Nuclear translocation of Axl contributes to the malignancy of oral cancer cells.

Background/purpose: Dysregulation of receptor tyrosine kinases is implicated in cancer development. This study aimed to investigate the nuclear translocation of Axl, a membrane protein and receptor tyrosine kinase in cancer malignancy. Materials and methods: We examined Axl's entry into the cell nucleus and validated it with the nuclear export inhibitor leptomycin. Transfection experiments with mutated nuclear localization signals were conducted to assess the impact of reduced nuclear Axl levels on cancer cell malignancy. Additionally, we evaluated the effects of decreased nuclear Axl on sensitivity to radiation and cisplatin, a chemotherapeutic drug. Results: In the present study, we observed nuclear translocation of Axl in cancer cells. Reducing nuclear Axl levels led to a decrease in cancer cell malignancy. This nuclear translocation was further validated using a nuclear export inhibitor, leptomycin. Additionally, transfection experiments with mutated nuclear localization signals confirmed the functional significance of Axl's nuclear localization. Notably, decreased nuclear Axl levels also increased the sensitivity of cancer cells to radiation and cisplatin treatment. Conclusion: This study suggests that Axl's nuclear translocation plays a significant role in cancer malignancy. Targeting Axl's nuclear localization could offer a potential strategy to inhibit cancer progression and improve the efficacy of radiation and chemotherapy treatments.

MiR-34a functions as a tumor suppressor in oral cancer through the inhibition of the Axl/Akt/GSK-3ß pathway.

Background/purpose: Oral cancer is a prevalent malignancy affecting men globally. This study aimed to investigate the regulatory role of miR-34a in oral cancer cells through the Axl/Akt/glycogen synthase kinase-3ß (GSK-3ß) pathway and its impact on cellular malignancy. Materials and methods: We examined the effects of miR-34a overexpression on the malignancy of oral cancer cells. Multiple oral cancer cell lines were assessed to determine the correlation between endogenous miR-34a and Axl levels. Transfection experiments with miR-34a were conducted to analyze its influence on Axl mRNA and protein expression. Luciferase reporter assays were performed to investigate miR-34a's modulation of Axl gene transcription. Manipulation of miR-34a expression was utilized to demonstrate its regulatory effects on oral cancer cells through the Axl/Akt/GSK-3ß pathway. Results: Overexpression of miR-34a significantly suppressed the malignancy of oral cancer cells. We observed an inverse correlation between endogenous miR-34a and Axl levels across multiple oral cancer cell lines. Transfection of miR-34a resulted in decreased Axl mRNA and protein expression, and luciferase reporter assays confirmed miR-34a-mediated modulation of Axl gene transcription. The study revealed regulatory effects of miR-34a on oral cancer cells through the Axl/Akt/GSK-3ß pathway, leading to alterations in downstream target genes involved in cellular proliferation and tumorigenesis. Conclusion: Our findings highlight the significance of the miR-34a/Axl/Akt/GSK-3ß signaling axis in modulating the malignancy of oral cancer cells. Targeting miR-34a may hold therapeutic potential in oral cancer treatment, as manipulating its expression can attenuate the aggressive behavior of oral cancer cells via the Axl/Akt/GSK-3ß pathway.

Endoscopic and Image Analysis of the Airway in Patients with Mucopolysaccharidosis Type IVA.

Mucopolysaccharidosis (MPS) is a hereditary disorder arising from lysosomal enzymes deficiency, with glycosaminoglycans (GAGs) storage in connective tissues and bones, which may compromise the airway. This retrospective study evaluated patients with MPS type IVA with airway obstruction detected via endoscopy and imaging modalities and the effects of surgical interventions based on symptoms. The data of 15 MPS type IVA patients (10 males, 5 females, mean age 17.8 years) were reviewed in detail. Fiberoptic bronchoscopy (FB) was used to distinguish adenotonsillar hypertrophy, prolapsed soft palate, secondary laryngomalacia, vocal cord granulation, cricoid thickness, tracheal stenosis, shape of tracheal lumen, nodular deposition, tracheal kinking, tracheomalacia with rigid tracheal wall, and bronchial collapse. Computed tomography (CT) helped to measure the deformed sternal angle, the cross-sectional area of the trachea, and its narrowest/widest ratio (NW ratio), while angiography with 3D reconstruction delineated tracheal torsion, kinking, or framework damage and external vascular compression of the trachea. The NW ratio correlated negatively with age (p < 0.01), showing that airway obstruction progressed gradually. Various types of airway surgery were performed to correct the respiratory dysfunction. MPS type IVA challenges the management of multifactorial airway obstruction. Preoperative airway evaluation with both FB and CT is strongly suggested to assess both intraluminal and extraluminal factors causing airway obstruction.

microRNA-1266-5p directly targets DAB2IP to enhance oncogenicity and metastasis in oral cancer.

