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.

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.

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.

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.

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.

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 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.

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.

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.

Physical activity and fitness in survivors of head and neck cancer.

PURPOSE: The purposes of the study were (1) to assess the physical activity (PA) status, muscle strength (MS), and flexibility of survivors of head and neck cancer (HNC) and compare these findings with normative data from national labor fitness measures; (2) to examine the differences among PA subgroups, as categorized using Godin's scores; and (3) to examine the association between stretching exercises and cervical range of motion (CROM). METHODS: A cross-sectional study with consecutive sampling was used to recruit HNC survivors from a medical center in Northern Taiwan who had completed either radiation therapy (RT) or multimodality treatments including RT within the current 5 years. The level of PA, daily function, fatigue, quality of life (QOL), MS (handgrip and hip flexor), BMI, and flexibility (CROM and fingertip-to-floor tests) of the participants were assessed. RESULTS: A total of 108 participants completed the assessments from 135 eligible patients (80% response rate). Although 60.2% reported engaging in PA, only 16.7% met WHO guidelines. Compared to subjects in the normative data, the survivors of HNC in this study had poorer handgrip strength, BMI, and CROM, but better forward flexion. The participants who were consistent with WHO PA guidelines reported less fatigue, better right hip flexor MS, and better QOL than those who did not engage in any PA. CONCLUSION: Lack of sufficient PA and generally poorer fitness were found in study subjects. Longitudinal research to explore changes in fitness and barriers to PA compliance is strongly suggested to better enhance HNC patients' PA and fitness.

Enrichment of Human CCR6+ Regulatory T Cells with Superior Suppressive Activity in Oral Cancer.

Human oral squamous cell carcinoma (OSCC) constitutes an inflammatory microenvironment enriched with chemokines such as CCL20, which promote cancer cell invasion and tumor progression. We found that in OSCC there is a correlation between the expression of CCL20 and FOXP3 mRNA. Therefore, we hypothesized that OSCC may favor the recruitment and retention of regulatory T (Treg) cells that express the CCL20 receptor, CCR6. Interestingly, most (∼60%) peripheral blood Treg cells express CCR6, and CCR6+ Treg cells exhibit an activated effector/memory phenotype. In contrast, a significant portion (>30%) of CCR6- Treg cells were found to be CD45RA+ naive Treg cells. Compared to CCR6- naive or memory Treg cells, CCR6+ Treg cells exhibit stronger suppressive activity and display higher FOXP3 expression along with lower methylation at the Treg-specific demethylated region of the FOXP3 gene. This predominance of CCR6+ Treg cells was also found in the draining lymph nodes and tumor-infiltrating lymphocytes of OSCC patients with early or late clinical staging. Moreover, CCR6+ Treg cells isolated from tumor-infiltrating lymphocytes or draining lymph nodes maintained similar phenotypic and suppressive characteristics ex vivo as did their counterparts isolated from peripheral blood. These results suggest that CCR6 marks activated effector or memory Treg phenotypes with superior suppressive activity in humans.

Ear, nose, and throat foreign bodies in adults: A population-based study in Taiwan.

BACKGROUND/PURPOSE: This study performed a population-based analysis in the managements of adult ear, nose, and throat FBs in Taiwan. METHODS: The Taiwan Longitudinal Health Insurance Database 2000 were used, which comprises 1,000,000 beneficiaries randomly sampled in 2000 with a follow-up period from 2000 to 2013. Patients aged >18 years with ear, nose, or throat FB were identified according to the International Codes of Diseases. RESULTS: In total, 94,312 adults with ear (n = 21,786), nose (n = 1007), throat (n = 62,986), airway (n = 419), or esophageal (n = 8114) FB were identified. Emergency department visits were most common among patients with esophageal or airway FB (33.3% and 25.1%, respectively). X-rays were most commonly performed for patients with esophageal FB (44.8%), and computed tomography (CT) was most commonly used for those with airway FB (4.3%). Hospitalization rate was the highest among patients with airway FB (7.4%), followed by those with esophageal (3.0%) and nose (0.7%) FB. Patients with airway FBs corresponded with the highest rate of intensive care unit stay (58.1%), longest hospital stay (10.5 days), and highest in-hospital mortality rate (25.8%). A multiple logistic regression model indicated that old age, medical comorbidities, undergoing CT, and airway or esophageal FB were associated with hospitalization among adults with FB. CONCLUSION: Disparities were identified in the treatment of ear, nose, and throat FB in adults. This study provides population-based data that may serve as a reference for otolaryngologists in clinical FB management.

