Long-Term Outcomes Following Definitive or Adjuvant Proton Radiotherapy for Adenoid Cystic Carcinoma.

Purpose: Adenoid cystic carcinoma (ACC) is a rare malignancy accounting for 1% of all head and neck cancers. Treatment for ACC has its challenges and risks, yet few outcomes studies exist. We present long-term outcomes of patients with ACC of the head and neck treated with proton therapy (PT). Materials and Methods: Under an institutional review board-approved, single-institutional prospective outcomes registry, we reviewed the records of 56 patients with de novo, nonmetastatic ACC of the head and neck treated with PT with definitive (n = 9) or adjuvant PT (n = 47) from June 2007 to December 2021. The median dose to the primary site was 72.6 gray relative biological equivalent (range, 64-74.4) delivered as either once (n = 19) or twice (n = 37) daily treatments. Thirty patients received concurrent chemotherapy. Thirty-one patients received nodal radiation, 30 electively and 1 for nodal involvement. Results: With a median follow-up of 6.2 years (range, 0.9-14.7), the 5-year local-regional control (LRC), disease-free survival, cause-specific survival, and overall survival rates were 88%, 85%, 89%, and 89%, respectively. Intracranial extension (P = .003) and gross residual tumor (P = .0388) were factors associated with LRC rates. While the LRC rate for those with a gross total resection was 96%, those with subtotal resection or biopsy alone were 81% and 76%, respectively. The 5-year cumulative incidence of clinically significant grade ≥3 toxicity was 15%, and the crude incidence at the most recent follow-up was 23% (n = 13). Conclusion: This is the largest sample size with the longest median follow-up to date of patients with ACC treated with PT. PT can provide excellent disease control for ACC of the head and neck with acceptable toxicity. T4 disease, intracranial involvement, and gross residual disease at the time of PT following either biopsy or subtotal resection were significant prognostic features for worse outcomes.

Comparison of the outcomes of split thickness skin graft versus thickness skin graft for closure of the radial forearm free flap donor site: A systematic review.

BACKGROUND: Radial forearm free flap (RFFF) donor site closure is traditionally performed with split thickness skin grafts (STSG), which can be associated with poor aesthetics, wrist stiffness, paresthesia, reduced strength, and tendon exposure. Full thickness skin grafts (FTSG) are potentially beneficial as they provide a more durable coverage, and the skin graft donor site can be closed primarily, which is more aesthetic. The aim of this systematic review is to compare the outcomes of STSG versus FTSG for closure of the RFFF donor site. METHODS: A systematic review was performed, following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The primary objective was to answer: do subjects undergoing RFFF harvest, utilizing FTSG to close the RFFF donor site, compared to STSG, achieve superior aesthetics at the RFFF donor site? Included papers compared FTSG and STSG with statistical data. Means were compared with t-test and proportions with Fisher's exact test. RESULTS: The initial search resulted in 1851 studies. After applying the inclusion/exclusion criteria, the search resulted in eight studies, with 366 total skin grafts, 197 STSG and 169 FTSG. Six studies evaluated aesthetics utilizing a Likert scale, with the scaled average aesthetic score for FTSG being 7.9/10 compared to 6.9/10 for STSG (p < .001). Tendon exposure was measured in five studies, with a rate of 13.1% for STSG versus 10.6% for FTSG (p = .555). No significant difference in function was observed, however, methods to quantify function were heterogeneous. CONCLUSION: FTSG compared to STSG, resulted in statistically significant improved aesthetics, with comparable rates of tendon exposure and function.

Mathematical Modeling of Vessel Geometry and Circumference in Microvascular Surgery.

