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Purpose To evaluate the contralateral lymph node recurrence rate (clLNRR) of stage IVA to IVB well-lateralized oral cavity cancer. To evaluate the risk factors of clLNRR. Materials and methods Pathologic stage IVA-B squamous cell carcinoma of oral cavity, originating from buccal mucosa, gingiva, or retromolar trigone were retrospectively recruited. Those who did not receive definitive surgery, with previous cancer history, or with contralateral nodal metastasis at diagnosis were excluded. Results From 2010 to 2017, 120 cases were enrolled, including 103 pT4 and 38 pN2. Thirty-one patients underwent contralateral neck dissection, and 18 had contralateral elective nodal irradiation. After median follow up of 35.1 months, the 3-year clLNRR was 15.7% (95% CI: 8.8 - 22.6%) as first event and was 17.1% (95% CI: 9.8 - 24.4%) for overall recurrences. The 3-year disease-free survival and overall survival were 52.8% and 63.1%, respectively. In multivariate analysis, positive nodal metastasis, gingival origin, and perineural invasion were associated with significantly higher clLNRR. Nodal metastasis was the strongest prognostic factor for clLNRR (pN1, HR: 17.1, p = 0.010; pN2, HR: 16.7, p = 0.004, comparing to pN0). The 3-year clLNRR were 2.9% for pN0 (n = 71, 95% CI: 0 - 6.8%), 37.7% for pN1 (n = 11, 95% CI: 8.3 - 67.1%), and 38.4% for pN2 (n = 38, 95% CI: 19.2 - 57.6%). Advanced T classification, elective contralateral neck dissection, and contralateral nodal irradiation did not have significant impact on clLNRR. Conclusions Positive homolateral nodal metastasis, gingival origin, and perineural invasion were risk factors correlated with significantly higher clLNRR. For patient without nodal metastasis, the clLNRR was low and elective contralateral neck management might be safely omitted. For patients with homolateral nodal disease, the contralateral nodal recurrence was not unusual. The optimal treatment for these high risk patients warrant further research.

Introduction: Foreign body ingestion is the most common reason for otolaryngology specialist consultations in emergency departments. Among the different types of foreign bodies, fish bones are the most common, particularly in Asian populations. In Taiwan, upper aerodigestive tract foreign bodies (UADT-FBs) are mostly managed by residents in the otorhinolaryngology (ORL) department. Considering the learning curve required for all procedures, different management types between residents, and possible resulting safety issues, this study explored the outcomes of UADT-FB management by residents in different years of ORL training. Materials and Methods: The medical records of 2,283 patients who visited Kaohsiung Veterans General Hospital’s Emergency Department for UADT-FB during June 2013–August 2019 were retrospectively reviewed. The reviewed data included the demographic data of enrolled patients, outcomes of foreign body management, and follow-up chart records of the patients. Results: Among the 2,283 patients, 1,324 (58%) were found to be negative for foreign bodies, and foreign bodies in 951 (41.7%) were removed immediately. In the negative finding (NF) group, 2 (4.9%) patients were later found to be positive for foreign bodies during follow-up in the outpatient department. One (2.4%) patient developed a deep neck infection and esophageal perforation. The percentage of NFs decreased from 62.58% in residents in the first half of their first year (R1a) to 54% for third-year residents (R3). Comparing R1a with R3, the number needed to harm for retained UADT-FBs after patients visited the emergency department was 12.2. Discussion/Conclusion: This study provides data from 1 referral center regarding the management of UADT-FBs. With increasing resident training, the percentage of NFs declined from 62.58 to 54%. Young residents, especially those in the first 6 months of their training, should have senior residents perform a second examination if UADT-FBs are not found in suspected cases.

To compare the treatment outcome and severe late adverse effects (AEs) between conventional volume and dose (CVD) and simultaneously reduced volume and dose (SRVD) of clinical target volume treatments in patients with nasopharyngeal carcinoma.This retrospective cohort study enrolled patients with nonmetastatic stage II to IV nasopharyngeal cancer from a single institute. Survival endpoints and severe (≥grade 3) late AEs and comorbidity were compared between groups. The correlation of severe late AEs, comorbidity, and overall survival (OS) were evaluated using Kaplan-Meier and Cox regression methods.From January 2012 to June 2017, this study enrolled 178 patients, 64 in the CVD group and 114 in the SRVD group. The 2 groups did not differ significantly in patient characteristics except for mean follow-up time (37.6 vs 48.8 months; P = .01). The SRVD group did not significantly differ from the CVD group in local control survival (82.0% vs 78.4%; P = .85), regional control survival (89.9% vs 86.0%; P = .62), or disease-free survival (76.4% vs 66.9%; P = .67). The SRVD group had significantly better OS (93.9% vs 67.0%; P.001) and salvage survival (79.3% vs 20.7%; P.01) and a significantly lower ratio of severe lung infection (1 of 113 vs 5 of 59; P = .02). The SRVD group had a significantly lower risk of mortality (hazard ratio [HR], 0.3; P = .03). The factors associated with a significantly higher risk of mortality were N3 (regional lymph node stage status of N3) (HR, 3.0; P = .02); comorbidities of diabetes, coronary artery disease, or chronic kidney disease (grades 2-3) (HR, 3.8; P = .009), and severe lung infection (HR, 6.3; P = .007).Simultaneously reduced volume and dose of clinical target volumes did not impair locoregional control or disease-free survival. The benefits of SRVD treatment may include significant reduction in severe late AEs, particularly lung infection, dysphagia, and xerostomia. However, additional studies with longer patient follow-up are required to confirm these benefits.

