Dexamethasone eluting polydopaminated polycaprolactone-poly (lactic-co-glycolic) acid for treatment of tracheal stenosis.

Tracheal stenosis is commonly caused by injury, resulting in inflammation and fibrosis. Inhibiting inflammation and promoting epithelization can reduce recurrence after initial successful treatment of tracheal stenosis. Steroids play an important role in tracheal stenosis management. This study in vitro evaluated effectiveness of a polydopaminated polycaprolactone stent coated with dexamethasone-eluting poly(lactic-co-glycolic) acid microparticles (µPLGA) for tracheal stenosis management. Polydopamination was characterized by Raman spectroscopy and promoted epithelialization while dexamethasone delivery reduced macrophage activity, assessed by individual cell area measurements and immunofluorescent staining for inducible nitric oxide synthase (iNOS). Dexamethasone release was quantified by high-performance liquid chromatography over 30 days. Activation-related increase in cell area and iNOS production by RAW 264.7 were both reduced significantly (p < .05) through dexamethasone release. Epithelial cell spreading was higher on polydopaminated polycaprolactone (PCL) than PCL-alone (p < .05). Force required for stent migration was measured by pullout tests of PCL-µPLGA stents from cadaveric rabbit and porcine tracheas (0.425 ± 0.068 N and 1.082 ± 0.064 N, respectively) were above forces estimated to occur during forced respiration. Biomechanical support provided by stents to prevent airway collapse was assessed by comparing compressive circumferential stiffness, and stiffness of the stent was about 1/10th of the rabbit trachea (0.156 ± 0.023 N/mm vs. 1.420 ± 0.194 N/mm, respectively). A dexamethasone-loaded PCL-µPLGA stent platform can deliver dexamethasone and exhibits sufficient mechanical properties to anchor within the trachea and polydopamination of PCL is conducive to epithelial layer formation. Therefore, a polydopaminated PCL-µPLGA stent is a promising candidate for in vivo evaluation for treatment of tracheal restenosis.

Efficacy of expansion pharyngoplasty and hypoglossal nerve stimulation in treating sleep apnea.

OBJECTIVE: We investigated whether a palatal conversion procedure combined with a second-stage hypoglossal nerve stimulator (HGNS) insertion can be beneficial for those patients who have a complete concentric velopharyngeal collapse and may initially not meet the criteria for use of HGNS. METHODS: A retrospective chart review included all patients who underwent a planned multi-level sleep surgery including expansion sphincter pharyngoplasty (ESP) followed by HGNS. All patients had a complete concentric collapse (CCC) of the velopharynx (VP) on pre-intervention drug-induced sleep endoscopy (DISE) and were initially not a candidate for HGNS. These patients then underwent ESP followed by a DISE to confirm elimination of the CCC of the VP. They then went on to HGNS implantation several months later followed by a sleep study. RESULTS: A total of 20 patients were identified and included in the retrospective chart analysis. All patients who underwent ESP successfully converted their VP from CCC to an anterior-posterior collapse pattern and thus met inclusion criteria for HGNS. After the HGNS was implanted, patients showed a significant reduction of the mean AHI from 53.9 before ESP to 8.2 after ESP and HGNS and a decrease in the Epworth Sleep Score (ESS) from a mean of 13.3 to 5.7. CONCLUSION: ESP can be effective in eliminating the CCC of the VP thus making patients become HGNS candidates. In selected OSA patients, who have multilevel upper airway obstruction with complete concentric VP collapse, the combination of ESP and HGNS insertion should be considered as a planned 2-staged approach.

PET/CT versus triple endoscopy in initial workup of HPV+ oropharyngeal squamous cell carcinoma.

BACKGROUND: Synchronous primary tumors (SPTs) are detected via triple endoscopy or positron emission tomography/computed tomography (PET/CT). Patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC) lack risk factors for SPTs. METHODS: We performed a single institution retrospective review of the efficacy of triple endoscopy and PET/CT in HPV+ OPSCC patients. RESULTS: Sixty-five HPV+ OPSCC patients underwent triple endoscopy and PET/CT. Patients were white (n = 48, 72.7%), male (n = 53, 81.5%), mean 58.7 ± 8.1 years old. SPT was detected in 1 (1.5%) patient via PET/CT. No SPTs were detected on triple endoscopy. PET/CT had 100% and 95.3% sensitivity and specificity, respectively. PET/CT positive predictive value (PPV) and negative predictive value (NPV) were 25.0% and 100%, respectively. Triple endoscopy specificity and NPV was 90.2% and 93.2%, respectively. CONCLUSIONS: PET/CT is superior to triple endoscopy in ruling out SPTs. With negative PET/CT, only direct laryngoscopy with biopsy may be necessary.