Background/purpose: Oral cancer has been recognized as one of the most common malignancies worldwide and ranks the fifth leading cause of cancer death in Taiwan. A variety of studies have demonstrated that microRNAs are involved in the regulation of the hallmarks of oral carcinogenesis. Nevertheless, the effect of miR-1266-5p on the tumorigenesis of oral cancer has not been investigated, and not to mention, its functional role in oral cancer. Materials and methods: The upregulation of miR-1266-5p in SASVO3 and SASM5 cells was identified by RNA-Seq and examined by qRT-PCR analysis. The phenotypic assays including proliferation activity, migration capacity, invasion, wound healing, and colony-forming abilities were conducted in oral cancer cells after knockdown of miR-1266-5p. Luciferase reporter and western blotting were used to validate DAB2IP was a direct target of miR-1266-5p in oral cancer. Results: We identified that miR-1266-5p was significantly overexpressed in highly tumorigenic SASVO3 cells and metastatic SASM5 cells. qRT-PCR revealed that miR-1266 significantly increased upregulated in oral cancer and lymph node metastatic tissues compared to normal counterparts We found that downregulation of miR-1266-5p inhibited the proliferation and clonogenicity capacities of SASVO3 cells. Knockdown of miR-1266-5p also inhibited migration/invasion and self-renewal abilities in SASM5 cells. Moreover, we validated miR-1266-5p directly bound to the 3'UTR of DAB2IP in oral cancer cells. We found that DAB2IP knockdown reversed the inhibitory effects of self-renewal and migration mediated by silencing of miR-1266-5p. Conclusion: miR-1266 functions as a biomarker in oral cancer patients, and downregulation of miR-1266 may ameliorate the oncogenic and metastasis potential of oral cancer by targeting DAB2IP.

Effect of resistance training on satellite cells in old mice - a transcriptome study : implications for sarcopenia.

AIMS: The decrease in the number of satellite cells (SCs), contributing to myofibre formation and reconstitution, and their proliferative capacity, leads to muscle loss, a condition known as sarcopenia. Resistance training can prevent muscle loss; however, the underlying mechanisms of resistance training effects on SCs are not well understood. We therefore conducted a comprehensive transcriptome analysis of SCs in a mouse model. METHODS: We compared the differentially expressed genes of SCs in young mice (eight weeks old), middle-aged (48-week-old) mice with resistance training intervention (MID+ T), and mice without exercise (MID) using next-generation sequencing and bioinformatics. RESULTS: After the bioinformatic analysis, the PI3K-Akt signalling pathway and the regulation of actin cytoskeleton in particular were highlighted among the top ten pathways with the most differentially expressed genes involved in the young/MID and MID+ T/MID groups. The expression of Gng5, Atf2, and Rtor in the PI3K-Akt signalling pathway was higher in the young and MID+ T groups compared with the MID group. Similarly, Limk1, Arhgef12, and Araf in the regulation of the actin cytoskeleton pathway had a similar bias. Moreover, the protein expression profiles of Atf2, Rptor, and Ccnd3 in each group were paralleled with the results of NGS. CONCLUSION: Our results revealed that age-induced muscle loss might result from age-influenced genes that contribute to muscle development in SCs. After resistance training, age-impaired genes were reactivated, and age-induced genes were depressed. The change fold in these genes in the young/MID mice resembled those in the MID + T/MID group, suggesting that resistance training can rejuvenate the self-renewing ability of SCs by recovering age-influenced genes to prevent sarcopenia. Cite this article: Bone Joint Res 2022;11(2):121-133.

Epidemiology of pediatric tracheotomy: A population-based study using National Health Insurance Research Database in Taiwan.

