Does Immediate Long-Span Nerve Allograft Reconstruction Affect the Incidence of Chronic Postsurgical and Neuropathic Pain in the Reconstructed Mandible Following Resection for Benign and Malignant Disease.

BACKGROUND: Peripheral nerve injury can lead to chronic postsurgical pain (CPSP) and neuropathic pain following major surgery. PURPOSE: Determine in patients undergoing ablative mandibular operations with transection of the trigeminal nerve: do those who undergo immediate repair, when compared to those whose nerves are not repaired, have a decreased or increased risk for CPSP or post-traumatic trigeminal neuropathic pain (PTTNp)? STUDY DESIGN, SETTING, SAMPLE: A multisite, retrospective cohort of patients who underwent resection of the mandible for benign or malignant disease with either no repair or immediate repair of the intentionally transected trigeminal nerve with a long-span nerve allograft were analyzed for the presence or absence of CPSP and PTTNp at 6 months. PREDICTOR VARIABLE: The primary predictor was the immediate repair or no repair of the trigeminal nerve. MAIN OUTCOME VARIABLE: The primary outcome was the presence or absence of CPSP and PTTNp at 6 months postsurgery. COVARIATES: There were 13 covariate variables, including age, sex, ethnicity, nerve injury, type of PTTNp, malignant or benign pathology and subtypes of each, use of radiation or chemotherapy, treatment of transected nerve end, longest follow-up time, pain scale, and onset of pain. ANALYSES: Two-tailed Student's t test and Welch's t test were performed on mean scores and post hoc logistics and linear regression modeling were performed when indicated. The confidence level for statistical significance was P value <.05. RESULTS: There were 103 and 94 subjects in the immediate and no-repair groups, respectively. The incidence of CPSP in the no-repair group was 22.3% and PTTNp was 2.12%, while there was 3.8% CPSP and 0% PTTNp in the repair group, which was statistically significant (P = <.001). Logistic regression modeling showed a statistically significant inverse relationship between the immediate repair and the incidence of CPSP/PTTNp with an odds ratio of 0.43, 95% confidence interval 0.18 to 1.01, P = .05. Greater age, malignant pathology, and chemo/radiation treatments were covariates found more frequently in the no repair group. CONCLUSION AND RELEVANCE: Immediate repair of an intentionally transected trigeminal nerve with a long-span nerve allograft during resection of the mandible for both benign and malignant disease appears to reduce CPSP and possibly eliminate the development of PTTNp.

Simultaneous maxillary and mandibular reconstruction with a single Osteocutaneous fibula free flap: A description of three cases.

Large defects that comprise both the maxilla and mandible prove to be difficult reconstructive endeavors and commonly require two free tissue transfers. Three cases are presented to discuss an option for simultaneous reconstruction of maxillary and mandibular defects using a single osteocutaneous fibula free flap. The first case describes a 16-year-old male with a history of extensive facial trauma sustained in a boat propeller accident resulting in a class IId maxillary and 5 cm mandibular defect status post three failed reconstructive surgeries; the second, a 33-year-old male with recurrent rhabdomyosarcoma of the muscles of mastication with resultant hemi-mandibulectomy and class IId maxillary defects; and lastly, a 48-year-old male presenting after a failed scapular free flap to reconstruct defects resulting from a self-inflicted gunshot wound, which included a 5 cm defect of the right mandibular body and 4.5 cm defect of the inferior maxillary bone. In all cases, a single osteocutaneous fibula free flap was used in two bone segments; one to obturate the maxillary defect and restore alveolar bone and the other to reconstruct the mandibular defect. The most recent patient was able to undergo implantable dental rehabilitation. Postoperatively, the free flaps were viable and masticatory function was restored in all patients during a follow-up range of 2-4 years.

Advances in Oromandibular Reconstruction with Three-Dimensional Printing.

The mandibular structures are a complex anatomical structure that is fundamental to many physiological and homeostatic functions. It may be involved in many pathological processes that require partial or complete removal. When this happens, reconstruction is mandatory to improve cosmetic outcome with its effect on social interaction as well as to provide an opportunity for complete dental rehabilitation with restoration of all physiological functions. This article will review the different reconstructive options available for complex defects of the mandibular complex. It will highlight the surgical options available to maximize functional restoration. Finally, it will discuss computer modeling to optimize reconstructive planning.

