Comparing the clinical outcomes of initial surgery and primary definitive radiotherapy with a dosage of 6600 cGy or higher in cT1-2N0M0 oral cavity squamous cell carcinoma: A nationwide cohort study.

BACKGROUND: To compare the clinical outcomes of two treatment modalities, initial surgery and primary definitive radiotherapy (RT), in Taiwanese patients diagnosed with cT1-2N0M0 oral cavity squamous cell carcinoma (OCSCC). METHODS: Between 2011 and 2019, we analyzed data for 13,542 cT1-2N0M0 patients who underwent initial surgery (n = 13,542) or definitive RT with a dosage of at least 6600 cGy (n = 145) for the treatment of OCSCC. To account for baseline differences, we employed propensity score (PS) matching, resulting in two well-balanced study groups (initial surgery, n = 580; definitive RT, n = 145). RESULTS: Before PS matching, the 5-year disease-specific survival (DSS) rates were 88% for the surgery group and 58% for the RT group. After PS matching, the 5-year DSS rates of the two groups were 86% and 58%, respectively. Similarly, the 5-year overall survival (OS) rates before PS matching were 80% for the surgery group and 36% for the RT group, whereas after PS matching, they were 73% and 36%, respectively. All these differences were statistically significant (p < 0.0001). A multivariable analysis identified treatment with RT, older age, stage II tumors, and a higher burden of comorbidities as independent risk factors for both DSS and OS. We also examined the 5-year outcomes for various subgroups (margin ≥5 mm, margin <5 mm, positive margins, RT combined with chemotherapy, and RT alone) as follows: DSS, 89%/88%/79%/63%/51%, respectively, p < 0.0001; OS, 82%/79%/68%/39%/32%, respectively, p < 0.0001. CONCLUSIONS: In Taiwanese patients with cT1-2N0M0 OCSCC, a remarkably low proportion (1.1%) completed definitive RT. A significant survival disparity of 30% was observed between patients who underwent initial surgery and those who received definitive RT. Interestingly, even patients from the surgical group with positive surgical margins exhibited a significantly superior survival compared to those in the definitive RT group.

Should sub-millimeter margins be deemed positive in oral cavity squamous cell carcinoma?

BACKGROUND: While several studies have indicated that a margin status of < 1 mm should be classified as a positive margin in oral cavity squamous cell carcinoma (OCSCC), there is a lack of extensive cohort studies comparing the clinical outcomes between patients with positive margins and margins < 1 mm. METHODS: Between 2011 and 2020, we identified 18,416 Taiwanese OCSCC patients who underwent tumor resection and neck dissection. Of these, 311 had margins < 1 mm and 1013 had positive margins. To compare patients with margins < 1 mm and those with positive margins, a propensity score (PS)-matched analysis (n = 253 in each group) was conducted. RESULTS: The group with margins < 1 mm displayed a notably higher prevalence of several variables: 1) tongue subsite, 2) younger age, 3) smaller depth of invasion), 4) early tumor stage, and 5) treatment with surgery alone. Patients with margins < 1 mm demonstrated significantly better disease-specific survival (DSS) and overall survival (OS) rates compared to those with positive margins (74 % versus 53 %, 65 % versus 43 %, both p < 0.0001). Multivariable analysis further confirmed that positive margins were an independent predictor of worse 5-year DSS (hazard ratio [HR] = 1.38, p = 0.0103) and OS (HR = 1.28, p = 0.0222). In the PS-matched cohort, the 5-year outcomes for patients with margins < 1 mm compared to positive margins were as follows: DSS, 71 % versus 59 %, respectively (p = 0.0127) and OS, 60 % versus 48 %, respectively (p = 0.0398). CONCLUSIONS: OCSCC patients with a margin status < 1 mm exhibited distinct clinicopathological characteristics and a more favorable prognosis compared to those with positive resection margins.

Is elective neck dissection justified in cT2N0M0 oral cavity cancer defined according to the AJCC eighth edition staging system?

