Objectives/Hypothesis To translate the Velopharyngeal Insufficiency Effects on Life Outcomes (VELO) instrument into Chinese and test its psychometric properties. Study Design Quality of life instrument translation and validation. Methods The original English version of the VELO instrument was translated into Mandarin, back-translated, and adapted among the Chinese population, based on the standardized guidelines for the cross-culture adaption process. Velopharyngeal insufficiency (VPI) patients were identified by a professional speech and language pathologist. Internal reliability of the VELO instrument was assessed by the Cronbach's alpha coefficient. Discriminant validity was tested by the Mann-Whitney U test. Construct validity was assessed by factor analysis. Results A total of 113 patients with VPI and 72 parents of the patients were enrolled. The mean age of the VPI patients was 14.8 years. Internal reliability was excellent; Cronbach's alpha coefficients were 0.92 and 0.94 for VPI patients and their parents, respectively. The Chinese VELO discriminated well between the VPI group and the controls, with a mean (standard deviation) score that was significantly lower for the VPI group (74.8 [25.7]) than the control group (98.0 [15.9]) (P < .001). The total scores and scores in the emotional domain or perception domain showed differences between VPI patients and their parents. Similar to the original study, the factor loading after rotation followed hypothesized domains largely, in spite of items from several domains loaded on the same factor. Conclusions The translated Chinese version of the VELO instrument demonstrated an acceptable reliability, discriminant validity, and construct validity. These psychometric properties suggested theoretical evidence for the further use of the VELO instrument among Chinese patients with VPI. Level of Evidence 3b Laryngoscope, 129:E395-E401, 2019
Objective To evaluate the extent of airway improvement and voice quality in patients with bilateral vocal fold paralysis (BVFP) who underwent selective laryngeal reinnervation surgery. Methods Seven patients with BVFP caused by thyroid surgeries were enrolled. They underwent selective laryngeal reinnervation surgery. Videostroboscopy data, voice perceptual data (grade [G]), acoustic data, laryngeal electromyography data, and pulmonary function test data were obtained preoperatively and postoperatively. Results Videostroboscopic videos showed that six patients could achieve moderate-to-maximal abduction in the bilateral vocal folds during inspiration, whereas all patients achieved adduction in the bilateral vocal folds during phonation at 4 to 7 months postoperatively. G score was decreased significantly versus preoperative values (P < 0.05), and vocal functional parameters were improved significantly at 12 months postoperatively (P < 0.05). The aerodynamic parameter of maximum phonation time was significantly longer than the preoperative value (P < 0.05). Most parameters in pulmonary function test recovered to normal reference levels as early as 3 months postoperatively, whereas maximal inspiratory pressure (PImax) values were still slightly lower than normal levels 12 months after surgery. All of these parameters improved significantly versus preoperative values. Electromyographic data at 12 months postoperatively showed full interference potentials in bilateral posterior cricoarytenoid muscles during inspiration and full interference potentials in bilateral thyroarytenoid muscles during phonation in all patients. Moderate electric potentials were seen in left interarytenoid muscle in one failed patient. Conclusion This new selective laryngeal reinnervation procedure can achieve physiological movements of the bilateral vocal folds in selected patients with BVFP. Level of Evidence 4. Laryngoscope, 129:2669-2673, 2019
Objectives To investigate the role of lingual lymph node (LLN) metastasis on locoregional control (LRC) in patients with locally advanced tongue squamous cell carcinoma (SCC). Methods A total of 231 patients were prospectively enrolled. Analyses focused on the association between the LLN metastasis and clinical pathologic variables as well as the significance of LLN metastasis in predicting prognosis. Results LLNs were noted in 58 patients, 33 of whom were positive for LLN metastasis. LLN metastasis was significantly related to adverse pathologic characteristics. In patients with LLN metastasis, the 5-year LRC rate was 45%. In patients without LLN metastasis, the 5-year LRC rate was 65% and the difference was significant (P = 0.013). Further, Cox model analysis confirmed the independence of LLN metastasis from prognosis prediction. Conclusion LLN metastasis in locally advanced tongue SCC is relatively uncommon; however, LLNs should be routinely dissected because they could significantly decrease locoregional control. Level of Evidence 2b. Laryngoscope, 129:2527-2530, 2019
