Microsurgical reconstruction for head and neck in patients with end-stage renal disease undergoing dialysis.

INTRODUCTION: Free flap transfer for head and neck defects has gained worldwide acceptance. Because flap failure is a devastating outcome, studies have attempted to identify risk factors-including renal failure. We sought to determine whether end-stage renal disease (ESRD) patients undergoing dialysis are at increased risk of flap failure following microsurgical head and neck reconstruction. PATIENTS AND METHODS: The study's participants were patients who underwent free flap reconstruction in the head and neck region at Hualien Tzu Chi Hospital between January 2010 and December 2019. We used the National Health Insurance "Specific Diagnosis and Treatment Code" to identify patients undergoing dialysis; these patients comprised the dialysis group, whose members were matched to a non-dialysis group for age and gender. The dependent variables were flap survival rate, take-back rate, and flap failure risk between the dialysis and non-dialysis groups. RESULTS: We included 154 patients in the dialysis (n = 14) and non-dialysis (n = 140) groups. The groups were similar in terms of age and most comorbidities, except diabetes mellitus, hypertension, and coronary artery disease, which were more prevalent in the dialysis group. The dialysis and non-dialysis groups had similar flap survival rates (100% vs. 92.9%; p = .600). Twenty-three patients underwent take-back surgery, most in the non-dialysis group (14.3% vs. 15.0%; p = 1.000). Patients in the dialysis group were more likely to have prolonged intensive care unit stays; however, dialysis alone did not predict flap failure (OR: 0.83; p = .864). CONCLUSION: This study found no significant differences in free flap survival and take-back rates between patients with and without dialysis. Dialysis did not increase the risk of flap failure following microsurgical head and neck reconstruction in this study; however, prospective, randomized controlled trials are needed.

Ossicular Reconstruction With Various Degrees of Malleus Preservation in Patients With Chronic Otitis Media.

Objective: We examined the relationship between factors of middle ear conditions and the outcome of ossiculoplasty in chronic otitis media (COM) by measuring the improvement in the air-bone gap (ABG) and air conduction threshold (TAC). Methods: This retrospective study analyzed 76 patients (77 ears) who underwent ossiculoplasty from among 520 COM patients who underwent tympanoplasty based on the maximum preservation of the original ossicles. The reconstructed ossicular chain was performed by preserving or utilizing the remaining malleus in all cases with the presence of the malleus manubrium. Patients with eardrum adhesion, cholesteatoma, and cholesterol granuloma were defined as having a compromised middle ear condition (Group A), and those without as having an uncompromised middle ear condition (Group B). In each group, pure-tone audiometry was performed preoperatively and postoperatively, and improvements in the ABG and TAC were compared. The effects of the types of tympanoplasty and the method of ossiculoplasty (columella versus incus interposition) on postoperative ABG and TAC were also compared. Results: The postoperative ABG improvement in Group B was significantly higher than that in Group A [ß = 7.31, 95% confidence interval (CI) = 1.93-12.69, P < .05]. Type III minor columella tympanoplasty yielded significantly better results than type III major and type Vb tympanoplasty (ß = 11.42, 95% CI = 5.16-17.68, P < .01). There were no significant differences in the postoperative ABG or TAC between the reconstruction groups with and without preservation of malleus. Conclusions: Our results indicate that complex cases compromised by adhesions, cholesteatoma, and cholesterol granuloma have worse outcomes regarding hearing improvement and success rates, while those with intact stapes suprastructure have better outcomes. Malleus was maximally preserved in the patients of this study; however, this showed no significant prognostic benefit in hearing.

Preconditioning of exosomes derived from human olfactory ensheathing cells improved motor coordination and balance in an SCA3/MJD mouse model: A new therapeutic approach.