BACKGROUND: The current NCCN guidelines recommend considering elective neck dissection (END) for early-stage oral cavity squamous cell carcinoma (OCSCC) with a depth of invasion (DOI) exceeding 3 mm. However, this DOI threshold, determined by evaluating the occult lymph node metastatic rate, lacks robust supporting evidence regarding its impact on patient outcomes. In this nationwide study, we sought to explore the specific indications for END in patients diagnosed with OCSCC at stage cT2N0M0, as defined by the AJCC Eighth Edition staging criteria. METHODS: We examined 4723 patients with cT2N0M0 OCSCC, of which 3744 underwent END and 979 were monitored through neck observation (NO). RESULTS: Patients who underwent END had better 5-year outcomes compared to those in the NO group. The END group had higher rates of neck control (95% vs. 84%, p < 0.0001), disease-specific survival (DSS; 87% vs. 84%, p = 0.0259), and overall survival (OS; 79% vs. 73%, p = 0.0002). Multivariable analysis identified NO, DOI ≥5.0 mm, and moderate-to-poor tumor differentiation as independent risk factors for 5-year neck control, DSS, and OS. Based on these prognostic variables, three distinct outcome subgroups were identified within the NO group. These included a low-risk subgroup (DOI <5 mm plus well-differentiated tumor), an intermediate-risk subgroup (DOI ≥5.0 mm or moderately differentiated tumor), and a high-risk subgroup (poorly differentiated tumor or DOI ≥5.0 mm plus moderately differentiated tumor). Notably, the 5-year survival outcomes (neck control/DSS/OS) for the low-risk subgroup within the NO group (97%/95%/85%, n = 251) were not inferior to those of the END group (95%/87%/79%). CONCLUSIONS: By implementing risk stratification within the NO group, we found that 26% (251/979) of low-risk patients achieved outcomes similar to those in the END group. Therefore, when making decisions regarding the implementation of END in patients with cT2N0M0 OCSCC, factors such as DOI and tumor differentiation should be taken into account.

Pathophysiological Mechanisms Underlying Unilateral Vocal Fold Paralysis in Female Patients: An Ultrasonographic Study.

OBJECTIVES: Laryngeal ultrasonography (LUS) has been suggested as an alternative diagnostic tool for unilateral vocal fold paralysis (UVFP). The present study applied LUS and quantitative laryngeal electromyography (LEMG) in female UVFP patients to investigate the pathophysiologic mechanisms of UVFP. METHODS: In this cross-sectional study, vocal fold (VF) length parameters included resting and phonating VF length measured using B-mode LUS, and color Doppler vibrating length (CDVL) measured using the color Doppler mode. RESULTS: Forty female patients with UVFP were enrolled, among whom 11 and 29 were assigned to the thyroarytenoid (TA) muscle+cricothyroid (CT) muscle group (with CT involvement) and the TA (without CT involvement) group, respectively. In the TA group, the turn frequency in thyroarytenoid-lateral cricoarytenoid (TA-LCA) on the paralyzed side, as observed through LEMG, correlated with the VF length during the resting phase (R=0.368, P=0.050) and CDVL values (R=0.627, P=0.000) on the paralyzed side. In the TA+CT group, the turn ratio in the CT muscle correlated with the normalized phonatory vocal length change (nPLC; R=0.621, P=0.041) on the paralyzed side. CONCLUSION: CDVL and nPLC are two parameters that can be utilized to predict the turn frequencies of TA-LCA in UVFP cases without CT involvement, and the turn ratio of CT in cases of UVFP with CT involvement, respectively. The findings suggest that LUS, as a noninvasive tool, can serve as an alternative method for assessing the severity of laryngeal nerve injury and offer valuable insights into the pathophysiology of UVFP.

Indications for elective neck dissection in cT1N0M0 oral cavity cancer according to the AJCC eight edition: A nationwide study.

OBJECTIVES: According to the NCCN guidelines, there is weak evidence to support the use of elective neck dissection (END) in early-stage oral cavity squamous cell carcinoma (OCSCC). We sought to examine the indications for END in patients with cT1N0M0 OCSCC defined according to the AJCC Staging Manual, Eight Edition. METHODS: Of the 3886 patients diagnosed with cT1N0M0 included in the study, 2065 underwent END and 1821 neck observation. RESULTS: The 5-year outcomes for patients who received END versus neck observation before and after propensity score matching (n = 1406 each) were as follows: neck control, 96 %/90 % (before matching), p < 0.0001; 96 %/90 % (after matching), p < 0.0001; disease-specific survival (DSS), 93 %/92 % (before matching), p = 0.0227; 93 %/92 % (after matching), p = 0.1436. Multivariable analyses revealed that neck observation, depth of invasion (DOI) > 2.5 mm, and poor differentiation were independent risk factors for 5-year outcomes. Upon the application of a scoring system ranging from 0 (no risk factor) to 3 (presence of the three risk factors), the following 5-year rates were observed: neck control, 98 %/95 %/84 %/85 %; DSS, 96 %/93 %/88 %/85 %; and overall survival, 90 %/86 %/79 %/59 %, respectively (all p < 0.0001). The survival outcomes of patients with scores of 0 and 1 were similar. The occult metastasis rates in the entire study cohort, DOI > 2.5 mm, and poor differentiation were 6.8 %/9.2 %/17.1 %, respectively. CONCLUSION: Because all patients who received neck observation had a score of 1 or higher, END should be performed when a DOI > 2.5 mm or poorly differentiated tumors are present. Under these circumstances, 48.6 % (1888/3886) of cT1N0M0 patients may avoid END without compromising oncological outcomes.

