Department of Otolaryngology—Head and Neck Surgery Works
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Item Pedicled Cervical Lymphoadipose Tissue for Volume Reconstruction after Superficial Parotidectomy(Hindawi, 2021-05-07) Davis, Kyle P.; Fraser, Amy L.; Shay, Elizabeth O.; Sim, Michael W.; Otolaryngology -- Head and Neck Surgery, School of MedicineVolume restoration is often required after parotidectomy due to the resultant facial contour deformity. Common procedures include local pedicled flaps, such as the sternocleidomastoid muscle flap, fat grafting, and even autologous free flaps, for more extensive defects. Local pedicled flaps have the advantage of a single surgical site, which spares the patient the added morbidity of a separate fat graft donor site, while simultaneously reducing the operative time. We report two cases of a novel reconstructive option using pedicled level I and II cervical lymphoadipose tissue for volume restoration after superficial parotidectomy. This reconstruction would be useful for patients with benign parotid lesions and inferior parotid defects. In addition, with maintained blood supply to this tissue, it would likely provide sustained bulk over time.Item Retropharyngeal lipoblastoma causing severe pediatric obstructive sleep apnea(Elsevier, 2022) Jones, Alexander Joseph; Puello Yocum, Bianca N.; Matt, Bruce H.; Burgin, Sarah J.M.; Otolaryngology -- Head and Neck Surgery, School of MedicineLipoblastomas are benign neoplasms of white adipose which usually occupy the trunk and limbs in pediatric patients. They can seldomly involve the head and neck, usually as a lateral cervical mass. Magnetic resonance imaging is the most useful modality for identifying these lesions. Treatment involves complete excision, and patients are followed with serial exams and/or imaging as recurrence is more common in the head and neck. Here we present an exceedingly rare case of retropharyngeal lipoblastoma in a two-year-old male causing severe obstructive sleep apnea which was identified during adenotonsillectomy. As this mass can be mistaken for other more common masses of the retropharyngeal space, we review the differential diagnoses, imaging, and histopathologic features of this neoplasm, which was responsible for upper airway obstruction in this case.Item Applications of Lipidomics to Age-Related Musculoskeletal Disorders(Springer Nature, 2021-04) Mo, Chenglin; Du, Yating; O’Connell, Thomas M.; Otolaryngology -- Head and Neck Surgery, School of MedicinePurpose of review: The goal of this review is to highlight the need for new biomarkers for the diagnosis and treatment of musculoskeletal disorders, especially osteoporosis and sarcopenia. These conditions are characterized by loss of bone and muscle mass, respectively, leading to functional deterioration and the development of disabilities. Advances in high-resolution lipidomics platforms are being used to help identify new lipid biomarkers for these diseases. Recent findings: It is now well established that bone and muscle have important endocrine functions, including the release of bioactive factors in response to mechanical and biochemical stimuli. Bioactive lipids are a prominent set of these factors and some of these lipids are directly related to the mass and function of bone and muscle. Recent lipidomics studies have shown significant dysregulation of lipids in aged muscle and bone, including alterations in diacylglycerols and ceramides. Studies have shown that alterations in some types of plasma lipids are associated with aging including reduced bone mineral density and the occurrence of osteoporosis. Musculoskeletal disorders are a major burden in our society, especially for older adults. The development and application of new lipidomics methods is making significant advances in identifying new biomarkers for these diseases. These studies will not only lead to improved detection, but new mechanistic insights that could lead to new therapeutic targets and interventions.Item Sarcopenia is associated with blood transfusions in head and neck cancer free flap surgery(Wiley, 2021-04) Jones, Alexander Joseph; Campiti, Vincent J.; Alwani, Mohamedkazim; Novinger, Leah J.; Tucker, Brady Jay; Bonetto, Andrea; Yesensky, Jessica A.; Sim, Michael W.; Moore, Michael G.; Mantravadi, Avinash V.; Otolaryngology -- Head and Neck Surgery, School of MedicineObjective: To determine if sarcopenia is a predictor of blood transfusion requirements in head and neck cancer free flap reconstruction (HNCFFR). Methods: A single-institution, retrospective review was performed of HNCFFR patients with preoperative abdominal imaging from 2014 to 2019. Demographics, comorbidities (modified Charlson Comorbidity Index [mCCI]), skeletal muscle index (cm2/m2), oncologic history, intraoperative data, and 30-day postoperative complications (Clavien-Dindo score [CD]) were collected. Binary logistic regression was performed to determine predictors of transfusion. Results: Eighty (33.5%), 66 (27.6%), and 110 (46.0%) of n = 239 total patients received an intraoperative, postoperative, or any perioperative blood transfusion, respectively. Sixty-two (25.9%) patients had sarcopenia. Patients receiving intraoperative transfusions had older age (P = .035), more frequent alcoholism (P = .028) and sarcopenia (P < .001), greater mCCI (P < .001), lower preoperative hemoglobin (P < .001), reconstruction with flaps other than forearm (P = .003), and greater operative times (P = .001), intravenous fluids (P < .001), and estimated blood loss (EBL, P < .001). Postoperative transfusions were associated with major complications (CD ≥ 3; P < .001). Multivariate regression determined sarcopenia (P = .023), mCCI (P = .013), preoperative hemoglobin (P = .002), operative time (P = .036), and EBL (P < .001) as independent predictors of intraoperative transfusion requirements. Postoperative transfusions were predicted by preoperative hemoglobin (P = .007), osseous flap (P = .036), and CD ≥ 3 (P < .001). A perioperative transfusion was predicted by sarcopenia (P = .021), preoperative hemoglobin (P < .001), operative time (P = .008), and CD ≥ 3 (P = .018). Conclusion: Sarcopenia is associated with increased blood transfusions in HNCFFR. Patients should be counseled preoperatively on the associated risks, and the increased blood product requirement should be accounted in resource-limited scenarios.Item Comment on Liu et al. Aberrant Expression of FBXO2 Disrupts Glucose Homeostasis Through Ubiquitin-Mediated Degradation of Insulin Receptor in Obese Mice. Diabetes 2017;66:689–698(American Diabetes Association, 2020-02) Wong, Siauyen; Nelson, Rick F.; Lu, Peiran; Paulson, Henry; Lin, Dingbo; Otolaryngology -- Head and Neck Surgery, School of MedicineItem Facial Nerve Sacrifice During Parotidectomy for Metastatic Cutaneous Squamous Cell Carcinoma(Sage, 2021-02-25) Yesensky, Jessica; Solis, Roberto N.; Bewley, Arnaud; Otolaryngology -- Head and Neck Surgery, School of MedicineObjective: We analyzed the incidence of facial nerve sacrifice during parotidectomy for metastatic cutaneous squamous cell carcinoma (CSCC). Study design: We retrospectively reviewed the charts of patients with cutaneous squamous cell carcinoma. Setting: We used our CSCC institutional database, which includes patients treated at the University of California-Davis from 2001 to 2018. Methods: We evaluated patients who presented with biopsy-proven head and neck CSCC who underwent parotidectomy as a part of surgical treatment. We assessed the frequency of facial nerve sacrifice required in patients with normal preoperative facial nerve function with metastatic disease to the parotid. We evaluated the association between sacrifice and high-risk tumor variables using multivariate analysis. Results: We identified 53 patients with parotid metastasis and normal preoperative facial nerve function. Thirteen percent of patients required sacrifice of the main trunk of the facial nerve and 27% required sacrifice of a branch of the facial nerve. All patients who underwent facial nerve sacrifice had extracapsular spread (ECS). Perineural invasion (PNI) in the primary tumor (odds ratio [OR], 9.11; P = .041) and location of metastasis within the parotid body (OR, 6.6; P = .044) were independently associated with facial nerve sacrifice. Conclusion: Patients with regionally metastatic CSCC to the parotid gland frequently require sacrifice of all or a component of the facial nerve despite normal preoperative function. The likelihood of nerve sacrifice is highest for tumors with PNI and metastatic disease within the body of the parotid.Item Building inner ears: recent advances and future challenges for in vitro organoid systems(Springer Nature, 2021-01) van der Valk, Wouter H.; Steinhart, Matthew R.; Zhang, Jingyuan; Koehler, Karl R.; Otolaryngology -- Head and Neck Surgery, School of MedicineWhile inner ear disorders are common, our ability to intervene and recover their sensory function is limited. In vitro models of the inner ear, like the organoid system, could aid in identifying new regenerative drugs and gene therapies. Here, we provide a perspective on the status of in vitro inner ear models and guidance on how to improve their applicability in translational research. We highlight the generation of inner ear cell types from pluripotent stem cells as a particularly promising focus of research. Several exciting recent studies have shown how the developmental signaling cues of embryonic and fetal development can be mimicked to differentiate stem cells into "inner ear organoids" containing otic progenitor cells, hair cells, and neurons. However, current differentiation protocols and our knowledge of embryonic