Digital imaging evaluation of the scapula for prediction of endosteal implant placement in reconstruction of oromandibular defects with scapular free flaps.

OBJECTIVE: Dental implant placement in scapular free flaps is challenging. This study examines the scapula with computed tomography to identify ideal locations for predictable implant placement during preoperative planning. METHODS: Sixty-eight adult patient chest CT scans (34 men, 34 women) captured for various medical indications, were analyzed for age, height, weight, and scapula length. The lateral border of the scapula was divided into six equal segments; the midpoints of each segment (labeled proximally to distally as 1M-6M) were analyzed in cross-section as potential recipient sites for 3.5 × 8 mm implants. Also, we present a case of a 77-year-old male with ameloblastoma of the mandible who underwent patient specific planning and received a scapular free flap with dental implant placement. RESULTS: There was greater bone availability in males with a mean depth of 8.3 ± 2.8 versus 5.1 ± 3.3 mm in females (p < .01). The proximal portion (1M) of the scapula in males and females had depths of 11.3 ± 1.5 and 9.5 ± 2.3 mm, respectively. Males had depths of 8.4 ± 3.0 in M3, 9.7 ± 1.7 in M4, and 8.9 ± 1.2 mm in M6. Depth of bone available for patients with heights ≥165 cm versus <165 cm had means of 10.4 ± 1.3 and 8.0 ± 1.6 mm (p < .01), respectively; but showed no significant differences between BMI (BMI <25 vs. ≥25) and bone availability (6.8 ± 1.7 vs. 6.8 ± 1.6, p = .07), or age (<55 years vs. ≥55 years) and bone availability (9.8 ± 1.6 vs. 9.8 ± 1.6, p = .11). In our case, the patient received 6 cm length of scapular bone with four 4.1 × 14 mm endosteal implants, which upon osseointegration was able to receive a fixed dental prosthesis. Three years after the initial surgery, the patient has had no difficulty with his prosthesis. CONCLUSION: In females the most proximal portion of the scapula will predictably accommodate a dental implant, while males have multiple sites including the proximal, middle, and distal portions.

A Case-and-Control, Multisite, Positive Controlled, Prospective Study of the Safety and Effectiveness of Immediate Inferior Alveolar Nerve Processed Nerve Allograft Reconstruction With Ablation of the Mandible for Benign Pathology.

PURPOSE: This study determined whether immediate reconstruction of the inferior alveolar nerve with a long (>4.5 cm) processed nerve allograft (PNA) in conjunction with simultaneous ablation and reconstruction of the mandible would be effective in safely restoring subjective sensation and achieving functional sensory recovery. MATERIALS AND METHODS: Patients (5 to 70 yr old) requiring resection of the unilateral or bilateral mandible for benign pathology were included. The graft had to be longer than 4.5 cm. Results of sensory nerve tests and 3 different surveys (Direct Path, Numerical Rating Scale, Word Choice) were collected before surgery and at 3, 6, and 12 months after surgery. Safety data were recorded. RESULTS: Twenty-six patients participated in this study. Three patients served as positive controls (no nerve repair). Five in the repair group and 1 in the positive control group were lost to follow-up. Data during a 1-year period were collected on 18 patients (7 male and 11 female; mean age, 26.4 yr; range, 10 to 64 yr). The mean length of the PNA was 62.7 mm (range, 45 to 70 mm). Seventeen of 18 patients had S4 sensory scores preoperatively and the postoperative score was S4 at 3 months in 3, at 6 months in 3, and at 1 year in 12. Scores for positive control patients never exceeded S2. Numerical rating scales and word choices were not statistically different from presurgical scores at 6 and 12 months. There were no adverse events. CONCLUSIONS: The PNA is safe and effective when immediately inserted with resection and reconstruction of the mandible: 90% of patients achieved functional sensory recovery and reported similar sensations to preoperative subjective values.

Morbidity and Functional Outcomes With Head and Neck Free Flap Reconstruction in Patients Aged 90 Years or Older.