Effect of Preoperative Weight Status and Disease Presentation on Postoperative Elevated Blood Pressure After Childhood Adenotonsillectomy.

OBJECTIVE: To investigate the risk factors of postoperative elevated blood pressure (BP) in children with childhood obstructive sleep apnea syndrome (OSAS) after adenotonsillectomy (AT). STUDY DESIGN: Case series with planned data collection. SETTING: Tertiary referral center. METHODS: Two hundred forty-five consecutive children (180 boys and 65 girls, median age 6.6 years) with polysomnography-diagnosed OSAS who underwent AT between January 2010 and August 2019. Clinical, polysomnographic, and evening BP data were assessed preoperatively and postoperatively (≥3 months after AT). Changes in the variables before and after AT and between individuals with and without hypertension were compared. RESULTS: Postoperatively, the median (interquartile range) apnea-hypopnea index significantly decreased from 10.4 (5.3-22.6) to 2.2 (1.0-3.8) events/h. In addition, the mean (standard deviation) evening diastolic BP z-score significantly decreased from 0.7 (0.94) to 0.5 (0.81) in the overall cohort, and both systolic (2.1 [0.94]-1.0 [1.31]) and diastolic BP z-scores (1.6 [0.98]-0.7 [0.85]) significantly decreased in the preoperative elevated BP subgroup. Multivariate logistic regression analysis showed that preoperative obesity (adjusted odds ratio = 4.36, 95% confidence interval = 2.24-8.49) and mean peripheral oxygen saturation <95% during sleep (adjusted odds ratio = 2.73, 95% confidence interval = 1.29-5.79) were independently associated with postoperative elevated BP. CONCLUSION: Preoperative obesity and mean peripheral oxygen saturation <95% during sleep were significantly associated with postoperative elevated BP in the children with OSAS, further indicating the importance of careful BP monitoring in this subgroup despite AT treatment.

Early relapse is an adverse prognostic factor for survival outcomes in patients with oral cavity squamous cell carcinoma: results from a nationwide registry study.

BACKGROUND: The prognostic significance of the relapse interval in patients with resected oral cavity squamous cell carcinoma (OCSCC) is a matter of ongoing debate. In this large-scale, registry-based, nationwide study, we examined whether the time interval between surgery and the first disease relapse may affect survival outcomes in Taiwanese patients with OCSCC. METHODS: Data made available by the Taiwan Health Promotion Administration as of 2004 were obtained. The study cohort consisted of patients who were included in the registry between 2011 and 2017. Disease staging was performed according to the American Joint Committee on Cancer (AJCC) Staging Manual, Eight Edition. We retrospectively reviewed the clinical records of 13,789 patients with OCSCC who received surgical treatment. A total of 2327 (16.9%) patients experienced a first disease relapse. The optimal cutoff value for the relapse interval was 330 days when both 5-year disease-specific survival (DSS) and overall survival (OS) (≤ 330/>330 days, n = 1630/697) were taken into account. In addition, we undertook a propensity score (PS)-matched analysis of patients (n = 654 each) with early (≤ 330 days) versus late (> 330 days) relapse. RESULTS: The median follow-up time in the entire study cohort was 702 days (433 and 2001 days in the early and late relapse groups, respectively). Compared with patients who experienced late relapse, those with early relapse showed a higher prevalence of the following adverse prognostic factors: pT4, pN3, pStage IV, poor differentiation, depth of invasion ≥ 10 mm, and extra-nodal extension. Multivariable analysis revealed that early relapse was an independent adverse prognostic factor for both 5-year DSS and OS (average hazard ratios [AHRs]: 3.24 and 3.91, respectively). In the PS-matched cohort, patients who experienced early relapse showed less favorable 5-year DSS: 58% versus 30%, p < 0.0001 (AHR: 3.10 [2.69 - 3.57]) and OS: 49% versus 22%, p < 0.0001 (AHR: 3.32 [2.89 - 3.81]). CONCLUSION: After adjustment for potential confounders and PS matching, early relapse was an adverse prognostic factor for survival outcomes in patients with OCSCC. Our findings may have significant implications for risk stratification.

Palatal hybrid surgery for obstructive sleep apnea-state-of-the-art annotation of uvulopalatopharyngoplasty.