Objective To reconstruct the auricle using a porous, hollow, three-dimensional (3D)-printed mold and autologous diced cartilage mixed with platelet-rich plasma (PRP). Methods Materialise Magics v20.03 was used to design a 3D, porous, hollow auricle mold. Ten molds were printed by selective laser sintering with polyamide. Cartilage grafts were harvested from one ear of a New Zealand rabbit, and PRP was prepared using 10 mL of auricular blood from the same animal. Ear cartilage was diced into 0.5- to 2.0-mm pieces, weighed, mixed with PRP, and then placed inside the hollow mold. Composite grafts were then implanted into the backs of respective rabbits (n = 10) for 4 months. The shape and composition of the diced cartilage were assessed histologically, and biomechanical testing was used to determine stiffness. Results The 3D-printed auricle molds were 0.6-mm thick and showed connectivity between the internal and external surfaces, with round pores of 0.1 to 0.3 cm. After 4 months, the diced cartilage pieces had fused into an auricular shape with high fidelity to the anthropotomy. The weight of the diced cartilage was 5.157 +/- 0.230 g (P > 0.05, compared with preoperative). Histological staining showed high chondrocyte viability and the production of collagen II, glycosaminoglycans, and other cartilaginous matrix components. In unrestricted compression tests, auricle stiffness was 0.158 +/- 0.187 N/mm, similar to that in humans. Conclusion Auricle grafts were constructed successfully through packing a 3D-printed, porous, hollow auricle mold with diced cartilage mixed with PRP. The auricle cartilage contained viable chondrocytes, appropriate extracellular matrix components, and good mechanical properties. Levels of Evidence NA. Laryngoscope, 129:2467-2474, 2019
Objectives To evaluate the feasibility of topical photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) for vocal fold leukoplakia. Study Design Ex vivo and in vivo. Methods 5-ALA was applied topically as a 20% solution to ex vivo canine vocal folds. The penetration depth and concentrations of 5-ALA in tissue were quantified using frozen sectioning and fluorescamine derivatization after 5-ALA contact incubation or topical spraying. Then, 5-ALA solution was sprayed on leporine vocal folds once, twice, or given systemically in vivo. Protoporphyrin IX (PPIX) location was visualized using fluorescence microscopy, and PPIX concentrations were measured using a fluorescent quantitative method. Hematoxylin and eosin (H&E) staining was performed to visualize the histological changes of vocal folds after PDT for each group. Results Topical incubation of 15 minutes with 5-ALA achieved a penetration depth of over 2 mm and similar concentrations within the superficial 500 mu m of epithelium, compared with longer incubation times. Topical spraying of 5-ALA produced sufficient concentrations in vocal folds, but the retention time is short. An in vivo leporine model showed that laryngeal spraying of 20% 5-ALA induced similar penetration depth and concentrations of PPIX compared to systemic administration of 5-ALA. Two sprays of 20% 5-ALA solution with an interval of 30 minutes are needed to produce complete exfoliation of vocal fold epithelium. Conclusion Topical PDT with laryngeal spraying of 20% 5-ALA solution achieves sufficient therapeutic effects and is potentially applicable for the treatment of vocal fold leukoplakia.
Objectives The goal of this study was to detect and explore the mechanisms of the succinate dehydrogenase (SDH) complex subunit-related gene mutations in cases of multiple paraganglioma (PGL) in the head and neck. Methods In Beijing Tongren Hospital (Capital Medical University, Beijing, People's Republic of China) between January 2013 and February 2017, 23 cases of head and neck multiple PGL were evaluated by genetic sequencing. From these cases, four hereditary families and 10 cases with sporadic occurrences were found. Gene mutations, including SDHD, SDHB, SDHC, SDHAF2, VHL and RET in germ cells and somatic cells, were detected by gene capture and high throughput sequencing. Results In family 1, 12 instances of SDHD gene mutation were detected, eight of which manifested as bilateral carotid body tumor (CBT) with one bilateral malignant CBT. In family 2, three cases of SDHD mutation were found with one case of bilateral CBT and two cases of unilateral CBT. In family 3, two cases of SDHD gene mutation were found, both characterized by vagus PGL and pheochromocytoma. Of the 10 patients with sporadic manifestations, five cases of SDHD gene mutation and one case of RET gene mutation were detected. Two novel gene mutations, c.387_393del7 mutation of SDHD gene and c.3247A>G mutation of RET gene, were also detected. Conclusion In patients with multiple PGL in the head and neck, these are accompanied by a genetic mutation of the germ cell. In this case study, this mutation was most commonly a mutation of the SDH gene.