PURPOSE: Morbidity of free tissue transfer in the extremes of age is controversial and not well studied in patients aged 90 years or older because of the rarity of these patients and many clinicians' natural hesitancy to perform such a large operation in patients of this group. The purpose of this study was to answer the following clinical question: Do patients aged 90 years or older who undergo free flap reconstruction have worse functional outcomes than their younger counterparts? MATERIALS AND METHODS: We performed a retrospective chart review of patients aged 90 years or older who underwent free flap reconstruction at Oregon Health and Science University Hospital from 2000 to 2015. All patients aged 90 years or older undergoing free flap reconstruction were included. Patients younger than 90 years during the same period were randomly selected to serve as controls. RESULTS: Free flap reconstructions were performed in 14 patients aged 90 years or older, who were then compared with their randomly selected controls. The only statistically significant difference observed in the outcome variables analyzed was the location of discharge from the hospital, with the older patients more likely to be discharged to a skilled nursing facility (P = .002). However, there was no difference in return-to-baseline level of care at last follow-up between the 2 groups. There also was no statistically significant difference in major or minor medical or surgical complication rates, duration of hospitalization, duration of tracheostomy, return to baseline respiratory status, or return to baseline feeding status between the 2 groups. CONCLUSIONS: Patients aged 90 years or older are more likely to be discharged to a skilled nursing facility than their younger counterparts, but otherwise have similar outcomes in terms of complications and return to baseline function. The results of this study suggest that age 90 years or older should not be a direct contraindication for free flap reconstruction in the head and neck.

Internal Mammary Vessels: Alternate Recipient Vessels in Microvascular Head and Neck Reconstruction.

The application of microvascular free tissue transfer for reconstruction of the head and neck is well established. Improved outcomes, as well as surgical and technologic advances, have broadened the applications of microvascular free flaps in these defects. Postoperative complications such as pharyngocutaneous fistulas, tracheal or esophageal stenoses, or recurrent pathology may occasionally require secondary or even tertiary reconstruction with free tissue transfers. The disrupted anatomy and fibrotic changes resulting from primary reconstruction, neck dissection, and irradiation present the surgeon with a high risk of provoking vascular or nervous injury when dissecting in previously operated or irradiated sites. This prompts a search for alternative recipient vessels for microvascular anastomosis. The transverse cervical, inferior thyroid, and thyrocervical trunk arteries have all been proposed as alternative recipient vessels. The internal mammary vessels (IMVs) have a proven record in breast reconstruction, but recently have been found to have an application in special circumstances in head and neck reconstruction. This investigation describes the advantages of the IMVs as suitable recipient vessels for head and neck reconstruction when access to traditional vasculature is unavailable.

Metastatic Melanotic Neuroectodermal Tumor of Infancy: Report of a Case and Review of the Literature.

Melanotic neuroectodermal tumors of infancy (MNTI) are rapidly growing pigmented tumors that occur predominantly within bony head and neck structures. There are fewer than 400 cases reported in the literature with the majority affecting the maxilla. Locations in other intraosseous and extraosseous structures have been characterized, including the mandible (6% of MNTIs). Infants in the first year of life are primarily affected. Surgical resection is the primary treatment modality with and without adjuvant chemotherapy for malignant tumors, which comprise less than 25 cases in the literature, and of metatstatic mandibular tumors, which has only been documented in one other case. The purpose of this investigation is to review associated literature and present a case highlighting treatment considerations of a metastatic mandibular MNTI. We present the case of a six month old boy with a rapidly growing bluish mass of the right mandible. Preoperatively incisional biopsy led to a diagnosis of MNTI and subsequent surgical planning involved hemimandibulectomy from the right mandibular condyle to the left posterior body region with one centimeter margins. At the time of initial surgery, enlarged lymph nodes removed from the neck demonstrated abnormality consistent with metastatic spread of the tumor. Islands of tumor cells were noted: small, round, bluestaining cells resembling neuroblasts with mitotic activity as well as pigmented cells containing melanin. Because of regional node metastasis, chemotherapy was completed following surgery. The patient recovered and was followed without evidence of recurrence. At 3.5 years postresection, a secondary reconstruction was completed using a fibula osteocutaneous free flap combined with a costochondral rib graft. In reviewing similar cases of malignant MNTI reported in the literature, a search of the MEDLINE database until 2014 was performed. These were evaluated based on management type and outcome, including surgical and chemotherapeutic treatments and the incidence of recurrence or metastasis.

Long-Term Plate Complications in Patient-Specific Plates Utilizing Computer-Aided Design.

