Donald T. Weed

Background/Objectives: Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, with a lifetime risk of 14–20% that is rising every year. Although prognosis for cSCC is generally good, certain high-risk features of cSCC portend increased rates of nodal and distant metastasis, recurrence, and disease-specific mortality. One such high-risk factor is perineural invasion (PNI), which is broadly defined as the invasion of cancer into and around nerves. Compared to other high-risk factors, PNI presence is associated with the highest risk for locoregional and distant metastasis. Still, the mechanisms underlying the pathogenesis of PNI remain poorly understood. Recent studies suggest the migration and invasion of tumors into nerves is a result of complex molecular crosstalk within the tumor-nerve microenvironment, wherein the milieu of signaling molecules simultaneously promote neuronal growth and tumor cell invasion. Methods: Understanding the molecular and cellular mechanisms that promote PNI will lead to future developments of targeted therapies that may improve locoregional control and survival. Results/Conclusions: In our article, we aim to provide a comprehensive review of recent findings about the pathogenesis of PNI, clinical implications of PNI-positive disease in cSCC, available treatment modalities, and potential future therapeutic targets.

Emerging evidence suggests that not only the frequency and composition of tumor-infiltrating leukocytes but also their spatial organization might be a major determinant of tumor progression and response to therapy. Therefore, mapping and analyzing the fine tumor immune architecture could potentially provide insights for predicting cancer prognosis. Here, we performed an explorative, prospective clinical study to assess whether structures within the tumor microenvironment can predict recurrence after salvage surgery in head and neck squamous cell carcinoma (HNSCC). The major immune subsets were measured using flow cytometry and co-detection by indexing (CODEX) multiparametric imaging. Flow cytometry underestimated the number of PMN-MDSCs and neutrophils in the tumor and overestimated the tumor-infiltrating lymphocyte frequency. An ad hoc computational framework was used to identify and analyze discrete cellular neighborhoods. A high frequency of tertiary lymphoid structures composed of CD31highCD38high plasma cells was associated with reduced recurrence after surgery in HNSCC. These data support the notion that the structural architecture of the tumor immune microenvironment plays an essential role in tumor progression and indicates that type 1 tertiary lymphoid structures and long-lived CD31highCD38high plasma cells are associated with good prognosis in HNSCC.Significance:Imaging the spatial tumor immune microenvironment and evaluating the presence of type 1 tertiary lymphoid structures enables prediction of recurrence after surgery in patients with head and neck squamous cell carcinoma.

Emerging evidence suggests that not only the frequency and composition of tumor-infiltrating leukocytes but also their spatial organization might be a major determinant of tumor progression and response to therapy. Therefore, mapping and analyzing the fine tumor immune architecture could potentially provide insights for predicting cancer prognosis. Here, we performed an explorative, prospective clinical study to assess whether structures within the tumor microenvironment can predict recurrence after salvage surgery in head and neck squamous cell carcinoma (HNSCC). The major immune subsets were measured using flow cytometry and co-detection by indexing (CODEX) multiparametric imaging. Flow cytometry underestimated the number of PMN-MDSCs and neutrophils in the tumor and overestimated the tumor-infiltrating lymphocyte frequency. An ad hoc computational framework was used to identify and analyze discrete cellular neighborhoods. A high frequency of tertiary lymphoid structures composed of CD31highCD38high plasma cells was associated with reduced recurrence after surgery in HNSCC. These data support the notion that the structural architecture of the tumor immune microenvironment plays an essential role in tumor progression and indicates that type 1 tertiary lymphoid structures and long-lived CD31highCD38high plasma cells are associated with good prognosis in HNSCC.Significance:Imaging the spatial tumor immune microenvironment and evaluating the presence of type 1 tertiary lymphoid structures enables prediction of recurrence after surgery in patients with head and neck squamous cell carcinoma.