and fetal inner ear development in general, have a bias toward the sensory epithelia of the inner ear. We propose that a more holistic view is needed to better model the inner ear in vitro. Moving forward, attention should be made to the broader diversity of neuroglial and mesenchymal cell types of the inner ear, and how they interact in space or time during development. With improved control of epithelial, neuroglial, and mesenchymal cell fate specification, inner ear organoids would have the ability to truly recapitulate neurosensory function and dysfunction. We conclude by discussing how single-cell atlases of the developing inner ear and technical innovations will be critical tools to advance inner ear organoid platforms for future pre-clinical applications.Item Use of a novel Chinchilla skull base repair model to test a photo-initiated thiol-ene biopolymer(Wiley, 2022) Terella, Adam M.; Mariner, Peter; Cool, Carlyne D.; Ramakrishnan, Vijay R.; Otolaryngology -- Head and Neck Surgery, School of MedicineItem Hürthle cell neoplasms of the thyroid: Pathologic outcomes and ultrasonographic analysis(Wiley, 2020-12) Shin, Timothy J.; Rabbani, Cyrus C.; Murthy, Henna D.; Traylor, Katie; Sim, Michael W.; Otolaryngology -- Head and Neck Surgery, School of MedicineBackground: Fine-needle aspiration (FNA) of thyroid nodules suspicious for Hürthle cell neoplasms (HCN) have uncertain rate of malignancy. We aim to characterize rate and predictors of malignancy at our institution and compare these findings with established literature to help guide management. Methods: Single tertiary-referral center, retrospective study of 166 adults who underwent hemithyroidectomy or total thyroidectomy following FNA suspicious for HCN from 1998-2018. Demographic information and surgical histopathologic results were collected. Preoperative ultrasonography was independently scored on the American College of Radiology Thyroid Imaging Reporting and Data System (TI-RADS) by a board-certified head and neck radiologist. Results: There were 39 males and 127 females. Overall, 25 (15.1%) patients had carcinoma, with 15 (9%) being Hürthle cell carcinoma (HCC). Men had higher incidence of carcinoma (25.6% v. 11.8%, P = .035), and especially older males. Contralateral carcinoma was seen in 3 of 13 (23.1%) patients that underwent completion thyroidectomy. Patients with carcinoma had larger nodules (average diameter 3.3 cm versus 2.5 cm, respectively, P = .01), but no association with TI-RADS. Conclusion: Adults with nodules suspicious for HCN have significant risk of malignancy consistent with prior studies. Older males and larger nodule diameter are associated with malignancy in this cohort, but TI-RADS grade is not. These findings provide a framework for management and counseling for lesions suspicious for HCN.Item Hair-bearing human skin generated entirely from pluripotent stem cells(Springer Nature, 2020-06) Lee, Jiyoon; Rabbani, Cyrus C.; Gao, Hongyu; Steinhart, Matthew R.; Woodruff, Benjamin M.; Pflum, Zachary E.; Kim, Alexander; Heller, Stefan; Liu, Yunlong; Shipchandler, Taha Z.; Koehler, Karl R.; Otolaryngology -- Head and Neck Surgery, School of MedicineThe skin is a multilayered organ, equipped with appendages (that is, follicles and glands), that is critical for regulating body temperature and the retention of bodily fluids, guarding against external stresses and mediating the sensation of touch and pain1,2. Reconstructing appendage-bearing skin in cultures and in bioengineered grafts is a biomedical challenge that has yet to be met3-9. Here we report an organoid culture system that generates complex skin from human pluripotent stem cells. We use stepwise modulation of the transforming growth factor β (TGFβ) and fibroblast growth factor (FGF) signalling pathways to co-induce cranial epithelial cells and neural crest cells within a spherical cell aggregate. During an incubation period of 4-5 months, we observe the emergence of a cyst-like skin organoid composed of stratified epidermis, fat-rich dermis and pigmented hair follicles that are equipped with sebaceous glands. A network of sensory neurons and Schwann cells form nerve-like bundles that target Merkel cells in organoid hair follicles, mimicking the neural circuitry associated with human touch. Single-cell RNA sequencing and direct comparison to fetal specimens suggest that the skin organoids are equivalent to the facial skin of human fetuses in the second trimester of development. Moreover, we show that skin organoids form planar hair-bearing skin when grafted onto nude mice. Together, our results demonstrate that nearly complete skin can self-assemble in vitro and be used to reconstitute skin in vivo. We anticipate that our skin organoids will provide a foundation for future studies of human skin development, disease modelling and reconstructive surgery.