OBJECTIVE: Assess the long-term plate complications with patient-specific plates (PSPs) created with computer-aided design (CAD) and computer-aided manufacturing (CAM) for fibula free flap reconstructions for mandibular defects. METHODS: Retrospective chart review from January 2010 to July 2022 of patients who underwent mandibular reconstruction with a fibula free flap and PSP. Primary outcome was plating-related complications, defined as plate exposure, fracture, loose screws, and plate removal. RESULTS: A total of 221 patients underwent PSP fibula reconstruction. Average age was 59.8 + 14.3 years old with male to female ratio of 2:1. Squamous cell carcinoma of the mandible was the most common reason for resection, 47.5%, n = 105. Plate removal occurred in 11% of patients (n = 25) about 17.4 months after the initial surgery. Plates were removed due to exposure (76%, n = 19) or screw loosening (24%, n = 6). Malignancy was associated with an increased risk of plate complications when compared to benign tumor (odds ratio [OR] 9.04, confidence interval [CI] 1.36-3.85), osteonecrosis (OR 1.38, CI 0.59-3.48), and trauma (OR 1.26, CI 0.23-12.8). Postoperative radiation therapy (OR 2.27, CI 1.07-4.82, p = 0.026) and surgical site infection (OR 9.22, CI 4.11-21.88, p = 0.001) were associated with more plate complications. CONCLUSIONS: CAD creates PSPs that remain stable in the majority of patients over the long term. Plate removal is less compared to non-PSP reconstruction. Consideration of the soft tissue envelope over the plate and management of perioperative infection at the time of surgery should be entertained. LEVEL OF EVIDENCE: Level 4 Laryngoscope, 2024.

Free flap reconstruction following head and neck trauma.

BACKGROUND: Free flap (FF) reconstruction of traumatic injuries to the head and neck is uncommon. METHODS: Multi-institutional retrospective case series of patients undergoing FF reconstruction for a traumatic injury (n = 103). RESULTS: Majority were gunshot wounds (GSW; 85%, n = 88) and motor vehicle accidents (11%, n = 11). Majority underwent osseous reconstruction (82%, n = 84). FF failures (9%, n = 9/103) occurred in GSW patients (100%, n = 9/9) and when multiple subsites were injured (89%, n = 8/9). Preoperative antibiotics correlated with lower rates of a neck washouts (4% vs. 19%) (p = 0.01) and 30-day readmissions (4% vs. 17%) (p = 0.02). CONCLUSIONS: All FF failures occurred in the setting of a GSW and the majority involved multiple subsites. Preoperative antibiotics correlated with lower rates of postoperative washout procedures and 30-day readmission.

Management of the Failing Flap.

Free tissue transfer has become the reconstructive modality of choice for replacing composite tissue defects. While the success rate in high-volume centers is reported to be greater than 95%, up to 10% of patients will require revision of their vascular anastomosis secondary to thrombosis or compromise to flow. In the intraoperative setting, immediate revision is successful in the majority of cases. Rarely, the flap cannot be revascularized and a secondary option must be used. In the perioperative setting revision is successful if the patient can be brought back to the operating room in a timely fashion. Revision rates up to 70% are reported. A small number of these patients may then suffer a second episode of compromise where revision is less successful at 30%. In these cases, consideration should be given to secondary reconstruction rather than attempting salvage. Finally, there are a small number of patients whose flaps will fail following discharge from the hospital. These patients can rarely be salvaged and secondary reconstructive options should be explored.

Outcomes of Cranioplasty Reconstructions: Review of Cranioplasty Implants and Free Flap Coverage Variables that Affect Implant Exposure.

