Phase II, Single-Arm Trial of Induction and Concurrent Vismodegib With Curative-Intent Radiation Therapy for Locally Advanced, Unresectable Basal Cell Carcinoma.

PURPOSE: Locally advanced, unresectable basal cell carcinoma (LA BCC) can be treated with radiation therapy (RT), but locoregional control (LRC) rates are unsatisfactory. Vismodegib is a hedgehog pathway inhibitor (HPI) active in BCC that may radiosensitize BCC. We evaluated the combination of vismodegib and RT for patients with LA BCC. METHODS: In this multicenter, single-arm, phase II study, patients with unresectable LA BCC received 12 weeks of induction vismodegib, followed by 7 weeks of concurrent vismodegib and RT. The primary end point was LRC rate at 1 year after the end of treatment. Secondary end points included objective response, progression-free survival (PFS), overall survival (OS), safety, and patient-reported quality of life (PRQOL). RESULTS: Twenty-four patients received vismodegib; five were unable to complete 12 weeks of induction therapy. LRC was achieved in 91% (95% CI, 68 to 98) of patients at 1 year. The response rate was 63% (95% CI, 38 to 84) after induction vismodegib and 83% (95% CI, 59 to 96) after concurrent vismodegib and RT. With a median follow-up of 5.7 years, 1-year PFS and OS rates were 100% and 96%, and at 5 years PFS and OS rates were 78% and 83%, respectively. Distant metastasis or BCC-related death has not been observed. The most frequent treatment-related adverse events (AEs) were dysgeusia, fatigue, and myalgias occurring in 83%, 75%, and 75% of patients. No grade 4 to 5 treatment-related AEs occurred. PRQOL demonstrated clinically meaningful improvements in all subscales, with emotions and functioning improvements persisting for a year after the end of treatment. CONCLUSION: In patients with unresectable LA BCC, the combination of vismodegib and RT yielded high rates of LRC and PFS and durable improvements in PRQOL.

Assessment of Variability in Free Flap Color Match to Facial Skin by Donor Site and Race.

OBJECTIVES: To use portable colorimetry to quantify color differences between facial skin and potential three head and neck microvascular free tissue transfer (MFTT) donor sites-radial forearm (RF), anterolateral thigh (ALT), and fibula (FF)-and compare these differences by pigmentation of the donor site skin and self-identified race. METHODS: In this cross-sectional cohort study, healthy volunteers consented to handheld colorimeter measurements at the three potential MFTT donor sites (RF, ALT, FF) to quantify color match to the facial skin using the CIE color space (DeltaE). The comparison of ipsilateral to contralateral cheek served as control for measurements. Cross-sectional measurements in healthy volunteers were then compared to measurements obtained in postoperative head and neck MFTT patients. RESULTS: DeltaE measurements were obtained for 128 healthy controls and 24 postoperative patients (N = 152). With increasing lightness (decreased pigmentation) of the skin at the donor site, the color match significantly worsened (higher DeltaE) across all potential MFTT donor sites (all p < 0.05). DeltaE from healthy controls closely approximated postoperative color match measurements in patients who underwent cervicofacial MFTT (DeltaE RF: 5.3 vs. 6.0, p = 0.432; DeltaE ALT: 6.2 vs. 6.4, p = 0.822; DeltaE FF: 6.0 vs. 6.4, p = 0.806). CONCLUSION: Patients with decreased skin pigmentation who are undergoing head and neck MFTT may experience worse color discrepancy between cervicofacial skin and the transferred skin paddle than those with more pigmented skin. Portable colorimetry may identify patients who could benefit from interventions such as dermis-resected free tissue reconstruction with skin grafting to improve postoperative appearance. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Through a New Lens: Skin-Grafted Free Flaps and Objective Facial Skin Color Matching.