Objective Divers with a history of decompression sickness may be at high risk for sleep problems. However, limited studies have investigated the relationship between diving exposure and sleep problems of occupational divers. This study investigated the association between diving exposure and sleep quality and quantity among male occupational divers in southern Taiwan. Methods This descriptive, cross-sectional study included 52 occupational divers and 121 non-divers recruited from southern Taiwan in 2018. Survey data were collected using the Taiwanese version of the Hospital Anxiety and Depression Scale, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and a self-report questionnaire that included demographic variables, diving exposure/protocols, and factors associated with sleep quality. Results Among all participants examined, occupational divers were significantly more likely to have both poor sleep quality (adjusted odds ratio [OR] = 3.00; 95% confidence interval [CI] = 1.48–6.06; P = 0.002) and excessive daytime sleepiness (adjusted OR = 4.49; 95% CI = 2.12–9.52; P < 0.001). The diving exposure time, depth, ascent rate, and decompression table use showed no significant associations between poor and good sleepers in the divers group. However, a history of decompression sickness was associated with poor sleep quality among divers (adjusted OR = 2.20; 95% CI = 1.07–4.54; P = 0.032). Conclusions Our results showed that occupational divers had poor sleep quality and more excessive sleepiness than non-divers. Decompression sickness likely contributes to poor sleep quality. Prevention and early detection of decompression sickness-related sleep problems should be an occupational health priority.

Background To assess the benefit of postoperative radiotherapy in patients with pT1-2N1M0 oral and oropharyngeal cancer by the quality of neck dissection. Methods In the Surveillance, Epidemiology, and End Results database, pT1-2N1M0 oral and oropharyngeal cancer patients treated by primary tumor resection and neck dissection with or without radiotherapy were included between 2004 and 2015. Univariate and multivariate analysis were used to explore the effect of adjuvant radiotherapy on 5-year overall survival (OS) and disease-specific survival (DSS) among different quality of neck dissection. Results Of the 1765 patients identified, 1108 (62.8%) had oral cancer, 1141 (64.6%) were men, and 1067 (60.5%) underwent adjuvant radiotherapy. After adjusting for confounding factors, postoperative radiotherapy reduced the adjusted hazard ratio (aHR) of 5-year OS to 0.64 (95% confidence interval [CI] 0.49–0.84) in those with Conclusion Radiotherapy was associated with improved survival in pT1-2N1M0 oral and oropharyngeal cancer patients without adequate neck dissection.

In-laboratory, polysomnography (PSG) is the gold standard for diagnosing obstructive sleep apnea syndrome (OSAS). However, the long waiting list and sleeping at a hospital make patients hesitate to undergo the examination, thereby delaying diagnosis. During coronavirus disease 2019 (COVID-19) pandemic, sleep labs are almost closed, and the delay is worsening. The home sleep test (HST) enables subjects to be tested at home, a familiar and comfortable environment, without a long waiting list. This study assessed the accuracy of a type III HST in diagnosing OSAS in the Taiwanese population and identified factors affecting the diagnostic accuracy.This retrospective study included 67 patients with clinically suspected OSAS. All patients were allocated to receive both PSG and the HST. The apnea-hypopnea index (AHI) measured through PSG was used as the standard. The sensitivity, specificity, and accuracy of the HST in diagnosing and evaluating the severity of OSAS were analyzed.Among the 67 patients, no significant difference was noted in the average AHI values obtained using PSG and the HST ( p = 0.103). The AHI obtained from HST was significantly correlated with that obtained from PSG, with the correlation coefficient being 0.779 ( p0.001). The sensitivity, specificity, and accuracy of the HST in diagnosing OSAS were 94.9%, 62.5%, and 91.0%, respectively, and 80.0%, 74.1%, and 77.6% in diagnosing moderate to severe OSAS. Furthermore, the difference in AHIs measured using the two tests were positively correlated with the severity of sleep apnea.The HST used in preliminary screening of patients with suspected OSAS achieved an accuracy of90%. For patients with moderate to severe OSAS, the accuracy was below 80%. Therefore, for patients who receive an OSAS diagnosis through the HST, arrangement of PSG is recommended for determining the severity of the OSAS and giving proper treatment.

Head and neck squamous cell carcinoma (HNSCC) is the most common malignancy in Taiwan. Therefore, refining the diagnostic sensitivity of biomarkers for early-stage tumours and identifying therapeutic targets are critical for improving the survival rate of HNSCC patients. Metabolic reprogramming contributes to cancer development and progression. Metabolic pathways, specifically, play a crucial role in these diverse biological and pathological processes, which include cell proliferation, differentiation, apoptosis and carcinogenesis. Here, we investigated the role and potential prognostic value of the ubiquitin-conjugating enzyme E2 (UBE2) family in HNSCC. Gene expression database analysis followed by tumour comparison with non-tumour tissue showed that UBE2C was upregulated in tumours and was associated with lymph node metastasis in HNSCC patients. Knockdown of UBE2C significantly reduced the invasion/migration abilities of SAS and CAL27 cells. UBE2C modulates glycolysis pathway activation and HIF-1α expression in SAS and CAL27 cells. CoCl