BACKGROUND: Complex scalp wounds with cranial/dural involvement are challenging to reconstruct. Successful reconstruction can be achieved with cranial implants/hardware and free flap coverage. Wounds can breakdown and require revision procedures. We addressed reconstructive outcomes of different implants requiring free flaps. OBJECTIVE: To determine the factors associated with implant exposure. DESIGN: Multi-institutional retrospective review of 82 patients, 2000-2020, repaired with cranial implants and free flap coverage. RESULTS: Implant exposure occurred in 13/82 (16%) reconstructions. Flap atrophy or thinning leading to implant exposure occurred in 11/82 (13%) reconstructions, including partial flap atrophy OR 0.05 (95% CI 0.0-0.35) and total flap atrophy OR 0.34 (95% CI 0.02-19.66). Revision surgeries that occurred subsequent to flap reconstruction were also associated with implant exposure (OR 0.02 (95% CI 0.0-0.19)). Implant exposure was not associated with radiation therapy, patient health history, implant type, flap type, or postoperative complications. CONCLUSIONS: Implant exposure is associated with free flap atrophy, leading to inadequate implant coverage and the need for revision surgeries. Completing reconstruction with adequate soft tissue bulk and coverage and avoiding revision surgery may decrease the risk for implant exposure over time. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2954-2958, 2023.

Clinical outcomes following intraoperative pedicle disruption in fibula free flaps.

OBJECTIVES: Iatrogenic injury of the fibula free flap pedicle is rare. Postoperative flap survival and reconstructive outcomes following intraoperative pedicle severance are unknown. This study assesses free flap outcomes following accidental severance of the peroneal vessels. METHODS: Multi-institutional retrospective chart review from 2000 to 2020. RESULTS: Of 2975 harvested fibula free flaps, 26 had a history of pedicle severance during surgical reconstruction. Reasons for intraoperative pedicle severance included transection during muscular dissection 10/26 (39%), accidental severance with the bone saw 12/26 (46%), and other 4/26 (15.6%). The surgeon responsible for pedicle severance included residents 5/26 (19%), fellows 10/26 (39%), attendings 10/26 (39%), and unknown 1/26 (3.9%). The pedicle artery and vein were severed 10/26 (39%), artery 8/26 (31%), and vein 8/26 (31%). Truncated pedicle vessels were used 3/26 (11.7%), intraoperative anastomoses were performed 23/26 (89%). Postoperative revision in the OR within 7 days of surgery was required 6/26 (23%); 4 flaps were salvaged and 2 flaps failed, both arterial thrombosis. Flap failure was attributed to vascular thrombosis. Long-term flap survival and successful reconstructions were reported 24/26 (92%). CONCLUSION: Accidental severance of fibula free flap pedicle vessels can be corrected with intraoperative repair, without affecting long-term flap survival or reconstructive outcomes. Protecting the flap vessels while using the bone saw and during intramuscular dissection prevents accidental severance.

Factors Impacting Discharge Destination Following Head and Neck Microvascular Reconstruction.

OBJECTIVE: Determine which variables impact postoperative discharge destination following head and neck microvascular free flap reconstruction. STUDY DESIGN: Retrospective review of prospectively collected databases. METHODS: Consecutive patients undergoing head and neck microvascular free flap reconstruction between January 2010 and December 2019 (n = 1972) were included. Preoperative, operative and postoperative variables were correlated with discharge destination (home, skilled nursing facility [SNF], rehabilitation facility, death). RESULTS: The mean age of patients discharged home was lower (60 SD ± 13, n = 1450) compared to those discharged to an SNF (68 SD ± 14, n = 168) or a rehabilitation facility (71 SD ± 14, n = 200; p < 0.0001). Operative duration greater than 10 h correlated with a higher percentage of patients being discharged to a rehabilitation or SNF (25% vs. 15%; p < 0.001). Patients were less likely to be discharged home if they had a known history of cardiac disease (71% vs. 82%; p < 0.0001). Patients were less likely to be discharged home if they experienced alcohol withdrawal (67% vs. 80%; p = 0.006), thromboembolism (59% vs. 80%; p = 0.001), a pulmonary complication (46% vs. 81%; p < 0.0001), a cardiac complication (46% vs. 80%; p < 0.0001), or a cerebral vascular event (25% vs. 80%; p < 0.0001). There was no correlation between discharge destination and occurrence of postoperative wound infection, salivary fistula, partial tissue necrosis or free flap failure. Thirty-day readmission rates were similar when stratified by discharge destination. CONCLUSION: There was no correlation with the anatomic site, free flap donor selection, or free flap survival and discharge destination. Patient age, operative duration and occurrence of a medical complication postoperatively did correlate with discharge destination. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:95-104, 2023.

Post-operative Outcomes in Pediatric Patients Following Facial Reconstruction With Fibula Free Flaps.