Emerging evidence suggests that not only the frequency and composition of tumor-infiltrating leukocytes but also their spatial organization might be a major determinant of tumor progression and response to therapy. Therefore, mapping and analyzing the fine tumor immune architecture could potentially provide insights for predicting cancer prognosis. Here, we performed an explorative, prospective clinical study to assess whether structures within the tumor microenvironment can predict recurrence after salvage surgery in head and neck squamous cell carcinoma (HNSCC). The major immune subsets were measured using flow cytometry and co-detection by indexing (CODEX) multiparametric imaging. Flow cytometry underestimated the number of PMN-MDSCs and neutrophils in the tumor and overestimated the tumor-infiltrating lymphocyte frequency. An ad hoc computational framework was used to identify and analyze discrete cellular neighborhoods. A high frequency of tertiary lymphoid structures composed of CD31highCD38high plasma cells was associated with reduced recurrence after surgery in HNSCC. These data support the notion that the structural architecture of the tumor immune microenvironment plays an essential role in tumor progression and indicates that type 1 tertiary lymphoid structures and long-lived CD31highCD38high plasma cells are associated with good prognosis in HNSCC.Significance: Imaging the spatial tumor immune microenvironment and evaluating the presence of type 1 tertiary lymphoid structures enables prediction of recurrence after surgery in patients with head and neck squamous cell carcinoma.

Background: The recent trends in education and geographic distribution of the head and neck surgery workforce have not been studied extensively. Methods: We reviewed publicly available sources to locate all fellowship‐trained head and neck surgeons and recent graduates. The number of surgeons in each state was compared against head and neck cancer incidence data from the Centers for Disease Control. Results: The number of graduates increased annually by 1 per 100 000 000 people from 2011–2020. The average number of fellowship‐trained surgeons per state was 10 (SD: 12). The average number of new head and neck cancer cases per surgeon was 247 (SD: 135). Ten states (20%) had cases >1 SD above the national average/surgeon, while 3 (6%) had cases >1 SD below the national average. Conclusion: Head and neck surgeons are located in most states, but not uniformly. Most states have approximately average density of surgeons; however, several states are outliers.

Background: A closed suction drain (CSD) is often utilized in head and neck surgical procedures to obliterate dead space. CSDs reduce seroma and hematoma formation, thereby improving skin apposition and wound healing. The use of drains for prolonged periods of time, however, may increase the risk of wound infection. Interestingly, the evidence regarding the need for, and management of, post-operative CSDs after head and neck surgery is scarce. The current criterion of drain removal when output is less than 30 cubic centimeters (cm³) within a 24-hour period and/or on the third post-operative day (POD) is widely utilized. The aforementioned criterion is based on anecdotal evidence from small studies with specific surgical procedures. In this study, we aim to evaluate the criteria for drain removal and to lay the groundwork for an updated paradigm for drain management in head and neck oncologic surgery. Study Design: Retrospective cohort study Setting: Academic tertiary care hospital Methods: A retrospective study was performed. Patients were included if they underwent head and neck surgery at the University of Miami Hospital between January 1, 2019 and July 1, 2020 and had at least one CSD. Volume of drain output on each POD was recorded until the day of drain removal. The development of post-operative wound complications (i.e., seroma, hematoma, infection/abscess, and dehiscence) was also recorded. Results: From our initial cohort of 302 patients, 145 patients met inclusion criteria. A total of 10 patients developed a post-operative wound complication. Patients had a mean age of 58.3 ± 15.0 years. The median inter-quartile range (IQR) drain output (cm³) on the day of CSD removal from patients who developed a wound complication was similar (15; IQR, 5-37.5) when compared to those who did not develop a wound complication (25; IQR, 10-30). This difference was not statistically significant (p = 0.60). Additionally, the cohort who developed a post-operative wound complication had their drain removed on an earlier POD (1; IQR, 1-1 (Mean 1.2)) when compared to the cohort who did not develop any complications (1; IQR, 1-1 (Mean 1.5)). This difference was also not statistically significant (p = 0.48) . Conclusion: There is no association between drain output (cm³) or day of CSD removal with the development of wound complications. These results warrant further studies to prospectively evaluate earlier CSD removal in head and neck surgery.

