Co-culture of chondrocytes and stem cells: a review of head and neck cell lines for cartilage regeneration.

INTRODUCTION: Bioprinting, using "bio-inks" consisting of living cells, supporting structures and biological motifs to create customized constructs, is an emerging technique that aims to overcome the challenges of cartilaginous reconstruction of head and neck structures. Several living cell lines and culturing methods have been explored as bio-inks with varying efficacy. Co-culture of primary chondrocytes and stem cells (SCs) is one technique, well established for degenerative joint disease treatment, with potential for use in expanding chondrocyte populations for bio-inks. This study aims to evaluate the techniques for co-culture of primary chondrocytes and SCs for head and neck cartilage regeneration. METHODS: A literature review was performed through OVID/Web of Science/MEDLINE/BIOSIS Previews/Embase. Studies reporting on chondrocytes and SCs in conjunction with co-culture or cartilage regeneration were included. Studies not reporting on findings from chondrocytes/SCs of the head and neck were excluded. Extracted data included cell sources, co-culture ratios and histological, biochemical and clinical outcomes. RESULTS: 15 studies met inclusion criteria. Auricular cartilage was the most common chondrocyte source (n=10), then nasal septum (n=5), articular (n=1) and tracheal cartilage (n=1). Bone marrow was the most common SC source (n=9) then adipose tissue (n=7). Techniques varied, with co-culture ratios ranging from 1:1 to 1:10. All studies reported co-culture to be superior to SC mono-culture by all outcomes. Most studies reported superiority or equivalence of co-culture to chondrocyte mono-culture by all outcomes. When comparing clinical outcomes, co-culture constructs were equivalent to chondrocyte mono-culture in diameter, and equivalent or inferior in wet weight and height. CONCLUSION: Co-culture of primary chondrocytes and SCs is a promising technique for expanding chondrocyte populations, with at least equivalence to chondrocyte mono-culture and superior to SC mono-culture when seeded at the same chondrocyte densities. However, there remains a lack of consensus regarding the optimal cell sources and co-culture ratios.

The phrenic nerve; the forgotten nerve in head and neck surgery.

BACKGROUND: Neck dissection is a commonly performed procedure for oncologic control of head and neck malignancy. With contemporary modified radical and selective neck dissections, haematoma, wound infection, tissue necrosis, chyle leak and injury involving the marginal mandibular, hypoglossal, vagus or accessory nerves are commonly described complications. Although the phrenic nerve courses within the surgical planes explored during a neck dissection and has a vital function in innervating the diaphragm, few studies have been performed to investigate the exact incidence of post-operative phrenic nerve paresis. This study aims to review the literature as to the rate of phrenic nerve injury following neck dissection. METHODS: A systematic literature review was conducted from 2000 to 2022 including studies reporting on phrenic nerve paresis following neck dissection. RESULTS: In total, 11 studies were included. The reported rate of immediate post-operative phrenic nerve paresis ranged from 0% to 5.3%, with an average rate of 0.613% (12/1959). The reported rate of phrenic nerve paresis at follow-up (1 month-127 months) ranged from 0% to 4.7%, with an average rate of 1.035% (5/483). There were no cases of bilateral phrenic nerve paresis reported in this period. CONCLUSIONS: Phrenic nerve paresis is an uncommon complication following neck dissection, often asymptomatic and potentially underreported. Bilateral phrenic nerve paresis is exceedingly rare. Injury can be avoided by staying superficial to the prevertebral fascia when dissecting around the anterior scalene muscle. Routine phrenic nerve integrity monitoring is not commonly utilized but may aid intra-operative phrenic nerve identification or confirmation of function.

Self-assembling RADA16 peptide hydrogel supports hemostasis, synechiae reduction, and wound healing in a sheep model of endoscopic nasal surgery.