Introduction: Microvascular anastomosis has traditionally been executed with a perpendicular transection through the vessel at the widest diameter to increase circumference and thus increase blood flow while decreasing resistance. In Chen's 2015 article, it was suggested that an "open Y" would improve vessel size match, and Wei and Mardini discuss angled transections of the vessels. This project aims to explore the geometric configurations feasible at the anastomotic transection and mathematically model the resulting hypothetical increases in circumference. Materials and Methods: The mathematical models were theoretically developed by our team. The formulas model increases in circumference of the transection at different distances in relation to the bifurcation of a blood vessel, as well as changes in circumference at different transection angulations. An in vitro exploration as to the anastomotic feasibility of each geometric cut was completed on ten poultry tissue specimens. Results: The mathematical models demonstrated the change in vessel circumference, with multiple geometric designs calculated, best shown through diagrams. For example, if the vessel width is 1 mm, the distance from the increasing vessel diameter to the final bifurcation is 1 mm, and the bifurcation angle is 45°, the circumference of the transected vessel increases by 82.8%. Models of transections at different angulations, for instance 30°, 45°, and 60°, yield an increase in elliptical circumference of 8.0%, 22.5%, and 58.1%, respectively. Additional derivations calculate the elliptical circumference at any angle in a single vessel, and at any angle in a bifurcating vessel. Conclusion: The theoretical and clinical aim of this project is to increase awareness of the anastomotic creativity and mathematically demonstrate the optimal anastomotic geometry, which has not been objectively explored to our knowledge. An in vivo study would further support clinical improvements, with the aim to map postoperative fluid dynamics through the geometric anastomoses.

The Role of Imaging in Mandibular Reconstruction with Microvascular Surgery.

Imaging plays a critical role in the diagnosis, staging, and management of segmental mandibular defects. Imaging allows mandibular defects to be classified which aids in microvascular free flap reconstruction. This review serves to complement the surgeon's clinical experience with image-based examples of mandibular pathology, defect classification systems, reconstruction options, treatment complications, and Virtual Surgical Planning.

Classification and Staging of Melanoma in the Head and Neck.

The rates of melanoma continue to rise, with recent estimates have shown that 18% to 22% of new melanoma cases occur within the head and neck in the United States each year. The mainstay of treatment of nonmetastatic primary melanomas of the head and neck includes the surgical resection and management of regional disease as indicated. Thorough knowledge of the classification and staging of melanoma is paramount to evaluate prognosis, determine the appropriate surgical intervention, and assess eligibility for adjuvant therapy and clinic trials. The traditional clinicopathologic classification of melanoma is based on morphologic aspects of the growth phase and distinguishes 4 of the most common subtypes as defined by the World Health Organization: superficial spreading, nodular, acral lentiginous, and lentigo maligna melanoma. The data used to derive the AJCC TNM Categories are based on superficial spreading melanoma and nodular subtypes. Melanoma is diagnosed histopathologically following initial biopsy that will assist with classifying the tumor to guide treatment. Classification is based on tumor thickness and ulceration (T stage, Breslow Staging), Regional Lymph Node Involvement (N Stage), and presence of metastasis (M Stage). Tumor thickness (Breslow thickness) and ulceration are 2 independent prognostic factors that have been shown to be the strongest predictors of survival and outcome. Clark level of invasion and mitotic rate are no longer incorporated into the current AJCC staging system, but still have shown to be important prognostic factors for cutaneous melanoma. For patients with metastatic (Stage IV) disease Lactate Dehydrogenase remains an independent predictor of survival. The Maxillofacial surgeon must remain up to date on the most current management strategies in this patient population. Classification systems and staging provide the foundation for clinical decision making and prognostication for the Maxillofacial surgeon when caring for these patients.

Passively Scattered Proton Therapy for Nonmelanoma Skin Cancer with Clinical Perineural Invasion.

PURPOSE: To report our experience with the delivery of passively scattered proton therapy in the management of nonmelanoma skin cancers with clinical perineural invasion. MATERIALS AND METHODS: We reviewed the medical records of patients who received definitive or postoperative proton therapy for nonmelanoma skin cancer with clinical perineural invasion at our institution and updated patient follow-up when possible. All patients were treated with curative intent with or without the delivery of concurrent systemic therapy. We report disease control rates and the rates of late toxicity among this cohort. RESULTS: Twenty-six patients treated between 2008 and 2017 were included in the analysis. Following proton therapy, the 3-year overall, cause-specific, and disease-free survival rates were 59%, 73%, and 60%, respectively. The 3-year local control, local regional control, and distant metastasis-free survival rates were 80%, 65%, and 96%, respectively. On univariate analysis, surgical resection before radiation therapy significantly improved local regional control rates at 3 years (55% versus 86%; P = .04). Grade 3+ late toxicities occurred in 13 patients (50%) and the most common toxicities included grade 3+ keratitis of the ipsilateral eye, which occurred in 4 patients (15%) and grade 3+ brain necrosis in 4 patients (15%). CONCLUSION: Proton therapy is effective in the management of nonmelanoma skin cancer with clinical perineural invasion. Although disease control and complication rates compare favorably to those previously published for photon-based radiation therapy, the risk for late toxicity is significant and patients should be appropriately counseled.