A Noninferiority Analysis of 3- vs 2-Incision Techniques for Hypoglossal Nerve Stimulator Implantation.

OBJECTIVE: The only hypoglossal nerve stimulation (HNS) device available for US clinical use is implanted through 3 incisions. A recently proposed 2-incision modification moved the respiratory sensing lead from the fifth to the second intercostal space to eliminate the third lower chest incision. This study compared perioperative data and therapeutic outcomes between the techniques. STUDY DESIGN: Noninferiority cohort analysis of a retrospective and prospective registry study. SETTING: Tertiary care and community surgical centers. METHODS: Patients with obstructive sleep apnea underwent HNS implantation via a modified 2-incision technique (I2). A cohort previously implanted via the standard 3-incision technique (I3) were 1:1 propensity score matched for a noninferiority analysis of postoperative outcomes. RESULTS: There were 404 I3 patients and 223 I2 patients across 6 participating centers. Operative time decreased from 128.7 minutes (95% CI, 124.5-132.9) in I3 patients to 86.6 minutes (95% CI, 83.7-97.6) in I2 patients (P < .001). Postoperative sleep study data were available for 76 I2 patients who were matched to I3 patients. The change in apnea-hypopnea index between the cohorts was statistically noninferior (a priori noninferiority margin: 7.5 events/h; mean difference, 1.51 [97.5% CI upper bound, 5.86]). There were no significant differences between the cohorts for baseline characteristics, perioperative adverse event rates, or change in Epworth Sleepiness Score (P > .05). CONCLUSION: In a multicenter registry, a 2-incision implant technique for a commercially available HNS device had a statistically noninferior therapeutic efficacy profile when compared with the standard 3-incision approach. The 2-incision technique is safe and effective for HNS implantation.

KTP Laser Treatment of Early Glottic Cancer: A Multi-Institutional Retrospective Study.

OBJECTIVES: The primary objectives were to report oncologic outcomes of transoral laser microsurgery with potassium-titanyl-phosphate (KTP) laser (TLM-KTP) ablation of early glottic cancer (EGC). The secondary objectives were to report vocal outcomes and to analyze factors that might influence outcomes. METHODS: A multi-institutional, retrospective analysis of consecutive patients treated for T1 or T2 glottic squamous cell carcinoma undergoing TLM-KTP ablation with at least 2 years of follow-up was performed. Patients with prior radiation or surgery for laryngeal disease were excluded. PRIMARY OUTCOME MEASURES INCLUDED: surgical failures requiring radiation or laryngectomy, disease-specific survival (DSS), and overall survival (OS). Secondary outcome measures included: pre- and postoperative Voice Handicap Index-10 (VHI-10) scores. The effects of smoking status, stage, and anterior commissure involvement on outcomes were analyzed. RESULTS: Overall 88 patients met inclusion criteria (83% male, 79.5% current or former smokers). Mean age was 68 (standard deviation (SD): 12). Mean follow-up was 39.5 months (SD: 15.3). Staging included 50 T1a, 21 T1b, and 20 T2 tumors, including three metachronous second primaries. Radiation and/or laryngectomy avoidance was achieved in 87/88 (98.9%) of patients, inclusive of 24 patients requiring KTP re-treatments. Two patients had biopsy-proven recurrence (2.3%), but only 21 of 24 re-treated patients received a formal biopsy. No patients died from laryngeal cancer. DSS and OS were 100% and 92.3%, respectively. The mean VHI-10 scores were 19.3 preoperatively, 3.8 at 6-months postop, and 3.8 at 2-years postop. Smokers had a longer interval to re-treatment (P = .03), patients with T2 lesions had a shorter interval to re-treatment (0.02), and patients with T2 lesions presented with worse initial VHI-10 scores (0.002). CONCLUSIONS: A multi-institutional, retrospective case series of TLM-KTP ablation of EGC demonstrated excellent oncologic outcomes when close surveillance and proactive re-treatments were utilized. Disease-specific survival, overall survival, and vocal function were excellent. Additional studies are necessary to further analyze the merits and risks of this treatment approach.

