Effect of Perioperative Antithrombotics on Postoperative Transfusion and Hematoma in Head and Neck Free Flaps.

Objective: To explore if antiplatelet or anticoagulant therapy increases the risk of transfusion requirement or postoperative hematoma formation in patients undergoing microvascular reconstruction for head and neck defects. Study Design: Retrospective cohort study. Setting: Departments of Otolaryngology-Head and Neck Surgery at the University of Alabama at Birmingham, the University of Colorado, and the University of California Irvine. Methods: A multi-institutional, retrospective review on microvascular reconstruction of the head and neck between August 2013 to July 2021. Perioperative antithrombotic data were collected to examine predictors of postoperative transfusion and hematoma. Results: A total of 843 free flaps were performed. Preoperative hemoglobin, hematocrit, operative time, and flap type were positive predictors of postoperative transfusion in both bivariate (P < .0001) and multivariate analyses (P < .0001). However, neither anticoagulation nor antiplatelet therapy were predictive of postoperative transfusion rates and hematoma formation. Conclusion: Antithrombotic regimens do not increase the risk of postoperative transfusion or hematoma in head and neck microvascular reconstruction. Based on this limited data, perioperative antithrombotic regimens can be considered in patients who may otherwise be at risk for these postoperative complications.

Effect of Perioperative Antithrombotics on Head and Neck Microvascular Free Flap Survival After Anastomotic Revision.

OBJECTIVE: To determine if antithrombotic therapy improves head and neck microvascular free flap survival following anastomotic revision. STUDY DESIGN: A retrospective review of all patients with microvascular free tissue transfer to the head and neck between August 2013 and July 2021. SETTING: Otolaryngology-Head and Neck Surgery Departments at University of Alabama at Birmingham, University of Colorado, and University of California Irvine. METHODS: Perioperative use of anticoagulation, antiplatelets, intraoperative heparin bolus, tissue plasminogen activator (tPA) and vasopressor use, and leech therapy were collected plus microvascular free flap outcomes. The primary endpoint was free flap failure. Analyses of free flaps that underwent anastomotic revision with or without thrombectomy were performed. RESULTS: A total of 843 microvascular free flaps were included. The overall rate of flap failure was 4.0% (n = 34). The overall rate of pedicle anastomosis revision (artery, vein, or both) was 5.0% (n = 42) with a failure rate of 47.6% (n = 20) after revision. Anastomotic revision significantly increased the risk of flap failure (odds ratio [OR] 52.68, 95% confidence interval [CI] [23.90, 121.1], p < .0001) especially when both the artery and vein were revised (OR 9.425, 95% CI [2.117, 52.33], p = .005). Free flap failure after the anastomotic revision was not affected by postoperative antiplatelet therapy, postoperative prophylactic anticoagulation, intraoperative heparin bolus, tPA, and therapeutic anticoagulation regardless of which vessels were revised and if a thrombus was identified. CONCLUSION: In cases of microvascular free tissue transfer pedicle anastomotic revision, the use of antithrombotic therapy does not appear to significantly change free flap survival outcomes.

Genome Sequence of Acetobacter tropicalis DmPark25_167, a Bacterium Isolated from a Drosophila melanogaster Genetic Model of Parkinson's Disease.

Here, we report the genome of Acetobacter tropicalis DmPark25_167, a bacterial strain isolated from a Drosophila melanogaster park25 mutant. The park25 mutant is an established genetic model of Parkinson's disease. DmPark25_167 has duplicated methionine metabolism and type IV secretion gene alleles compared with another strain of A. tropicalis.

Comparative effectiveness of posttreatment imaging modalities for Medicare patients with advanced head and neck cancer.