Exosome therapy is a novel trend in regeneration medicine. However, identifying a suitable biomarker that can associate the therapeutic efficacy of exosomes with SCA3/MJD is essential. In this study, parental cells were preconditioned with butylidenephthalide (Bdph) for exosome preparation to evaluate the therapeutic effect of SCA3/MJD. The therapeutic agent hsa-miRNA-6780-5p was enriched up to 98-fold in exosomes derived from butylidenephthalide (Bdph)-preconditioned human olfactory ensheathing cells (hOECs) compared with that in naïve hOECs exosomes. The particle sizes of exosomes derived from naïve hOECs and those derived from hOECs preconditioned with Bdph were approximately 113.0 ± 3.5 nm and 128.9 ± 0.7 nm, respectively. A liposome system was used to demonstrate the role of hsa-miRNA-6780-5p, wherein hsa-miRNA-6780-5p was found to enhance autophagy and inhibit the expression of spinocerebellar ataxia type 3 (SCA3) disease proteins with the polyglutamine (polyQ) tract. Exosomes with enriched hsa-miRNA-6780-5p were further applied to HEK-293-84Q cells, leading to decreased expression of polyQ and increased autophagy. The results were reversed when 3MA, an autophagy inhibitor, was added to the cells treated with hsa-miRNA-6780-5p-enriched exosomes, indicating that the decreased polyQ expression was modulated via autophagy. SCA3 mice showed improved motor coordination behavior when they intracranially received exosomes enriched with hsa-miRNA-6780-5p. SCA3 mouse cerebellar tissues treated with hsa-miRNA-6780-5p-enriched exosomes showed decreased expression of polyQ and increased expression of LC3II/I, an autophagy marker. In conclusion, our findings can serve as a basis for developing an alternative therapeutic strategy for SCA3 disease treatment using miRNA-enriched exosomes derived from chemically preconditioned cells.

Association of Neutrophil-to-Lymphocyte Ratio and Bloodstream Infections with Survival after Curative-Intent Treatment in Elderly Patients with Oral Cavity Squamous Cell Carcinoma.

Patients with oral cavity squamous cell carcinoma (OSCC) undergoing curative-intent treatment may become immunocompromised. This study aimed to investigate the association of pretreatment sarcopenia, nutritional status, comorbidities, and blood-based inflammation prognostic biomarkers in bloodstream infection (BSI) with survival status in elderly patients with OSCC. Retrospective data were collected from 235 patients who were newly diagnosed with OSCC, were aged ≥ 65 years, had undergone curative-intent treatment, and were classified into either the BSI group or the no-BSI group within 6 months after surgery and/or adjuvant therapy initiation. Of the 235 elderly patients, 27 presented with BSI episodes. A preoperative high neutrophil-to-lymphocyte ratio (NLR) was a significant independent risk factor for BSI. BSI was not significantly associated with survival status. Ever betel nut chewing, hypoalbuminemia, and advanced tumor stage were associated with shorter overall survival. Moreover, a high NLR was an independent risk factor associated with disease-free survival. A high NLR was associated with BSI and resistance to curative-intent treatment. Pretreatment of NLR could act as an independent prognostic indicator and help inform treatment strategies for older patients with OSCC.

Esophageal Hypervigilance and Visceral Anxiety Contribute to Symptom Severity of Laryngopharyngeal Reflux.