Wen-Shan Liu,1– 3 Ju-Chun Chien,1 Yu-Hsien Huang,1 Po-Chun Chen,4,5 Wei-Lun Huang,1 Shao-Wei Chiang,1 Ching-Chih Lee,6 Bor-Hwang Kang,3,6 Yu-Chang Hu1 1Department of Radiation Oncology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 2Department of Nursing, Meiho University, Pingtung, Taiwan; 3School of Medicine, National Defense Medical Center, Taipei, Taiwan; 4Department of Radiation Oncology, Pingtung Christian Hospital, Pingtung, Taiwan; 5Graduate Institute of Bioresources, National Pingtung University of Science and Technology, Pingtung, Taiwan; 6Department of Otorhinolaryngology - Head and Neck Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, TaiwanCorrespondence: Wen-Shan Liu, Department of Radiation Oncology, Kaohsiung Veterans General Hospital, No. 386, Dazhong 1st Road, Zuoying Dist., Kaohsiung City, 813414, Taiwan, Tel +886934075313, Email wsliu@vghks.gov.twPurpose: The study aimed to evaluate 1) the correlation of doses of swallowing-related organs at risk (OAR) with severe swallowing-related late adverse effects (AE) in nasopharyngeal carcinoma (NPC) patients and 2) the effect of high mean doses of OARs on overall survival (OS).Patients and Methods: This retrospective cohort study enrolled non-metastatic Stage I–IV NPC patients from January 2012 to June 2017. OAR mean doses and severe (≥G3) swallowing-related late AE (xerostomia, dysphagia, and lung infection) were evaluated by t-test and validated using receiver operating characteristic curves. The risk factors of OS were calculated by Cox regression methods.Results: This study enrolled 185 (43 female, 142 male) NPC patients, mean age 52.4 years, primarily with Stage III (93, 50.3%) or Stage IV (67, 36.2%) disease. The mean doses of pharyngeal constrictor muscle (PCM), superior-middle PCM (SMPCM), and superior PCM (SPCM) were significantly higher in those with severe (≥G3) lung infection than in those without (65.7 vs 62.2 Gy, p = 0.036; 68.1 vs 64.2 Gy, p = 0.015; and 70.0 vs 65.9 Gy, p = 0.012, respectively). Patients with severe (≥G3) dysphagia had significant higher mean doses of base of tongue (56.2 vs 50.2 Gy, p = 0.008), laryngeal box (50.6 vs 46.4 Gy, p = 0.036), PCM (65.4 vs 62.1 Gy, p = 0.008), SMPCM (67.1 vs 64.2 Gy, p = 0.014), and SPCM (69.3 vs 65.8 Gy, p = 0.004). Mean SMPCM dose > 64.9 Gy (adjusted hazard ratio [aHR] = 3.2, 95% confidence interval [CI] 1.2– 8.8, p = 0.021), age > 62 years (aHR = 2.7, 95% CI 1.1– 6.9, p = 0.032), N3 status (aHR = 4.0, 95% CI 1.8– 9.0, p = 001), and severe late AE of lung infection (aHR = 4.6, 95% CI 1.5– 14.0, p = 0.007) significantly affected OS.Conclusion: Severe lung infection and dysphagia were associated with significantly higher mean doses of PCM, SMPCM, and SPCM. Among these OARs, only a high SMPCM mean dose was a risk factor for OS in NPC patients.Keywords: nasopharyngeal carcinoma, late adverse effect, pneumonia, dysphagia, pharyngeal constrictor muscle, intensity-modulated radiotherapy

Warthin tumor with ulceration of the surrounding skin is extremely rare, making it difficult to differentiate from parotid cancer in the clinical setting. We report a 65-year-old man with a Warthin tumor in the right parotid gland that had ulceration of the overlying skin. The patient presented with right upper neck mass 2 years ago. Ultrasound and fine needle aspiration were done, and Warthin tumor was suspected. One year later, the mass was enlarged with ulceration of the skin. Superficial parotidectomy with fusiform excision of the skin was performed, and histopathological diagnosis revealed a Warthin tumor with inflammatory change. We proposed that this unique manifestation may have been induced by fine needle aspiration, enlargement of the tumor, and ischemic changes secondary to pulmonary arteriovenous malformations.

A 73-year-old woman having a throat lump sensation and dysphagia for the past several months presented at our otorhinolaryngology outpatient clinic. A physical examination disclosed a protruding subepithelial mass over the right tonsil fossa. The mass was not tender and had no mucosal lesions or signs of active infection. Therefore, we arranged face and neck computed tomography scans, which reported a solitary osseous lesion over the anterior-right aspect of the C1-2 joint. Considering the rarity and unfamiliar anatomy of this disease, we built a 3D-printed model to assist with the surgical rehearsal of the procedure as well as with a preoperation discussion with the patient and her family. We arranged a combined Otolaryngology-Neurosurgery department approach after discussion with the neurosurgeon and successfully removed the lesion without sacrificing the overlying longus capitis muscle. The pathology examination revealed no evidence of malignancy. The final diagnosis was cervical spine solitary osteochondroma. The patient had a complete recovery of both oral cavity and normal swallowing function. No tumor recurred during the 3-year follow-up. On the basis of this case, in-house 3D-printing technology can offer a rapid, reliable model for an interdisciplinary team to use to enhance personalized presurgical planning, thus providing better patient engagement during hospitalization.