BACKGROUND: Persistent controversy exists with regard to how and when patients with head and neck cancer should undergo imaging after definitive therapy. The current study was conducted to evaluate whether the type of imaging modality used in posttreatment imaging impacts cancer-specific survival for patients with advanced head and neck squamous cell carcinoma. METHODS: A retrospective study of National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program-Medicare-linked data in patients with an advanced stage of the 3 most common head and neck malignancies (oral cavity, oropharynx, and larynx) was conducted. Hazard ratios and 95% CIs for cancer-specific survival were estimated for patients diagnosed with any of these cancers between 2006 and 2015. RESULTS: Significant improvement with regard to cancer-specific survival was observed among patients with American Joint Committee on Cancer stage III and stage IVA laryngeal cancer who underwent positron emission tomography (PET) and/or computed tomography (CT) imaging during the first 6 months after receipt of definitive treatment (hazard ratio, 0.517; 95% CI, 0.33-0.811) compared with those who underwent CT. There was a trend toward an improvement in cancer-specific survival among patients with oral cavity or oropharyngeal malignancies who underwent PET/CT imaging, but it did not reach statistical significance. CONCLUSIONS: Compared with CT imaging, posttreatment imaging with PET was associated with improved survival in patients with advanced laryngeal carcinoma.

Elderly Black Non-Hispanic Patients With Head and Neck Squamous Cell Cancer Have the Worst Survival Outcomes.

BACKGROUND: In this population study, we compared head and neck cancer (HNC) prognosis and risk factors in 2 underserved minority groups (Hispanic and Black non-Hispanic patients) with those in other racial/ethnicity groups. METHODS: In this SEER-Medicare database study in patients with HNC diagnosed in 2006 through 2015, we evaluated cancer-specific survival (CSS) between different racial/ethnic cohorts as the main outcome. Patient demographics, tumor factors, socioeconomic status, and treatments were analyzed in relation to the primary outcomes between racial/ethnic groups. RESULTS: Black non-Hispanic patients had significantly worse CSS than all other racial/ethnic groups, including Hispanic patients, in unadjusted univariate analysis (Black non-Hispanic patients: hazard ratio, 1.48; 95% CI, 1.33-1.65; Hispanic patients: hazard ratio, 1.12; 95% CI, 0.99-1.28). To investigate the association of several variables with CSS, data were stratified for multivariate analysis using forward Cox regression. This identified socioeconomic status, cancer stage, and receipt of treatment as predictive factors for the survival differences. Black non-Hispanic patients were most likely to present at a later stage (odds ratio, 1.62; 95% CI, 1.38-1.90) and to receive less treatment (odds ratio, 0.67; 95% CI, 0.55-0.81). Unmarried status, high poverty areas, increased emergency department visits, and receipt of healthcare at non-NCI/nonteaching hospitals also significantly impacted stage and treatment. CONCLUSIONS: Black non-Hispanic patients have a worse HNC prognosis than patients in all other racial/ethnic groups, including Hispanic patients. Modifiable risk factors include access to nonemergent care and prevention measures, such as tobacco cessation; presence of social support; communication barriers; and access to tertiary centers for appropriate treatment of their cancers.

Free Flap Versus Pedicled Flap Reconstruction of Laryngopharyngeal Defects: A 10-Year National Surgical Quality Improvement Program Analysis.

OBJECTIVES/HYPOTHESIS: Large defects after total laryngectomy (TL) and total laryngopharyngectomy (TLP) often benefit from free flap (FF) or pedicled flap (PF) reconstruction to maintain continuity of the aerodigestive tract, protect great vessels, or reinforce pharyngeal closure. Although both techniques are commonly used, no consensus exists as to which results in fewer complications. The goal of this study was to determine if 30-day morbidity/mortality outcomes differ between PF and FF reconstruction in patients undergoing TL/TLP. STUDY DESIGN: Retrospective cohort study. METHODS: Patients were analyzed who underwent TL/TLP with reconstruction using records from the American College of Surgeons National Surgical Quality Improvement Program database (2005-2015). RESULTS: A total of 347 patients were included; 204 received FF reconstruction, whereas 143 received PF reconstruction. FF reconstruction was more commonly used with TLP defects (P = .001). The total operative time in the FF (590 ± 140 minutes) was longer than the PF (441 ± 125 minutes) group (P < .0001). There was a higher rate of postoperative transfusions in those undergoing FF reconstruction (P = .022). There was no significant difference in complication rates among TLP patients. Among TL patients only, FF reconstruction had a higher association with wound infections than PFs (P = .040). On multivariate analysis, low hematocrit was associated with complications (P = .031). Age (P = .031) and congestive heart failure exacerbation (P < .001) were associated with increased hospital stay. Overall, there were no differences in readmissions, reoperations, or deaths between the groups. CONCLUSIONS: Reported complication rates after TL/TLP remain high, despite widespread usage of vascularized flaps in reconstruction. This comparison reveals no significant difference in postoperative complications between patients who received PF and FF laryngopharyngeal reconstruction. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:105-112, 2019.