Pectoralis Major Onlay vs Interpositional Reconstruction Fistulation After Salvage Total Laryngectomy: Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the difference in pharygocutaneous fistula (PCF) development between pectoralis major flap onlay and interpositional reconstructions after salvage total laryngectomy (STL). DATA SOURCES: Medline, Cochrane, Embase, Web of Science, CINAHL, and ClinicalTrials.gov. REVIEW METHODS: A systematic review was performed during January 2020. English articles were included that described minor and major PCF rates after STL reconstructed with pectoralis major onlay or interposition. PCFs were classified as major when conservative therapy was unsuccessful and/or revision surgery was needed. Articles describing total laryngopharyngectomies were excluded. Meta-analyses of the resulting data were performed. RESULTS: Twenty-four articles met final criteria amassing 1304 patients. Three articles compared onlay with interposition, and 18 compared onlay with primary closure. Pectoralis interposition demonstrated elevated odds ratio (OR) of PCF formation as compared with onlay (OR, 2.34; P < .001). Onlay reconstruction reduced overall (OR, 0.32; P < .001) and major (OR, 0.21; P < .001) PCF development as compared with primary pharyngeal closure alone. Data were insufficient to compare interposition against primary closure. CONCLUSIONS: This research shows evidence that pectoralis onlay after STL diminishes the odds of total and major PCF development. Pectoralis interposition reconstruction showed elevated odds of PCF formation as compared with pectoralis onlay.

Superior Laryngeal Nerve Neuralgia: Case Series and Review of Anterior Neck Pain Syndromes.

Superior laryngeal nerve neuralgia (SLNN) is an anterior neck pain syndrome that is underrecognized and, as a result, is often misdiagnosed. We present a series of patients who were diagnosed with and subsequently treated for SLNN. Nineteen patients were treated with oral nonsteroidal anti-inflammatory drugs (NSAIDs) and/or a therapeutic neck injection with 2% lidocaine and 40% triamcinolone acetonide. All patients completed a visual analog scale (VAS) to rate the level of pain before and after treatment. Four patients rated their pain as mild, 14 as moderate, and 1 as severe according to the VAS. Of the 19 patients, 8 chose to proceed with a 2-week course of NSAIDs and only 1 of them had complete resolution of their symptoms. A total of 18 patients underwent therapeutic neck injections, with a complete response to injection therapy in 10 patients. Five patients described a minimal residual foreign body sensation and 3 patients complained of mild residual pain. In this study, we found that therapeutic neck injections are effective not only in confirming the diagnosis but also in treating pain.

Upper Airway Stimulation for Obstructive Sleep Apnea: Results from the ADHERE Registry.

Objective Upper airway stimulation (UAS) is an alternative treatment option for patients unable to tolerate continuous positive airway pressure (CPAP) for the treatment of obstructive sleep apnea (OSA). Studies support the safety and efficacy of this therapy. The aim of this registry is to collect retrospective and prospective objective and subjective outcome measures across multiple institutions in the United States and Germany. To date, it represents the largest cohort of patients studied with this therapy. Study Design Retrospective and prospective registry study. Setting Ten tertiary care hospitals in the United States and Germany. Subjects and Methods Patients were included who had moderate to severe OSA, were intolerant to CPAP, and were undergoing UAS implantation. Baseline demographic and sleep study data were collected. Objective and subjective treatment outcomes, adverse events, and patient and physician satisfaction were reviewed. Results The registry enrolled 301 patients between October 2016 and September 2017. Mean ± SD AHI decreased from 35.6 ± 15.3 to 10.2 ± 12.9 events per hour ( P < .0001), and Epworth Sleepiness Scale scores decreased from 11.9 ± 5.5 to 7.5 ± 4.7 ( P < .0001) from baseline to the posttitration visit. Patients utilized therapy for 6.5 hours per night. There were low rates of procedure- and device-related complications. Clinical global impression scores demonstrated that the majority of physicians (94%) saw improvement in their patients' symptoms with therapy. The majority of patients (90%) were more satisfied with UAS than CPAP. Conclusions Across a multi-institutional registry, UAS therapy demonstrates significant improvement in subjective and objective OSA outcomes, good therapy adherence, and high patient satisfaction.

