Salvage therapy for refractory sudden sensorineural hearing loss (RSSNHL): a systematic review and network meta-analysis.

OBJECTIVE: Approximately 30-50% of sudden sensorineural hearing loss (SSNHL) patients show poor response to systemic steroid therapy. Additionally, the most appropriate treatment for patients with refractory sudden sensorineural hearing loss (RSSNHL) is unknown. This study aimed to explore the best treatment for RSSNHL. DESIGN: Using a frequentist contrast-based model and PRISMA guidelines, this study compared five salvage regimes: intratympanic injection of steroids (ITS), hyperbaric oxygen (HBO) therapy, post auricle steroid injection (PSI), ITS combined with HBO therapy, and continued systemic steroids. STUDY SAMPLE: We searched the PubMed, EMBASE, Web of Science, and Cochrane Library databases for randomised controlled trials and cohort studies comparing treatment regimens for RSSNHL. RESULTS: Compared with the control group (no additional treatment), PSI and ITS demonstrated significant improvements. The mean hearing gain was greater after PSI (11.1 dB [95% CI, 4.4-17.9]) than after ITS (7.7 dB [95% CI, 4.8-10.7]). When a restricted definition of RSSNHL was used, the ITS + HBO therapy showed the largest difference in improvement for pure tone average compared with the control group (14.5 dB [95% CI, 4.2-25.0]). CONCLUSIONS: The administration of either PSI or ITS leads to the greatest therapeutic effect in patients with RSSNHL. However, a consensus on the definition of RSSNHL is needed.

H1-antihistamine use and head and neck cancer risk in type 2 diabetes mellitus.

This study aimed to examine the association between the use of H1-antihistamines (AHs) and head and neck cancer (HNC) risk in patients with type 2 diabetes mellitus (T2DM). Data from the National Health Insurance Research Database of Taiwan were analyzed for the period from 2008 to 2018. A propensity-score-matched cohort of 54,384 patients each in the AH user and nonuser groups was created and analyzed using Kaplan-Meier method and Cox proportional hazards regression. The results showed that the risk of HNC was significantly lower in AH users (adjusted hazard ratio: 0.55, 95% CI: 0.48 to 0.64) and the incidence rate was also lower (5.16 vs. 8.10 per 100,000 person-years). The lower HNC incidence rate in AH users (95% CI: 0.63; 0.55 to 0.73) suggests that AH use may reduce the risk of HNC in T2DM patients.

Comparison of medical resource consumption between oral cavity squamous cell carcinoma with and without sarcopenia: A nationwide population-based cohort study.

PURPOSE: No study has compared long-term medical resource consumption between patients with oral cavity squamous cell carcinoma (OCSCC) with and without sarcopenia receiving curative surgery. PATIENTS AND METHODS: Generalized linear mixed and logistic regression models were employed to evaluate the number of postoperative visits and medical reimbursement for head and neck cancer or complications and the number of hospitalizations for treatment-related complications over 5 years after curative surgery, respectively. RESULTS: The mean difference (95% CI) in total medical claims amounts between the nonsarcopenia and sarcopenia groups were new Taiwan dollars (NTD) 47 820 (35 864-59 776, p < 0.0001), 11 902 (4897-18 908, p = 0.0009), 17 282 (10 666-23 898, p < 0.0001), 17 364 (9644-25 084, p < 0.0001), and 8236 (111-16 362, p = 0.0470) for the first, second, third, fourth, and fifth years, respectively. CONCLUSION: The long-term medical resource consumption was higher in the sarcopenia group than in the nonsarcopenia group.

SN-38, an active metabolite of irinotecan, enhances anti-PD-1 treatment efficacy in head and neck squamous cell carcinoma.

Anti-programmed cell death 1 (anti-PD-1) therapy shows definite but modest activity in patients with advanced/metastatic head and neck squamous cell carcinoma (HNSCC). Preliminary evidence suggests that SN-38, an activated form of irinotecan that increases expression of the transcription factor FoxO3a, can suppress programmed cell death ligand-1 (PD-L1) expression in breast and ovarian tumor models. We analyzed the SN-38-mediated activation of natural killer cells in vitro and explored the efficacy of SN-38 in combination with anti-PD-1 for treatment in vivo. In vitro, SN-38 enhanced the expression of FoxO3a and reduced the expression of c-Myc and PD-L1 dose-dependently in tumor cells. Low-dose SN-38 increased interferon-γ secretion by NK cells and promoted NK cell-mediated cytotoxicity in tumor cells. In vivo studies revealed that at non-cytotoxic drug concentrations, SN-38 significantly enhanced anti-PD-1 activity in suppressing murine tumor growth. We found increased NK cell and CD8+ T-cell infiltration in post-treatment tumors. RNA-seq analysis indicated that SN-38 increased the enrichment of immune cells and biological function genes related to the immune responses. SN-38 is a potentially beneficial adjunct to checkpoint inhibitor therapy in HNSCC. Further studies exploring its mechanism of action and possible applications are necessary. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Spindle Cell Carcinoma of the Head and Neck: Clinical Characteristics and Molecular Signatures.