Current practice trends in microvascular free flap reconstruction by fellowship-trained otolaryngologists.

PURPOSE: In the field of head and neck microvascular surgery, there are currently no clear, universally accepted recommendations on the intraoperative, preoperative, and postoperative management of these patients. MATERIALS AND METHODS: A 23-question cross-sectional survey was distributed to otolaryngologists who perform microvascular reconstruction. Information about practice setting, fellowship training background, intraoperative practice, postoperative practice, and surgical complications were analyzed. RESULTS: Complete survey responses were received from 102 (32.8% response rate) of surveyed otolaryngologists who perform microvascular surgery. A great degree of variability was noted in intraoperative and postoperative care of free flap patients. Overall, self-reported free flap survival-rates were relatively high, despite the variability in practice, with the majority of surgeons (74%) reporting flap survival rate of 96-100%. Complication rates requiring return to the operating room were low; all respondents reported <20% overall complications with <10% re-operation rates due to vascular complications. CONCLUSION: An increasing number of microvascular-trained otolaryngologists are performing free flaps. Self-reported free flap survival rates are high and complication rates are low, despite significant variability in intraoperative and postoperative practices among otolaryngologists performing microvascular flap reconstruction. By identifying these differences among surgeons, we hope to provide the impetus for further academic dialog and prospective trials.

Antibiotic prophylaxis in clean-contaminated head and neck cases with microvascular free flap reconstruction: A systematic review and meta-analysis.

BACKGROUND: Optimal antibiotic prophylaxis duration in head and neck clean-contaminated free-flap cases is unknown. METHODS: A systematic review/meta-analysis was conducted using PubMed/MEDLINE, Cochrane Library, Web-of-Science, and Scopus databases. RESULTS: Of the 3755 searched articles, 5 articles were included for a total of 861 patients. The recipient surgical site infection risk was significantly higher in patients receiving prophylactic antibiotics for ≤24 hours compared to >24 hours (relative risk [RR] 1.56; 95% confidence interval [CI] 1.13-2.14). In the post hoc multivariate analysis based on available individual-level data on 697 patients from 3 studies, the risk of surgical site infection for ≤24 hours versus >24 hours was not significant after adjusting for antibiotic type (RR 1.09; 95% CI 0.78-1.55). When compared to ampicillin-sulbactam, patients who received clindamycin prophylaxis had an increased likelihood of recipient surgical site infection (RR 2.85; 95% CI 1.95-4.17). CONCLUSION: Less than or equal to 24 hours of antibiotic prophylaxis in head and neck clean-contaminated free-flap is likely sufficient but a strong conclusion remains elusive. Clindamycin prophylaxis increases the risk of recipient surgical site infection. Further prospective trials are necessary to clarify.

A comprehensive comparative analysis of treatment modalities for sinonasal malignancies.

BACKGROUND: Sinonasal malignancies are a rare and heterogeneous group of tumors for which there is a paucity of robust data with which to guide management decisions. The authors used the National Cancer Data Base to better understand the presenting characteristics of these tumors and to compare outcomes by treatment modality. METHODS: The National Cancer Data Base was queried for sinonasal malignancies diagnosed between 2004 and 2012. Overall survival was assessed using multivariate analyses and propensity score matching. RESULTS: A total of 11,160 patients were identified for the initial analysis. The majority were male, aged 40 to 69 years, with tumors of the nasal cavity or maxillary sinus. Squamous cell histology was most common. The majority of patients presented with advanced tumor stage but without locoregional lymph node or distant metastases. Treatment modalities were compared for squamous cell carcinomas. In multivariate analysis, compared with surgery alone, patients who received adjuvant radiotherapy (hazard ratio [HR], 0.658 [P<.001]), adjuvant chemoradiotherapy (HR, 0.696 [P = .002]), or neoadjuvant therapy (HR, 0.656 [P = .007]) had improved overall survival. Patients who received radiotherapy alone (HR, 1.294 [P = .001]) or chemotherapy alone (HR, 1.834 [P<.001]) had worse outcomes. These findings were validated in propensity score matching. It is important to note that neoadjuvant chemoradiotherapy was associated with achieving a negative surgical margin (odds ratio, 2.641 [P = .045]). CONCLUSIONS: Surgery is the mainstay of therapy for patients with sinonasal malignancies, but multimodality therapy is associated with improved overall survival. Cancer 2017;123:3040-49. © 2017 American Cancer Society.

