Factors associated with skin graft take in fibula and radial forearm free flap donor sites.

LEARNING OBJECTIVES: Identify factors associated with skin graft take in fibula free flaps (FFF) and radial forearm free flaps (RFFF) donor sites. STUDY OBJECTIVES: To determine which factors are associated with decreased skin graft take at the donor site in FFF and RFFF in head and neck patients. DESIGN: Retrospective Chart Review Case Series. SETTING: Multicenter Tertiary Care. METHODS: A multicenter retrospective review was performed at three institutions identifying patients who underwent free tissue transfer, specifically either FFF or RFFF, between 2007 and 2017. Patient demographics, medical history, and social history were examined including age, gender, BMI, smoking status, diabetes and preoperative anticoagulation use. Preoperative, intraoperative data, and postoperative data were also examined including tourniquet use, type of flap, area of skin graft, if the skin graft had a donor site or if it was taken from the flap, wound NPWT use, cast use, use of physical therapy, DVT prophylaxis, limb ischemia, heparin drip, and postoperative aspirin use. Statistical analysis was used to determine which factors were significantly associated with skin graft take. RESULTS: 1415 patients underwent a forearm or fibula flap and 938 patients underwent split-thickness skin graft. Of these, 592 patients had sufficient information and were included in the final analysis. There were 371 males and 220 females. The average age was 55.7. Complete skin graft take was seen in 480 patients (81.1%). On univariate analysis, patients with diabetes (p = .003), type of flap (fibula p < .001), skin graft area (p = .006), tourniquet use (p = .003), DVT prophylaxis (p = .008) and casting (p = .003) were significantly associated with decreased skin graft take rate. In a multivariate analysis, diabetes (OR 2.17 (95%CI 1.16-3.98)), fibula flaps (OR 2.86 (95%CI 1.79-4.76)), an increase in skin graft area (OR 1.01 (95%CI 1.01-1.01)), post-operative aspirin (OR 2.63 (95%CI 1.15-5.88), and casting (OR 2.94 (95%CI 1.22-7.14)) were associated with poor rates of skin graft take. CONCLUSION: Several factors affect skin graft take rate and should be considered when performing a skin graft for a donor site defect.

Tourniquet use and factors associated with hematoma formation in free tissue transfer.

PURPOSE: Our objective was to understand which variables are associated with hematoma formation at both the donor and recipient sites in head and neck free tissue transfer and if hematoma rates are affected by tourniquet use. METHODS: Patients were identified who underwent free tissue transfer at three institutions, specifically either a radial forearm free flap (RFFF) or a fibula free flap (FFF), between 2007 and 2017. Variables including use of tourniquet, anticoagulation, treatment factors, demographics, and post-operative factors were examined to see if they influenced hematoma formation at either the free tissue donor or recipient site. RESULTS: 1410 patients at three institutions were included in the analysis. There were 692 (49.1%) RFFF and 718 (50.9%) FFF. Tourniquets were used in 764 (54.1%) cases. There were 121 (8.5%) hematomas. Heparin drips (p < .001) and DVT prophylaxis (p = .03) were significantly associated with hematoma formation (OR 95% CI 12.23 (4.98-30.07), 3.46 (1.15-10.44) respectively) on multivariable analysis. CONCLUSIONS: Heparin Drips and DVT prophylaxis significantly increased hematoma rates in free flap patients while tourniquets did not affect rates of hematoma.

Free Flap Reconstruction of the Anterior Skull Base: A Systematic Review.

Objectives Given the limitations in the available literature, the precise indications, techniques, and outcomes of anterior skull base free flap reconstruction remain uncertain. The objective of this study was to perform a systematic review of published literature and evaluate indications, methods, and complications for anterior skull base free flap reconstruction. Methods A systematic review of the literature was performed using a set of search criteria to identify patients who underwent free flap reconstruction of the anterior skull base. Articles were reviewed for inclusion based on relevance, with the primary outcome being surgical complications. Results After a comprehensive search, 406 articles were obtained and 16 articles were ultimately found to be relevant to this review-79 patients undergoing free flap reconstruction were identified. Overall complication rates were 17.7% (95% confidence interval [CI]: 16.6-33.1%) for major complications and 19.0% (95% CI: 17.8-35.5%) for minor complications. Conclusion Microvascular reconstruction of the anterior skull base is feasible with high reliability reported in the literature.