Background: Head and neck ablative surgery can impose aesthetic disfigurement, particularly when severe color mismatch exists between native and reconstructed facial skin. To date, the accuracy, objectivity, and modifiability of facial skin color matching remains poorly understood. Objective: To measure skin color match outcomes after head and neck reconstruction using handheld colorimetry. Methods: Patients undergoing complex head and neck reconstruction involving facial skin were included. A variety of skin paddle donor sites were studied, including split-thickness skin graft (STSG) placement over myocutaneous or adipofasciocutaneous free flaps after de-epithelization. Skin color match (deltaE) was measured during follow-up using a handheld colorimeter. Results: Forty-seven patients were included, with median age 69. The most common flap type was the anterolateral thigh (n = 31, 66%). Twenty patients underwent STSG to the skin paddle. DeltaE measurements among the patients with STSGs demonstrated better color match (lowest deltaE), compared with patients with unaltered skin paddles (3.4 ± 1.0 vs. 6.5 ± 2.5, p < 0.0001). Conclusion: We found the use of STSGs over de-epithelialized myogenous or adipofasciocutaneous flaps improves color match, as measured by handheld colorimetry.

The Impact of Venous Anastomosis Technique on Outcomes of Free Tissue Transfer to the Head and Neck.

Objectives: To evaluate the impact of different techniques of microvascular venous anastomosis on the outcome of free tissue transfer to the head and neck. Methods: Retrospective case series of patients undergoing microvascular free tissue transfer (MFTT) from January 2006 to September 2021. Chi-square tests and t-tests were utilized to identify differences in flap outcomes by technique, and log-binomial regression analyses were utilized to identify differences in flap outcomes by technique. Results: A total of 1055 consecutive MFTTs were analyzed. One hundred four cases required a return to the operating room for any reason, and 19 were attributed to venous compromise (18.0%). Ultimately, there were 22 FTT failures requiring complete revision (2.1%). In total, 1055 MFTTs involved 1352 venous anastomoses, ranging from 1 to 3 anastomoses in each case. End-to-end (ETE) was used 1040 times (76.9%) and end-to-side (ETS) 204 times (15.0%). The calculated risk ratio for venous complication for ETS compared with ETE was 1.17 (0.34-3.98). A microvascular coupler was used in 355 cases (33.6%). The calculated risk ratio for coupler compared with suture anastomoses was 0.92 (0.35-2.39). Conclusions: There were no significant difference in regard to outcomes of MFTT when comparing ETE with ETS, nor when comparing coupler with suture anastomoses.

Increasing Pedicle Reach with Musculocutaneous Perforator Dissection in Anterolateral Thigh Free Flaps.

OBJECTIVE: To measure the increase in effective pedicle reach with microdissection of musculocutaneous perforators during anterolateral thigh (ALT) free tissue harvest. METHODS: A review of our institution's free flap database was performed to identify ALT free tissue transfers. The distance from pedicle vessel origin to its perforator's insertion at the fascia lata (effective pedicle length [EPL]) was measured prior to and following intramuscular dissection of musculocutaneous perforators. Pertinent clinicopathologic variables were abstracted from the electronic medical record. RESULTS: A total of 314 ALT free flaps were performed between February 2017 and August 2022. Of these, 85 had documentation of EPL before and after musculocutaneous perforator dissection. ALT reconstruction was primarily performed for reconstruction of oncologic ablative defects (66, 78%). The mean EPL prior to perforator microdissection was 8.8 cm (standard deviation, SD 2.8 cm; range 3-15 cm). Following perforator dissection, mean EPL significantly increased to 14.0 cm (SD 3.0 cm; range 7-22 cm) with a mean net gain of 5.2 cm in distance (95% confidence interval 4.8-5.6 cm; p < 0.001). Nine patients (11%) required operating room take-back for anastomosis revision (3, 3.5%), recipient site hematoma evacuation (4, 4.7%), and wound dehiscence (2, 2.3%); one complete flap loss due to venous thrombosis was observed. CONCLUSION: Dissection of musculocutaneous perforators during ALT free flap harvest can increase effective pedicle reach by 5.2 cm or nearly 60%. This harvest technique can facilitate the performance of tension-free anastomoses when substantial vascular pedicle length or vascular pedicle tunneling is required. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:666-670, 2024.

Microvascular Free Flap Outcomes in Maxillectomy Defects from Invasive Fungal Sinusitis.