EDUCATIONAL OBJECTIVE: Assess outcomes of pediatric facial reconstruction with fibula free flaps. OBJECTIVES: Free flap reconstruction of complex maxillofacial defects in pediatric patients is rare. Post-operative complications, donor site morbidity, impact on craniofacial growth, and oro-dental rehabilitation are unknown. Our study assesses the outcomes of pediatric maxillofacial reconstruction with composite fibula free flaps. STUDY DESIGN: Retrospective chart review. METHODS: Multi-institutional retrospective chart review from 2000 to 2020 on pediatric patients undergoing maxillomandibular reconstruction with fibula free flaps. RESULTS: Eighty-seven patients underwent 89 surgeries; 5 maxillary and 84 mandibular defects. Median age: 12 years. Defects were acquired following resection of sarcoma/carcinoma 44% or benign tumors 50%. 73% of cases had immediate free flap reconstruction. Closing osteotomies were reported in 74%; 1 in 40%, 2 in 27%, and more than 2 in 6.7%. Hardware was used in 98% and removed in 25%. 9.2% demonstrated long-term hardware exposure, greater than 3 months following reconstruction. Short-term complications: wound infection 6.7%, flap salvage/failure 2.2%, fistula 1.1%, and compromised craniofacial growth: 23%. Two patients developed trismus. Long-term fibula donor site complications: hypertrophic scarring: 3.4%, dysesthesia: 1.1%, and long-term gait abnormality: 1.1%. Dental rehabilitation was performed in 33%. Post-operative speech outcomes showed 94% with fully intelligible speech. CONCLUSION: Pediatric maxillary and mandible defects repaired with fibula free flaps demonstrated complication rates comparable to the adult free flap population. Long-term follow-up did not demonstrate adverse outcomes for craniofacial growth. Hardware for flap retention was utilized and remained in place with minimal exposure. Post-operative gait abnormality is rare. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:302-306, 2023.

Association of Head and Neck Anatomic Zones with Microvascular Reconstruction Outcomes.

Background: Head and neck free flap survival relies on adequate tissue perfusion from the external carotid artery (ECA), and vessel length is inversely proportional to blood flow rate. Objective: Investigate whether distance from the ECA (as a proxy for pedicle vessel length) predicts flap survival or complications. Methods: Retrospective review of free flaps performed at three academic centers from 9/2006 to 8/2021. Flaps were categorized by distance from the ECA: orbit and above (zone 1), maxilla to parotid (zone 2), and mandible and below (zone 3). Secondary analysis assessed flap outcomes stratified by average historical pedicle length. Results: A total of 2,369 flaps were identified in zones 1 (n = 109), 2 (n = 1878), and 3 (n = 382). Rates of flap failure (4.9%) and perioperative complications (36.3%) did not differ by zone or pedicle length. Zone 3 flaps, most commonly located in the larynx and hypopharynx, had significantly higher rates of fistula and infection. Conversely, 30-day readmission rates were significantly lower in patients with zone 2 flaps (p < 0.001). Rates of all other complications did not differ significantly between zones. Conclusions: Proximity to mucosal anatomic sites was a more powerful predictor of free flap viability than pedicle length or ECA proximity.

Osteocutaneous Radial Forearm Free Flap Fixed to a Prior Osteocutaneous Free Flap: Two Case Reports.

Reconstruction of mandibular defects is best accomplished by composite bony tissue. When the fibula is not available other sources must be used. Occasionaly tumor recurence will neccesitate a further resection and bony reconstruction. We report two cases in which osteocutaneous radial forearm free tissue transfer was used for secondary reconstructio after prior bony free flap reconstruction. Laryngoscope, 132:2177-2179, 2022.

Functional proteomics of patient derived head and neck squamous cell carcinoma cells reveal novel applications of trametinib.