Revision adenoidectomy in children: a population-based cohort study in Taiwan.

There is a lack of population-level analysis of revision adenoidectomy in children. This study reveals the revision rates and factors associated with paediatric revision adenoidectomy in Taiwan. From the Taiwan National Health Insurance Research Database, we identified all in-hospital children (age <18 years) who underwent adenoidectomy between 2000 and 2007. All children had received at least 5 years of follow-up from the index date, and the clinical records until 2012 were examined. Factors affecting the paediatric revision adenoidectomy were analysed using the multivariable Cox proportional hazards model. A total of 10,396 children were enrolled (mean age 7.3 years; 66% boys; mean follow-up period 8.7 years). Two hundred and seventy-five children underwent revision adenoidectomy, and the mean interval between primary adenoidectomy and revision surgery was 2.97 years. Only 58.5% of children underwent revision surgery at the initial hospital. The incidence of revision surgery was highest in the second year (0.69%), followed by the third year (0.53%) after primary adenoidectomy. The multivariable Cox proportional hazards model revealed that young age [hazard ratio (HR) = 0.8], male gender (HR = 1.57), surgery at an eastern hospital (HR = 2.08), surgical indication of adenoid hypertrophy (HR = 1.51), and concurrent ventilation tube insertion (HR = 2.61) or nasal surgeries (HR = 4.84) were associated with revision adenoidectomy. The incidence of revision adenoidectomy in Taiwan was 2.6%. Male gender, young age, concurrent nasal or ventilation tube insertion, and surgery at an eastern hospital increased the risk of revision.

Transcutaneous Ultrasonography for Diagnosis of Nasolabial Cyst.

Nasolabial cyst is usually diagnosed by computerized tomography and magnetic resonance imaging. Ultrasonography could be a simple, office-based diagnostic imaging tool for nasolabial cyst. The authors report a 46-year-old woman with painful swelling on the bilateral anterior nostrils. The high-frequency (13 MHz) linear array transducer of the ultrasound (Hitachi Hivision Avius with EUP-L74M, Hitachi Aloka Medical, Tokyo, Japan) was transversely placed on the upper lip to scan the anterior nasal floor. Ultrasonography showed 2 well-defined anechoic oval cystic lesions in the anterior nasal floor, which were compatible with nasolabial cysts. Magnetic resonance imaging, which was done for her nasopharyngeal carcinoma 3 years ago, showed the same cystic lesions in the anterior nostril floor. Transcutaneous ultrasonography could be a simple, first-line imaging tool for diagnosis of nasolabial cyst in an office-based clinical setting.

Application of ultrasound-guided core biopsy to minimize the non-diagnostic results and the requirement of diagnostic surgery in extrapulmonary tuberculosis of the head and neck.

PURPOSE: Head and neck extrapulmonary tuberculosis (ETB) presenting as lymphadenopathy poses a great threat by potentially increasing the deterioration of clinical outcomes. Tissue sampling for diagnostic confirmation of ETB is the only invasive procedure during the entire clinical course. It is, therefore, necessary to establish ETB sampling methods with accuracy and minimal invasiveness. METHODS: From 2009 to 2014, consecutive patients suspected of ETB receiving ultrasound-guided core biopsy (USCB), fine needle aspiration (FNA), and open biopsy (OB) were enrolled for comparison. RESULTS: There were 52 cases in the USCB group, 58 cases in the FNA group, and 78 cases in the OB group. For USCB, FNA, and OB groups, the diagnostic rates were 84.6 %, 8.6 %, and 100 % and the positive rates of acid-fast stain were 28.6 %, 0 %, and 37.5 %, respectively. The diagnostic rates of culture were 9.6 %, 0 %, and 50 %, respectively. For head and neck ETB, USCB procedure is timesaving, without leaving poor-healing wounds, scars, and the need for general anaesthesia and hospitalization. CONCLUSIONS: This study helps to optimize the ETB sampling method in head and neck based on diagnostic accuracy and minimal invasiveness. USCB can serve as the first-line diagnostic tool for ETB by reducing non-diagnostic results and the need for diagnostic surgery. KEY POINTS: • USCB shows higher diagnostic accuracy of ETB than FNA (84.6 % vs. 8.6 %). • USCB diminishes wound complications caused by surgical intervention for ETB. • USCB avoids general anaesthesia and hospitalization for diagnosing ETB. • USCB saves time and reduces the medical costs of diagnosing ETB.