OBJECTIVES: Microvascular free tissue transfer is routinely used for reconstructing midface defects in patients with malignancy, however, studies regarding reconstructive outcomes in invasive fungal sinusitis (IFS) are lacking. We aim to describe outcomes of free flap reconstruction for IFS defects, determine the optimal time to perform reconstruction, and if anti-fungal medications or other risk factors of an immunocompromised patient population affect reconstructive outcomes. METHODS: Retrospective review of reconstruction for IFS (2010-2022). Age, BMI, hemoglobin A1c, number of surgical debridements, and interval from the last debridement to reconstruction were compared between patients with delayed wound healing versus those without. Predictor variables for delayed wound healing and the effect of time on free flap reconstruction were analyzed. RESULTS: Twenty-seven patients underwent free flap reconstruction for IFS. Three patients were immunocompromised from leukemia and 21 had diabetes mellitus (DM). Patients underwent an average of four surgical debridements for treatment of IFS. The interval from the last IFS debridement to flap reconstruction was 5.58 months (±5.5). Seven flaps (25.9%) had delayed wound healing. A shorter interval of less than 2 months between the last debridement for IFS and reconstructive free flap procedure was associated with delayed wound healing (Fisher Exact Test p = 0.0062). Other factors including DM, BMI, HgA1c, and bone reconstruction were not associated with delayed wound healing. CONCLUSION: Patients with maxillectomy defects from IFS can undergo microvascular-free flap reconstruction with good outcomes while on anti-fungal medication. Early reconstruction in the first 2 months after the last IFS debridement is associated with delayed wound healing. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1642-1647, 2024.

Assessing the Prevalence of Burnout Among Female Microvascular Head and Neck Surgeons.

Background: Research has not explicitly explored differences between male and female microvascular head and neck (MHN) surgeon burnout, which should be identified and addressed to ensure career satisfaction and longevity. Objective: To measure and compare the prevalence of burnout among male versus female MHN surgeons. Methods: A prospective questionnaire based on the Maslach Burnout Inventory (MBI) was distributed through a web-based survey to the American Association of Facial Plastic and Reconstructive Surgeons and American Head and Neck Society in 2021 and 2022. Additional variables collected included demographics, relationship and parental status, academic rank, annual salary, and COVID-19-related questions. Results: One hundred thirteen surveys were collected. Twenty-nine (25.7%) were women and all completed MHN surgery fellowships. Women trended toward more emotional exhaustion than men (2.8 mean MBI vs. 2.3 mean MBI) but reported similar personal achievement (4.8 mean MBI vs. 4.9 mean MBI). Men experienced less workplace sexual harassment (p < 0.001). Women experienced more burnout (69% vs. 39%, p = 0.006) during the COVID-19 pandemic. Conclusion: Female MHN surgeons reported in this survey to experience more workplace sexual harassment and higher COVID-19-related burnout than their male counterparts.

Outcomes Associated with Multiple Free Tissue Transfers Performed in a Single Day.

Background: Although microvascular free tissue transfer (MFTT) remains technically challenging, surgeons may need to perform >1 MFTT operations in a given day. Objective: To compare MFTT outcomes in cases where surgeons completed one versus two flaps per day by measuring flap viability and complication rates. Methods: A retrospective review was conducted of MFTT cases from January 2011 to February 2022 with >30-day follow-up. Outcomes, including flap survival and operating room takeback, were compared using multivariate logistic regression analysis. Results: Of 1096 patients meeting inclusion criteria (1105 flaps), there was a male predominance (n = 721, 66%). Mean age was 63.0 ± 14.4 years. Complications requiring takeback were identified in 108 flaps (9.8%) and were greatest for double flaps in the same patient (SP) (27.8%, p = 0.06). Flap failure occurred in 23 (2.1%) cases and was also greatest for double flaps in the SP (16.7%, p = 0.001). Takeback (p = 0.06) and failure (p = 0.70) rates were not different between days with one versus two unique patient flaps. Conclusions: Among patients undergoing MFTT, those treated on days in which surgeons perform two unique cases compared with single cases will demonstrate no difference in outcomes, as measured by flap survival and takeback, whereas patients with defects requiring multiple flaps will experience greater takeback and failure rates.

Patterns of Postoperative Trismus Following Mandibulectomy and Fibula Free Flap Reconstruction.