OBJECTIVE/HYPOTHESIS: Spindle cell carcinoma of the head and neck (HNSpCC) is a rare variant of head and neck squamous cell carcinoma (HNSCC). This study evaluated the clinical characteristics and molecular signatures of such tumors. STUDY DESIGN: Retrospective analysis. METHODS: Medical records of patients diagnosed with HNSpCC from 1996 to 2018 were reviewed. The clinicopathologic features, treatment modalities, and survival status were carefully recorded. Whole exome sequencing (WES) was performed to evaluate the genetic signatures of HNSpCC. RESULTS: We found that among all 71 patients included in this study, the majority of them were male, with tumors developing predominantly in the oral cavity. The 1-, 3-, and 5-year disease-specific survival (DSS) rates were 64.6%, 49.5%, and 43.9%, respectively. A high local recurrence (LR) and distant metastasis (DM) rate (47.9%-25.3%, respectively) were observed. A significant proportion (28.2%) of patients with the worst prognosis had history of previous head and neck cancer (HNC) and had been treated with radiotherapy (RT). WES revealed that those post-RT SpCC shared common mutations with their previous HNC (pre-RT SCC), but gained additional genetic traits, such as hypoxia and cell-ECM interaction that were favorable for survival in an irradiated microenvironment. Distinct genetic landscapes in primary and post-RT SpCC were also found. CONCLUSIONS: This study demonstrates that HNSpCC is a unique entity with more aggressive behavior than conventional HNSCC. HNSpCC arising from a previously irradiated field is a predictor of dismal survival. Both genetic and microenvironmental factors contribute to this highly invasive tumor. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2183-2191, 2023.

Incorporation of ultrasound-guided core biopsy with flow cytometry to assist the diagnosis of cervical lymphoma.

PURPOSE: The main purpose of surgery for cervical lymphoma is only for tissue sampling. To establish a patient-friendly diagnostic approach, we investigated the feasibility of ultrasound-guided core biopsy with flow cytometry in the patients with suspected cervical lymphoma. METHODS: We prospectively recruited patients with suspected cervical lymphoma from Nov 2017 till Jan 2021 in a referral medical center and performed retrospective interpretation of the prospectively acquired data. Ultrasound-guided core biopsy as the tissue sampling approach for the targeted lesions was performed in all patients. The ultrasound-guided core biopsy samples were analyzed by immunohistochemical stains and flow cytometry. The sample quality and the rate of definite and decisive diagnosis obtained by ultrasound-guided core biopsy alone and ultrasound-guided core biopsy with flow cytometry were evaluated. RESULTS: Total 81 consecutive patients were recruited for analysis. All ultrasound-guided core biopsy samples were qualified for analysis of pathology and flow cytometry. Pathologically, the diagnoses were definite and compatible with their flow cytometry results in 70 patients (86.42%). Either newly-diagnosed or recurrent cervical lymphoma/lymphoproliferative disorders with histologic transformation could be diagnosed by ultrasound-guided core biopsy with flow cytometry. Nine of the 11 patients with pathologically indefinite diagnosis became clinically decisive when flow cytometry was incorporated into the process, which improved the rate of decisive diagnosis to 98.77% (Odds ratio [95% CI]: 6.21 [1.28, 58.96]). CONCLUSION: Ultrasound-guided core biopsy combined with flow cytometry is suggested to serve as the first-line and patient-friendly diagnostic approach for the patients with suspected cervical lymphoma.

Return to work in head and neck cancer survivors: its relationship with functional, psychological, and disease-treatment factors.