Buccal mucosa squamous cell carcinoma (BMSCC) is one of major subsites of oral cancer and is associated with a high rate of metastasis and poor prognosis. Heat shock proteins (HSPs) act as potential prognostic biomarkers in many cancer types. However, the role of HSPD1 in oral cancer, especially in BMSCC, is still unknown. Through data analysis with The Cancer Genome Atlas (TCGA), we found the association of HSPD1 gene expression with tumorigenesis and poor prognosis in oral cancer patients. Our cohort study showed that higher HSPD1 protein level was associated with tumorigenesis and poor prognosis in BMSCC patients with lymph node invasion, suggesting that HSPD1 may be involved in tumor metastasis. Moreover, knockdown of HSPD1 induced E-cadherin expression and decreased the migration and invasion of BMSCC cells. In contrast, ectopic expression of HSPD1 diminished E-cadherin expression and promoted the migration/invasion of BMSCC cells. Further, HSPD1 regulated RelA activation to repress E-cadherin expression, enhancing the migration and invasion of BMSCC cells. Furthermore, HSPD1 protein level was inversely correlated with E-cadherin protein level in tumor tissues and co-expression of high HSPD1/low E-cadherin showed a significant association with poor prognosis in BMSCC patients. Taken together, HSPD1 might repress E-cadherin expression and promote metastatic characters of BMSCC cells for poor prognosis of BMSCC patients.

Background: The development of a hyperglycemic crisis in platinum-based chemotherapy-treated head and neck cancer patients, such as hyperosmolar hyperglycemic state (HHS), has been reported. Hyperglycemic crises are associated with a high risk of comorbidity and may delay cancer treatment if not promptly managed. Methods: This is a retrospective study using cancer registry data from a tertiary medical center. Head and neck cancer patients who had been treated with platinum-based chemotherapy from January 2014 to December 2015 were enrolled for review. Exclusion criteria included patients with a known history of type 2 diabetes mellitus (DM). Characteristics of patients who developed type 2 DM after initiation of chemotherapy were compared with non-DM patients, following which the clinical course of the patients developing a hyperglycemic crisis were reviewed. Results: A total of 185 patients were enrolled, of which seven patients (3.8%) had developed type 2 DM after initiation of platinum-based chemotherapy. No statistically significant differences in age, body mass index, sex, cancer subsite, cancer stage, or chemotherapy regimen were found when comparing new-onset type 2 DM patients with the rest of the patients. Three patients developed diabetic ketoacidosis, HHS, or impending HHS after initiating chemotherapy treatment. The incidence of hyperglycemic crises was 3 out of 185 (1.6%) in this patient group. Conclusion: Hyperglycemic crisis after cisplatin may be underestimated and may lead to a life-threatening condition. We suggest regular weekly follow-ups of serum glucose level after platinum-based chemotherapy for early detection of hyperglycemia and prevention of a life-threatening crisis. Keywords: Diabetic ketoacidosis, Hyperglycemia, Hyperglycemic hyperosmolar nonketotic coma, Platinum, Squamous cell carcinoma

Background High quality lymph node (LN) yield could increase survival, however strategies to improve LN yield have been seldom reported. This study aimed to assess the multiple-step action to promote quality of neck dissection in oral cancer. Methods A total of 400 patients with oral cancer who underwent primary tumor resection and neck dissection, including elective and radical neck dissection, were recruited after propensity score matching by clinical T and N categories between January 2009 and September 2018. Patients were treated by two independent departments in our institute. A multiple-step action was initiated in October 2015 in one department, and another department was as a control group. The impact of multiple-step action on LN yield and regional recurrence were analyzed using multivariate analysis and difference-in-differences (DID) linear regression analysis. Results The mean patient age was 55.2 + 11.1 years, and 92% were male. A total of 180 (45%) patients had T3-4 disease, and 129 (32%) patients had N2-3 disease. The multivariate linear regression and DID analyses revealed that multiple-step action had a positive effect on LN yield. A net improvement of LN yield with a coefficient of 13.78 (p p = 0.072) through DID analysis was noted. Conclusions Multiple-step action was associated with increased LN yield and decreased regional recurrence in patients with oral cancer. The observed activity may promote surgeons to improve the quality of neck dissections, is feasible, and could be applied to a widespread patient population.

Additional file 2: Figure S1. The overall survival rates between different groups and periods.

Additional file 1: The relationship and multivariate analyses regarding 5-year overall and disease-free survivals between different quality of neck dissection.

Additional file 1: Table S1. Mean lymph node yield in different groups and periods. Table S2. Difference between real LN yield and estimated number from liner regression.

Background: To assess the benefit of postoperative radiotherapy in patients with pT1-2N1M0 oral and oropharyngeal cancer by the quality of neck dissection.Methods: In the Surveillance, Epidemiology, and End Results database, pT1-2N1M0 oral and oropharyngeal cancer patients treated by primary tumor resection and neck dissection with or without radiotherapy were enrolled between 2004 and 2015. Univariate and multivariate analysis were used to explore the effect of adjuvant radiotherapy on 5-year overall survival (OS) and disease-specific survival(DSS).Results: Of the 1,765 patients identified, 1,108 (62.8%) had oral cancer, 1,141 (64.6%) were men, and 1,067 (60.5%) underwent adjuvant radiotherapy. After adjusting for confounding factors, postoperative radiotherapy reduced the adjusted hazard ratio (aHR) of 5-year OS to 0.64 (95% confidence interval[CI], 0.49-0.84) in those with >25 lymph nodes removed (aHR, 0.96; 95% CI, 0.75-1.24). For 5-year DSS, similar effect was observed. The adjusted hazard ratio was 0.66 (95% confidence interval, 0.45-0.97) in those with >25 lymph nodes (aHR, 1.12; 95% CI, 0.81-1.56). Sensitivity testing also showed a robust protective effect of postoperative radiotherapy in patients with Conclusion: Radiotherapy significantly improved survival in patients with pT1-2N1M0 oral and oropharyngeal cancer without adequate neck dissection.