Background: The extent of cervical lymphadenectomy required for primary parotid cancer is not well‐established.Methods: In this retrospective case–control study, 84 patients who underwent primary parotidectomy and neck dissection for primary parotid cancer between 2010 and 2019 were identified and analyzed.Results: Of the 84 patients, 37 underwent elective level V neck dissection. All six (16.0%) who had occult level V nodes had clinically evident, preoperative anterior cervical metastases, a statistically significant finding. No other clinical factors are correlated with posterior neck involvement. There was no significant difference in disease‐free or overall survival for patients with occult level V disease relative to positive lymph nodes in other levels.Conclusions: Patients with clinically evident anterolateral cervical lymphatic metastases from parotid cancer preoperatively have high rates of occult level V nodes. Level V neck dissection can be avoided in cN0 patients and offered no survival advantage.

Background: The present study aims to assess the quality and availability of online information about fellowships accredited by the American Head & Neck Society (AHNS).Methods: AHNS directory pages and institutional web sites of 50 AHNS‐accredited fellowships were identified. Web pages were scored using 20 standardized criteria including general information, application information, alumni, surgical training, research, and quality‐of‐life.Results: Median scores for AHNS directory pages and institutional web sites were 11 (range: 7–14) and 10 (4–15), respectively. Faculty listings, contact information, program location, number of positions, and breadth of surgical exposure were the most commonly listed criteria. Less common criteria included didactic schedule, protected academic time, previous research projects, year of accreditation, work‐life balance, fellow selection criteria, interview information, and salary.Conclusions: The AHNS directory and institutional web sites are most comprehensive in general program information and details about surgical training. Information about the application process, work‐life balance, and research opportunities were less common.

The most common oral cavity cancer is squamous cell carcinoma (SCC), of which perineural invasion (PNI) is a significant prognostic factor associated with decreased survival and an increased rate of locoregional recurrence. In the classical theory of PNI, cancer was believed to invade nerves directly through the path of least resistance in the perineural space; however, more recent evidence suggests that PNI requires reciprocal signaling interactions between tumor cells and nerve components, particularly Schwann cells. Specifically, head and neck SCC can express neurotrophins and neurotrophin receptors that may contribute to cancer migration towards nerves, PNI, and neuritogenesis towards cancer. Through reciprocal signaling, recent studies also suggest that Schwann cells may play an important role in promoting PNI by migrating toward cancer cells, intercalating, and dispersing cancer, and facilitating cancer migration toward nerves. The interactions of neurotrophins with their high affinity receptors is a new area of interest in the development of pharmaceutical therapies for many types of cancer. In this comprehensive review, we discuss diagnosis and treatment of oral cavity SCC, how PNI affects locoregional recurrence and survival, and the impact of adjuvant therapies on tumors with PNI. We also describe the molecular and cellular mechanisms associated with PNI, including the expression of neurotrophins and their receptors, and highlight potential targets for therapeutic intervention for PNI in oral SCC.

Background Head and neck surgical oncology and reconstruction are uniquely suited to address burdens of disease in underserved areas. Since these efforts are not well known in our specialty, we sought to understand global outreach throughout our society of surgeons. Methods Survey distributed to members of the American Head and Neck Surgery involved in international humanitarian head and neck surgical outreach trips. Results Thirty surgeons reported an average of seven trips to over 70 destinations. Identification of candidates, finances, on‐site patient care, complications, long‐term post‐surgical care, ethics, and educational goals are reported. We report a success rate of 90% on 125 free flaps performed in these settings. Conclusions The effort to answer the call for alleviating the global burden of surgical disease is strong within our specialty. There is a shared focus on humanitarian effort and teaching. Ethics of high resource surgeries such as free flap reconstruction remains controversial.