PURPOSE: Return to work (RTW) is important for survivors of head and neck cancer (HNC). The purposes of the study were to investigate the RTW ratio among HNC survivors and identify factors significantly affecting RTW in this population. METHODS: A cross-sectional study with consecutive sampling was conducted in a medical center in Taiwan, with 111 patients with HNC who had completed major treatments within 5 years and were employed before their cancer diagnosis enrolled as participants. Cervical range of motion (CROM) functionality, handgrip and hip flexor strength, maximal mouth opening (MMO), selected symptoms, depression, and disease/treatment-related factors were assessed. All of the factors were analyzed using t-test, chi-square test, and multiple logistic regression. RESULTS: Less than half (44.1%, n = 49) of the participants had returned to work. The t-test/chi-square test results showed the RTW group to be younger in age and better educated; have better handgrip/hip flexor strength, MMO, and CROM; have less speech difficulty and pain; and have less-advanced cancer than the non-RTW group. Further analysis of the above significant variables by logistic regression revealed early cancer stage, dominant handgrip strength, and less speech difficulty were the robust factors related to RTW. CONCLUSIONS: The RTW ratio is low in HNC survivors. RTW in HNC survivors is a multifactorial and complicated issue and needs to be further examined. IMPLICATIONS FOR CANCER SURVIVORS: Assessing the factors related to RTW systematically and developing comprehensive interventions and rehabilitation programs to reduce related dysfunctions are necessary to enhance RTW ability in HNC survivors.

Revision of endoscopic sinus surgery in adults: A population-based study in Taiwan.

OBJECTIVE: This study aimed to elucidate the revision rate, time to revision, and factors associated with revision of endoscopic sinus surgery (ESS) in Taiwan. DESIGN: Retrospective study. SETTING: Population-based analysis. PARTICIPANT: We identified all in-hospital patients, aged >20 years, who underwent ESS between 2000 and 2008 from the Taiwan National Health Insurance Research Database, and followed up with them until 2018. MAIN OUTCOME MEASURES: Factors associated with revision surgery were analyzed using multivariable Cox proportional hazard model. RESULTS: Overall, 66 592 patients were identified (mean age, 46.3 years; 62% males). The revision rate was 14.5% (9644/66 592) and time to revision surgery was 5.9 years. Multivariable Cox proportional hazard model showed that young age, male gender (hazard ratio [HR] = 1.18; 95% confidence interval [CI], 1.13-1.23), having nasal polyposis (HR = 1.17; 95% CI, 1.12-1.22), having allergic rhinitis (HR = 1.08; 95% CI, 1.04-1.13), having asthma (HR = 1.26; 95% CI, 1.14-1.39), and surgical time of >4 h (HR = 1.11; 95% CI, 1.06-1.16) were associated with increased risk of revision surgery. Concurrent septal surgery (HR = 0.81; 95% CI, 0.76-0.87), turbinate surgery (HR = 0.91; 95% CI, 0.85-0.97), or septal and turbinate surgery (HR = 0.68; 95% CI, 0.64-0.73) were associated with decreased risks of revision surgery. CONCLUSION: In Taiwan, risk factors for revision ESS are young age, male gender, having nasal polyposis, having allergic rhinitis, having asthma, and long surgical times. Concurrent septal or turbinate surgery decreases the risk of revision.

Proactive Swallowing Rehabilitation in Patients with Recurrent Oral Cancer Receiving Salvage Treatment: Long-Term Swallowing-Related Outcomes.

The present study aimed to evaluate the impact of proactive swallowing rehabilitation on swallowing function and quality of life in patients with recurrent oral cancer in the first 2 years after salvage treatment. Consecutive adult patients with recurrent oral cancer who received salvage surgery and free flap reconstruction were recruited prospectively, to whom proactive swallowing rehabilitation was provided. Body weight (BW); fiberoptic endoscopic evaluation of swallowing (FEES), functional oral intake scale (FOIS), and diet level; 10-item eating assessment tool (EAT-10), and MD Anderson Dysphagia Inventory (MDADI); and adherence at baseline, 1, 3, 6, 12, 18 and 24 months were evaluated. A total of 50 patients were included during May 2018 to July 2020. Compared to the baseline, significant deterioration in BW, FOIS, and MDADI was noted at one month. However, a trend of recovery was observed in BW and FOIS from one month, and in MDADI from three months. All patients were free of tube feeding at 18-24 months and tolerated diet with special preparations or compensation. Safe swallowing could be achieved in approximately 80% participants after 12 months of diet modification or compensatory maneuvers. Proactive swallowing therapy was feasible in patients with recurrent oral cancer receiving salvage treatment. Although this patient population might have pre-existing dysphagia from previous treatments, rehabilitation could facilitate safe per oral intake and maintain adequate nutrition with adaptive maneuvers or compensatory strategies. Patients who underwent proactive swallowing rehabilitation had better recovery in the functional oral intake level.