Ubiquitin-conjugating enzyme 2C (UBE2C) involves in numerous cellular processes and the tumor progression in many cancers. However, its role in oral squamous cell carcinoma (OSCC) is unclear. We aimed to investigate the role and clinical significance of UBE2C in OSCC. The expression levels of UBE2C were examined by immunohistochemistry in 185 buccal mucosa squamous cell carcinomas, 247 tongue squamous cell carcinomas (TSCCs) and 75 lip squamous cell carcinomas. The roles of UBE2C in cell growth, invasion/migration and cancer stemness were also examined in OSCC cells. The expression levels of UBE2C protein were higher in tumor tissues than they were in the corresponding tumor adjacent normal tissues from OSCC patients. Higher UBE2C expression was associated with poor cell differentiation and lymph node invasion in OSCC patients. High UBE2C expression was also correlated with shorter disease-specific survival in TSCC patients having poor cell differentiation, advanced pathological stages, lymph node metastasis as well as receiving radiation therapy. Compared to control cells, OSCC cells in which UBE2C was silenced showed decreased cell proliferation, migration/invasion and colony formation and they exhibited lower expression levels of the following cancer stemness markers&mdash, ALDH1/A2, CD44, CD166 and EpCAM. High co-expression levels of UBE2C/CD44, UBE2C/CD166 and UBE2C/EpCAM were associated with poor prognosis in oral cancer patients from The Cancer Genome Atlas database. Our findings indicated that UBE2C might be a potential biomarker for tumorigenesis and prognosis in TSCC.

Objective To investigate the latency and amplitude of auditory brainstem response (ABR) and hearing prognosis in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). Methods Patients with ISSNHL were classified into four different recovery groups. All patients' clinical and demographic features were analyzed. Two-channel ABRs were collected in response to click stimuli at 90 dB nHL. ABR amplitudes for wave I and ABR latency for waves I, III, and V were analyzed. Results One hundred and two patients (54 men and 48 women) were included in the study. Hearing recovery was observed in 72 cases (70.6%). Waves I, III, and V latencies were significantly prolonged in the affected ears compared with the unaffected ears. A smaller wave I amplitude was found in the affected ear compared with the unaffected ear in the three recovery groups. There was a significant association between wave I latency and hearing outcome (p = 0.009) with a prolonged trend from complete to slight hearing recovery group. Conclusions There was a significant correlation between wave I latency and hearing outcome in patients with ISSNHL. The finding may provide diagnostic information and serve as a potential prognostic indicator in patients with ISSNHL.

Schwannomas are rare slow-growing benign tumors arising from Schwann cells lining the nerve sheaths. Head and neck schwannomas account for about one-third of all cases, and only 4% of them arise from the sinonasal tract. Its diagnosis is based on histology and immunohistochemistry. Complete surgical excision is the most recommended treatment option, and endoscopic surgery has been widely performed in recent years. In this study, we presented a case of a 55-year-old female with schwannoma arising from the lateral wall of the nasal cavity, causing epistaxis and rhinorrhea. The patient underwent endoscopic excision with prompt resolution of symptoms. The reported cases of nasal cavity schwannoma were reviewed and summarized for educational purposes.

Dysfunctional microRNAs (miRNAs) play a crucial role in oral squamous cell carcinoma (OSCC) progression. In the present study, we performed next-generation sequencing for miRNA profiling of the OSCC tissues and corresponding adjacent normal tissues in two patients with OSCC. We observed that 45 miRNAs were substantially up-regulated and 17 miRNAs were down-regulated in OSCC tissues. Since information on the biological role of miR-21-3p (passenger strand) in OSCC is limited, the expression levels of miR-21-3p were further evaluated in 95 OSCC tissue samples by a stem-loop real-time polymerase chain reaction. Our results revealed that miR-21-3p is significantly overexpressed in the OSCC tissues compared with the corresponding adjacent normal tissues (p

Background Neural crest stem cells (NCSCs) are a population of adult multipotent stem cells. We are interested in studying whether oxygen tensions affect the capability of NCSCs to self-renew and repair damaged tissues. NCSCs extracted from the hair follicle bulge region of the rat whisker pad were cultured in vitro under different oxygen tensions. Results We found significantly increased and decreased rates of cell proliferation in rat NCSCs (rNCSCs) cultured, respectively, at 0.5% and 80% oxygen levels. At 0.5% oxygen, the expression of both hypoxia-inducible factor (HIF) 1α and CXCR4 was greatly enhanced in the rNCSC nuclei and was suppressed by incubation with the CXCR4-specific antagonist AMD3100. In addition, the rate of cell apoptosis in the rNCSCs cultured at 80% oxygen was dramatically increased, associated with increased nuclear expression of TP53, decreased cytoplasmic expression of TPM1 (tropomyosin-1), and increased nuclear-to-cytoplasmic translocation of S100A2. Incubation of rNCSCs with the antioxidant N-acetylcysteine (NAC) overcame the inhibitory effect of 80% oxygen on proliferation and survival of rNCSCs. Conclusions Our results show for the first time that extreme oxygen tensions directly control NCSC proliferation differentially via distinct regulatory pathways of proteins, with hypoxia via the HIF1α-CXCR4 pathway and hyperoxia via the TP53-TPM1 pathway. Developmental Dynamics 246:162-185, 2017. © 2016 Wiley Periodicals, Inc.

