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.

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.

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.

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.

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.

Concomitant induction of apoptosis and autophagy by prostate apoptosis response-4 in hypopharyngeal carcinoma cells.

The tumor-suppressive activity of prostate apoptosis response-4 (Par-4) has been demonstrated in a variety of human cancers. In this study, for the first time to our knowledge, we demonstrated that a higher intensity of Par-4 was significantly correlated with a better response in patients with hypopharyngeal carcinoma undergoing radiotherapy alone or concurrent chemoradiotherapy. Mechanistically, an elevated expression of Par-4 induced apoptosis of hypopharyngeal carcinoma cells and sensitized cells toward chemotherapeutic agents or X-ray irradiation. Along with apoptotic incitation, intriguingly, autophagic flux also increased on Par-4 stimulation and contributed to cell death. Moreover, the expressions of multiple common regulators involved in apoptosis and autophagy were regulated by Par-4. Taken together, our results suggested a prognostic role of Par-4 in hypopharyngeal carcinoma and showed novel activity of Par-4 in apoptosis and autophagy induction.

The proximal lateral lower leg perforator flap revisited: anatomical study and clinical applications.

BACKGROUND: The proximal lateral lower leg flap is a flap suited for the reconstruction of small and thin defects. The purpose of this study was to map the position and consistency of the perforator vessels and to review its reliability and technical considerations clinically. METHODS: The location, number, and size of perforator vessels in the proximal third of the lateral lower leg were investigated in 20 fresh frozen cadaveric lower limbs. This was analyzed together with 22 clinical cases. RESULTS: Cadaveric dissection showed that there were 1-2 perforators in the proximal third of the lateral lower leg and these perforator vessels were found to be 63% septocutaneous and 37% musculocutaneous. The source vessel of the perforators was variable. Clinically the recipient site consisted of the head and neck in 8 cases, the foot and ankle region in 13 cases, and 1 case in the hand. The mean thickness of this flap was 5.8 ± 0.8 mm. Vascular pedicle length ranged from 5 to 8.5 cm. The mean diameter of flap artery was 1.3 ± 0.3 mm. One flap failure was seen due to arterial thrombosis. The overall flap survival rate was 95%. CONCLUSIONS: The proximal lateral lower leg flap has the advantages of being thin and pliable, quick to harvest with no major arteries sacrificed. There is minimal donor site morbidity and primary closure of the donor site is possible in the majority of cases.

Prognostic factors of profound idiopathic sudden sensorineural hearing loss.

Profound idiopathic sudden sensorineural hearing loss is thought to have a poor prognosis, but few studies have focused on this condition. We aimed to assess the impact of patient factors, audiologic parameters, and salvage intratympanic steroid injection therapy on the prognosis of profound idiopathic sudden sensorineural hearing loss. The demographic, clinical, and audiologic data, degree of hearing recovery, and efficacy of intratympanic steroid injection therapy in 576 patients with profound idiopathic sudden sensorineural hearing loss (mean age 56.2 ± 14.9 years) who had been admitted at four tertiary referral centers between 2000 and 2011 were retrospectively reviewed. The mean hearing level at the initial presentation was 108.1 ± 9.5 dB. Many patients experienced vertigo (52.1%) and tinnitus (77.4%). At the 2-month follow-up, 172 (29.8%) patients showed some degree of hearing recovery, but only 21 (3.6%) patients recovered normal hearing. Further, the 116 patients who had received salvage intratympanic steroid injections showed a better audiologic outcome (improvement, 26.1 ± 24.3 vs. 15.7 ± 22.1 dB; P = 0.000) than those who had not (n = 429). In conclusion, a higher degree of hearing loss at the initial presentation indicates a poorer prognosis. Salvage intratympanic steroid injection therapy may improve the hearing of patients with profound idiopathic sudden sensorineural hearing loss after the failure of systemic steroid therapy.

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.

A comparison between proximal lateral leg flap and radial forearm flap for intraoral reconstruction.

Free flaps have become a popular option for the reconstruction of intraoral defects. The radial forearm flap used to be the workhorse flap for small and thin defects, but was associated with numerous donor-site morbidities. The proximal lateral leg flap can provide a thin and pliable tissue similar to the radial forearm flap but without the related donor-site morbidities. We compared the differences between these 2 flaps. Thirty-four patients with intraoral defects from September 2005 to October 2011 were reconstructed, using the radial forearm flap in 23 cases, and the proximal lateral leg flap in 11 cases. The radial forearm flap group had a success rate of 95.6%. The flap survival rate was 100% in the proximal lateral leg flap group. However, the difference was statistically insignificant. Skin graft was required in 22 of the 23 cases for the donor site of the radial forearm flap. Partial loss of the skin graft occurred in 5/22 (23%) of the patients, with exposure of tendons in 3/22 (14%). Delay in healing of the donor sites occurred in 6/23 (26%) of the patients. The donor sites of the proximal lateral leg flap were all closed primarily. One case developed wound dehiscence and this healed by conservative treatment. Long-term follow-up showed functional impairment of the donor forearm (reduced extension or grip strength) in 17% of the patients. Thirty percent of the patients developed sensory disturbance and 48% complained of poor outcome of the donor forearms. In the proximal lateral leg flap group, no motor or sensory functional deficits were seen. No patients complained of poor outcome of the donor legs. Primary closure of the donor site of the proximal lateral leg flap could be performed if the flap width was less than 6 cm. This flap is useful for patients with small and thin intraoral defects and is associated with minimal donor-site morbidity when compared to the radial forearm flap.