OBJECTIVES: Complications of endoscopic sinus/nasal turbinate surgery include postoperative hemorrhage, synechiae formation, and poor wound healing. Our primary objectives were to evaluate whether a topical hydrogel based on self-assembling RADA16 peptides: i) reduces bleeding and synechiae formation, and ii) supports wound healing, using a sheep nasal surgery model. METHODS: Thirty sheep received endoscopic surgery-created bilateral nasal mucosal injuries on the middle turbinate/opposing septum. Injuries were randomly assigned RADA16, Gelatin-thrombin, or no treatment. Outcomes included intra-operative hemostasis, scar tissue/synechiae formation and wound healing at 2 weeks and the 6-week study terminus, and histopathology. RESULTS: Intra-operative hemostasis time improved with RADA16 and Gelatin-thrombin versus Control wounds (139.7±56.2 s, 145.4±58.1 s, and 224.0±69.9 s, respectively; p < 0.0001 for both comparisons). Two-week synechiae scores (maximum 4 points) were similar in Controls (2.9±1.8 points) and Gelatin-thrombin (3.1±1.6 points) wounds (p > 0.05), but were reduced in RADA16 sites by 91% versus Controls and 92% versus Gelatin-thrombin treatment (0.3±0.6 points; p < 0.0001 for both comparisons). Six-week synechiae scores were similar in Control (1.1±1.7 points) and Gelatin-thrombin (1.7±2.0 points) wounds (p > 0.05), but reduced 100% in RADA16-treated wounds. Synechiae occurred in fewer RADA16-treated sites at 2 weeks (20%) versus Gelatin-thrombin (80%) and Controls (75%; p < 0.01) and at 6 weeks (0%, 50% and 35%, respectively; p < 0.01). RADA16 was associated with significantly lower 6-week histopathology scores, driven by reduced submucosal fibrosis and angiogenesis. CONCLUSION: Although RADA16 and Gelatin-thrombin similarly accelerated hemostasis in this sheep endoscopic sinus surgery model, only RADA16 reduced postoperative synechiae formation at 2 weeks with an absence of synechiae at 6 weeks. Histology suggested RADA16 enhanced mucosal regeneration.

Giant Cholesteatoma: A Case Report and Review of the Literature.

OBJECTIVE: To present a case of giant cholesteatoma and review of the contemporary literature. PATIENTS: A 61-year-old male presented with foul-smelling discharge from his right ear in the setting of a previous canal wall down mastoidectomy. Otomicroscopy demonstrated a mastoid cavity filled with infected keratinous debris. Neuro-imaging revealed soft tissue inflammatory changes in the mastoid cavity, with involvement of the temporomandibular joint (TMJ) and parotid gland and tegmen erosion. Biopsies showed evidence of desquamated epithelium consistent with cholesteatoma, with no malignant cells identified. Audiogram demonstrated a mean hearing loss of 65 dB on the right ear and an air-bone gap of 45 dB. Review of literature was also performed on giant cholesteatoma. INTERVENTIONS: He underwent a modified Fisch Type B infratemporal fossa approach to completely remove the cholesteatoma and a vascularized free flap was utilized to fill the surgical defect. MAIN OUTCOME MEASURES: Complete extirpation of choles-teatoma and resolution of otorrhoea. RESULTS: Repeat imaging showed complete removal of cholesteatoma and clinically there was resolution of the otorrhea. Review of the literature has shown a lack of consensus around the definition of giant cholesteatoma. Most cases in the literature demonstrated extensive involvement of anatomical spaces beyond the confines of the temporal bone to qualify for the diagnosis of giant cholesteatoma. CONCLUSIONS: Giant cholesteatoma should be suspected in cases of recurrent ear discharge following canal wall down mastoidectomy. The case we report add to the literature to benefit future patients in preoperative counseling and better inform management.

Middle ear myoclonus: Systematic review of results and complications for various treatment approaches.

OBJECTIVE: To perform a systematic review of the diagnosis and treatment of patients with pulsatile tinnitus secondary to middle ear myoclonus. DATABASES REVIEWED: PubMed, EMBASE, and Scopus. METHODS: A systematic review was performed using standardized methodology. Computerized and manual searches were performed to identify studies of all ages (patients) who had middle ear myoclonus (intervention). All study designs were assessed. Extracted data included demographics, clinical features, duration of followup as well as the diagnosis and reversibility of symptoms with medical or surgical intervention. Studies were included if they included subjects with middle ear myoclonus. Exclusion criteria included letters/commentaries and reviews. RESULTS: Twenty articles representing 115 subjects with middle ear myoclonus were included. The mean age was 29.7 (range 6-67). The follow-up period ranged from 5 weeks to 36 months. Primary treatment consists of medical therapy utilising anxiolytics, antiepileptics, botulinum toxin and surgical treatment involving division of middle ear muscular tendon(s). In total, 60 patients underwent middle ear muscular tenotomies, with division of both stapedius and tensor tympani tendons being the most prevalent (88%). Limitations in the data arose from study design, related comorbidities such as palatal myoclonus, and concomitant drug administration. No study provided any objective criteria to diagnose this condition or evaluate post-treatment outcome. CONCLUSION: Middle ear myoclonus is an entity that is poorly assessed in the literature. There is a lack of consensus regarding the criteria and strategies for both diagnosing and treating this condition. Although level of evidence of current studies remains modest, it is felt that a stepwise approach is deemed best, with therapeutic decisions being made on an individual basis, evaluating each patient's specific circumstances and priorities.