Background: In nasopharyngeal carcinoma (NPC), the cut-off value of cumulative cisplatin dose (CCD) associated with survival benefits remains controversial. This study aimed to determine a CCD cut-off value for favorable survival outcomes and to identify specific patient groups benefitting from higher CCDs. Methods: We retrospectively reviewed the records of 161 patients (male-to-female ratio of 2.6:1.0) with NPC receiving concurrent chemoradiotherapy ± adjuvant chemotherapy (AC) from February 2006 through September 2015 at our referral center. The CCD was calculated for each patient, and 3-year locoregional-free survival (LRFS), distant-metastasis free survival (DMFS), disease-specific survival (DSS), and overall survival (OS) were analyzed using a multivariable Cox regression model. Results: Stage N3 patients and stage IV patients had lower DMFS, DSS, and OS. A CCD ≥ 200 mg/m 2 or AC was not associated with survival benefits. After adjusting for other factors, N3 status remained robustly correlated with DMFS ( p < 0.001) and DSS ( p = 0.001). In subgroup analyses, stage N3 patients treated with CCD ≥ 200 mg/m 2 exhibited evident trends toward higher OS (one-sided p = 0.062), DSS (one-sided p = 0.100), DMFS (one-sided p = 0.059), and LRFS (one-sided p = 0.059) than patients treated with CCD < 200 mg/m 2 . Conclusions: A CCD ≥ 200 mg/m 2 might result in better survival outcomes in stage N3 patients. Larger CCDs may be exclusively used in cases of regionally advanced disease to avoid rigorous toxicity.

Buccal mucosa squamous cell carcinoma (BMSCC) is one of major subsites of oral cancer and is associated with a high rate of metastasis and poor prognosis. Heat shock proteins (HSPs) act as potential prognostic biomarkers in many cancer types. However, the role of HSPD1 in oral cancer, especially in BMSCC, is still unknown. Through data analysis with The Cancer Genome Atlas (TCGA), we found the association of HSPD1 gene expression with tumorigenesis and poor prognosis in oral cancer patients. Our cohort study showed that higher HSPD1 protein level was associated with tumorigenesis and poor prognosis in BMSCC patients with lymph node invasion, suggesting that HSPD1 may be involved in tumor metastasis. Moreover, knockdown of HSPD1 induced E-cadherin expression and decreased the migration and invasion of BMSCC cells. In contrast, ectopic expression of HSPD1 diminished E-cadherin expression and promoted the migration/invasion of BMSCC cells. Further, HSPD1 regulated RelA activation to repress E-cadherin expression, enhancing the migration and invasion of BMSCC cells. Furthermore, HSPD1 protein level was inversely correlated with E-cadherin protein level in tumor tissues and co-expression of high HSPD1/low E-cadherin showed a significant association with poor prognosis in BMSCC patients. Taken together, HSPD1 might repress E-cadherin expression and promote metastatic characters of BMSCC cells for poor prognosis of BMSCC patients.

Although periorbital emphysema (PE) is commonly associated with orbital fractures, it may develop without any fracture or significant trauma in circumstances such as post-surgery, infection, forceful nose blowing, sneezing, and weight lifting. We report on a healthy military diver who developed PE following a wet chamber dive. A diagnosis of PE secondary to sinus barotrauma was reached. He was treated conservatively without medication and his symptoms recovered completely within 10 days. To the best of our knowledge, only five cases of diving-related PE have been reported in the literature. Analysis of these cases and ours revealed that facial trauma, repeated forceful Valsalva manoeuvres and recent upper respiratory tract infection are probable risk factors for diving-related PE.

We hope to establish a new readmission prediction score for patients with head and neck cancer (HNC) after major cancer surgery. A retrospective cohort study was conducted from the clinical and cancer registry data at Kaohsiung Veterans General Hospital. We included the data of patients with newly diagnosed HNC who underwent surgical treatment between Nov 2010 and Dec 2017. Multivariate logistic regression was performed to determine independent factors for 30-day readmission rate and establish a new prediction score. We compared the discriminatory ability of our new prediction score, HOSPTIAL score, and LACE index using linear trend chi-square test, the Akaike information criterion (AIC), and c-statistic. The 487 patients with HNC who underwent major surgery were discharged from the medical center. Of these patients, 40 (8.2%) were readmitted to the same hospital within 30 days. Our prediction score, namely LIST (representing leukocytosis, Charlson comorbidity index score of > 0, length of stay of top 33% for the total population, and advanced tumor stage) was derived through multivariate logistic regression. Compared with the HOSPITAL score and LACE index, LIST had a higher linear trend chi-square value (27.8 vs 4.3 and 6.3), higher prediction accuracy (0.743 vs 0.586 and 0.589), and lower AIC value (251 vs 274 and 272). The LIST can estimate 30-day readmission rates in patients with HNC. More intensive discharge planning and transition of care along with patient education can be applied to this high-risk group before discharge.