Laryngeal alveolar soft part sarcoma: A case report of a rare malignancy in an atypical location.

Laryngeal sarcoma is a rare and potentially aggressive malignancy. In this case report, we present a 23year-old-male with four-years of progressive hoarseness who was found to have a large left paraglottic mass. A partial laryngectomy was successful at completely excising the lesion. Final pathology returned as alveolar soft part sarcoma. Alveolar soft part sarcomas of the larynx are extremely rare with only five cases published in the current literature. This article provides a case presentation with literature review of alveolar soft part sarcoma of the head and neck.

Adult onset xanthogranuloma presenting as laryngeal mass.

Histiocytic disorders can be classified according to the distribution pattern of the lesions and the organs involved. Non-Langerhans-cell histiocytosis is a rare group of diseases that have varied clinical presentations ranging from isolated masses to diffuse systemic eruptions. We discuss a patient who initially presented with a vocal cord lesion and was ultimately diagnosed with adult onset xanthogranuloma.

Prevention of postoperative cerebrospinal fluid leaks with multilayered reconstruction using titanium mesh-hydroxyapatite cement cranioplasty after translabyrinthine resection of acoustic neuroma.

OBJECT: Several prophylactic surgical methods have been tried to prevent CSF leakage after translabyrinthine resection of acoustic neuroma (TLAN). The authors report an improvised technique for multilayer watertight closure using titanium mesh-hydroxyapatite cement (HAC) cranioplasty in addition to dural substitute and abdominal fat graft after TLAN. METHODS: The study was limited to 42 patients who underwent TLAN at University Hospitals Case Medical Center using this new technique from 2006 to 2012. Systematic closure of the surgical wound in layers using temporalis fascia, dural substitute, dural sealant, adipose graft, titanium mesh, and then HAC was performed in each case. Temporalis muscle and eustachian tube obliteration were not used. The main variables studied were patient age, tumor size, tumor location, cosmetic outcome, length of hospitalization, and the incidence of CSF leak, pseudomeningocele, and infection. RESULTS: Excellent cosmetic outcome was achieved in all patients. There were no cases of postoperative CSF rhinorrhea, incisional CSF leak, or meningitis. Cosmetic results were comparable to those achieved using HAC alone. This cost-effective technique used only a third of the HAC required for traditional closure in which the entire mastoid defect is filled with cement, predisposing to infection. Postoperative CT and MRI showed excellent bony contouring and dural reconstitution, respectively. CONCLUSIONS: The authors report on successful use of titanium mesh-HAC cranioplasty in preventing postoperative CSF leak after TLAN in all cases in their series. The titanium mesh provides a well-defined anatomical dissection plane that would make reoperation easier than working through scarred soft tissue. The mesh bolsters the fat graft and keeps HAC out of direct contact with mastoid air cells, thereby reducing the risk of infection. The cement cranioplasty does not preclude subsequent implantation of a bone-anchored hearing aid.

Methods for producing scaffold-free engineered cartilage sheets from auricular and articular chondrocyte cell sources and attachment to porous tantalum.

Scaffold-free cartilage engineering techniques may provide a simple alternative to traditional methods employing scaffolds. We previously reported auricular chondrocyte-derived constructs for use in an engineered trachea model; however, the construct generation methods were not reported in detail. In this study, methods for cartilage construct generation from auricular and articular cell sources are described in detail, and the resulting constructs are compared for use in a joint resurfacing model. Attachment of cartilage sheets to porous tantalum is also investigated as a potential vehicle for future attachment to subchondral bone. Large scaffold-free cartilage constructs were produced from culture-expanded chondrocytes from skeletally mature rabbits, and redifferentiated in a chemically-defined culture medium. Auricular constructs contained more glycosaminoglycan (39.6±12.7 vs. 9.7±1.9 µg/mg wet weight, mean and standard deviation) and collagen (2.7±0.45 vs. 1.1±0.2 µg/mg wet weight, mean and standard deviation) than articular constructs. Aggregate modulus was also higher for auricular constructs vs. articular constructs (0.23±0.07 vs. 0.12±0.03 MPa, mean and standard deviation). Attachment of constructs to porous tantalum was achieved by neocartilage ingrowth into tantalum pores. These results demonstrate that large scaffold-free neocartilage constructs can be produced from mature culture-expanded chondrocytes in a chemically-defined medium, and that these constructs can be attached to porous tantalum.