Objectives/Hypothesis To assess the somatosensory dysfunction of the auricle and periotic skin in patients undergoing otitis media surgery. Study Design Retrospective study. Methods Symptoms of periotic somatosensory function after surgery were investigated in 100 patients (42 males, 58 females, mean age 41.39 years) who underwent otitis media surgery. Questionnaires on periotic somatosensory disturbance were answered after surgery at least over 1 year postoperatively. Results Of 100 tympanoplasties, all patients were completed within a postauricular approach. The highest incidence rates of periotic sensory disturbance were found in the postauricular region (75%), followed by the auricular region (20.83%); lower rates were found in the preauricular region (2.08%) and the earlobe (2.08%). Periotic somatosensory dysfunction occurred in 48 patients (48%). The most prevalent somatosensory abnormality was tactile hypoaesthesia/numbness, evident in 28% of the patients; more remarkable, inferior postauricular region. Periotic pain was reported by 21% of the cases, mostly located in the upper auricle. Compared to the recovery time of tactile hypoaesthesia (7.36 months), patients' periotic somatosensory pain improved significantly within 4.07 months, which has obvious statistical significance (P < 0.01). Conclusion The likelihood of periotic cutaneous sensory dysfunction should be emphasized to patients undergoing otitis media surgery via postauricular approaches, which occurred in nearly half of patients; the majority recovered within 1 year. Furthermore, the postauricular region is the most vulnerable location to sensory disturbance, followed by the auricular region. Functionally, periotic somatosensory pain was more easily resilient, relative to tactile hypoaesthesia/numbness.
Objectives The purpose of this study was to introduce a new narrow band imaging (NBI) endoscopic classification for the diagnosis of vocal cord leukoplakia. Study Design Case series. Methods From January 2010 to February 2018, a total of 120 cases of vocal cord leukoplakia were enrolled in this study. The NBI endoscopic system was used to examine the vocal cords. Each lesion was observed by NBI endoscopy and evaluated according to the detailed morphologic findings of intraepithelial papillary capillary loop (IPCL). The superficial IPCL patterns were classified into six types (types I-VI). The differential diagnosis abilities of NBI classification for benign and malignant leukoplakia were investigated. Results Out of the 120 cases of vocal cord leukoplakia, 81% (97 of 120) related to benign lesions (including inflammation, epithelial proliferation, hyperkeratosis, dyskeratosis, mild dysplasia, and moderate dysplasia); the remaining 19% (23 of 120) consisted of malignant lesions (including severe dysplasia, carcinoma in situ, and invasive carcinoma). The accuracy of differential diagnosis for vocal cord leukoplakia using NBI endoscopy was up to 90.8% (109 of 120), significantly higher than that of white light imaging (70.0%, 84 of 120) (chi(2) = 16.536, P = 0.000). The sensitivity, specificity, and positive and negative predictive values of the diagnosis for malignant vocal cord leukoplakia under the NBI endoscope were 82.6%, 92.8%, 73.1%, and 95.7%, respectively. There is relatively good consistency between the NBI endoscopic diagnosis and pathological diagnosis (kappa = 0.718, P = 0.000). Conclusion The new NBI endoscopic classification of vocal cord leukoplakia can improve the accuracy of distinguishing benign and malignant leukoplakia.