OBJECTIVE: Tracheostomy in children is a surgical procedure with considerable morbidity and mortality. However, there is still a lack of population-based survey in pediatric tracheostomy. This study analyses population-based data in pediatric tracheostomy among different ages in Taiwan. METHODS: This study used National Health Insurance Research Database in Taiwan. All children (aged <18 years) who underwent tracheostomy during 1997-2016 were identified. We retrieved data regarding baseline characteristics, perioperative care, and mortality associated with pediatric tracheostomy, and compared differences in variables between different age groups. RESULTS: We observed that 2300 children received tracheostomy (mean age, 8.7 years; 64% boys). Regarding the age group distribution of the patients, 585 (25.4%) were infants (<1 year), 227 (9.9%) were toddlers (1-3 years), 175 (7.6%) were preschool-aged children (3-6 years), 317 (13.8%) were school-aged children (6-12 years), and 996 (43.3%) were adolescents (12-18 years). Surgical indications included pulmonary disorders (64.9%), neurological disorders (38.4%), trauma (32.3%), head injury (25.2%), and congenital anomalies (21.5%). Of these patients, 94.9% required intensive care unit (ICU) care, with the mean length of ICU stay being 63.8 days. The mean length of hospital stay was 74.5 days. The overall mortality at the last follow-up was 43.96% (1011/2300), and the tracheostomy related mortality at the last follow-up was 1.43% (33/2300). Compared with adolescents, infants more commonly underwent tracheostomy in the northern area (66.7% vs 37.2%, P < .001), more commonly received tracheostomy indicated by congenital anomalies (53.7 vs 4.6%, P < .001), had longer ICU stays, had longer hospital stays (100.7 vs 57.5 days, P < .001), and had a higher 5-year mortality rate (42.4 vs 29.6%, P < .001). Multivariable logistic and Cox regression models revealed that young age was associated with an increased risk of prolonged hospital stay and long-term mortality, respectively. CONCLUSIONS: This study elaborates the epidemiology of pediatric tracheostomy in different age groups.

Trajectory of ambulatory blood pressure after adenotonsillectomy in children with obstructive sleep apnea: comparison at three- and six-month follow-up.

OBJECTIVE: Limited information is currently available on 24-h ambulatory blood pressure (ABP) changes after adenotonsillectomy (T&A) in children with obstructive sleep apnea (OSA). In this study, the trajectory of 24-h ABP changes after surgery in children with OSA was examined at three-month and six-month follow-up. METHODS: Children aged 4-16 years with clinical symptoms of OSA and polysomnography (PSG)-diagnosed OSA (apnea-hypopnea index [AHI] >1) were included. All the children received T&A. PSG was conducted before and after surgery. Twenty four hour ABP was monitored using the linear mixed model before, three months after, and six months after surgery. RESULTS: In total, 122 children were examined (mean age: 7.9 years; 71% were boys). The AHI significantly decreased from 12.7 ± 16.7 to 2.4 ± 3.2 events/h after T&A (P < 0.001). Overall diastolic blood pressure (DBP; from 65.1 to 63.4 mmHg, P = 0.01) and night-time DBP (from 57.4 to 55.4 mmHg, P = 0.032) decreased nonsignificantly during the six-month postoperative period. The OSA children with presurgical hypertension exhibited significant reductions in overall systolic blood pressure (SBP), overall DBP, daytime DBP, night-time SBP, and night-time DBP at the three-month and six-month postoperative follow-up (all P < 0.05). The three-month and six-month ABP data did not differ significantly in the entire cohort, even between children with presurgical hypertension and non-hypertensive children. CONCLUSION: The 24-h ABP decreased significantly in the OSA children with hypertension at three and six months after surgery. Moreover, ABP findings did not differ significantly between the three- and six-month follow-up.

Mechanistic and compositional studies of the autophagy-inducing areca nut ingredient.