Survival impact of induction chemotherapy in advanced head and neck cancer: A National Cancer Database analysis.

BACKGROUND: Adding induction chemotherapy to concurrent chemotherapy and radiotherapy (RT) has generally not improved the overall survival (OS) in randomized trials of patients with head and neck cancer. This failure may stem from inadequate power or inappropriate patient selection, prompting this National Cancer Data Base analysis. METHODS: 8031 patients with T4 or N2b to N3 disease undergoing RT and chemotherapy were divided into induction chemotherapy and concurrent chemotherapy cohorts. Multivariate analysis was used to explore the association of treatment with survival and to identify predictors of radiation dose. RESULTS: On multivariate analysis incorporating sociodemographic and clinical variables, survival of the induction chemotherapy cohort was not significantly different from that of the concurrent cohort (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.88-1.05; p = .35), nor on subgroup analyses of advanced disease. Multivariate analysis demonstrated increased odds of receiving <66 Gy among the patients in the induction chemotherapy cohort (p < .01). CONCLUSION: Induction chemotherapy subjects experienced no survival advantage over concurrent chemotherapy subjects but were more likely to receive lower RT doses. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1113-1121, 2017.

The Utility of In-Office Ultrasound in the Diagnosis of Parotid Lesions.

Objective To determine whether the use of in-office ultrasound (US) by a head and neck surgeon is a useful adjunct to clinical assessment of parotid lesions and decrease the need of additional imaging, such as magnetic resonance imaging (MRI) or computed tomography (CT). Study Design Case series with chart review. Setting Tertiary care academic center. Subjects Seventy patients presenting with a parotid lesion who obtained an in-office US and ultrasound-guided fine-needle aspiration (USGFNA) from a head and neck surgeon from 2006 to 2015. Methods US images were retrospectively reviewed for 70 patients and characterized by a radiologist and a head and neck surgeon. Results Of the 70 patients, 6 had US characteristics that demonstrated a statistically significant association with a benign/malignant diagnosis: depth from surface; irregular borders; presence of calcifications, which included either micro- or macro-calcifications; posterior echogenicity enhancement; irregular shape; and homogeneous/heterogeneous echotexture. Imaging was performed prior to referral in 25 cases (35.7%); of those, 17 (68%) were for superficial, small (<2 cm) tumors where prereferral imaging studies did not provide additional information to that obtained with US. Of the 55 patients without MRI or CT performed prior to referral, MRI or positron emission tomography-CT scan was obtained in only 4 patients (7.3%) in cases involving recurrent parotid lesions, large tumors, or workup of a malignant neoplasm. Conclusions Several US characteristics individually assist in lesion characterization. In-office US and USGFNA are an appropriate first-line modality in the assessment of parotid lesions, can allow for immediate parotid lesion assessment, and can decrease the need for additional imaging.

A comparison of overall survival for patients with T4 larynx cancer treated with surgical versus organ-preservation approaches: A National Cancer Data Base analysis.