Objective To compare survival effects of comprehensive neck dissection (CND) and selective neck dissection (SND) for patients with nasopharyngeal carcinoma (NPC) with only regional failure. Methods A total of 294 recurrent T0N1-3M0 NPC patients who underwent neck dissection in Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China, between January 1984 and February 2014, were enrolled in the survival and interaction analyses. Using propensity scores to adjust for potential prognostic factors, an additional well-balanced cohort of 210 patients was constructed by matching each patient who received SND with one patient who underwent CND (1:1); the differences were then compared between SND and CND in terms of overall survival (OS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), and distant metastasis-free survival (DMFS). Results Both univariate and multivariate analyses showed that SND was not inferior to CND (P > 0.05) but demonstrated that extracapsular spread (ECS) (hazard ratio [HR] 3.49, 95% confidence interval [CI] 2.30-5.29, P < 0.001), recurrent N stage (rN stage) (HR 1.96, 95% CI 1.29-2.97, P = 0.002), and positive margins (HR 3.67, 95% CI 2.40-5.62, P < 0.001) were independent poor prognostic factors for OS. The interaction effects between the dissection style and each independent factor were not significant for OS, LRFS, RRFS, or DMFS (P > 0.05). Furthermore, no survival differences were found between SND and CND in the case-matched cohort in terms of OS, LRFS, RRFS, or DMFS (P = 0.550, 0.930, 0.214, and 0.146, respectively). Conclusion With a similar radical dissection extent around the tumor rather than dissection of extensive lymph region distal to the lesion, SND is not inferior to CND for patients with NPC with only cervical failure. ECS, rN stage, and positive margins were adverse independent prognostic factors for patients with NPC.
Objective Activation of mast cells associates with eosinophilic inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). The disease-specific mast cell-triggering mechanisms apart from immunoglobulin E are poorly understood in CRSwNP. CD30L/CD30 are members of the tumor necrosis factor/receptor superfamily and display immune modulatory function on mast cells. The aim of this study was to explore the expression and function of CD30 and CD30L in CRSwNP. Methods The mRNA expression of CD30 and CD30L was analyzed by real-time polymerase chain reaction. The cellular expression of CD30L was determined by immunofluorescence staining. The soluble CD30 levels in nasal tissues were detected by enzyme-linked immunosorbent assay. HMC-1 cells, a human mast cell line, were cultured and stimulated with CD30. Results Compared with control tissues, CD30 mRNA expression levels were increased in eosinophilic polyps, and soluble CD30 protein levels were upregulated in both eosinophilic and noneosinophilic polyps with a greater increase in eosinophilic type. CD30 was expressed by T cells and B cells in nasal polyps. The CD30L mRNA expression levels and the number of CD30L(+) cells and CD30L(+)tryptase(+) mast cells were increased in eosinophilic polyps but not in noneosinophilic polyps as compared with control tissues. Mast cells accounted for 60% of CD30L(+) cells in eosinophilic polyps. CD30 induced HMC-1 cells to produce interleukin (IL)-4 and IL-13 without degranulation. Mast cells expressed IL-4 and IL-13 in eosinophilic polyps. The number of CD30L(+)tryptase(+) mast cells was positively correlated with the number of eosinophils and total inflammatory cells in eosinophilic polyps. Conclusion CD30/CD30L-mediated mast cell activation may promote the eosinophilic inflammation in CRSwNP.