Serial Perioperative Assessment of Free Flap Perfusion With Laser Angiography.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: Reconstruction with microvascular free flaps is quite predictable but excessive fluids intraoperatively and excessive use of vasopressors have been implicated in postoperative complications. However, vasopressors assist in limiting fluid administration and counteract vasodilatory effects of general anesthetics, while maintaining proper intravascular volume. This is of paramount importance during surgery to ensure adequate tissue and organ perfusion. The purpose of this study is to quantify perfusion changes in free flaps at specific time points during peri- and postoperative periods, incorporating SPY technology. METHODS: A prospective study of patients who underwent free flap reconstruction was conducted (n = 9), using SPY laser angiography with indocyanine green to assess effects of general anesthetics and vasopressors on flap perfusion. Free flaps were evaluated prior to pedicle division, after inset and anastomosis, and in the immediate postoperative setting. Mean perfusion, mean arterial pressure, total operative time, fluid shifts, and vasopressor use were recorded. Data were analyzed with univariate and multivariable analyses. RESULTS: Those with major complications in this cohort, on average received less vasopressors, had shorter operation times and less blood loss, however, they received more fluids intraoperatively. CONCLUSION: Changes in mean perfusion to the free flap during the intraoperative and immediate postoperative period are nominal.

Prognostic significance of venous invasion in node-negative head and neck squamous cell carcinoma.

BACKGROUND: Venous invasion (VI) is not frequently evaluated on routine histologic examination of head and neck squamous cell carcinoma (HNSCC), and the prognostic significance is largely unknown. Studies have shown that extramural venous invasion is an adverse prognostic factor in colorectal carcinoma. To our knowledge, this is the first study evaluating the prognostic significance of venous invasion in node-negative (without clinical or pathologic evidence of lymph node involvement) HNSCC, utilizing the elastic stain. METHODS: A total of 105 consecutive lymph node-negative (N0) HNSCC were evaluated for the presence of venous channel invasion by tumor utilizing the elastin stain. Clinical, demographic, and follow-up data were recorded. RESULTS: Of 37 patients with venous invasion, 19% had loco-regional recurrence, as opposed to 12% of those without. Univariate analysis revealed statistically significant decreased recurrence-free survival in the presence of venous invasion (log-rank [Mantel-Cox] test P-value .025). CONCLUSION: Identification of VI is greatly aided by elastic stain. In patients with node-negative HNSCC, presence of VI resulted in decreased recurrence-free survival on univariate analysis. The impact of VI as a prognostic marker should be further evaluated.

Isolated leptomeningeal progression from sinonasal carcinomas: Implications for staging workup and treatment.

PURPOSE: To evaluate the rate and risk factors of isolated leptomeningeal progression in sinonasal carcinomas. METHODS: We retrospectively reviewed imaging and clinical records to determine progression patterns, and estimated rates using the Kaplan-Meier method. We evaluated risk factors using proportional hazard regression. RESULTS: We analyzed 120 patients who received adjuvant or primary radiotherapy for sinonasal carcinomas. Most patients had T4 disease (68%) and underwent surgery (84%) and chemotherapy (72%). Twenty-seven (23%) patients developed distant metastases (DM), including 20 (17%) with isolated DMs. Leptomeningeal progression was the most common site of isolated DMs (n = 9; 45%) with an average disease-free interval of 1.2 years (0.1-4.3 years). High-grade histology (P = 0.0003), intracranial invasion (P < 0.0001), and neuroendocrine histology (P = 0.06) were associated with increased risk. CONCLUSIONS: Isolated leptomeningeal progression is a common pattern of DM in advanced sinonasal carcinomas. We recommend adding cerebrospinal fluid cytology and contrast-enhanced spine MRI to routine staging evaluations for high-risk patients.

Tracheostomy in the Morbidly Obese: Difficulties and Challenges.