BACKGROUND/PURPOSE: We previously found that the partially purified 30-100 kDa fraction of areca-nut-extract (ANE 30-100K) induces autophagy in different types of cells including oral carcinoma OECM-1 cells. This study was to analyze the composition and possible mechanisms of ANE 30-100K-induced autophagy (AIA). MATERIALS AND METHODS: Phenol-sulfuric acid method and high performance anion exchange chromatography were utilized to analyze the composition of ANE 30-100K. OECM-1 and esophageal CE81T/VGH cells were taken as the experimental models. Microscope and transmission electron microscope were used to observe morphological changes. Cell viability and specific proteins were respectively measured by XTT and Western bot assay. shRNA and chemical inhibitors were applied to assess the involvement of Atg5, caveolin, and proteasome in AIA. RESULTS: ANE 30-100K contains ∼67% carbohydrate, which is composed of fucose (5.938%), arabinose (24.631%), glucosamine (8.066%), galactose (26.820%), glucose (21.388%), and mannose (13.157%). After ANE 30-100K stimulation, CE81T/VGH cells showed intracellular vacuoles, acidic vesicles, double-membrane vacuoles, and elevated LC3-II level. ANE 30-100K-induced cytotoxicity and LC3-II accumulation were significantly inhibited by Atg5 knockdown. Furthermore, the endocytosis inhibitor (methyl-ß-cyclodextrin) and two caveolin shRNAs, as well as two proteasome inhibitors (lactacystin and epoxomicin), were shown to significantly attenuate ANE 30-100K-induced cytotoxicity and LC3-II accumulation in both OECM-1 and CE81T/VGH cells. CONCLUSION: The major components of ANE 30-100K are carbohydrates. CE81T/VGH also exhibited autophagic responses to ANE 30-100K. Caveolin-mediated endocytosis and proteasome are involved in AIA. This study may have provided new knowledges of the action mechanisms and compositions of ANE 30-100K.

Effect of Adenotonsillectomy on Ambulatory Blood Pressure in Pediatric Obstructive Sleep Apnea: 6-Month Follow-up Study.

OBJECTIVE: To investigate 24-hour ambulatory blood pressure changes 6 months after surgery among children with obstructive sleep apnea. STUDY DESIGN: Prospective interventional study. SETTING: Tertiary medical hospital. SUBJECTS AND METHODS: Children aged 4 to 16 years with symptoms of obstructive sleep apnea (apnea-hypopnea index >1) were recruited. All children underwent adenotonsillectomy and postoperative polysomnography overnight. The 24-hour ambulatory blood pressure was measured before and 6 months after surgery. RESULTS: The study cohort enrolled 124 children: mean (SD) age, 7.3 (3.1) years; 73% boys. After surgery, the apnea-hypopnea index significantly decreased from 13.3 (18.1) to 3.3 (7.2) events per hour ( P < .001). Overall systolic blood pressure and diastolic blood pressure were not significantly different following surgery, while daytime systolic blood pressure was slightly increased (114.3 to 117.3 mm Hg, P < .01) postoperatively. The hypertensive group (n = 43) exhibited significantly decreased levels of overall diastolic, nighttime systolic, and nighttime diastolic blood pressure ( P < .05), and 54% of hypertensive children became nonhypertensive after surgery. The nonhypertensive group (n = 81) showed slightly increased levels of nocturnal overall systolic, daytime systolic, and nighttime systolic blood pressure. A generalized linear mixed model revealed that children with hypertension had a greater decrease in systolic and diastolic ambulatory blood pressure during the daytime and nighttime (all P < .05) than those without hypertension. CONCLUSIONS: Ambulatory blood pressure changes after adenotonsillectomy among children with obstructive sleep apnea are minimal. The decrease in ambulatory blood pressure after surgery is more prominent for hypertensive children than nonhypertensive children.

Ultrasonographic Evaluation of Upper Airway Structures in Children With Obstructive Sleep Apnea.