An alternative surgical technique for advanced tongue/tongue base cancer without free flap reconstruction.

BACKGROUND/PURPOSE: Locally advanced tongue or tongue base cancer is recommended to be treated by radical resection that is usually detrimental to physiological functions. This study reports the efficacy and treatment outcome of the patients who had received total glossectomy and laryngeal suspension without lip-split mandibulotomy and free flap reconstruction to preserve laryngopharyngeal function. METHODS: From 2010 to 2018, 37 consecutive patients who had received the surgery were retrospectively recruited. RESULTS: The overall five-year survival is 72%. The postoperative dependent rate of feeding tube and tracheostomy largely decreases within 1-year follow-up. Treated by this surgical method, these patients are free from facial disfiguration, donor site morbidity, and destructive mastication and occlusion. It is also feasible to perform this surgical technique in the recurrent cases previously treated by chemoradiation. CONCLUSION: Total glossectomy with laryngeal suspension can be successfully applied to locally advanced tongue or tongue base cancer, and benefits the patients with improved survival and preserved physiological function. Especially surgeons for free flap reconstruction are understaffed at some regional or district hospitals.

Effect of Sleep Surgery on Inflammatory Cytokines in Adult Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate whether sleep surgery is associated with inflammatory cytokine changes. This study hypothesizes cytokines may change after surgery in adult obstructive sleep apnea (OSA). STUDY DESIGN: Systematic review and meta-analysis. METHODS: The study protocol was registered on PROSPERO (CRD42020154425). Two authors independently searched PubMed, Embase, and Cochrane review databases from their inception to June 2021. The keywords used were sleep apnea, inflammatory markers, cytokines, and surgery. The effects of sleep surgery on the apnea-hypopnea index (AHI) and inflammatory cytokines were evaluated using a random-effects model. Both mean difference (MD) and standardized mean difference (SMD) of the changes in cytokines were calculated. RESULTS: Nine studies with 235 adults were included (mean age: 43 years; 82% were men). After sleep surgery, AHI significantly reduced by -11.3 events/h (95% confidence interval [CI], -15.8 to -6.9). In total, 8 and 6 studies were pooled for examining tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels, respectively. Sleep surgery significantly reduced TNF-α levels, with an MD of -2.8 pg/ml (95% CI, -5.1 to -0.6) and an SMD of -0.56 (95% CI, -0.85 to -0.27). Furthermore, sleep surgery reduced IL-6 levels, with an MD of -0.6 pg/ml (95% CI, -1.0 to -0.2) and an SMD of -0.66 (95% CI, -0.89 to -0.43). No covariates were identified to be correlated with cytokine changes in subgroup and meta-regression analyses. Funnel plots showed possible publication bias in current data. CONCLUSIONS: In adults, OSA treatment with sleep surgery improves inflammatory cytokines. Laryngoscope, 132:2275-2284, 2022.

Effect of sleep surgery on lipid profiles in adults with obstructive sleep apnea: a meta-analysis.

PURPOSE: The effects of sleep surgery on the lipid profile of adults diagnosed as having obstructive sleep apnea (OSA) remain unclear. This meta-analysis aimed to clarify whether sleep surgeries improve patients' lipid profile. METHODS: The study protocol was registered on PROSPERO (CRD42020154425). Two authors independently searched the PubMed, MEDLINE, EMBASE, and Cochrane review databases up to September 2020 using keywords such as sleep apnea, OSA, sleep apnea syndromes, lipids, and surgery. The effects of sleep surgery on the apnea-hypopnea index (AHI) and lipid profile parameters were evaluated using a random-effects model. RESULTS: Thirteen studies were included, with a total of 710 patients (mean age: 42.0 years; 85% men; mean sample size: 54.6 patients). The summary estimate of AHI change was - 20.6 events/h (95% CI - 25.9 to - 15.3) and the Epworth Sleepiness Scale score was - 4.2 (95% CI - 5.9 to - 2.5). Sleep surgery lowered total cholesterol (mean - 7.7 mg/dL; 95% CI - 12.2 to - 3.2), low-density lipoprotein (mean - 7.2 mg/dL; 95% CI - 11.0 to - 3.3), and triglyceride (mean - 14.0 mg/dL; 95% CI - 22.2 to - 5.8) levels but did not affect high-density lipoprotein (mean 1.5 mg/dL; 95% CI - 0.6 to 3.7) levels. Subgroup analysis revealed that the lipid profile changes were not associated with the surgical procedure but with the degree of OSA improvement. Meta-regression analyses demonstrated that the improvement in the lipid profile was positively correlated with AHI reduction. CONCLUSION: Surgeries for OSA may improve the lipid profile, which is positively correlated with the degree of OSA improvement.