BACKGROUND: Surgery for obstructive sleep apnea (OSA) has changed in concept and technique that transformed from radical excision to functional reconstruction. The aim of this study was to investigate the safety and effectiveness of palatal hybrid surgery in OSA patients. METHODS: Palatal hybrid surgery is a tissue-specific technique (mucosa-preservation, tonsil-excision, fat-ablation, muscle-relocation/suspension) used in treating OSA patients with velopharyngeal obstruction. The study included 46 consecutive adults OSA patients. The palatal hybrid surgery annotates uvulopalatopharyngoplasty in stereoscopic reconstruction of tonsillar fossa (pharyngoplasty), omni-suspension of the soft palate (palatoplasty) and advancement of uvula (uvuloplasty). RESULTS: No patient experienced airway compromise, voice change or persistent nasal regurgitation following palatal hybrid surgery. One patient existed postoperative tonsillar fossa bleeding received conservative treatment. Postoperative pain in visual analogue scale (VAS) showed average score of 3, 3, 2, 0 at the 1st, 3rd, 7th, 14th day, respectively. Perioperative snoring severity (VAS) (8.7 vs 2.6) and daytime sleepiness (Epworth Sleepiness Scale) (11.3 vs 5.5) all improved significantly (p < 0.001). Posterior air space in retropalatal area increased from 8.4 to 11.1 mm (p < 0.001). Home sleep test showed that apnea-hypopnea index significantly reduced from 41.8 to 18.2 event/h and minimal oxygen saturation increased from 72.4 to 81.5% (p < 0.001). The success rate in individual Friedman stage was 100% (stage I), 63% (stage II) and 58% (stage III) with a total success rate of 63%. CONCLUSION: Palatal hybrid surgery using tissue-specific maneuver annotates UPPP in concept and technique. The results show that palatal hybrid surgery is mini-invasive with low morbid and is effective in improving subjective clinic symptoms, objective sleep parameters and success rate of OSA.

Isolated Epiglottic Manifestations of HIV Infection: Two Cases Reports.

Diagnosis of the Human Immunodeficiency Virus (HIV) remains challenging due to non-specific clinical presentations and mostly flu-like symptoms, e.g., fever, headache, sore throat, and general weakness. Oral lesions, such as oral candidiasis and Kaposi sarcoma, are also frequently associated with HIV infection, whereas laryngeal manifestations are rare. We report two cases of newly diagnosed HIV patients with clinical presentations of sore throat, and endoscopy revealed an epiglottic ulcerative tumor-like lesion. A laryngomicrosurgical biopsy of the lesions was performed for persistent symptoms and suspicion of malignancy. The result revealed acute and chronic inflammation without a conclusive pathology diagnosis. Further laboratory analysis was arranged in consideration of autoimmune diseases, Epstein-Barr virus (EBV), and HIV infection due to their persistent and atypical symptoms. The results were positive for HIV infection. These patients were treated successfully with antiviral treatment and the laryngeal symptoms improved within weeks. In patients with idiopathic and persistent epiglottitis or an epiglottic ulcer after medical treatment, HIV infection needs to be considered as a potential etiology in order to institute proper treatment.

Optimizing margin status for improving prognosis in patients with oral cavity squamous cell carcinoma: A retrospective study from the two highest-volume Taiwanese hospitals.

Background: In the treatment of oral cavity squamous cell carcinoma (OCSCC), surgical quality measures which are expected to affect outcomes, including the achievement of a clear margin, are surgeon-dependent but might not be invariably associated with hospital volume. Our objective was to explore surgical margin variations and survival differences of OCSCC between two highest-volume hospitals in Taiwan. Materials and methods: A total of 2009 and 1019 patients with OCSCC who were treated at the two highest-volume Taiwanese hospitals (termed Hospital 1 and Hospital 2, respectively) were included. We examined how a pathological margin <5 mm impacted patient outcomes before and after propensity score (PS) matching. Results: The prevalence of margins <5 mm was markedly lower in Hospital 1 than in Hospital 2 (34.5%/65.2%, p<0.0001). Compared with Hospital 2, tumor severity was higher in Hospital 1. On univariable analysis, being treated in Hospital 2 (versus Hospital 1; hazard ratio [HR] for 5-year disease-specific survival [DSS] = 1.34, p=0.0002; HR for 5-year overall survival [OS] = 1.17, p=0.0271) and margins <5 mm (versus ≥5 mm; HR for 5-year DSS = 1.63, p<0.0001; HR for 5-year OS = 1.48, p<0.0001) were identified as adverse factors. The associations of treatment in Hospital 2 and margins <5 mm with less favorable outcomes remained significant after adjustment for potential confounders in multivariable analyses, as well as in the PS-matched cohort. The 5-year survival differences between patients operated in Hospital 1 and Hospital 2 were even more pronounced in the PS-matched cohort (before PS matching: DSS, 79%/74%, p=0.0002; OS, 71%/68%, p=0.0269; after PS matching: DSS, 84%/72%, p<0.0001; OS, 75%/66%, p<0.0001). In the entire cohort, the rate of adjuvant therapy was found to be lower in patients with margins ≥5 mm than in those with margins <5 mm (42.7%/57.0%, p<0.0001). Conclusions: Within the two highest-volume hospitals in Taiwan, patients with OCSCC with a clear margin status (≥5 mm) achieved more favorable outcomes. These results have clinical implications and show how initiatives aimed at improving the margin quality can translate in better outcomes. A clear margin status can reduce the need for adjuvant therapy, ultimately improving quality of life.