OBJECTIVE This study aimed to determine the impact or survival of low skeletal muscle mass (SMM) among patients with oral squamous cell carcinoma (OSCC) undergoing primary surgery. DESIGN This study was a retrospective cohort study. SETTING Oral squamous cell carcinoma patients treated at our referral centre from April 2005 to March 2014 were examined. PARTICIPANTS The cohort comprised 276 patients with OSCC undergoing primary surgery. MAIN OUTCOME MEASURES Estimated SMM was measured by calculating the cervical skeletal muscle mass from a CT scan of the head and neck. The 5-year overall survival (OS) and disease-specific survival (DSS) were analysed using a multivariable Cox regression model. RESULTS There were 276 patients with a male-to-female ratio of 12:1. A low SMM (

OBJECTIVE We examined whether dynamic margin criteria margin-to-thickness (MTR) ratio has superior predictive value compared with the resection margin or tumour thickness alone in the survival outcome in oral squamous cell carcinoma (OSCC). DESIGN This is a retrospective cohort study. SETTING Oral squamous cell carcinoma patients treated in Kaohsiung Veterans General Hospital Cancer Center between January 2006 and December 2013. PARTICIPANTS A cohort of 302 patients with OSCC who had undergone surgical management. MAIN OUTCOMES MEASURES Log MTR was calculated for each patient, and survival data were analysed using a multivariable Cox regression model. Discriminative analysis was performed using chi-square, Akaike information criterion (AIC) and Harrell's C tests. RESULTS After assessing for discriminative ability, the linear trend of log MTR surpassed those of resection margin and tumour thickness in chi-square, AIC and Harrell's C tests for the advanced pathologic T (pT) category. A multivariate Cox proportional hazard regression model revealed that log MTR

Introduction: The Republic of China Navy instituted the pressure test as one of the selection tools for diving troops and submarine crews. We analyzed factors associated with failure in the pressure test. Methods: This was a retrospective cohort study designed to investigate pressure test failure in Navy recruits between January 2010 and August 2015. The recruits received pressurization in a hyperbaric chamber to a simulated depth of 112 feet of seawater (fsw) at a rate of 25 fsw/minute. Data describing trainee demographics, disease history, causes and depth of failure, as well as type of injury, were extracted from case notes and facility databases for statistical analysis. Results: Of 3,608 trial cohorts, there were 435 failures, with an overall failure rate of 12.06%. About 95% of these failure trials were within a simulated depth of 60 fsw. Fifty- seven (57) failures did not record causes of failure. Among the other 378 failures, the most commonly identified causes were ear barotrauma (365 trials, 96.56 %) and sinus barotrauma (10 trials, 2.65%). Statistical analysis revealed that recent upper respiratory tract infection, allergic rhinitis, and cigarette smoking were all significantly associated with higher incidence of middle ear barotrauma. Conclusions: Our results suggest that pressure testing to a depth of 60 fsw is effective in disqualifying personnel entering diving and submarine service. Recent infection of the upper respiratory tract, allergic rhinitis and cigarette smoking are risk factors for middle ear barotrauma, resulting in failure of the pressure test.

Background: Traditional Chinese medicine (TCM) is widely used in the treatment of patients with several types of cancer. However, no large-scale clinical studies have evaluated whether TCM is associated with better survival in patients with head and neck cancer (HNC). Methods: The Taiwan National Health Insurance Research Database was used to conduct a retrospective cohort study of patients with HNC between 2001 and 2011. The patients with HNC were separated into TCM users and non-users, and Cox regression models were applied to determine the association between the use of TCM and survival outcome. Results: The TCM and comparison cohorts comprised data for 2966 and 2670 patients, respectively. The mean age was 51.3 years in the TCM cohort and 51.7 years in the comparison cohort. Multivariate analysis demonstrated that the use of TCM was significantly associated with lower risk of all-cause mortality by 32% (adjusted hazard ratio, 0.68; 95% confidence interval, 0.62–0.75). Patients with longer TCM use had a lower mortality rate ( P for trend

We aimed to investigate the association of the expression levels of five epithelial–mesenchymal transition (EMT)-related proteins (Snail, Twist, E-cadherin, N-cadherin, and Vimentin) with tumorigenesis, pathologic parameters and prognosis in tongue squamous cell carcinoma (TSCC) patients by immunohistochemistry of tissue microarray. The expression levels of Snail, E-cadherin, N-cadherin and Vimentin were significantly different between the tumor adjacent normal and tumor tissues. In tumor tissues, lower E-cadherin and higher N-cadherin levels were associated with a higher grade of cell differentiation, advanced stage of disease, and lymph node metastasis. However, higher Vimentin expression was associated with poor cell differentiation and lymph node metastasis. Patients with low E-cadherin expression had poor disease-specific survival (DSS). Conversely, positive N-cadherin and higher Vimentin expression levels were associated with poor DSS and disease-free survival. Notably, our multivariate Cox regression model indicated that high Vimentin expression was an adverse prognostic factor for DSS in TSCC patients, even after the adjustment for cell differentiation, pathological stage, and expression levels of Snail, Twist, E-cadherin, and N-cadherin. Snail, E-cadherin, N-cadherin, and Vimentin were associated with tumorigenesis and pathological outcomes. Among the five EMT-related proteins, Vimentin was a potential prognostic factor for TSCC patients.

Apoptosis plays a dual role in cancer development and malignancy. The role of apoptosis-related caspases in cancer remains controversial, particularly in oral tongue squamous cell carcinoma (OTSCC). In this study, we examined the protein levels of cleaved caspase-3, caspase-3, caspase-8, and caspase-9 on tissue microarrays consisting of samples from 246 OTSCC patients by immunohistochemistry. Wilcoxon signed-rank test indicated that the protein levels of cleaved caspase-3, caspase-3, caspase-8, and caspase-9 in tumor tissues were significantly higher compared to those in adjacent normal tissues (all p