INTRODUCTION: Laryngopharyngeal reflux (LPR) is a clinical conundrum without a diagnostic gold standard. The Esophageal Hypervigilance and Anxiety Scale (EHAS) is a questionnaire designed for cognitive-affective evaluation of visceral sensitivity. We hypothesized that esophageal hypervigilance and symptom-specific anxiety have an etiopathological role in generation of LPR symptoms, especially when gastroesophageal reflux disease (GERD) cannot explain these symptoms. METHODS: Consecutive patients with LPR and/or GERD symptoms lasting >3 months were prospectively enrolled and characterized using the Reflux Symptom Index, GERD questionnaire, and EHAS. Eligible patients with negative endoscopy underwent 24-hour impedance-pH monitoring off acid suppression for phenotyping GERD and assessment of reflux burden, using conventional metrics (acid exposure time and number of reflux episodes) and novel metrics (mean nocturnal baseline impedance and postreflux swallow-induced peristaltic wave index). RESULTS: Of 269 enrolled patients (mean age 47.1 years, 21-65 years, 60.6% female), 90 patients were with concomitant GERD and LPR symptoms, 32 patients were with dominant LPR symptoms, 102 patients were with dominant GERD symptoms, and 45 were controls. Patients with concomitant GERD and LPR symptoms had higher EHAS than those with dominant GERD symptoms and controls ( P ≤ 0.001); patients with dominant LPR symptoms had higher EHAS than controls ( P = 0.007). On Pearson correlation, EHAS positively correlated with the Reflux Symptom Index. DISCUSSION: Esophageal hypervigilance and symptom-specific anxiety may be more important than reflux burden in LPR symptom perception.

Nurse-Led Counseling Intervention of Postoperative Home-Based Exercise Training Improves Shoulder Pain, Shoulder Disability, and Quality of Life in Newly Diagnosed Head and Neck Cancer Patients.

This randomized controlled trial investigated the effectiveness of the nurse-led counseling intervention (NLCI) of postoperative home-based exercise training (HBET) on functional outcomes in patients with newly diagnosed head and neck cancer (NDHNC). Forty NDHNC patients were randomly and equally divided into the control and intervention groups. Both groups received routine care, and were instructed to undergo a HBET program with 40 min moderate-intensity exercise 3-4 times per day for 12 weeks after their surgery. Only the intervention group received the NLCI with a bedside demonstration, coaching, consultation, and a weekly telephone follow-up. Shoulder pain (SP), shoulder disability (SD), and quality of life (QOL) scores were assessed using questionnaires at 2 weeks presurgery and at several timepoints postsurgery. Over the 12-week study period, all three scores remained relatively stable in the control group. By contrast, the SP, SD, and QOL scores significantly improved in the intervention group. The generalized estimating equation analysis revealed a significant time effect, group effect, and group-time interaction. The analysis of covariance revealed that all three scores significantly improved in the intervention group compared with those in the control group at 12 weeks postsurgery. We concluded that the NLCI of postoperative HBET improved the SP, SD, and QOL of NDHNC patients.

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.

Identification of Prognostic Biomarkers Originating From the Tumor Stroma of Betel Quid-Associated Oral Cancer Tissues.

BACKGROUND: Partial epithelial-mesenchymal transition (p-EMT) is a distinct clinicopathological feature prevalent in oral cavity tumors of The Cancer Genome Atlas. Located at the invasion front, p-EMT cells require additional support from the tumor stroma for collective cell migration, including track clearing, extracellular matrix remodeling and immune evasion. The pathological roles of otherwise nonmalignant cancer-associated fibroblasts (CAFs) in cancer progression are emerging. METHODS: Gene set enrichment analysis was used to reveal differentially enriched genes and molecular pathways in OC3 and TW2.6 xenograft tissues, representing mesenchymal and p-EMT tumors, respectively. R packages of genomic data science were executed for statistical evaluations and data visualization. Immunohistochemistry and Alcian blue staining were conducted to validate the bioinformatic results. Univariate and multivariate Cox proportional hazards models were performed to identify covariates significantly associated with overall survival in clinical datasets. Kaplan-Meier curves of estimated overall survival were compared for statistical difference using the log-rank test. RESULTS: Compared to mesenchymal OC3 cells, tumor stroma derived from p-EMT TW2.6 cells was significantly enriched in microvessel density, tumor-excluded macrophages, inflammatory CAFs, and extracellular hyaluronan deposition. By translating these results to clinical transcriptomic datasets of oral cancer specimens, including the Puram single-cell RNA-seq cohort comprising ~6000 cells, we identified the expression of stromal TGFBI and HYAL1 as independent poor and protective biomarkers, respectively, for 40 Taiwanese oral cancer tissues that were all derived from betel quid users. In The Cancer Genome Atlas, TGFBI was a poor marker not only for head and neck cancer but also for additional six cancer types and HYAL1 was a good indicator for four tumor cohorts, suggesting common stromal effects existing in different cancer types. CONCLUSIONS: As the tumor stroma coevolves with cancer progression, the cellular origins of molecular markers identified from conventional whole tissue mRNA-based analyses should be cautiously interpreted. By incorporating disease-matched xenograft tissue and single-cell RNA-seq results, we suggested that TGFBI and HYAL1, primarily expressed by stromal CAFs and endothelial cells, respectively, could serve as robust prognostic biomarkers for oral cancer control.