Persistence of lower vocal intensity in vocal fold paralysis with cricothyroid impairment after hyaluronate injection.

Background: Unilateral vocal fold paralysis (UVFP) affects the glottal gap, voice, and aerodynamics, whereas injection laryngoplasty (IL) using hyaluronate is an effective treatment for UVFP by decreasing the glottal gap to improve voice. Previous studies have shown that the involvement of cricothyroid (CT) muscle in UVFP patients further affects patients' aerodynamics, but it remains unclear whether the difference remains after IL. This study investigates whether the aerodynamic features observed in UVFP with CT involvement could still be observed after IL. Methods: This study recruited UVFP patients with dysphonia, and IL was performed within 6 months of initial symptoms. All subjects received assessments including videolaryngoscopy, voice analysis, and aerodynamics at three time points: before IL, 1 month after IL, and 6 months after IL. The glottal gap, voice, and aerodynamics between patients with and without CT involvement (the CT+ and CT- groups) were compared, and the change (Δ) before and after IL and repeated-measures analysis of variance (ANOVA) were also compared between the two groups. Result: A total of 71 patients with UVFP (22 in the CT+ group and 49 in the CT- group) were analyzed. After IL, the CT+ group showed a lower sound pressure level (SPL), higher Δair pressure, and smaller Δaerodynamic power than the CT- group. Conclusion: The CT+ group had a lower SPL, even after elevating air pressure to attempt to achieve a higher vocal intensity. The results suggest that although closure of the glottal gap was achieved by IL, the CT+ group still had a lower loudness and needed to sustain a higher peak air pressure when producing voice. Level of evidence: Level 4.

Combined Airway and Bariatric Surgery (CABS) for Obstructive Sleep Apnea Patients with Morbid Obesity: A Comprehensive Alternative Preliminary Study.

Although continuous positive airway pressure is the gold standard for obstructive sleep apnea (OSA), it does not improve obesity. By contrast, bariatric surgery significantly improves obesity but with sustained OSA in the majority of patients. This study proposes a comprehensive technique­combined airway and bariatric surgery (CABS)­to improve both obesity and OSA. The aims of the study are to evaluate the feasibility, safety and efficacy of CABS in morbidly obese OSA patients. The retrospective study enrolled 20 morbidly obese OSA patients (13 males; median age, 44 years; median apnea−hypopnea index (AHI), 63.2 event/h; median body mass index (BMI), 41.4 kg/m2). The study population was divided into two groups based on patients' volition after shared decision making. The bariatric surgery (BS) group included laparoscopic sleeve gastrectomy (LSG, n = 8) and laparoscopic Roux-en-Y gastric bypass (LRYGB, n = 2). CABS involved bariatric surgery­LSG (n = 8) and LRYGB (n = 2) in conjunction with airway surgery (concurrent nasal/palatal/lingual surgery [n = 8], concurrent palatal/lingual surgery [n = 2]). Patients received a home sleep apnea test at baseline and one year after surgery. The two patient groups were not different in age, sex, preoperative AHI or preoperative BMI. There was no airway compromise, wound bleeding or infection throughout the postoperative period. One year after surgery, patients in both groups achieved significant improvement in AHI and BMI. Furthermore, the improvement in AHI was significantly higher (p = 0.04) in the CABS group than in the BS group despite the insignificant change in BMI reduction (p = 0.63) between the two groups. In the CABS group, the BMI dropped from 40.4 to 28.4 kg/m2 (p < 0.0001) and the AHI decreased from 75.1 to 4.5 event/h (p = 0.0004). The classic success rate for OSA was 90% and the cure rate was 60% in the CABS group. A perioperative assessment of CABS group patients also revealed a significant improvement in the Epworth sleepiness scale, minimal O2 saturation, snoring index and heart rate. CABS is feasible and safe in treating OSA with morbid obesity. CABS achieves more reduction in AHI than BS alone with high success and cure rates for OSA. CABS can also significantly improve quality of life and general health and offers a comprehensive alternative for morbidly obese OSA patients.