The factors that contribute to postoperative trismus after mandibulectomy and fibula free flap reconstruction (FFFR) are undefined. We retrospectively assessed postoperative trismus (defined as a maximum interincisal opening ≤35 mm) in 106 patients undergoing mandibulectomy with FFFR, employing logistic regression to identify risk factors associated with this sequela. The surgical indication was primary ablation in 64%, salvage for recurrence in 24%, and osteonecrosis in 12%. Forty-five percent of patients had existing preoperative trismus, and 58% of patients received adjuvant radiation/chemoradiation following surgery. The overall rates of postoperative trismus were 76% in the early postoperative period (≤3 months after surgery) and 67% in the late postoperative period (>6 months after surgery). Late postoperative trismus occurred more frequently in patients with ramus-involving vs. ramus-preserving posterior mandibulotomies (82% vs. 46%, p = 0.004). A ramus-involving mandibulotomy was the only variable significantly associated with trismus >6 months postoperatively on multivariable logistic regression (OR, 7.94; 95% CI, 1.85−33.97; p = 0.005). This work demonstrates that trismus is common after mandibulectomy and FFFR, and suggests that posterior mandibulotomies that involve or remove the ramus may predispose to a higher risk of persistent postoperative trismus.

Long-Term Appearance-Related Outcomes of Facial Reconstruction After Skin Cancer Resection.

Background: Aesthetic outcomes of facial reconstruction after skin cancer resection (RSCR) may affect long-term quality of life. Objective: To evaluate postoperative patient perceptions of skin cancer defect reconstruction using patient-reported outcome measures. Methods: Patients who underwent RSCR from 2016 to 2021 completed validated FACE-Q scales, including Satisfaction with Facial Appearance (SFA), Scar Appearance, and Appearance-Related Distress (ARD). Scores were scaled 0-100 and compared. Results: Sixty-one respondents completed the survey at a median of 3.0 (interquartile range: 1.6-4.1) years post-treatment. The majority had basal cell carcinomas (n = 41, 67%) and nasal defects (n = 40, 66%). Patients who received either revision surgery or office-based procedures to improve scarring reported lower satisfaction with scar appearance (65.8 ± 31.8 vs. 80.1 ± 20.8, p = 0.048). Dissatisfaction with scar appearance was correlated with decreased SFA (mean score: 76.6 ± 24.5; r = 0.44, p = 0.0004) and greater ARD (mean score: 23.8 ± 24.3; r = -0.66, p < 0.0001). Younger patients were also more likely to experience ARD (ß = -0.54, 95% confidence interval: [-0.96, -0.12, p = 0.014). SFA and ARD did not differ by operative factors, including reconstruction type, or single- versus multistage reconstruction. Conclusion: Although overall SFA after RSCR is high, regardless of reconstruction type, decreased satisfaction is correlated to poorer psychosocial function. Younger patients and those requiring revision procedures may be at greatest risk.

Outcomes of Vascularized Versus Nonvascularized Adipofascial Grafts for Parotidectomy Reconstruction.

Objectives: Parotidectomy defects can leave patients with considerable functional and cosmetic deformities. We aim to compare the success rates and complications associated with vascularized versus nonvascularized adipofascial grafts for reconstruction, including flap failure, return to surgery, infection, and delay to adjuvant treatment. Methods: Retrospective case series of patients undergoing either adipofascial anterolateral thigh (AFALT) free tissue transfer or free fat transfer (FFT) after parotidectomy from January 2010 to January 2020. Group comparisons and logistic regression were used to determine predictors of outcome measures. Results: Seventy-six patients underwent AFALT reconstruction, and 73 patients underwent FFT reconstruction. Patients treated with AFALT reconstruction had more aggressive tumor characteristics and underwent more complex resections, most commonly radical parotidectomy (n = 55, 72.4%). Postoperative complications at both the donor and recipient sites were more common in the FFT group (N = 20, 27.4% in FFT vs. N = 11, 14.5% in AFALT, odds ratio = 0.45, 95% confidence interval = 0.20-1.02, p = 0.052). Conclusions: Although used in more advanced disease and in a more heavily treated wound bed, the AFALT free flap was safe and associated with fewer infectious complications than that offered by FFT.

Restarting Therapeutic Antibiotics Following Postoperative Prophylaxis in Head and Neck Microvascular Free Tissue Transfer.