Scaffold-free tissue-engineered cartilage implants for laryngotracheal reconstruction.

OBJECTIVES/HYPOTHESIS: Donor site morbidity, including pneumothorax, can be a considerable problem when harvesting cartilage grafts for laryngotracheal reconstruction (LTR). Tissue engineered cartilage may offer a solution to this problem. This study investigated the feasibility of using autologous chondrocytes to tissue-engineer scaffold-free cartilage grafts for LTR in rabbits to avoid degradation that often arises from an inflammatory reaction to scaffold carrier matrix. STUDY DESIGN: Animal study. METHODS: Auricular cartilage was harvested from seven New Zealand white rabbits, the chondrocytes expanded and loaded onto a custom-made bioreactor for 7 to 8 weeks to fabricate autologous scaffold-free cartilage sheets. The sheets were cut to size and used for LTR, and the rabbits were sacrificed 4, 8, and 12 weeks after the LTR and prepared for histology. RESULTS: None of the seven rabbits showed signs of respiratory distress. A smooth, noninflammatory scar was visible intraluminally; the remainder of the tracheal lumen was unremarkable. Histologically, the grafts showed no signs of degradation or inflammatory reaction, were covered with mucosal epithelium, but did show signs of mechanical failure at the implantation site. CONCLUSIONS: These results show that autologous chondrocytes can be used to fabricate an implantable sheet of cartilage that retains a cartilage phenotype, becomes integrated, and does not produce a significant inflammatory reaction. These findings suggest that with the design of stronger implants, these implants can be successfully used as a graft for LTR.

Tissue-engineered trachea for airway reconstruction.

OBJECTIVES/HYPOTHESIS: Scaffold-free cartilage has been used to engineer biocompatible and mechanically stable neotracheas in vivo. The purpose of this animal study was to determine if neotracheal constructs, implanted paratracheally, could successfully be used for segmental tracheal reconstruction. STUDY DESIGN: Animal study. METHODS: Culture-expanded auricular rabbit chondrocytes were used to engineer scaffold-free cartilage sheets. Cartilage and a strap muscle flap were wrapped around a tube and implanted paratracheally. At 12 to 14 weeks postimplantation neotracheas were used to reconstruct 20 mm tracheal defects. Surgical technique was modified several times in an attempt to decrease the amount of neotracheal obstruction and fibrosis. In one of the six rabbits, neotrachea with its intact strap muscle flap was dropped into the defect followed by an end-to-end anastomosis; in two animals the muscle flap was partially, and in one rabbit completely removed. In two animals the muscle flap was partially removed, the tube reinserted, and the construct reimplanted for 5 weeks to allow formation of a fibrous lining over the exposed cartilage followed by tracheal reconstruction. RESULTS: All implants developed into vascularized and mechanically sound neotracheas. Following reconstruction, none of the animals showed immediate signs of respiratory distress; however, one died after 24 hours due to extensive endotracheal muscle flap edema, whereas rabbits who had undergone partial or complete muscle flap removal survived up to 39 days before developing cicatricial stenosis. CONCLUSIONS: Tissue-engineered neotracheas proved to have excellent biocompatibility and stability to function under physiologic conditions, but lacked adequate endotracheal lining resulting in neotracheal stenosis.

Effects of olfactory training in patients with olfactory loss.