Transoral Tongue Suspension for Obstructive Sleep Apnea-A Preliminary Study.

Objectives: To evaluate the safety and efficacy of a novel technique for transoral tongue suspension (TOTS) in obstructive sleep apnea (OSA) patients. Material and Methods: The retrospective study enrolled 24 consecutive OSA patients (21 males; average age, 43 years; average apnea−hypopnea index (AHI), 42.2 event/h; average body mass index (BMI), 25.7 kg/m2) with tongue obstruction confirmed by drug-induced sleep endoscopy. All patients received TOTS as the main procedure in conjunction with uvulopalatopharyngoplasty (UPPP). Key procedures of TOTS included a transoral sublabial approach, drilling two holes on the mandible, passing the polypropylene through the hole to the tongue base using a suture passer and returning the polypropylene through loop traction, and tying the polypropylene to the mandible. Lingual tonsil ablation (n = 8) was also implemented in hypertrophic lingual tonsils (grades III and IV). Results: The operation time for TOTS was around 30 min. No wound bleeding or airway compromise occurred throughout the postoperative period. Minor complications were temporary and included swelling of the tongue, numbness of the lower incisor, and sublabial wound dehiscence (n = 2). The quality of life improved significantly in the patients' subjective daytime sleepiness according to the Epworth Sleepiness Scale (11.4 ± 3.2 vs. 5.7 ± 1.6, p < 0.001). The objective parameters of OSA also improved significantly in the apnea/hypopnea index (42.2 ± 21.8 vs. 19.5 ± 16.2, p < 0.001), minimal oxygen saturation (77.1 ± 12.2 vs. 81.7 ± 8.1, p = 0.026), and snoring index (207 ± 141 vs. 101 ± 91, p = 0.03). Conclusions: The demonstrated TOTS showed its advantage in low morbidity with a scarless exterior and easy performance with free availability in treating adult OSA patients with tongue obstruction. TOTS combined with UPPP significantly improved AHI and daytime sleepiness. TOTS can be implemented with lingual tonsillectomy to achieve both stabilization of the tongue and widening of hypopharyngeal airway.

Mild simulator sickness can alter heart rate variability, mental workload, and learning outcomes in a 360° virtual reality application for medical education: a post hoc analysis of a randomized controlled trial.

Virtual reality (VR) applications could be beneficial for education, training, and treatment. However, VR may induce symptoms of simulator sickness (SS) such as difficulty focusing, difficulty concentrating, or dizziness that could impair autonomic nervous system function, affect mental workload, and worsen interventional outcomes. In the original randomized controlled trial, which explored the effectiveness of using a 360° VR video versus a two-dimensional VR video to learn history taking and physical examination skills, only the former group participants had SS. Therefore, 28 undergraduate medical students who participated in a 360° VR learning module were included in this post hoc study using a repeated measures design. Data of the Simulator Sickness Questionnaire (SSQ), heart rate variability (HRV) analysis, Task Load Index, and Mini-Clinical Evaluation Exercise were retrospectively reviewed and statistically analyzed. Ten (36%) participants had mild SS (total score > 0 and ≤ 20), and 18 (64%) had no SS symptom. Total SSQ score was positively related to the very low frequency (VLF) band power, physical demand subscale, and frustration subscale, and inversely related to physical examination score. Using multilevel modeling, the VLF power mediated the relationship between total SSQ score and physical examination score. Furthermore, frustration subscale moderated the mediating effects of the VLF power. Our results highlight the importance of documenting SS to evaluate a 360° VR training program. Furthermore, the combination of HRV analysis with mental workload measurement and outcome assessments provided the important clinical value in evaluating the effects of SS in VR applications in medical education.

Towards an Improved Pathological Node Classification for Prognostic Stratification of Patients With Oral Cavity Squamous Cell Carcinoma: Results From a Nationwide Registry Study.