Objectives/Hypothesis The overlying inflammatory mucosa plays a crucial role in the initiation of osteitis; however, the molecular mechanism is unclear. The objective of this study was to explore the bone morphogenetic protein (BMP) pathway and to correlate the expression of key signaling molecules with the degree of osteitis in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Study Design Prospective experimental analysis. Methods This was an institutional review board-approved study in which mucosal samples were obtained from sites of osteitis in CRSwNP and compared to nonosteitic healthy controls (n = 10/group). Protein expression of key BMP pathway was quantified by aptamer-based protein array and confirmed by a set of selected mRNA analyses. Degree of osteitis was assessed using both Kennedy Osteitis Score and Global Osteitis Score (GOS). Results Pro-osteoblastic expression of BMP7 (fold change [FC] = -1.18, P = .017) and BMP9 (FC = -1.32, P = .023), their receptors, BMP receptor type-1A (BMPR1A) (FC = -2.56, P = .005) and BMP receptor type-2 (FC = -1.28, P = .022), and two enhancers of BMP signaling pathway, the repulsive guidance molecule domain family member B (FC = -1.13, P = .008) and the chordin-like protein 1 (FC = -1.18, P = .027), were all significantly downregulated in CRSwNP. Conversely, the pro-osteoclastic factor, tartrate-resistant acid phosphatase type 5 (ACP5) (FC = 2.36, P = .001), was significantly increased in CRSwNP. GOS was inversely correlated with levels of BMP7 (r = -0.684, P = .005) and BMPR1A (r = -0.864, P = .005) and positively correlated with levels of ACP5 (r = 0.815, P = .004). The FCs among the proteins studied significantly and positively correlated with the FCs of their mRNA expression (r = 0.908, P = .002). Conclusions Downregulated pro-osteoblastic mucosal BMP signaling is strongly and significantly associated with increased osteitis in CRSwNP.
Objectives/Hypothesis To suggest a strategy for transoral removal of hilar and intraparenchymal submandibular stones. Study Design Retrospective case series. Methods Retrospective evaluation was performed for 514 consecutive patients with hilar and intraparenchymal submandibular stones treated via endoscopy-assisted surgery from January 2006 to June 2018. Three patients had bilateral stones. The stones were classified as: hilar (type I), posthilar (type II), intraparenchymal (type III), and multiple stones (type IV). Results The affected glands included 311 with type I, 84 with type II, 65 with type III, and 57 with type IV stones. Stones were successfully removed in 478 glands (92.5%, 478/517). Main treatment techniques included hilum ductotomy in 311 glands, intraparenchymal ductotomy in 68, submandibulotomy in 14, intraductal retrieval in 74, and hilum ductotomy accompanied by intraductal retrieval in 11. At a mean 40-months follow-up of 478 successful cases, clinical outcomes were good in 425, fair in 27, and poor in 26 glands. Postoperative sialograms in 75 stone-free patients were categorized as: type I, normal (n = 6); type II, ectasia or stenosis in the main duct and no persistent contrast on functional films (n = 44); type III, ectasia or stenosis in the main duct and mild contrast retention (n = 15); and type IV, poor shape of the main duct and evident contrast retention (n = 10). Postoperative sialometry of 32 patients revealed no significant differences of the gland function between the two sides. Conclusions Appropriate use of various endoscopy-assisted approaches helps preserve the gland and facilitates recovery of gland function in patients with different depths of hilo-parenchymal submandibular stones. Level of Evidence 4 Laryngoscope, 2019
Objectives/HypothesisCryotherapy has been shown to be a scarless treatment modality for dermal lesions; however, there are limited data addressing the effect of cryotherapy on vocal fold tissue. The aim of this study was to clarify the effectiveness of cryotherapy for prevention of postsurgical vocal fold scarring. Study DesignProspective animal study in rabbits. MethodsThe lamina propria of 20 rabbit vocal folds was bilaterally stripped, followed by randomized unilateral cryotherapy. Five larynges were harvested for real-time polymerase chain reaction (RT-PCR) analysis at 1 day, 3 days, and 7 days postinjury. The remaining five were harvested for histologic analysis at 3 months. Images of the healing phase were recorded by laryngoscopy. Analyses of RT-PCR for cyclooxygenase (COX)-2, interleukin (IL)-6, collagen I, collagen III, matrix metallopeptidase 1 (MMP1), transforming growth factor (TGF1), smooth