Stanniocalcin-1 (STC1) is an endogenous glycoprotein whose anti-inflammatory effects occur through induction of uncoupling proteins to reduce oxidative stress. In this study, we tested the hypothesis that exogenous recombinant human STC1 (rhSTC1) protects against lipopolysaccharide (LPS)-induced acute lung injury in mice. Anesthetized C57BL/6 mice underwent intratracheal spraying of LPS (20 µg/10 g body wt), and lung injury was assessed 24h later by analyzing pulmonary edema, bronchoalveolar lavage fluid, and lung histopathology. Lung inflammation, oxidative stress, and expression of STC1 and its downstream uncoupling protein 2 (UCP2) were analyzed at specific time points. Expression of UCP2 was suppressed initially but was subsequently upregulated after STC1 elevation in response to intratracheal administration of LPS. Intratracheal rhSTC1 treatment 1h before or after LPS spraying significantly attenuated pulmonary inflammation, oxidative stress, cell apoptosis, and acute lung injury. Pretreatment with STC1 short interfering RNA 48 h before LPS spraying inhibited the expression of STC1 and UCP2 and significantly increased the extent of lung injury. These findings suggest that STC1 is an endogenous stress protein that may counteract LPS-induced lung injury by inhibiting the inflammatory cascade and inducing antioxidant and antiapoptotic mechanisms. However, the potential clinical application of STC1 and the direct linkage between UCP2 and LPS-induced lung injury remain to be further investigated.

Background: While chemoradiotherapy being widely recognized as primary treatment for nasopharyngeal carcinoma (NPC), optimal salvage modalities for locoregionally recurrent NPC (LRrNPC) are still under debate. This study aimed to explore outcomes of different salvage modalities for LRrNPC. Methods: Non-metastatic LRrNPCs were retrospectively recruited. Clinical factors and salvage treatments were evaluated. The primary and secondary endpoint were locoregional-progression-free survival (LRPFS) and overall survival (OS), respectively. Outcomes were compared among re-irradiation (reRT), surgical resection (SR), combination therapy (SR + reRT), and systemic treatment only (STx). Results: From 2006–2017, 29 consecutive LRrNPCs were enrolled, including 37.9% rT1-2 and 62.1% rT3-4 diseases. Salvage treatments included 14 reRT, 6 SR, 6 SR + reRT, and 3 STx. All re-irradiations were intensity-modulated radiotherapy (IMRT) and 83.3% SRs were done by endoscopic approach. After median follow-up of 36 months, the 3-year LRPFS was 56.5% and 3-year OS was 64.1%. When compared to STx, reRT and SR + reRT both showed superior LRPFS (re-RT, HR: 0.06, P=0.009; SR + reRT, HR: 0.07, P=0.021, adjusted for rT), while SR revealed no significant benefit. However, there was no significant difference in LRPFS among the three local treatment modalities. Severe complication rates were 51.7% for ≥grade 3 and 6.9% for grade 5. Conclusions: For LRrNPCs, locoregional treatments including reRT and SR + reRT might have additional local control benefit from systemic therapy. The risk of fatal toxicity decreased with increasing use of IMRT and endoscopic resection. Considering the limited case number and retrospective design, prospective trials are warranted to further evaluate the efficacy and safety.

Tornwaldt’s Cyst A 60-year-old man presented with worsening nasal obstruction and postnasal drip. Nasopharyngoscopy showed a smooth, pink, cystic mass in the midline of nasopharynx, consistent with...

Objectives This case-control study evaluated the association of the single nucleotide polymorphism rs7372209 (T>C) in pri-mir-26a-1 with the risk and progression of betel quid (BQ)–related oral premalignant lesions (OPLs) and oral squamous cell carcinoma (OSCC). Study Design In total, 597 BQ chewers were recruited: 196 healthy controls, 241 patients with OPLs, and 160 patients with OSCC. Genotypes were determined using the TaqMan real-time assay. Results The C/T + T/T genotypes and T allele in pri-mir-26a-1 were correlated with a decreased risk of BQ-related OPLs (P = .038 and .005, respectively), oral leukoplakia (P = .01 and .001, respectively), and advanced-stage OSCC (P = .021 and .004, respectively). The effects of the C/T + T/T genotypes and T allele on the decreased risk of OPLs were potent in the older age group (both Pinteraction Conclusions BQ chewers carrying the T allele or C/T + T/T genotypes in pri-mir-26a-1 may have a decreased risk of oral leukoplakia, OPLs, and advanced-stage OSCC.

Neural crest stem cells (NCSCs) are a population of adult multipotent stem cells. We are interested in studying whether oxygen tensions affect the capability of NCSCs to self-renew and repair damaged tissues. NCSCs extracted from the hair follicle bulge region of the rat whisker pad were cultured in vitro under different oxygen tensions.We found significantly increased and decreased rates of cell proliferation in rat NCSCs (rNCSCs) cultured, respectively, at 0.5% and 80% oxygen levels. At 0.5% oxygen, the expression of both hypoxia-inducible factor (HIF) 1α and CXCR4 was greatly enhanced in the rNCSC nuclei and was suppressed by incubation with the CXCR4-specific antagonist AMD3100. In addition, the rate of cell apoptosis in the rNCSCs cultured at 80% oxygen was dramatically increased, associated with increased nuclear expression of TP53, decreased cytoplasmic expression of TPM1 (tropomyosin-1), and increased nuclear-to-cytoplasmic translocation of S100A2. Incubation of rNCSCs with the antioxidant N-acetylcysteine (NAC) overcame the inhibitory effect of 80% oxygen on proliferation and survival of rNCSCs.Our results show for the first time that extreme oxygen tensions directly control NCSC proliferation differentially via distinct regulatory pathways of proteins, with hypoxia via the HIF1α-CXCR4 pathway and hyperoxia via the TP53-TPM1 pathway. Developmental Dynamics 246:162-185, 2017. © 2016 Wiley Periodicals, Inc.