PURPOSE: This study evaluated the difficulties and challenges associated with open tracheostomy in the morbidly obese patient (body mass index [BMI] ≥30 kg/m2). PATIENTS AND METHODS: Forty patients met all the inclusion criteria. A retrospective chart review was performed to evaluate indications for tracheostomy, duration of intubation before tracheostomy, history of tracheostomy, duration of operative procedure, duration in the operating room, and all perioperative complications. RESULTS: Complications were classified as intraoperative (5%) and postoperative (17.5%). The average BMI was 46 kg/m2 (range, 31.1 to 75.3 kg/m2). The average duration of intubation before tracheostomy was 11 days. Ten patients (25%) previously underwent tracheostomy. The average operating time was 60 minutes (range, 20 to 95 minutes). The average total time in the operating room was 100 minutes (range, 45 to 146 minutes). CONCLUSION: This study shows that although open tracheostomy in the morbidly obese patient is increasing in demand, the procedure can be predictably performed albeit at a much longer duration and a higher perioperative complication rate compared with the traditional tracheostomy.

Analysis of primary risk factors for oral cancer from select US states with increasing rates.

OBJECTIVES: To examine the primary risk factor for oral cancer in the US, smoking and tobacco use, among the specific US states that experienced short-term increases in oral cancer incidence and mortality. METHODS: Population-based data on oral cancer morbidity and mortality in the US were obtained from the National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results (SEER) database for analysis of recent trends. Data were also obtained from the Centers for Disease Control and Prevention (CDC) Behavioral Risk Factor Surveillance System (BRFSS) to measure current and former trends of tobacco usage. To comprehensive measures of previous state tobacco use and tobacco-related policies, the Initial Outcomes Index (IOI, 1992-1993) and the Strength of Tobacco Control index (SoTC, 1999-2000) were also used for evaluation and comparison. RESULTS: Analysis of the NCI-SEER data confirmed a previous report of geographic increases in oral cancer and demonstrated these were state-specific, were not regional, and were unrelated to previously observed increases among females and minorities. Analysis of the CDC-BRFSS data revealed these states had relatively higher percentages of smokers currently, as well as historically. In addition, analysis of the IOI and SoTC indexes suggest that many factors, including cigarette pricing, taxes and home or workplace bans, may have had significant influence on smoking prevalence in these areas. Trend analysis of these data uncovered a recent and significant reversal in smoking rates that suggest oral cancer incidence and mortality may also begin to decline in the near future. CONCLUSION: Due to the rising costs of health care in the US and the limited resources available for health prevention efforts, it is essential to organize and direct more effective efforts by public health officials and epidemiologists, as well as funding from local, state and federal governments, to reduce and eliminate identified health disparities. This study provides evidence how these efforts may be directed to specific geographic areas, and towards the white males, previously thought to be unaffected by the increases in oral cancer among females and minorities.

High risk HPV types 18 and 16 are potent modulators of oral squamous cell carcinoma phenotypes in vitro.

BACKGROUND: Human papillomavirus (HPV) has been confirmed as the primary etiological factor that transforms cervical epithelia into cancer. The presence of HPV in oral cancers suggests that HPV may play a similar role in transforming the oral epithelia. A high degree of variability in the prevalence of HPV in oral cancers has been found, however, raising questions regarding its role in the transformation and development of oral cancers. The goal of this study was to test our hypothesis that high-risk HPV strains HPV16 and HPV18 will alter the phenotype of transformed oral squamous cell carcinoma cell lines, CAL27, SCC-15 and SCC-25 in vitro. RESULTS: CAL27 cells transfected with HPV18, HPV16, as well as HPV16/18 co-transfectants, demonstrated significant increases in proliferation, adhesion and cell spreading compared with non-transfected controls. These observed differences were correlated with a small level of increased cell survival. SCC-15 cells, however, displayed a differential response to HPV transfection, with only HPV18-transfectants demonstrated changes to proliferation. Interestingly, SCC-25 cells displayed a more complex response, with HPV16-induced increases in cell proliferation, viability and cell spreading, while HPV18- and 16/18-transfectants exhibited reduced adhesion and proliferation. CONCLUSION: Determining the potential of specific high-risk HPV strains to alter phenotypic behaviors of already transformed oral carcinomas is a critical step in providing more accurate prognosis and treatment options for oral cancer patients. The identification of differential responses to specific HPV strains among oral cancers suggests a more significant, complex and multifactorial role of HPV, not only in transforming, but also in modulating, the phenotype and treatment responsiveness of precancerous and cancerous oral lesions. This study provides some of the first evidence to help identify the important molecular markers for pathways that could be used to determine the most effective and appropriate treatment plans for oral cancer patients with concomitant oral HPV infections.