Autophagy is deficient and inversely correlated with COX-2 expression in nasal polyps: a novel insight into the inflammation mechanism.

BACKGROUND: Nasal polyposis is characterised by persistent inflammation of the upper airways. Autophagy has been implicated in many chronic inflammatory diseases. Whether autophagy plays a role in nasal polyp (NP) inflammation is completely unknown and deserves investigation. METHODS: LC3 and COX-2 expression, the common autophagy and inflammation indicators, respectively, was analysed by immunoblotting in fresh tissues of NP and control nasal mucosa (NM). Primary cultures of NP-derived fibroblasts (NPDFs) and NMDFs were established for in vitro studies. Autophagy was induced by amino acid starvation and LC3 ectopic overexpression or inhibited by 3-methyladenine in the fibroblasts. Inflammation was induced by IL1-ß and TNF-α. LC3 and COX-2 expression was confirmed in NP specimens by immunohistochemistry. RESULTS: LC3 expression was decreased while COX-2 expression was significantly increased in fresh NP tissues compared with the NM control. In NMDFs and NPDFs, autophagy induction by starvation and LC3 overexpression downregulated COX-2 expression. Conversely, autophagy inhibition by 3-methyladenine enhanced COX-2 expression. However, IL1-ß and TNF-α had no effect on autophagy. Immunohistochemical studies on the NP specimens showed that most displayed low LC3 expression, whereas COX-2 was highly expressed in >50% of the specimens. Examination of two consecutive NP sections from the same tissue blocks revealed a negative correlation between LC3 and COX-2 expression. CONCLUSION: Autophagy is deficient in NP tissues and COX-2 is negatively regulated by autophagy in NP-derived fibroblasts. Since COX-2 is essential for the production of pro-inflammatory mediators, this study might help interpret persistent mucosal inflammation in NP. Attenuation of inflammation by restoring autophagy might be a therapeutic strategy for treating NP.

Inhibition of G9a induces DUSP4-dependent autophagic cell death in head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a common cancer worldwide. Emerging evidence indicates that alteration of epigenetics might be a key event in HNSCC progression. Abnormal expression of histone methyltransferase G9a, which contributes to transcriptional repression of tumor suppressors, has been implicated in promoting cancerous malignancies. However, its role in HNSCC has not been previously characterized. In this study, we elucidate the function of G9a and its downstream mechanism in HNSCC. METHODS: We investigated the clinical relevance of G9a in HNSCC using immunohistochemistry (IHC) staining. In vitro cell proliferation and tumorigenesis ability of G9a-manipulated HNSCC cells were examined with MTT assays, clonogenic assays, and soft agar assays. We examined different routes of cell death in HNSCC cells induced by G9a-depletion or enzymatic inhibition by immunoblot, flow cytometry, fluorescent and transmission electron microscopy analysis. Specific targets of G9a were identified by affymetrix microarray and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Lastly, functions of G9a in vivo were confirmed with a xenograft tumor model. RESULTS: G9a expression is positively correlated to proliferation marker Ki-67 and to poor prognosis in HNSCC patients. Genetic or pharmacological inhibition of G9a reduced cell proliferation without inducing necrosis or apoptosis. Instead, autophagic cell death was the major consequence, and our investigation of mechanisms suggested it is mediated via the dual specificity phosphatase-4 (DUSP4) dependent ERK inactivation pathway. An orthotopic tumor model further confirmed the growth inhibiting effect and induction of autophagy that followed suppression of G9a. CONCLUSIONS: In this study, we provide evidence that G9a confers the survival advantage of HNSCC. Genetic or pharmacological inhibition of G9a induces autophagic cell death; this finding provides a basis for new therapeutic targets for treating HNSCC.