Rising incidence of HPV positive oropharyngeal cancer in Taiwan between 1999 and 2014 where betel nut chewing is common.

BACKGROUND: The incidence of human papillomavirus (HPV) positive oropharyngeal cancer (OPC) is rising but HPV negative OPC is decreasing in Western countries. In Taiwan, the incidence of HPV negative OPC is common but the incidence of HPV positive OPC remains unknown. The objective of this study is to estimate the incidence trend and the survival of HPV positive OPC in Taiwan. METHODS: Between 1999 and 2014, primary tumor tissues from 425 incident OPCs were obtained from 5 medical centers in Taiwan. 408 OPCs were evaluated by the EasyChip HPV genotyping (King-Car, I-Lan, Taiwan) and 369 OPCs by p16 staining. The clinical data were retrospectively obtained from the medical records. RESULTS: In our study, 29% of OPCs were HPV positive. The percentage of HPV positive OPC was stable from 1999 to 2014 (25% (1999-2002), 30% (2003-2006), 30% (2007-2010), 29% (2011-2014)). The estimated crude incidence rate of HPV positive OPC increased significantly from 0.62 (1999-2002), 1.06 (2003-2006), 1.52 (2007-2010) to 1.74 (2011-2014) per 100,000 person-year. The sensitivity and specificity of p16 staining for positive HPV infection were 92% and 91%, respectively. The 5-year overall survival rates for patients with HPV positive OPC and with HPV negative OPC were 67.8% and 49.0%, respectively (HR = 0.52 (0.35-0.76), p = 0.0005). Patients with HPV positive OPC but no betel nut/cigarette exposure had the best overall survival (5-year: 88.2%, p < 0.0001). Patients with HPV negative OPC and betel nut/cigarette exposure had the worst overall survival (5-year: 46.6%, p < 0.0001). Patients with HPV positive OPC but also with betel nut/cigarette exposure had poorer 5-year overall survival (48.3%, p < 0.01). CONCLUSION: The incidence of HPV positive OPC is increasing along with HPV negative OPC, which leads to stably low percentage of HPV positive OPC in Taiwan. HPV positive OPC may become an important head and neck cancer when the incidence of HPV negative OPC declines in the near future. P16 is a useful surrogate marker for HPV infection in OPC and a good prognostic indicator for treatment outcome of OPC. Patients with HPV positive OPC but no betel nut/cigarette exposure has an excellent prognosis. Betel nut/cigarette exposure significantly worsens the prognosis of HPV positive OPC.

Effect of sleep surgery on blood pressure in adults with obstructive sleep apnea: A Systematic Review and meta-analysis.

This meta-analysis evaluates the effect of sleep surgery on blood pressure (BP) in adults with OSA. The study protocol was registered on PROSPERO (CRD42020154425). The PubMed, MEDLINE, EMBASE, and Cochrane databases were independently searched by 2 authors up to March 2020. The keywords used were sleep apnea, OSA, sleep apnea syndromes, surgery, and BP. In 26 studies with 1218 patients (mean age: 46.2 years; 82% men), the mean AHI significantly decreased by 26.2 (95% confidence interval [CI], 21.2 to 31.1) events/hour after sleep surgery. Overall, sleep surgery resulted in a significant reduction in office systolic and diastolic BP by 5.6 mmHg (95% CI, 2.9 to 8.3) and 3.9 mmHg (95% CI, 1.8 to 6.0), respectively, in adults with OSA. According to subgroup analyses, differences in the office BP after sleep surgery were nonsignificant between regions (ie, western vs eastern countries), sample sizes, surgical procedures (ie, pharyngeal surgery vs other surgical procedures), and follow-up periods. Meta-regression analyses revealed that reductions in systolic and diastolic BP were positively correlated with the AHI reduction. In conclusion, sleep surgery significantly reduces BP and AHI in adults with OSA. The BP reduction degree after sleep surgery is positively correlated with the OSA improvement degree.