Comparison of Hearing Preservation Outcomes Using Extended Versus Single-Dose Steroid Therapy in Cochlear Implantation.

OBJECTIVES: The purpose of this study was to compare the hearing preservation outcomes of patients who received extended versus single-dose steroid therapy in cochlear implant surgery. DESIGN: Case-control. SETTING: Tertiary referral centers in Taiwan from April 2017 to 2019. PARTICIPANTS: A total of 70 patients aged 1 to 78 years old (mean = 18.04, standard deviation [SD] = 21.51) who received cochlear implantation via the round window approach were included in the study. Prospectively, 35 cases were enrolled for cochlear implantation with single-dose therapy. Thirty-five controls who underwent cochlear implantation with extended therapy were retrospectively enrolled after frequency matching. OUTCOME MEASURES: The main outcome measure was the rate of hearing preservation. This was calculated based on the HEARRING Network formula and results were categorized as complete, partial, and minimal. Impedances served as secondary outcomes. RESULTS: There was no significant difference in the complete hearing preservation rates between the extended and single-dose groups at 6 months postoperatively. Impedances were significantly lower in the extended group after 1 month and 6 months of follow up. When the complete and partial hearing preservation groups were compared, the size of round window opening and speed of insertion were found to be statistically significant. CONCLUSIONS: Both extended and single-dose therapies result in good hearing preservation in patients who undergo cochlear implantation. However, better impedances can be expected from patients who received extended therapy. A slower speed of insertion and a widely opened round window play a role in hearing preservation.

Patients with oral cancer do not undergo surgery as primary treatment: A population-based study in Taiwan.

BACKGROUND: There are still oral cancer patients without surgery. To improve the survival, it is necessary to know the causes of the oral cancer patients without surgery. METHODS: 23,217 patients with a newly-diagnosed oral cancer in Taiwan Cancer Registry (TCR) database between 2011 and 2015 were enrolled. Data from TCR database named "Reason for No Surgery of Primary Site" were extracted for analysis of the causes of those without surgery. Overall survival plots were presented using the Kaplan-Meier method with log-rank test. RESULTS: 3263 (14%) patients did not received surgery. Among them, there were 720 patients (group 3) without surgery although surgery was advised, 154 patients (group 2) because of poor condition or death before surgery, and 2389 patients (group 1) because of other causes. Twenty-four percent of the patients with surgery were treated one month and more after diagnosis. The 5-year overall survival rates were 68.7%, 25.2%, 9.1% and 17.3% for surgery group, group 3, 2 and 1, respectively (p < 0.001). The mean age of the patients with and without surgery were 54.8 and 59.3, respectively (p < 0.01). Female patients were commoner in group 3 (p < 0.01). The patients without surgery was commoner in the middle (15.7%) and southern (14.8%) than in Northern Taiwan (12.1%). All groups without surgery had more advanced stage and lower BMI (p < 0.01). CONCLUSION: One-sevenths of patients were not treated surgically because of refusal, poor condition, older age, low BMI, and advanced stage. It is necessary to encourage the patients to undergo surgery with shortening the diagnosis-to-treatment interval.