In this study, we report a differential response of mitogen-activated protein kinase-kinase (MEK) inhibitor trametinib in 20 head and neck squamous cell carcinoma (HNSCC) patients' tumor-derived cell cultures. Relatively sensitive and resistant cases to trametinib were identified using high throughput metabolic assays and validated in extended dose response studies in vitro. High throughput metabolic assays exploring combination therapies with trametinib were subjected to synergy models and maximal synergistic dose analyses. These yielded several candidates, including axtinib, GDC-0032, GSK-690693, and SGX-523. The combination regimen of trametinib and AXL/MET/VEGFR inhibitor glesatinib showed initial efficacy both in vitro and in vivo (92% reduction in tumor volume). Sensitivity was validated in vivo in a patient-derived xenograft (PDX) model in which trametinib as a single agent effected reduction in tumor volume up to 72%. Reverse Phase Protein Arrays (RPPA) demonstrated differentially expressed proteins and phosphoproteins upon trametinib treatment. Furthermore, resistant cell lines showed a compensatory mechanism via increases in MAPK and non-MAPK pathway proteins that may represent targets for future combination regimens. Intrinsic-targeted options have potential to address paucity of medical treatment options for HNSCC cancer patients, enhance response to extrinsic targeted agents, and/or reduce morbidity as neoadjuvant to surgical treatments.

Age and Comorbidities Impact Medical Complications and Mortality Following Free Flap Reconstruction.

OBJECTIVE: Determine if age correlated with surgical or medical complications following head and neck free flap reconstruction. STUDY DESIGN: Retrospective review of prospectively collected databases. METHODS: Patients undergoing head and neck free flap reconstruction at three tertiary care institutions were included (n = 1972). Cohorts were based on age (<65, 65-75, 75-85, and >85). Outcomes reviewed operative duration, length of stay, surgical complications (free flap failure, fistula, hematoma, dehiscence, and infection), and medical complications (thromboembolism, stroke, cardiac, and pulmonary). RESULTS: Anatomic site (P < .0001) and donor site varied by age (P < .0001). There was no difference in operative duration (P = .3) or length of hospitalization (P = .8) by age. The incidence of medical complications increased with increasing age. Pulmonary complication rates: <65 (3.9%), 65 to 75 (4.8%), 75 to 85 (7.1%), and >85 (11%) (P = .02). Cardiac complication rates: <65 (2.0%), 65 to 75 (7.3%), 75 to 85 (6.1%), and >85 (16.4%) (P < .0001). Mortality increased with age: <65 (0.4%), 65 to 75 (0.8%), 75 to 85 (1.1%), and >85 (4.1%) (P < .003). Medical complications correlated with mortality rates: pulmonary (3.5% vs. 0.6%; OR: 5.5; 95% CI: 1.5-20.0; P = .004); cardiac (3.3% vs. 0.6%; OR: 6.0; 95% CI: 1.6-21.8; P = .002); thromboembolism (4.6% vs. 0.7%; OR: 7.3; 95% CI: 1.6-33.6; P = .003); stroke (42% vs. 0.5%; OR: 149; 95% CI: 40-558; P < .0001); and sepsis (5% vs. 0.7%; OR 7.5; 95% CI: 1.0-60.5; P = .03). Age did not correlate with free flap success (P = .5), surgical complications (hematoma, P = .33; fistula, P = .23; infection, P = .07; and dehiscence, P = .37), or thirty-day readmission (P = .3). CONCLUSION: Following free flap reconstruction, patient age did not correlate with development of a surgical complication. Patient age did correlate with development of a medical complication. Postoperative medical complications were found to correlate with perioperative mortality. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:772-780, 2022.

Impact of preoperative and intraoperative management on outcomes in osteoradionecrosis requiring free flap reconstruction.

BACKGROUND: Perioperative management of advanced osteoradionecrosis of the head and neck requiring free flap (FF) reconstruction varies. Our objectives included assessment of practice patterns and outcomes. METHODS: Multi-institutional, retrospective review of FF reconstruction for head and neck osteoradionecrosis (n = 260). RESULTS: Administration of preoperative antibiotics did not correlate with reduction in postoperative complications. Preoperative alcohol use correlated with higher rates of hardware exposure (p = 0.03) and 30-day readmission (p = 0.04). Patients with FF compromise had higher TSH (p = 0.04) and lower albumin levels (p = 0.005). Prealbumin levels were lower in patients who required neck washouts (p = 0.02) or a second FF (p = 0.03). TSH levels were higher in patients undergoing postoperative debridement (p = 0.03) or local flap procedures (p = 0.04). CONCLUSION: Malnutrition, hypothyroidism, and substance abuse correlated with a higher incidence of postoperative wound complications in patients undergoing FF reconstruction for advanced osteoradionecrosis. Preoperative antibiotics use did not correlate with a reduction in postoperative wound complications.