Importance: Adenotonsillar hypertrophy is an important cause of obstructive sleep apnea (OSA) in children. However, residual OSA and abnormal polysomnographic findings have been reported in up to 75% of cases after adenotonsillectomy. Other anatomical and functional factors that influence upper airway structures, including the lateral pharyngeal wall, have rarely been studied in children with OSA. Objective: To determine whether the upper airway structures can be evaluated using head and neck ultrasonography and if there is an association between the ultrasonographic measurements for these structures and severity of OSA seen on polysomnography in children. Design, Setting, and Participants: Prospective, single-center, observational study of 82 children younger than 18 years with a diagnosis of sleep-disordered breathing (20 with primary snoring, 62 with OSA, as determined by the apnea-hypopnea index) and admitted to a tertiary teaching hospital for adenotonsillectomy. Exposures: Ultrasonography and polysomnography. Main Outcomes and Measures: Ultrasonographic measurements of upper airway structures. Results: Of the 82 children studied, 62 (76%) were boys; mean (SD) age, 7.7 (6.2). There was no significant difference found in tonsillar dimensions or volume between the children with OSA and those with primary snoring. However, the mean (SD) total lateral pharyngeal wall and the total neck thicknesses at the retropalatal level were both greater in children with OSA than in those with primary snoring at rest (24.9 [4.4] mm vs 21.3 [2.6] mm; difference, 3.61 mm; 95% CI of difference, 1.48-5.74 mm for lateral pharyngeal wall; and 59.9 [14.4] mm vs 49.9 [11.2] mm; difference, 10.9 mm, 95% CI of difference, 3.8-17.9 mm for the total neck). Conclusions and Relevance: Estimated tonsillar volume measured using ultrasonography had no relationship with the apnea-hypopnea index in childhood sleep-disordered breathing. However, the lateral pharyngeal wall was significantly thicker in children with OSA than in those with primary snoring at rest.

Correction: Berberine-targeted miR-21 chemosensitizes oral carcinomas stem cells.

[This corrects the article DOI: 10.18632/oncotarget.20723.].

24-Hour Ambulatory Blood Pressure after Adenotonsillectomy in Childhood Sleep Apnea.

OBJECTIVE: To assess the effects of adenotonsillectomy (T&A) on ambulatory blood pressure (ABP) in childhood obstructive sleep apnea (OSA). STUDY DESIGN: From 2012 to 2017, children aged 4-16 years with symptoms and polysomnography-diagnosed OSA (apnea-hypopnea index [AHI] >1) underwent T&A. PSG studies and 24-hour ABP monitoring were performed before and at 3 months after surgery. RESULTS: In total, 159 children were enrolled (mean age, 7.8 ± 3.3 years; 72% male). T&A significantly reduced the AHI from 12.4 ± 15.9 events/hour to 2.7 ± 5.7 events/hour (P < .001). A decrease was observed in the children's overall diastolic blood pressure (65.1 ± 6.1 mm Hg to 63.8 ± 7.4 mm Hg, P = .04) after surgery. In subgroup analysis, 100 (63%) patients were classified as nonhypertensive, and 59 (37%) were classified as hypertensive. Linear mixed model analysis revealed that compared with the children without hypertension, those with hypertension had superior improvement in systolic and diastolic blood pressure during daytime and nighttime (all P values < .01). The ABP changes after surgery were not correlated with the AHI changes. Finally, preoperative hypertension was an independent risk factor of postoperative hypertension among these children (OR 3.66; 95% CI 1.70-7.86). CONCLUSIONS: Overall, in children with OSA, the 24-hour ABP change after T&A is small. However, among children with preoperative hypertension, there is significant BP improvement after T&A surgery.

LncRNA GAS5-AS1 inhibits myofibroblasts activities in oral submucous fibrosis.

BACKGROUND/PURPOSE: Emerging research findings suggest that long non-coding RNAs (lncRNAs) are key regulators to fibrosis formation. Nevertheless, the role of lncRNA GAS5-AS1 in the progression of precancerous oral submucous fibrosis (OSF) remains to be elucidated. METHODS: Quantitative real-time PCR were used to examine the expression of GAS5-AS1 in OSF tissues. The activities of myofibroblasts, including collagen contractility and cell migration, as well as the marker α-smooth muscle actin (SMA) were assessed following overexpression of GAS5-AS1. Also, we analyzed the expression of Smad activity in order to gain insight into the downstream regulator. RESULTS: The level of GAS5-AS1 was found significantly downregulated in the OSF tissues and fibrotic buccal mucosal fibroblasts (fBMFs). Ectopic expression of GAS5-AS1 significantly reduced the abilities of collagen gel contraction and migration in fBMFs or arecoline-treated BMFs. Moreover, we have shown that overexpression of GAS5-AS1 inhibited the expression of p-Smad and the marker of myofibroblasts. CONCLUSION: We showed the reduced expression of GAS5-AS1 in OSF tissues and demonstrated its effect on the myofibroblast activities and the level of p-Smad and α-SMA, indicating its potential contribution in OSF pathogenesis.