Diagnostic performance of core needle biopsy for nodal recurrences in patients with head and neck squamous cell carcinoma.

This study investigated the diagnostic accuracy and affecting factors of ultrasound (US)-guided core-needle biopsy (CNB) in patients with treated head and neck squamous cell carcinoma (HNSCC). We retrospectively reviewed patients with treated HNSCC who received US-guided CNB from January 2011 to December 2018 with corresponding imaging. Pathological necrosis and fibrosis of targeted lymph nodes (LNs) were evaluated. We analyzed the correlation between CNB accuracy and clinical and pathological characteristics. In total, 260 patients were included. The overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of CNB for nodal recurrence were 84.47%, 100%, 100%, 54.67%, and 86.92%, respectively. CNB of fibrotic LNs had significantly worse sensitivity, NPV, and accuracy than that of non-fibrotic LNs. Similarly, CNB of necrotic LNs had significantly worse sensitivity, NPV, and accuracy than non-necrotic LNs. Multivariate regression revealed that fibrotic LN was the only independent factor for a true positive rate, whereas both necrotic LN and fibrotic LN were independent factors for a false negative rate. The diagnostic accuracy of CNB in treated HNSCC patients is affected by LN necrosis and fibrosis. Therefore, CNB results, particularly for necrotic or fibrotic LNs, should be interpreted carefully.

Impact of invasion into cervical esophagus for patients with hypopharyngeal squamous cell carcinoma.

OBJECTIVES: The invasion into cervical esophagus (ICE) sometimes could be encountered in patients with hypopharyngeal squamous cell carcinoma (HypoSCC). However, the incidence, predictive factors, and prognostic impact of ICE on the patients with HypoSCC remain unclear. MATERIALS AND METHODS: Patient diagnosis with HypoSCC at the National Taiwan University Hospital between January 2007 and December 2018 were reviewed. All patients were classified into two groups: with and without ICE. The curative treatment included upfront laryngectomy or pharyngo-laryngo-esophagectomy (PLE) with adjuvant chemoradiation, or definite organ-sparing chemoradiation. RESULTS: We analyzed 527 HypoSCC patients, 71 (13.47%) with and 456 (86.53%) without ICE. ICE presented more frequently in females (odds ratio (OR) = 3.01, p = 0.03) and posterior pharyngeal wall (OR = 2.34, p = 0.04). The 5-year disease-free survival of patients with and without ICE were 21.7% and 54.1%, respectively (p < 0.0001) and the 5-year overall survival were 13.1% and 53.8%, respectively (p < 0.0001). Among patients with ICE, the disease-free and overall survival of patients with upfront PLE were worse than the patients without upfront PLE (p = 0.21 and p = 0.27, respectively). After multivariant cox analysis, ICE was an independent risk factor for disease-free survival (p < 0.001) and overall survival (p < 0.001). CONCLUSION: ICE was occasionally present (13.47%) in HypoSCC patients. Unfortunately, the presence of ICE had a significant impact on disease-free and overall survival. For the HypoSCC patients with ICE, organ-sparing chemoradiation should be considered first as upfront PLE had no additional benefit.

Radiation-induced swallowing dysfunction in patients with head and neck cancer: A literature review.

Swallowing dysfunction is a prevailing state following radiotherapy in patients with head and neck cancer. Following the advancement of cancer treatment in recent years, the survival rate of head and neck cancer has gradually increased. Simultaneously, patients with head and neck cancer suffer due to the long-duration and more prominent swallowing dysfunction states. Based on an extensive literature review, we aimed to explore the mechanisms, risk factors, and clinical evaluations of swallowing dysfunction and their related symptoms following radiotherapy. These include functional changes of the muscles, trismus, xerostomia, neuropathy, and lymphedema. When swallowing dysfunction occurs, patients usually seek medical help and are referred for rehabilitation therapy, such as muscle strengthening and tongue resistance exercise. Furthermore, clinicians should discuss with patients how and when to place the feeding tube. Only through detailed evaluation and management can swallowing dysfunction resolve and improve the quality of life of patients with head and neck cancer following radiotherapy.

Incidence and prognostic significance of extranodal extension in isolated nodal recurrence of oral squamous cell carcinoma.