OBJECTIVES: Olfactory function is known to be modulated by repeated exposure to odors. The aim of this investigation was whether patients with olfactory loss would benefit from "Training" with odors in terms of an improvement of their general olfactory function. It was hypothesized that olfactory Training should produce both an improved sensitivity towards the odors used in the Training process and an overall increase of olfactory function. STUDY DESIGN: The prospective study was performed in patients with olfactory dysfunction. METHODS: One group of patients performed the Training (n = 40), whereas another part did not (n = 16). Exclusion criteria for patients were sinunasal disease. Olfactory training was performed over a period of 12 weeks. Patients exposed themselves twice daily to four intense odors (phenyl ethyl alcohol: rose, eucalyptol: eucalyptus, citronellal: lemon, and eugenol: cloves). Olfactory testing was performed before and after training using the "Sniffin' Sticks" (thresholds for phenyl ethyl alcohol, tests for odor discrimination and odor identification) in addition to threshold tests for the odors used in the training process. RESULTS: Compared to baseline, training patients experienced an increase in their olfactory function, which was observed for the Sniffin' Sticks test score and for thresholds for the odors used in the training process. In contrast, olfactory function was unchanged in patients who did not perform olfactory training. The present results indicate that the structured, short-term exposure to selected odors may increase olfactory sensitivity.

Fabrication of a neotrachea using engineered cartilage.

OBJECTIVES: Surgical management of long-segment tracheal stenosis is an ongoing problem. Many types of tracheal prostheses have been tried but with limited success because of immune rejection, graft ischemia, or restenosis. Tissue engineered cartilage may offer a solution to this problem, although scaffolds, which are currently often used for support, can lead to biocompatibility problems. This study investigated the feasibility of scaffold-free cartilage to tissue engineer a vascularized neotrachea in rabbits. STUDY DESIGN: Animal study. METHODS: Autologous neotracheal constructs were implanted in the abdomen of six New Zealand white rabbits. Auricular chondrocytes were used to engineer scaffold-free cartilage sheets. A muscle flap raised from the external abdominal oblique muscle and the engineered cartilage were wrapped around a silicone stent to fabricate a vascularized neotrachea in vivo. In two of the six rabbits, a full thickness skin graft was used to create an epithelial lining. The constructs were harvested after either 6 or 10 weeks. RESULTS: All neotracheal constructs were healthy with well-vascularized and integrated layers. The implanted engineered cartilage underwent a remodeling process, forming a solid tracheal framework. Constructs harvested after 10 weeks proved to have significantly better mechanical properties than after 6 weeks and were comparable with the rabbit's native trachea. CONCLUSION: Scaffold-free engineered cartilage can successfully fabricate a well-vascularized, autologous neotrachea with excellent mechanical properties. The results suggest that this approach can be used to reconstruct tracheal defects in rabbits.

Hyaluronan-based scaffolds to tissue-engineer cartilage implants for laryngotracheal reconstruction.

OBJECTIVES: Donor site morbidity, including pneumothorax, can be a considerable problem when harvesting cartilage grafts for laryngotracheal reconstruction (LTR). Tissue-engineered cartilage may offer a solution to this problem. This study investigated the feasibility of using Hyalograft C combined with autologous chondrocytes to tissue engineer cartilage grafts for LTR in rabbits. STUDY DESIGN: Animal study. METHODS: Eighteen New Zealand white rabbits underwent LTR: 12 rabbits received autologous tissue-engineered cartilage grafts and 6 animals, serving as a positive control group, native auricular cartilage. To determine any differences in response to the site of implantation and any potential immune response to the scaffold, a second piece of engineered neocartilage and a non-cell-loaded scaffold were inserted paralaryngeally into a subset of the rabbits. The rabbits were sacrificed 3, 6, 8, 10, and 12 weeks after the LTR and their larynx examined. RESULTS: None of the 18 rabbits showed signs of respiratory distress. A smooth, noninflammatory scar was visible intraluminally. Histologically, the native auricular cartilage implants showed excellent integration without any signs of inflammation or cartilage degradation. In contrast, all tissue-engineered grafts and empty scaffolds revealed marked signs of an unspecific foreign body reaction, leading to a complete degradation of the neocartilage, whether implanted para- or intralaryngeally. CONCLUSION: In contrast to the success with which Hyalograft C has been applied in articular defect repair, our results indicate that, in rabbits, Hyalograft C initiates a foreign body reaction if implanted intra- or paralaryngeally, leading to cartilage degradation and possible graft failure. These findings suggest limitations on the environment in which Hyalograft C can be applied.