Background: To assess the prognostic significance of different nodal parameters [i.e., number of pathologically positive nodes, log odds of positive lymph nodes, lymph node ratio (LNR), and extra-nodal extension (ENE)] in Taiwanese patients with oral cavity squamous cell carcinoma (OCSCC), and to devise an optimized pN classification system for predicting survival in OCSCC. Methods: A total of 4287 Taiwanese patients with first primary OCSCC and nodal metastases were enrolled. Cox proportional hazards regression analysis with the spline method was applied to identify the optimal cut-off values for LNR, log odds of positive lymph nodes, and number of pathologically positive nodes. Results: On multivariable analysis, we identified a LNR ≥0.078/0.079, the presence of at least three pathologically positive nodes, and ENE as independent prognosticators for 5-year disease-specific survival (DSS) and overall survival (OS) rates. We therefore devised a four-point prognostic scoring system according to the presence or absence of each variable. The 5-year DSS and OS rates of patients with scores of 0-3 were 70%/62%/50%/36% (p <0.0001) and 61%/52%/40%25%, respectively (p <0.0001). On analyzing the AJCC 2017 pN classification, patients with pN3a displayed better survival rates than those with pN2 disease. The 5-year DSS and OS rates of patients with pN1/pN2/pN3a/pN3b disease were 72%/60%/67%/43% (p <0.0001) and 63%/51%/67%/33%, respectively (p <0.0001). Conclusions: Three nodal parameters (i.e., a LNR ≥0.078/0.079, the presence of at least three pathologically positive nodes, and ENE) assessed in combination provided a better prognostic stratification than the traditional AJCC pN classification.

LigaSure versus Conventional Parotidectomy: A Systematic Review and Meta-Analysis.

Surgery with parotidectomy is the preferable treatment for most parotid tumors. Our meta-analysis compared the differences between the use of the LigaSure (LS) device and the conventional suture ligation technique (CT) in parotidectomies. A literature search in databases including EMBASE, MEDLINE, and the Cochrane Library was carried out. Studies including parotidectomy using LS and CT were included with the intraoperative and postoperative parameters collected. Continuous operative time data were measured by mean differences (MDs). Discrete data on postoperative complications, including facial palsy, postoperative bleeding, and salivary complications, were evaluated with risk differences (RDs). All values were reported with 95% confidence intervals (CIs). Five studies were included in our meta-analysis. The pooled analysis demonstrated a significant reduction in operative time in the LS group (MD: -21.92; 95% CI, -30.18 to -13.66). In addition, the analysis indicated that the incidence of postoperative complications, including permanent facial palsy (RD, -0.01; 95% CI, -0.06 to 0.05), temporary facial palsy (RD, 0.00; 95% CI, -0.03 to 0.04), salivary complications (RD, -0.01; 95% CI, -0.08 to 0.06), and postoperative bleeding (RD, -0.02; 95% CI, -0.07 to 0.04), were all similar between the LS group and the CT group. According to the results, the LS device appears to be a safe and useful tool and could shorten the operative time in patients needing parotidectomy.

Clinical outcomes of patients with pT4a and pT4b oral cavity squamous cell carcinoma who had undergone surgery: Results from a Taiwanese registry-based, nationwide cohort study.

OBJECTIVES: While the NCCN guidelines maintain that T4b oral cavity squamous cell carcinoma (OCSCC) should undergo either non-surgical treatments or clinical trials, promising outcomes of T4b OCSCC having surgical excision have been reported. We analyzed and compared the clinical outcomes of Taiwanese patients with pT4a and pT4b OCSCC who had undergone surgical treatment. METHODS: From 2011 to 2017, a total of 4031 and 355 patients with first primary pT4a and pT4b OCSCC were identified. A propensity score (PS)-matched analysis of patients (n = 351 each) for pT4a and pT4b tumors was also performed. RESULTS: The 5-year disease-specific and overall survival (DSS/OS) rates were more favorable in patients with pT4a than in those with pT4b OCSCC (64%/55%, p < 0.0001; 55%/43%, p < 0.0001, respectively). Compared with pT4a, those with pT4b tumors had a higher burden of the following risk factors: buccal/retromolar/hard palate subsite, male sex, depth ≥ 10 mm, and positive margins. Before PS matching, multivariable analyses revealed that pT4b tumors (versus pT4a) were an adverse prognosticator for both 5-year DSS and OS (hazard ratios: 1.32 and 1.39, respectively). However, in the PS-matched cohort, no significant differences in 5-year DSS and OS rates were observed between pT4a and pT4b OCSCC (57%/56%, p = 0.4024; 48%/44%, p = 0.1807, respectively) CONCLUSIONS: No significant outcome differences were evident between pT4b and pT4a OCSCC after PS matching. The most plausible hypothesis for the observed survival difference between T4a and T4b tumors is that it was driven by positive margins. We suggest that T4b OCSCC should undergo initial surgical excision if adequate resection is possible.

Clinical application of PEAK PlasmaBlade to remove distal tracheal granulation in patients after tracheostomy.