Pedicle Corridors and Vessel Options for Free Flap Reconstruction following Endoscopic Endonasal Skull Base Surgery: A Systematic Review.

Introduction Microvascular free flaps offer an alternative to local and regional flaps for coverage of complex or large skull base defects. Routes and approaches to these reconstructive options are complicated and require an understanding of complex head and neck anatomy. Methods A systematic review of the literature was performed using a set of search terms with the help of a qualified librarian. Articles were reviewed and selected for inclusion based on relevance. We were interested in reporting possible routes for free flap accessibility to the skull base as well as microvascular vessel options, as this choice may affect the geometry and accessibility to the defect. Results A total of 1,917 articles were obtained from a comprehensive search and 11 articles were ultimately found to be relevant to this review. Published options for vessel anastomosis and corridors to the skull base following endoscopic endonasal surgery are reviewed, including Caldwell-Luc/transbuccal space, prevertebral space, transpterygoid/parapharyngeal, and transmaxillary approaches. Conclusion The field of endoscopic surgery has continued to advance and provide options for tumors of the skull base. This has led to a need for creative routes to the skull base for free flap reconstruction.

Endothelial growth factor receptor inhibitors in recurrent metastatic cancer of the head and neck.

Targeted therapy has become an important new class of therapeutic agents used in squamous cell carcinoma of the head and neck (SCCHN). Among them epidermal growth factor receptor (EGFR) inhibitors have been studied the most. Today, two classes of EGFR inhibitors are routinely used in the clinic; anti-EGFR monoclonal antibodies and small-molecule inhibitors of the EGFR tyrosine kinase activity. These agents have been used clinically in the recurrent metastatic (R/M) settings but only cetuximab has reached a regulatory approval. Current research is focused on innovative compound design, predictive biomarker discovery, and combination strategies in order to overcome resistance. Efforts should also be focused on endpoints other than overall survival, which is the current gold standard, such as surrogate endpoints. This article summarizes the clinical evidence of the anticancer activity of EGFR inhibitors in patients with R/M SCCHN, and analyzes the current, controversial clinical issues with respect to their interpretation. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2221-E2228, 2016.

Neoadjuvant Therapy in Differentiated Thyroid Cancer.

Objectives. Invasion of differentiated thyroid cancer (DTC) into surrounding structures can lead to morbid procedures such as laryngectomy and tracheal resection. In these patients, there is a potential role for neoadjuvant therapy. Methods. We identified three studies involving the treatment of DTC with neoadjuvant chemotherapy: two from Slovenia and one from Japan. Results. These studies demonstrate that in selected situations, neoadjuvant chemotherapy can have a good response and allow for a more complete surgical resection, the treatment of DTC. Additionally, the SELECT trial shows that the targeted therapy lenvatinib is effective in the treatment of DTC and could be useful as neoadjuvant therapy for this disease due to its short time to response. Pazopanib has also demonstrated promise in phase II data. Conclusions. Thus, chemotherapy in the neoadjuvant setting could possibly be useful for managing advanced DTC. Additionally, some of the new tyrosine kinase inhibitors (TKIs) hold promise for use in the neoadjuvant setting in DTC.

Clinical Outcomes in Patients with Recurrent or Metastatic Human Papilloma Virus-positive Head and Neck Cancer.

BACKGROUND: There are few data regarding the role of human papilloma virus (HPV) in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: A retrospective chart review was carried out using our electronic medical record (EPIC) for all patients diagnosed with HPV-positive R/M HNSCC between 2010 and 2014 with minimum of 6 months of follow-up in order to assess progression-free survival (PFS) and overall survival (OS). RESULTS: We assessed 11 patients who underwent a variety of treatments. PFS and OS were 7 and 34+ months, respectively. Four patients (36%) were still alive and disease-free (median OS of 39+ months). Three disease-free patients had been treated with taxane, platinum and 5-fluorouracil as aggressive curative systemic therapy. Another patient treated with TPF was disease-free for 25 months and died of disease at 42 months. CONCLUSION: Our study demonstrates favorable prognosis for patients with HPV-positive R/M HNSCC and that aggressive systemic treatment can lead to a prolonged disease-free period or possibly cure, even after metastasis.

Analysis of the techniques for thoracic- and lumbar-level localization during posterior spine surgery and the occurrence of wrong-level surgery: results from a national survey.