BACKGROUND: Although laryngectomy is the treatment of choice for patients with T4 larynx cancer, many patients are unable or unwilling to undergo laryngectomy and instead pursue larynx-preservation strategies combining radiotherapy (RT) and chemotherapy. Herein, the authors analyzed the National Cancer Data Base to evaluate overall survival (OS) between patients treated with surgical and organ-preserving modalities. METHODS: The National Cancer Data Base was queried for patients diagnosed from 2004 through 2012 with T4M0 laryngeal cancer who underwent either laryngectomy (surgery) with adjuvant RT (SRT), chemotherapy starting concurrently within 7 days of RT (CCRT), or multiagent induction chemotherapy starting 43 to 98 days before RT (ICRT). Multivariate analysis and propensity score matching were used to explore the association between the intervention and OS. Recursive partitioning analysis was performed to identify groups benefiting from particular modalities. RESULTS: A total of 1559 patients who underwent SRT, 1597 patients who underwent CCRT, and 386 patients who underwent ICRT were included. Adjusting for covariates, CCRT was found to be associated with inferior OS compared with SRT (hazard ratio [HR], 1.55; 95% confidence interval [95% CI], 1.41-1.70 [P<.01]) and with ICRT (HR, 1.25; 95% CI, 1.07-1.45 [P<.01]). OS among the patients treated with SRT did not appear to differ significantly from that of the ICRT cohort (HR, 0.87; 95% CI, 0.73-1.03 [P = 0.10]), a finding confirmed with propensity score matching. Recursive partitioning analysis identified no subset of patients that derived an OS benefit from either approach over the other. CONCLUSIONS: OS among patients undergoing SRT was found to be superior to that of patients treated with CCRT but did not significantly differ from that of those undergoing ICRT. Because these intriguing findings require validation, SRT should remain the standard of care for patients with this disease. However, organ preservation with ICRT may be a reasonable alternative in certain patients. Cancer 2017;123:600-608. © 2016 American Cancer Society.

In vivo cross-sectional imaging of the phonating larynx using long-range Doppler optical coherence tomography.

Diagnosis and treatment of vocal fold lesions has been a long-evolving science for the otolaryngologist. Contemporary practice requires biopsy of a glottal lesion in the operating room under general anesthesia for diagnosis. Current in-office technology is limited to visualizing the surface of the vocal folds with fiber-optic or rigid endoscopy and using stroboscopic or high-speed video to infer information about submucosal processes. Previous efforts using optical coherence tomography (OCT) have been limited by small working distances and imaging ranges. Here we report the first full field, high-speed, and long-range OCT images of awake patients' vocal folds as well as cross-sectional video and Doppler analysis of their vocal fold motions during phonation. These vertical-cavity surface-emitting laser source (VCSEL) OCT images offer depth resolved, high-resolution, high-speed, and panoramic images of both the true and false vocal folds. This technology has the potential to revolutionize in-office imaging of the larynx.

A patient tumor transplant model of squamous cell cancer identifies PI3K inhibitors as candidate therapeutics in defined molecular bins.

Targeted therapy development in head and neck squamous cell carcinoma (HNSCC) is challenging given the rarity of activating mutations. Additionally, HNSCC incidence is increasing related to human papillomavirus (HPV). We sought to develop an in vivo model derived from patients reflecting the evolving HNSCC epidemiologic landscape, and use it to identify new therapies. Primary and relapsed tumors from HNSCC patients, both HPV+ and HPV-, were implanted on mice, giving rise to 25 strains. Resulting xenografts were characterized by detecting key mutations, measuring protein expression by IHC and gene expression/pathway analysis by mRNA-sequencing. Drug efficacy studies were run with representative xenografts using the approved drug cetuximab as well as the new PI3K inhibitor PX-866. Tumors maintained their original morphology, genetic profiles and drug susceptibilities through serial passaging. The genetic makeup of these tumors was consistent with known frequencies of TP53, PI3KCA, NOTCH1 and NOTCH2 mutations. Because the EGFR inhibitor cetuximab is a standard HNSCC therapy, we tested its efficacy and observed a wide spectrum of efficacy. Cetuximab-resistant strains had higher PI3K/Akt pathway gene expression and protein activation than cetuximab-sensitive strains. The PI3K inhibitor PX-866 had anti-tumor efficacy in HNSCC models with PIK3CA alterations. Finally, PI3K inhibition was effective in two cases with NOTCH1 inactivating mutations. In summary, we have developed an HNSCC model covering its clinical spectrum whose major genetic alterations and susceptibility to anticancer agents represent contemporary HNSCC. This model enables to prospectively test therapeutic-oriented hypotheses leading to personalized medicine.