OBJECTIVE: To determine factors associated with restarting therapeutic antibiotics within 30 days of head and neck microvascular free tissue transfer (HN-MFTT). STUDY DESIGN: Retrospective study of consecutive HN-MFTTs performed from January 2015 to July 2020. SETTING: Tertiary academic medical center. METHODS: Thirty-day postoperative antibiotic use and post-HN-MFTT surgical and medical complications were assessed. Univariable analyses and multivariable logistic regression were used to evaluate risk factors associated with restarting antibiotics. RESULTS: overall 482 patients with 501 HN-MFTTs were stratified by duration of prophylaxis: ≤24 hours (n = 136, 27.1%), 25-72 hours (n = 54, 10.8%), and >72 hours (n = 311, 62.1%). Antibiotics were restarted in 199 patients (209 procedures, 42%). The most common indications for antibiotic reinitiation were flap recipient site infection (n = 59, 28%); hospital-acquired pneumonia (n = 44, 21%); and wound dehiscence, fluctuance, or change in quality of drain output (n = 44, 21%). Shorter antibiotic prophylaxis (≤24 hours) (odds ratio [OR], 1.95; 95% CI, 1.2-3.0; P = .003), osteocutaneous flaps (OR, 2.15; 95% CI, 1.3-3.4; P = .001), and prior immunotherapy/chemotherapy (OR, 2.29; 95% CI, 1.2-4.3; P = .01) were associated with reinitiation of antibiotics for surgical infections. Restarting antimicrobials for nosocomial infections was associated with aerodigestive defects (OR, 2.45; 95% CI, 1.1-5.2; P = .019), cardiovascular disease (OR, 3.00; 95% CI, 1.5-5.9; P = .001), and medical comorbidities approximated by American Society of Anesthesiologists class 3 or 4 (OR, 2.83; 95% CI, 1.5-5.4; P = .002). CONCLUSION: Aerodigestive reconstruction, 24-hour postoperative antimicrobial prophylaxis, American Society of Anesthesiologists class 3 and 4, prior chemotherapy/immunotherapy, cardiovascular disease, and osteocutaneous flaps are associated with reinitiation of antibiotics within 30 days of HN-MFTT.

Anterolateral Thigh Free Flap Versus Thigh Split Thickness Skin Graft: Comparison of Morbidity in the First 30 Days.

Background: An anterior thigh split thickness skin graft (AT-STSG) is frequently needed to close the radial forearm free flap (RFFF) donor site, conferring morbidity to two extremities. The anterolateral thigh (ALT) free flap is virtually always closed primarily. Objective: To compare donor site pain, sensation, motor function, and cosmesis associated with the AT-STSG and the ALT. Methods: Patients undergoing an ALT or an RFFF with AT-STSG were enrolled in a prospective observational cohort study. Pain, tingling, numbness, lower extremity function, and subjective donor site cosmetic satisfaction were measured at 1 week and 1 month postoperation using validated instruments. Results: Forty-eight patients were included, with a mean age of 64.2 years (female 31.2%). There were no differences in age or medical comorbidities between the two groups. The average donor defect was 50 and 180 cm2 for the AT-STSG and ALT cohorts, respectively. At 1 week and 1 month postoperatively, we did not detect a difference in donor site pain, pruritus, numbness or tingling, lower extremity function, or subjective cosmetic satisfaction between the two cohorts. Conclusion: ALT primary donor site morbidity, including pain, sensory function, motor function, and cosmesis, is equivalent to RFFF secondary donor site morbidity at 1 week and 1 month postoperatively.

Objective Outcomes of Trichophytic Brow Lift and Hairline Advancement in Facial Feminization Surgery.

Importance: The upper facial third is an important area to address in facial feminization surgery (FFS). Objective: This study seeks to quantify the changes in eyebrow, hairline, and forehead heights associated with brow lift and hairline advancement surgery in the transgender patient population. Design, Setting, and Participants: A cohort study performed at an academic medical center. Main Outcomes and Measures: Pre- and postoperative frontal view photographs underwent computer-aided photograph analysis. Brow position, hairline position, and forehead height were measured. Patient self-identified race, ethnicity, as well as other demographic factors were also collected. Results: Forty-six patients underwent FFS with brow lift and hairline advancement with photographs permitting measurement. Eyebrow analysis was performed in 33 patients. Hairline and forehead analyses were accomplished in 30 patients. The mean brow elevation was 4.6 mm across all locations. The forehead reduction achieved was 9.8-11.3 mm. Conclusion and Relevance: Trichophytic brow lifting with hairline advancement outcomes was able to be reliably quantified from standardized clinical photographs. On average, 4-5 mm of brow lift, 6-7 mm of hairline lowering, and 10-11 mm of forehead reduction were achieved, contributing to a more feminine appearance of the upper facial third.