BACKGROUND CONTEXT: Despite the frequency with which surgeons perform posterior spinal surgery and the precautions against wrong-site surgery, operations on incorrect levels still occur. Wrong-level exposure is documented in 0.32% to 15% of cases. Additionally, there is little consensus as to what is the most accurate method for localizing the correct spinal level. PURPOSE: The purpose of this study is to investigate the most commonly used localization methods and their association with wrong-level surgery, to determine the prevalence of wrong-level localization, and to identify circumstances commonly associated with wrong-level surgery, and to offer recommendations that may reduce the incidence of these errors. STUDY DESIGN/SETTING: This was an online survey study that was distributed to North American Spine Society (NASS) members (including both orthopedic surgeons and neurosurgeons). The survey was sent as a Web link within an e-mail. PATIENT SAMPLE: A total of 2,338 surgeons received the survey, 532 opened the survey, and 173 completed it (7.4% response rate). The survey was only sent once, as recommended by NASS. Of those that responded, 72% (124 of 173) were orthopedic surgeons, 28% (49 of 173) were neurosurgeons, and 73% (126 of 173) were spine fellowship trained. OUTCOME MEASURES: We sought to investigate self-reported localization methods that are most commonly used (both anatomic landmarks and imaging techniques), the prevalence of wrong-level surgery, and any correlations between localization method and wrong-level surgery. METHODS: An eight-question anonymous survey was distributed to members of NASS, including orthopedic surgeons and neurosurgeons. There was no pilot testing or validation performed for this survey. The survey was sent as a Web link within an e-mail. Some questions asked surgeons to select as many responses as applicable, and others allowed surgeons to describe in detail any cases of wrong-level surgery. This study neither requires nor receives funding; additionally, no conflicts of interests were reported. RESULTS: Fluoroscopy was the most commonly used imaging technique for thoracic and lumbar surgeries (89% and 86%, respectively), followed by plain radiographs (54% and 58%, respectively). Surgeons were allowed to select as many responses as applicable, and 76 surgeons reported using both plain radiographs and fluoroscopy. The facet joint with corresponding pedicle was the most commonly used anatomic landmark for localization of thoracic and lumbar surgeries (67% and 59%, respectively), followed by the spinous process (49% and 52%, respectively). Sixty-eight percent of surgeons admitted to wrong-level localization, some of which were rectified intraoperatively, during their careers. Fifty-six percent of these surgeons reported using plain radiographs and 44% used fluoroscopy when the errors occurred. Common sources of preoperative errors included failure to visualize known reference points, recognize unconventional spinal anatomy, and adequately visualize the level because of large body habitus. Common sources of intraoperative errors included poor communication, failure to relocalize after exposure, and poor counting methods. CONCLUSIONS: Despite the variety of localization modalities, most surgeons use only a few. Whereas wrong-level localization is relatively rare, the ideal frequency is never. There is no standard approach that will entirely eliminate these mistakes; however, using a localization time out and increasing awareness of common sources of error may help decrease the incidence of wrong-level spine surgery.

The adaptor protein GULP promotes Jedi-1-mediated phagocytosis through a clathrin-dependent mechanism.

During the development of the peripheral nervous system, the large number of apoptotic neurons generated are phagocytosed by glial precursor cells. This clearance is mediated, in part, through the mammalian engulfment receptor Jedi-1. However, the mechanisms by which Jedi-1 mediates phagocytosis are poorly understood. Here we demonstrate that Jedi-1 associates with GULP, the mammalian homologue of CED-6, an adaptor protein required for phagocytosis mediated by the nematode engulfment receptor CED-1. Silencing GULP or mutating the NPXY motif in Jedi-1, which is required for GULP binding, prevents Jedi-1-mediated phagocytosis. How GULP promotes engulfment is not known. Of interest, we find that Jedi-1-induced phagocytosis requires GULP binding to clathrin heavy chain (CHC). During engulfment, CHC is tyrosine phosphorylated, which is required for Jedi-mediated engulfment. Both phosphoclathrin and actin accumulate around engulfed microspheres. Furthermore, knockdown of CHC in HeLa cells prevents Jedi-1-mediated engulfment of microspheres, and knockdown in glial precursors prevents the engulfment of apoptotic neurons. Taken together, these results reveal that Jedi-1 signals through recruitment of GULP, which promotes phagocytosis through a noncanonical phosphoclathrin-dependent mechanism.