Berberine-targeted miR-21 chemosensitizes oral carcinomas stem cells.

Cancer recurrence and chemoresistance are two major obstacles to the treatment of oral squamous cell carcinomas (OSCC). And cancer stem cells (CSCs) have been found to possess tumor initiating, self-renewal and metastasis abilities, resulting in the relapse and chemoresistance of OSCC. In the present study, we investigated the anti-CSCs effect of berberine, a phenanthrene alkaloid isolated from the Berberis genus. Our results demonstrated that berberine dose dependently downregulated the oncogenicity in vitro, including ALDH1 activity, self-renewal property, and colony formation and invasion abilities as well as potentiated chemosensitivity of OSCC-CSCs. In addition, tumor growth in mice was attenuated after oral gavage treatment of berberine. We showed that the expression of miR-21 was suppressed following administration of berberine in OSCC-CSCs. And inhibition of endogenous miR-21 reduced the characteristics of CSCs, including self-renewal, migration, invasion capabilities and ALDH1 activity. Taken together, we demonstrated the anti-CSC effect of berberine in oral cancer and its potential to serve as adjuvant to traditional chemotherapy to improve treatment effect.

Klf8 regulates left-right asymmetric patterning through modulation of Kupffer's vesicle morphogenesis and spaw expression.

BACKGROUND: Although vertebrates are bilaterally symmetric organisms, their internal organs are distributed asymmetrically along a left-right axis. Disruption of left-right axis asymmetric patterning often occurs in human genetic disorders. In zebrafish embryos, Kupffer's vesicle, like the mouse node, breaks symmetry by inducing asymmetric expression of the Nodal-related gene, spaw, in the left lateral plate mesoderm (LPM). Spaw then stimulates transcription of itself and downstream genes, including lft1, lft2, and pitx2, specifically in the left side of the diencephalon, heart and LPM. This developmental step is essential to establish subsequent asymmetric organ positioning. In this study, we evaluated the role of krüppel-like factor 8 (klf8) in regulating left-right asymmetric patterning in zebrafish embryos. METHODS: Zebrafish klf8 expression was disrupted by both morpholino antisense oligomer-mediated knockdown and a CRISPR-Cas9 system. Whole-mount in situ hybridization was conducted to evaluate gene expression patterns of Nodal signalling components and the positions of heart and visceral organs. Dorsal forerunner cell number was evaluated in Tg(sox17:gfp) embryos and the length and number of cilia in Kupffer's vesicle were analyzed by immunocytochemistry using an acetylated tubulin antibody. RESULTS: Heart jogging, looping and visceral organ positioning were all defective in zebrafish klf8 morphants. At the 18-22 s stages, klf8 morphants showed reduced expression of genes encoding Nodal signalling components (spaw, lft1, lft2, and pitx2) in the left LPM, diencephalon, and heart. Co-injection of klf8 mRNA with klf8 morpholino partially rescued spaw expression. Furthermore, klf8 but not klf8△zf overexpressing embryos showed dysregulated bilateral expression of Nodal signalling components at late somite stages. At the 10s stage, klf8 morphants exhibited reductions in length and number of cilia in Kupffer's vesicle, while at 75% epiboly, fewer dorsal forerunner cells were observed. Interestingly, klf8 mutant embryos, generated by a CRISPR-Cas9 system, showed bilateral spaw expression in the LPM at late somite stages. This observation may be partly attributed to compensatory upregulation of klf12b, because klf12b knockdown reduced the percentage of klf8 mutants exhibiting bilateral spaw expression. CONCLUSIONS: Our results demonstrate that zebrafish Klf8 regulates left-right asymmetric patterning by modulating both Kupffer's vesicle morphogenesis and spaw expression in the left LPM.

The application of ultrasound in detecting lymph nodal recurrence in the treated neck of head and neck cancer patients.