Intra-auricular modification of facelift incision decreased the risk of Frey syndrome.

OBJECTIVE: Frey syndrome is a complication followed by parotidectomy which caused gustatory sweating and facial flush. There were several methods for the prevention of Frey syndrome, but most of them had no obvious effects. In this study, we compare the intra-auricular modification of facelift incision with the traditional lazy-S incision to see if it can decrease the risk of Frey syndrome. MATERIALS AND METHODS: This is a retrospective study. From 2003 to 2009, a total of 61 patients with benign parotid tumor who received parotidectomy at Hualien Tzu Chi Hospital and were followed at outpatient department for at least 5 years were enrolled. Patients were divided into two groups according to the type of incisions during operation: (1) Group M: intra-auricular modification of facelift incision or (2) Group S: traditional lazy-S incision. All patients received the partial thickness sternocleidomastoid muscle flap. Clinical data including age, gender, pathologic result, presentation of Frey syndrome, size of tumor, length of operation, blood loss from surgery, length of placement of drain, total amount of drainage, and length of stay were collected and analyzed. RESULTS: Sixty-one patients were enrolled. Eighteen patients were in Group M and forty-three were in Group S. There was no significant difference of age, gender, and size of tumor between the two groups. The pathologic results included parotitis, pleomorphic adenoma, Warthin's tumor, and others. No significant difference of pathologic results, blood loss from surgery, length of placement of drain, total amount of drainage, and length of stay between two groups was obtained. The length of operation was longer in Group M (P = 0.001) and the incidence of Frey syndrome was lower in Group M than Group S (P < 0.05). CONCLUSIONS: The use of intra-auricular modification of facelift incision can decrease the incidence of Frey syndrome.

Enhanced aerobic glycolysis of nasopharyngeal carcinoma cells by Epstein-Barr virus latent membrane protein 1.

Latent membrane protein 1 (LMP1) is a principal viral oncoprotein in Epstein-Barr virus (EBV)-associated malignancies, including nasopharyngeal carcinoma (NPC), which acts through regulating tumorigenesis and metabolic reprogramming of cancers. In the presence of oxygen, we demonstrated that glucose consumption, lactate production and lactate dehydrogenase (LDH) activity were significantly increased upon LMP1 expression in NPC cells and in a LMP1 variant derived from NPC patients-transformed BALB/c-3T3 cells. The amounts of the α subunit of hypoxia-inducible factor-1 (HIF-1α), a key regulator of aerobic glycolysis, and its targets, pyruvate dehydrogenase kinase 1 (PDK1) and the pyruvate kinase M2 (PKM2) isoform, were also consistently elevated by LMP1. Moreover, in parallel with reductions in the oxygen consumption rate and mitochondrial membrane potential in cells, an augmented extracellular lactate concentration was observed due to LMP1 induction. In conclusion, our results proved facilitation of the Warburg effect by LMP1 through alteration of mitochondrial function in NPC cells.

Comparative clinical outcomes of Taiwanese patients with resected buccal and tongue squamous cell carcinomas.

OBJECTIVES: Although patients with buccal squamous cell carcinoma (SCC) usually show acceptable outcomes, local control and survival rates are generally lower than those observed for tongue SCC. This study was designed to compare the clinical outcomes of Taiwanese patients with these two common oral cavity malignancies. METHODS: Patients with first primary buccal or tongue SCC who were included in the Taiwanese Cancer Registry Database between 2004 and 2012 were eligible. The study sample consisted of 16,379 patients (7870 buccal SCC and 8509 tongue SCC) who received surgery with or without adjuvant therapy. The 5-year disease-specific survival (DSS) and overall survival (OS) rates served as the outcome measures. RESULTS: Compared with tongue SCC, patients with buccal SCC had a higher prevalence of males (95.7% vs. 86.4%, p<0.0001), pT4 disease (21.4% vs. 12.7%, p<0.0001), and p-Stage IV (30.4% vs. 24.8%, p<0.0001) but a lower frequency of pN2 disease (15.2% vs. 18.5%, p<0.0001). The 5-year DSS and OS rates of buccal SCC patients were slightly higher than those of tongue SCC (78% vs. 77%, p=0.0297; and 71% vs. 69%, p=0.0231, respectively). Multivariate analysis identified tumor site (tongue vs. buccal SCC), sex (male vs. female), age (≥65 vs. <65years), pT classification (T4/T3/T2 vs. T1), and pN classification (N3/N2/N1vs. N0) as independent prognostic factors in the entire study cohort. CONCLUSIONS: The survival advantage of buccal SCC over tongue SCC appears significant in large clinical samples, despite a higher prevalence of p-Stage IV disease in the former.