OBJECTIVE: Tracheal granulation is one of the common long term complications in patients after tracheostomy. Hypertrophic tracheal granulation may cause airway obstruction and further operation may be required to recreate an airway. Distal tracheal granulation is clinically challenging because of its position and surgical field limitation. This retrospective case review study evaluated the outcomes of PEAK PlasmaBlade-assisted tracheal surgery in patients with distal tracheal granulation. METHODS: This study retrospectively reviewed patients with distal tracheal granulation following long-term tracheostomy. All patients received PEAK PlasmaBlade assistance tracheal surgery (PATS) between February 2013 and December 2019. The surgery was performed using the PEAK PlasmaBlade with TnA type tip, powered by a PULSAR Generator, and guided by a 45 ° rigid endoscope. Patients were regularly followed up for a minimum of 12 months. RESULTS: A total 21 patients had completed PATS. None of the patients experience immediate life-threatening complications during or after the procedure. All the 21 patients were free of recurrent obstructive granulation within 12 months after operation. CONCLUSION: PATS is practical, effective, and safe for distal tracheal granulation and can be performed by single surgeon. Furthermore, it is technically less demanding than other surgical approaches and it has a rapid learning curve.

Carcinoma Showing Thymus-like Differentiation (CASTLE) with Synchronous Papillary Thyroid Carcinoma: A Case Report and Review.

Carcinoma showing thymus-like differentiation (CASTLE) is a rare malignant tumor that accounts for 0.1%-0.15% of all thyroid cancers. More than half of the patients have tumor extension to adjacent organs, including the recurrent laryngeal nerve, trachea, and esophagus. The diagnosis of CASTLE is based on histology and immunohistochemistry. A 58-year-old female patient complained of hoarseness for one and half years. Right side vocal cord palsy was diagnosed by fiberscopy. Thyroid sonography revealed right thyroid tumors, which were reported to be papillary thyroid carcinoma through FNAC. Total thyroidectomy with central lymph node dissection was performed. Pathologist found 2 isolated malignancy tumors. One patient in the right thyroid lobe had papillary thyroid carcinoma features. The other extrathyroid tumor seemed to be separated from the first tumor and invaded the thyroid capsule. After multiple immunohistochemical studies, PTC synchronous CASTLE was the final diagnosis. Coexisting PTC and CASTLE is very rare. This is the first report to describe a case showing PTC at first, while subsequent pathologic examination revealed the presence of CASTLE in addition to PTC. Since the prognosis of CASTLE is favorable, the treatment is different from other aggressive thyroid cancers, such as poorly differentiated or anaplastic thyroid carcinoma.

Improved prognostic stratification of patients with pN3b oral cavity cancer based on maximum standardized uptake value of metastatic nodes, lymph node ratio, and level of cervical nodal metastases.

OBJECTIVES: The prognosis of pN3b oral cavity squamous cell carcinoma (OCSCC) remains heterogeneous. We sought to improve the prognostic stratification of patients with pN3b OCSCC through a combined analysis of FDG-PET parameters and clinicopathological risk factors (RFs). METHODS: From 2001 to 2019, complete data on maximum standardized uptake values derived from FDG-PET of neck metastatic nodes (SUV-nodal-max) and clinicopathological RFs were available for 257 patients with pN3b disease. RESULTS: Using the 5-year disease-free survival (DFS) as the outcome of interest, the optimal cutoff points for SUV-nodal-max and lymph node ratio (LNR) were 15.9 and 0.17, respectively. The 5-year DFS rates/(number of cases) for patients with pN3b disease were as follows: SUV-nodal-max < 15.9 versus ≥ 15.9, 49%(226)/21%(31), p = 0.000003; LNR < 0.17 versus ≥ 0.17, 49%(230)/17%(27), p = 0.000117; absence versus presence of neck level IV/V metastases, 49%(230)/15%(27), p = 0.000004. Multivariable analyses revealed that SUV-nodal-max ≥ 15.9, LNR ≥ 0.17, and level IV/V metastases were independent prognosticators for 5-year distant metastases (DM), DFS, disease-specific survival (DSS), and overall survival (OS) rates. Based on these variables, we devised a scoring system that identified three distinct prognostic subgroups at low (score 0, n = 190), intermediate (score 1, n = 51), and high (scores 2-3, n = 16) risk. The 5-year rates of patients with pN3b disease deemed to be at low/intermediate/high risk were as follows: DM, 31%/52%/89%; DFS, 54%/26%/0%; DSS, 59%/36%/8%; OS, 42%/31%/6%, respectively; all p < 0.001. CONCLUSIONS: A scoring system based on SUV-nodal-max, LNR, and level IV/V metastases improves the prognostic stratification of OCSCC patients with pN3b disease.