Early detection of neck lymph node (LN) recurrence is paramount in improving the prognosis of treated head and neck cancer patients. Ultrasound (US) with US-guided fine needle aspiration (FNA) and core needle biopsy (CNB) have been shown to have great accuracy for LN diagnoses in the untreated neck. However, in the treated neck with fibrosis, their roles are not clarified. Here, we retrospectively review 153 treated head and neck cancer patients who had received US and US-guided FNA/CNB. In multivariate logistic regression analyses, size (short-axis diameter >0.8 cm) (odds ratio (OR) 4.19, P = 0.007), round shape (short/long axis ratio >0.5) (OR 3.44, P = 0.03), heterogeneous internal echo (OR 3.92, P = 0.009) and irregular margin (OR 7.32, P < 0.001) are effective US features in predicting recurrent LNs in the treated neck. However, hypoechogenicity (OR 2.38, P = 0.289) and chaotic/absent vascular pattern (OR 3.04, P = 0.33) are ineffective. US-guided FNA (sensitivity/specificity: 95.24%/97.92%) is effective in the treated neck, though with high non-diagnostic rate (29.69%). US-guided CNB (sensitivity/specificity: 84.62%/100%) is also effective, though with low negative predictive value (62.5%). Overall, US with US-guided FNA/CNB are still effective diagnostic tools for neck nodal recurrence surveillance.

Implication for second primary cancer from visible oral and oropharyngeal premalignant lesions in betel-nut chewing related oral cancer.

BACKGROUND: Visible oral and oropharyngeal premalignant lesions may be used to monitor for a second primary oral cancer. To control for bias, we focused on the visible oral and oropharyngeal premalignant lesions of patients with oral cancer with a positive betel-nut chewing habit. Visible oral and oropharyngeal premalignant lesions that can predict second primary oral cancers were studied. METHODS: Nine hundred ninety-seven patients with positive betel-nut chewing habits and oral cancer were enrolled in this retrospective cohort study. We analyzed the relevance of their visible oral and oropharyngeal premalignant lesion incidence and relative clinicopathological variables to the development of a second primary oral cancer. RESULTS: Second primary oral cancer risk was significantly higher in patients with positive visible oral and oropharyngeal premalignant lesions (P < .0001), especially in younger patients (P = .0023; ≤40 years: adjusted odds ratio [OR] 2.66; 40-60 years: adjusted OR 2.61). The heterogeneous leukoplakia was (adjusted OR 2.17) higher than homogeneous leukoplakia. CONCLUSION: The predictive value and practicality of visible oral and oropharyngeal premalignant lesions make it a potentially valuable marker in follow-ups of patients with a positive betel-nut chewing habit with oral cancer, especially young patients with heterogeneous leukoplakia.

Saliva protein biomarkers to detect oral squamous cell carcinoma in a high-risk population in Taiwan.

Most cases of oral squamous cell carcinoma (OSCC) develop from visible oral potentially malignant disorders (OPMDs). The latter exhibit heterogeneous subtypes with different transformation potentials, complicating the early detection of OSCC during routine visual oral cancer screenings. To develop clinically applicable biomarkers, we collected saliva samples from 96 healthy controls, 103 low-risk OPMDs, 130 high-risk OPMDs, and 131 OSCC subjects. These individuals were enrolled in Taiwan's Oral Cancer Screening Program. We identified 302 protein biomarkers reported in the literature and/or through in-house studies and prioritized 49 proteins for quantification in the saliva samples using multiple reaction monitoring-MS. Twenty-eight proteins were successfully quantified with high confidence. The quantification data from non-OSCC subjects (healthy controls + low-risk OPMDs) and OSCC subjects in the training set were subjected to classification and regression tree analyses, through which we generated a four-protein panel consisting of MMP1, KNG1, ANXA2, and HSPA5. A risk-score scheme was established, and the panel showed high sensitivity (87.5%) and specificity (80.5%) in the test set to distinguish OSCC samples from non-OSCC samples. The risk score >0.4 detected 84% (42/50) of the stage I OSCCs and a significant portion (42%) of the high-risk OPMDs. Moreover, among 88 high-risk OPMD patients with available follow-up results, 18 developed OSCC within 5 y; of them, 77.8% (14/18) had risk scores >0.4. Our four-protein panel may therefore offer a clinically effective tool for detecting OSCC and monitoring high-risk OPMDs through a readily available biofluid.

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.