muscle actin (-SMA), and hyaluronan synthase 1 (HAS1) were completed. Histological samples were completed for collagen and hyaluronic acid analysis. ResultsRT-PCR results revealed that higher expressions of HAS1 and MMP1 and lower expressions of COX-2, IL-6, collagen I, collagen III, TGF1, and -SMA were observed, and histological examination showed significantly increased hyaluronic acid, decreased deposition, and more organized configuration of collagen in injury with the cryotherapy cohort compared with the injury cohort. ConclusionsCryotherapy can inhibit the inflammatory reaction and simulate a fetal healing environment in extracellular matrix synthesis to regenerate vocal fold tissue with less fibrosis. Histological results showed that cryotherapy achieves a mature healing result with less scar, which tends to return to normal. In summary, the findings of this study suggest that administration of cryotherapy at the time of injury has the potential to minimize vocal fold scarring. Level of EvidenceNA Laryngoscope, 129:E151-E157, 2019
Objectives/HypothesisVocal fold scarring remains a major treatment challenge, and scar prevention without residual lesions remains a dilemma. Cryotherapy has shown cosmetic outcomes on skin lesions with minimal scarring. The aim of this study was to clarify the beneficial effects of cryotherapy for the prevention and the treatment of vocal fold scarring. Study DesignIn vitro. MethodsPrimary cultures of human vocal fold fibroblasts (VFFs) were used in this study. Myofibroblast differentiation was stimulated by transforming growth factor 1 (TGF-1). We mimicked the cryotherapy effect on vocal fold healing in vivo by freezing VFFs TGF-1 in vitro. The influence of freezing on cell viability, proliferation, migration, and contractile properties were analyzed. The expression of collagen I, collagen III, fibronectin, TGF-1, matrix metallopeptidase 1 (MMP1), hyaluronan synthase 1 (HAS1) were investigated by real-time polymerase chain reaction (RT-PCR), and the expression of alpha smooth muscle actin (-SMA) and decorin were investigated by RT-PCR and Western blot. ResultsFreezing was found to modify extracellular matrix (ECM) synthesis and differentiation of VFFs. Expression of collagen I, collagen III, fibronectin, -SMA, and TGF-1 was downregulated, and MMP1 was upregulated in VFFs + TGF-1 (myofibroblast) by freezing. HAS1 and decorin were upregulated in both VFFs TGF-1 by freezing. Freezing VFFs + TGF-1 (myofibroblast) with fast thawing had a lower expression of -SMA when compared with slow thawing. Freezing reduced the migration and collagen contraction of VFFs + TGF-1 (myofibroblast). ConclusionCryotherapy induces antifibrotic and regenerative ECM alterations in VFFs. These data provide insight into the prevention and the treatment of vocal fold scarring with cryotherapy in phonomicrosurgery. Level of EvidenceNA Laryngoscope, 129:E143-E150, 2019
Objectives/HypothesisProbe-based confocal laser endomicroscopy (pCLE) is a novel technique allowing real-time evaluation of the histological features of tissues in vivo at the cellular level. This study aimed to evaluate the feasibility of using pCLE in the diagnosis of nasopharyngeal carcinoma (NPC). Study DesignFeasibility study. MethodsIn this study, the pCLE images of the lesions, as well as the surrounding or contralateral normal mucosa of the lesions, were acquired in vivo from each patient after intravenous injecting of 2.5mL fluorescein. Biopsy specimens were collected at the imaged sites followed by a histopathological diagnosis by the pathologists, which was used as the gold standard. The pCLE images were compared to histopathological diagnosis of visualized sites by using sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). ResultsDiagnoses based on pCLE images correlated well with the gold standard diagnoses based on tissue histology. The overall sensitivity, specificity, PPV, and NPV for diagnosis of carcinoma versus nondysplasia were 93.8% (67.7%-99.7%), 90.5% (68.2%-98.3%), 88.2% (62.3%-97.9%), and 95.0% (73.1%-99.7%), respectively, and the four indices for pCLE diagnosis of dysplasia versus nondysplasia were 60.0% (17.0%-92.7%), 80.9% (57.4%-93.7%), 42.9% (11.8%-79.8%), and 89.5% (65.5%-98.2%), respectively. The overall sensitivity for diagnosis of carcinoma versus dysplasia was 93.8% (67.7%-99.7%), specificity was 40% (7.3%-83.0%), PPV was 83.3% (57.7%-95.6%), and the NPV was 66.7% (12.5%-98.2%). ConclusionsCLE is a suitable and valid method for otolaryngologists to diagnose of NPC in vivo. Level of EvidenceNA Laryngoscope, 129:897-902, 2019