Positive regulation of HIF-1A expression by EBV oncoprotein LMP1 in nasopharyngeal carcinoma cells.

Latent membrane protein 1 (LMP1) is a pivotal viral oncoprotein that contributes to the carcinogenesis of Epstein-Barr virus (EBV)-associated malignancies, including nasopharyngeal carcinoma (NPC). We investigated the regulation of hypoxia-inducible factor 1-α (HIF-1α) by LMP1. In NPC cells, we found that LMP1 significantly enhanced the HIF-1α mRNA level, and not only the protein amount as described previously. Mechanistically, the stability of the HIF-1α transcript was remarkably prolonged by LMP1 via reduced expressions of RNA-destabilizing proteins tristetraprolin (TTP) and pumilio RNA-binding family member 2 (PUM2) through C-terminal activation region 1 (CTAR1) and CTAR3 interaction with the ERK1/2 and STAT3 signaling pathways, respectively, in parallel with hindrance of PUM2 binding to the HIF-1α mRNA 3'-untranslated region (3'-UTR). On the other hand, HIF-1A promoter activity was also obviously facilitated by the LMP1 CTAR1-recruited ERK1/2/NF-κB pathway. Intriguingly, in this scenario, augmented HIF-1α further exhibited positive auto-regulation of its own gene transcription. Our results showed the first time that LMP1 directly up-regulates HIF-1A transcription and post-transcription in NPC cells, in addition to providing evidence of an increase in the HIF-1α mRNA level caused by a tumor-associated virus under normoxic conditions.

Resected tumours of the sublingual gland: 15 years' experience.

Sublingual gland tumours are rare, and we have evaluated the clinical features and prognosis of patients treated at a tertiary medical centre in eastern Taiwan. We retrospectively reviewed the cases of nine patients with sublingual gland tumours that were resected from December 1993 to November 2008, four of whom were men and five women. The median (range) age at diagnosis was 52 (39-63) years. Seven had malignant tumours, of which adenoid cystic carcinoma was the most common. All patients with malignant tumours had neck dissections, and four had cervical lymph node metastases. The incidence of lymph node metastases was much higher in patients with advanced primary tumours (T1/2 compared with T3/4: one out of three compared with three out of four). All patients with malignant tumours were given adjuvant radiotherapy. There were no local failures. One patient had regional recurrence in the neck and had a successful further resection. Three patients developed distant metastases, and two died during the follow-up period. Our results suggest that radical resection with postoperative radiotherapy offers adequate local and regional control for malignant sublingual gland tumours. Neck dissection is beneficial, especially for T3/4 disease.

Prognostic factors of paranasal sinusitis with intracranial invasion: A 14-year review of cases at Hualien Buddhist Tzu Chi Hospital.

