. Increased comorbidity, as quantified by the Charlson Comorbidity Index, was observed in patients with AO-RRP. AO-RRP and control groups were similar across many other variables, including birth history, smoking history, alcohol use, drug use, education, income, and the Short Form Health Survey scores. CONCLUSIONS: AO-RRP was not associated with previously proposed risk factors for juvenile-onset RRP and may be associated with an increased number of lifetime sexual partners.

Effect of mitomycin C on concentrations of vascular endothelial growth factor and its receptors in bladder cancer cells and in bladders of rats intravesically instilled with mitomycin C.

OBJECTIVES: • To examine, using in vitro and in vivo models, the largely unexamined effect of mitomycin C (MMC), an effective intravesical treatment for superficial bladder cancer and carcinoma in situ, on expression of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR-2), which mediates many of the angiogenic properties of VEGF. • To measure, as a positive control, concentrations of the inhibitor of apoptosis, survivin, as an assessment of MMC effectiveness. • To measure MMC-induced changes in proliferation in the presence and absence of VEGF-A small interfering RNA (siRNA). MATERIALS AND METHODS: • After treatment with increasing MMC concentrations (5-200 µg/mL), we measured proliferation, as well as VEGF, survivin, VEGF receptor-1 (VEGFR-1) and VEGFR-2 concentrations in RT-4 and T-24 bladder cancer cells. • The effect of pre-treatment of VEGF siRNA and survivin siRNA on MMC-induced decreases in proliferation was measured. • Urinary VEGF concentrations and bladder and kidney concentrations of VEGF-A, VEGFR-1, VEGFR-2 and interleukin-6 (IL-6) mRNA were measured in rats intravesically instilled with saline or MMC (200 µg/mL). RESULTS: • Although MMC treatment inhibited cell proliferation and decreased survivin mRNA expression in T-24 and RT4 cells, MMC (12-50 µg/mL) increased VEGF-A mRNA and VEGFR-2 mRNA and protein expression. • Pre-treatment with VEGF-A siRNA or survivin siRNA before MMC treatment reduced proliferation more than MMC alone. • MMC-induced reductions in proliferation were reduced additively by pre-treatment with survivin siRNA, but were potentiated by pre-treatment with VEGF-A siRNA. • VEGFR-2 mRNA and protein concentrations and urinary VEGF concentrations were increased in bladders of rats instilled with MMC. CONCLUSIONS: • Intravesically instilled MMC increases urinary VEGF and bladder VEGFR-2 protein and mRNA in rats. • MMC increases VEGF mRNA and VEGFR-2 protein and mRNA concentrations in bladder cancer cells. Therefore, we speculate that MMC could increase the angiogenic potential of both cancer and normal cells. • In cancer cells this effect is largest at lower MMC concentrations. • Combining MMC with agents that reduce EGF concentrations could be of value in treatment of transitional cell carcinoma of the bladder (TCC).