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.

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.

Using multi-stimulus auditory steady state response to predict hearing thresholds in high-risk infants.

The purpose of this study was to investigate whether multi-stimulus auditory steady-state responses were capable of estimating hearing thresholds in high-risk infants. A retrospective chart review study. Three tertiary referral centers. Infants born between January 2004 and December 2006 who met the criteria for risk factors of congenital hearing loss were enrolled in the study. While under sedation, the multi-stimulus auditory steady-state response was used to determine multi-channel auditory steady-state response thresholds for high-risk infants younger than 13 months. Conditioned play audiometry was then applied to these children at 23-48 months of age to obtain pure tone audiograms. Auditory steady-state response thresholds and pure tone thresholds were then compared. A total of 249 high-risk infants were enrolled in the study. 39 infants were lost during follow-up. The remaining 216 infants completed both examinations. The Pearson correlation coefficients (r) between the ASSR levels and pure tone thresholds were 0.88, 0.94, 0.94 and 0.97 at 500, 1,000, 2,000 and 4,000 Hz, respectively. The strength of the relationship between the auditory steady-state responses and pure tone thresholds increased with more severe degrees of hearing loss and higher frequencies. We conclude that initial multichannel ASSR thresholds measured under sedation are highly correlated with pure tone thresholds obtained 2 or 3 years later. ASSR can be used to predict the frequency-specific hearing thresholds of high-risk infants and can provide information for early hearing intervention.

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.

Familial tendency and risk of nasopharyngeal carcinoma in taiwan: effects of covariates on risk.

In the present study, the authors compared the long-term risk of nasopharyngeal carcinoma (NPC) of male participants in an NPC multiplex family cohort with that of controls in a community cohort in Taiwan after adjustment for anti-Epstein-Barr virus (EBV) seromarkers and cigarette smoking. A total of 43 incident NPC cases were identified from the 1,019 males in the NPC multiplex family cohort and the 9,622 males in the community cohort, for a total of 8,061 person-years and 185,587 person-years, respectively. The adjusted hazard ratio was 6.8 (95% confidence interval (CI): 2.3, 20.1) for the multiplex family cohort compared with the community cohort. In the evaluation of anti-EBV viral capsid antigen immunoglobulin A and anti-EBV deoxyribonuclease, the adjusted hazard ratios were 2.8 (95% CI: 1.3, 6.0) and 15.1 (95% CI: 4.2, 54.1) for those positive for 1 EBV seromarker and positive for both seromarkers, respectively, compared with those negative for both EBV seromarkers. The adjusted hazard ratio was 31.0 (95% CI: 9.7, 98.7) for participants who reported a family history of NPC and who were anti-EBV-seropositive compared with individuals without such a history who were anti-EBV-seronegative. The findings suggest that both family history of NPC and anti-EBV seropositivity are important determinants of subsequent NPC risk and that the effect of family history on NPC risk cannot be fully explained by mediation through EBV serologic responses.

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.

Upregulated claudin-1 expression confers resistance to cell death of nasopharyngeal carcinoma cells.

Accumulating evidence reveals that aberrant expression of claudins manifests in various tumors; however, their biological functions are poorly understood. Here, we report on the elevated expression of claudin-1 in nasopharyngeal carcinoma (NPC) cell lines under serum deprivation or fluorouracil (5-FU) treatment. Interestingly, an increase in expression of claudin-1 considerably reduced apoptosis rather than enhancing cell proliferation. However, claudin-1 expression and activity were unaffected by external stimuli or Akt and NF-kappaB activation. Notably, predominant cytoplasmic and nuclear localization of claudin-1 in NPC cells reflected the aforementioned feature. On the other hand, loss of epithelial morphology and E-cadherin expression was associated with serum withdrawal in NPC cells. Interestingly, restoration of E-cadherin inhibited the protein elevation and antiapoptotic activity of claudin-1. In conclusion, our data demonstrate the regulation and novel biological function of claudin-1 and indicate the important role of claudin-1 in NPC tumorigenesis.

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.

Surgical outcome in patients with oral verrucous carcinoma: long-term follow-up in an endemic betel quid chewing area.

BACKGROUND/AIMS: To evaluate the clinical features and prognosis of patients with oral verrucous carcinoma (OVC) in an endemic betel quid chewing area. METHODS: A retrospective review was conducted in 39 patients with OVC treated surgically from 1991 to 2002. RESULTS: Thirty-seven patients (94.9%) were male. The median age at diagnosis was 53.8 years. All patients had been exposed to betel quid, cigarette smoking, and/or alcohol. The most common site of tumor origin was the buccal mucosa (64.1%). The tumor control rate was 97.4% after the first surgical procedure. Second/multiple primary tumors (SPTs/MPTs) were found in 21 patients. There were 13 deaths during the follow-up period, with SPTs/MPTs being the most common cause. The cancer-specific survival rate was 89.1% at 5 years, but continued to decrease thereafter. CONCLUSION: Surgery was effective for controlling OVC. However, long-term follow-up was necessary because of the high incidence of SPTs/MPTs and its impact on patient survival.