BACKGROUND: Extranodal extension (ENE) is a crucial prognostic factor of oral squamous cell carcinoma (OSCC). However, the role of ENE in regional recurrence (rENE) remains unclear. The purpose of our study is to assess the salvage outcome according to the presence of rENE in oral cancer patients with isolated nodal recurrence. METHODS: Oral cancer patients diagnosed with isolated nodal recurrence at the National Taiwan University Hospital between January 2010 and December 2015 were reviewed. All patients were classified into two groups: with and without rENE. The treatment included salvage neck dissection (ND) ± metronomic chemotherapy, salvage ND and radiation (RT)/concurrent chemoradiation (CCRT), Salvage RT/CCRT alone, metronomic chemotherapy, or supportive care. RESULTS: We analyzed 198 patients, 156 with rENE and 42 without rENE. rENE presented more frequently in patients with initial ENE+ (OR = 3.17, p = 0.04), prior RT+ (OR = 2.96, p = 0.02), initial N2/N3 (OR = 2.76, p = 0.01), and recurrent LN size >1.5 cm (OR = 2.33, p = 0.03). The extent of rENE were also significantly different in these patients. The 2-year disease-free survival for patients with and without rENE were 15.7% and 31.7%, respectively (p = 0.002). The 2-year overall survival for patients with and without rENE were 19.6% and 43.9%, respectively (p = 0.004). For patients without rENE, those received salvage ND had better survival outcome (p < 0.001). By contrast, for patients with rENE, those received salvage RT/CCRT had better survival outcome (p < 0.001). CONCLUSION: The rENE is frequently present (78.79%) in OSCC patients with isolated nodal recurrence. Individualized treatment modalities based on the presence of rENE should be recommended to achieve better salvage outcomes.

Effects of Interleukin-6 on STAT3-regulated signaling in oral cancer and as a prognosticator of patient survival.

OBJECTIVES: Human oral squamous cell carcinoma (OSCC) produces an inflammatory microenvironment enriched with cytokines including interleukin-6 (IL-6); however, the underlying molecular mechanisms of OSCC progression are unclear. We aimed to delineate the STAT3-mediated signaling pathways involved in tumor cell survival and growth. MATERIALS AND METHODS: Immunohistochemistry was used to semi-quantitate IL-6 and STAT3 in 111 OSCC tissues. IL-6-induced STAT3 signaling pathways and effects on tumor cell survival and progression were investigated in vitro and in xenograft mouse models. Effects of blocking IL-6-induced activation of STAT3 in an OSCC cell line were determined in vitro. RESULTS: A higher level of IL-6 or STAT3 in situ was associated with an unfavorable prognosis in OSCC patients with regard to both disease-free and overall survival rates. Overexpressed or exogenous IL-6 could induce SAS cell proliferationin vitroand significantly enhanced tumor growthin vivo. In addition, knockdown or inhibition of STAT3 expression in SAS cells significantly reduced tumor growth and abolished the responsiveness to IL-6 stimulation. Siltuximab or Tocilizumab could also significantly suppress IL-6-induced STAT3 phosphorylation and STAT3 nuclear translocation, resulting in a significant decrease of downstream anti-apoptotic proteins Bcl-2, Bcl-xL, and survivin. CONCLUSION: The IL-6 level in the tumor microenvironment could serve as a stage-independent predictor of OSCC progression and survival. Further, IL-6 may play a role in this disease through STAT3-dependent upregulation of anti-apoptotic genes and subsequent proliferation of tumor cells.

Outcomes of salvage treatment in patients with recurrent oral squamous cell carcinoma.

BACKGROUND: The survival outcomes of different salvage treatments for patients with recurrent oral cancer remain unclear. METHODS: A total of 556 patients with recurrent oral cancer between 2010 and 2015 were reviewed. Clinical/pathological risk factors and different salvage treatments were analyzed. RESULTS: The 2-year disease-free survival rates after recurrence in patients not receiving salvage operation (305 patients), receiving salvage operation with (121 patients), and without (130 patients) major pathological risk factors (margin or extranodal extension) were 5.3%, 32.4%, and 77.2%, respectively (p < 0.001). The 2-year overall survival rates were 20.3%, 58.4%, and 89.2%, respectively (p < 0.001). A late-onset recurrence, salvage radiation, and salvage operation were independent factors for good disease-free and overall survival. Salvage radiation showed survival benefits among patients not indicated for salvage operations. CONCLUSIONS: Salvage operation was the first choice for recurrent oral cancer. Patients who received the salvage operation without major risk factors had the best survival.