Intracranial invasion of paranasal sinusitis is an emergency condition that requires surgical and medical intervention in order to avoid further deterioration. We surveyed patients at the Buddhist Tzu Chi Hospital (Hualien, Taiwan) who had paranasal sinusitis with intracranial invasion. A total of 505 patients with paranasal sinusitis were surveyed at Hualien Buddhist Tzu Chi Hospital over a 14-year period (2000-2013). Data on clinical presentations, microbiology, host factors, postinterventional morbidity, and postinterventional mortality are presented. Of the 505 patients, nine had intracranial invasions (incidence rate, 1.8%). The mortality rate was high among these patients (44.4%, 4/9). Among the various risk factors identified, diabetes had the greatest influence (66.7%, 6/9), which in combination with an immunocompromised condition and cirrhosis is indicative of a poor prognosis.

Methylation status of insulin-like growth factor-binding protein 7 concurs with the malignance of oral tongue cancer.

BACKGROUND: Aberrant insulin-like growth factor-binding protein 7 (IGFBP-7) expression has been found in various cancers such as prostate, breast, and colon. IGFBP-7 induced the apoptosis of tumor and potentially predicted the clinical outcome in some cancers is further demonstrated. This study investigates the causes and underlying mechanisms of aberrant IGFBP-7 expression in unravelling head and neck squamous cell carcinoma (HNSCC). METHODS: A total of 47 oral tongue cancer patient samples were primarily analyzed for the methylation status in 5' region of IGFBP-7 by methylation-specific PCR (MS-PCR). Subsequently the invasion, overexpression, and knockdown of IGFBP-7 in the HNSCC A253 invasive subpopulation were employed to examine the effect of IGFBP-7. The epithelial-mesenchymal transition (EMT) marker genes and AKT/GSK3ß/ß-catenin signaling were further evaluated by Western blot for the understanding the role of aberrant IGFBP-7 expression and thereof putative mechanism. RESULTS: EMT expressed in the invasive subpopulation of HNSCC cell lines (A253 and RPMI 2650) was contemporary with the down-regulation of IGFBP-7. After treatment with 5-AZA-2' deoxycytidine, the de-methylated CpG sites in the 5' region of IGFBP-7 were observed and IGFBP-7 mRNA expression was also restored. Accordingly, re-expression IGFBP-7 in invasive subpopulation of A253 could induce the mesenchymal-epithelial transition (MET) and concurrently inhibited the cell invasion. Moreover, IGFBP-7 methylation status of 47 oral tongue tumors showed a positive correlation to invasive depth of the tumor, loco-regional recurrence, and cancer sequence. CONCLUSIONS: IGFBP-7 can alter EMT relative marker genes and suppress cell invasion in A253 cell through AKT/GSK3ß/ß-catenin signaling. The epigenetic control of IGFBP-7 in the invasion and metastasis of HNSCC was reported, suggesting that IGFBP-7 could be a prognostic factor for the probability of invasion and a therapeutic remedy.

Residual hearing preservation after cochlear implantation via round window or cochleostomy approach.

OBJECTIVES/HYPOTHESIS: The purpose of the study was to investigate whether cochlear implantation using the round window approach provided better preservation of residual hearing than the cochleostomy approach. STUDY DESIGN: Case-control study. METHODS: We designed a case-control study including 40 patients from a tertiary referral center who underwent cochlear implantation surgeries using devices from MED-EL Co., Innsbruck, Austria. Between November 2013 and July 2014, we prospectively enrolled 20 subjects for cochlear implantation surgery using the round window insertion approach. In addition, 20 age- and sex-matched control subjects from the database of cochlear implantees treated using the cochleostomy approach between January 2008 and October 2013 were retrospectively enrolled. The residual hearing of the operated ear was measured before and after surgery. The variables analyzed were the pure-tone average threshold at 250, 500, and 1,000 Hz and the residual hearing at frequencies of 250 to 8,000 Hz. The residual hearing was considered as preserved when the audiometric changes were <10 dB hearing loss for each variable. The audiological results of the two groups were compared. RESULTS: No statistically significant difference in the preservation of residual hearing was found in the two groups (P > .05 for all of the variables). CONCLUSIONS: The round window and cochleostomy approaches for cochlear implant surgery may preserve residual hearing at similar rates across a range of frequencies.