Use of transnasal endoscopy for screening of esophageal squamous cell carcinoma in high-risk patients: yield rate, completion rate, and safety.

BACKGROUND: Patients with head and neck squamous cell carcinoma are at high risk for synchronous and/or metachronous esophageal cancer. The present study aimed to evaluate the feasibility and safety of unsedated transnasal endoscopy (TNE) for screening these high-risk patients. PATIENTS AND METHODS: Consecutive high-risk patients including patients with suspicious or diagnosed head and neck cancer or patients with alarming symptoms received screening TNE. All endoscopic procedures, including sequential conventional white-light, narrow-band imaging, and Lugol chromoendoscopy, were done without sedation. All suspicious lesions in the esophagus were biopsied for histological evaluation. The completion rate, procedure time, and significant adverse events of all endoscopic procedures were recorded and analyzed. RESULTS: From May 2007 to August 2011, a total of 500 TNE were carried out in 441 high-risk patients. Among them, 294 patients (66.7%) had diagnosed head and neck squamous cellcarcinoma, and most were hypopharyngeal cancer (n = 186). Esophageal squamous cell carcinomas and high-grade intraepithelial neoplasms were detected in 10.1% and 7.3%, respectively, of the cases. Completion rate of TNE in head and neck cancer was 96.7%; tumor obstruction and stenosis of anastomosis site were the main reasons for incomplete procedures. Mean duration of the endoscopic procedure was 14.6 min. One patient had post-endoscopic epistaxis while another patient had post-biopsy hemoptysis, both of whom were treated conservatively. No procedure-related mortality or significant morbidity occurred. CONCLUSION: Unsedated TNE is safe and feasible for screening synchronous or metachronous esophageal neoplasms in high-risk patients, especially those with head and neck cancer.

Magnetic resonance imaging following endoscopic nasopharyngectomy with a potassium-titanyl-phosphate (KTP) laser for early locally recurrent nasopharyngeal carcinoma.

INTRODUCTION: This study aims to investigate the spectrum of magnetic resonance imaging (MRI) features following endoscopic potassium-titanyl-phosphate (KTP) laser nasopharyngectomy. METHODS: From January 2005 to December 2010, a total of 35 patients underwent KTP laser nasopharyngectomy for early recurrent NPC (rT1 or rT2) at our institute. Those who were lost to follow-up (N = 2) were excluded. Among the remaining patients, ten were proved to have locally recurrent disease and the other 23 not locally recurrent within 2 years of postoperative follow-up. Their serial MRIs were evaluated. RESULTS: Postoperative nasopharyngeal mucosal changes were present in all of the subjects on first follow-up MRI, ranged from focal mucosal thinning (19/33, 57.6 %), focal mucosal thickening (8/33, 24.2 %) to mixed thinning and thickening (6/33, 18.2 %). Nasopharyngeal submucosal soft tissue volume loss was found in 23 (23/33, 69.7 %), and parapharyngeal soft tissue necrosis was found in 3 (3/33, 9.1 %). Postoperative bone marrow change involved the clivus in 31 (31/33, 93.9 %) and the petrous or pterygoid in 17 (17/33, 51.5 %). There were no significant differences between the two groups in the changes of mucosa, adjacent soft tissue, and skull base on the first MRI. The evaluation of serial MRIs disclosed that the patients in the recurrent group were more likely to develop new or enlarging mucosal masses (p = 0.01) and enlarging skull base changes (p = 0.0001). CONCLUSIONS: KTP laser nasopharyngectomy induces mucosal and skull base changes that could be misinterpreted as tumor progression on early postoperative MRI scans. Sequential imaging is required to distinguish between postoperative changes and progressive disease.

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.