[The analysis of unconventional lymph node metastasis in tongue squamous cell carcinoma].

Objective: To analyze the characteristics of cervical lymph node metastasis in tongue squamous cell carcinoma (TSCC). Methods: A retrospective study was conducted. A total of 329 patients with TSCC who underwent en bloc resection of primary tumor and neck dissection in the Second Xiangya Hospital of Central South University from June 2010 to March 2018 were included. There were 283 males and 46 females, aged from 26 to 80 years. All patients underwent the modified neck dissection. The main difference between the modified neck dissection and the traditional neck dissection lay in the managements of unconventional lymph nodes. The lymphatic adipose tissues adjacent to the superior thyroid artery, the base of facial artery and the branches of external carotid artery were thoroughly dissected. The primary tumor as well as lingual artery, tissues along the lingual artery and lymph nodes in the mouth floor were resected. χ2 test was used for comparison of count data, and linear regression model was used for multivariate analysis. Results: Cervical lymph node metastases were found in 136 patients (41.3%). Among 142 patients (T1-2cN0) with supraomohyoid neck dissection, 22 patients had pathologically occult lymph node metastases (15.5%), with a 5-year overall survival rate of 90.2%, which was similar to the 5-year overall survival rate of 92.1% in 120 patients without lymph node metastasis (χ2=0.156, P=0.693). Multivariate linear regression analysis showed that T stage, clinical stage and unconventional lymph node metastasis were important factors for cervical lymph node metastasis in tongue cancer patients (P<0.05). Unconventional lymph node metastases occurred in 30 patients (9.1%), including the metastases of lymph nodes in the floor of mouth (3.0%), the lingual artery (2.4%), the base of the external maxillary artery (2.1%), the superior thyroid artery (0.9%), and the external carotid artery (0.6%). There were significant differences in the unconventional lymph node metastasis rates between patients with negative and positive conventional lymph node metastases [4.9%(10/203) vs. 15.9%(20/126), χ2=11.242, P=0.001] and also between patients with depth of invasion ≤5 mm, 5 mm 10 mm [3.1%(2/64) vs. 5.7%(6/106) vs. 13.8%(22/159), χ2=7.907, P=0.005]. Conclusion: Supraomohyoid neck dissection can achieve reliable control efficacy in patients with cN0 tongue cancer. All patients with lymph node dissection should undergo unconventional lymph node dissection. Unconventional lymph node dissection is strongly recommended for patients with conventional lymph node metastasis.

MicroRNA expression as a prognostic biomarker of tongue squamous cell carcinoma (TSCC): a systematic review and meta-analysis.

BACKGROUND: Recent studies have indicated that microRNA (miRNA) expression in tumour tissues has prognostic significance in Tongue squamous cell carcinoma (TSCC) patients. This study explored the possible prognostic value of miRNAs for TSCC based on published research. METHODS: A comprehensive literature search of multiple databases was conducted according to predefined eligibility criteria. Data were extracted from the included studies by two researchers, and HR results were determined based on Kaplan‒Meier curves according to the Tierney method. The Newcastle‒Ottawa Scale (NOS) and GRADE (Grading of Recommendations Assessment, Development, and Evaluation) pro-GDT were applied to assess the quality of all studies. Publication bias was estimated by funnel plot, Egger's rank correlation test and sensitivity analysis. RESULTS: Eleven studies (891patients) were included, of which 6 reported up-regulated miRNAs and 7 mentioned down-regulated miRNAs. The pooled hazard ratio (HR) from the prognostic indicator overall survival (OS) was 1.34 (1.25-1.44), p < 0.00001, indicating a significant difference in miRNA expression between TSCC patients with better or worse prognosis. CONCLUSION: MiRNAs may have high prognostic value and could be used as prognostic biomarkers of TSCC.

Tongue prosthesis after total glossectomy: a case report.

Squamous cell carcinoma (SCC) is the type of cancer that most frequently affects the oral cavity, mainly in men older than 50 years of age. Treatment for oral SCC often involves surgical excision of the affected margins, resulting in mutilation that affects the patient's quality of life. The objective of this case report is to describe the prosthetic treatment of a 56-year-old man who underwent total glossectomy, resulting in speech and swallowing difficulties. The proposed treatment was a tongue prosthesis retained by orthodontic clasps on the mandibular first molars. After maxillary and mandibular complete-arch impressions were performed and casts were prepared for prosthetic planning, an acrylic resin plate and 3 tongue prototypes were fabricated. Esthetic and functional tests were carried out, and 2 tongue models (1 for speech and 1 for eating) were selected for acrylization, finishing, and polishing. After placement of the prostheses, the patient was referred for follow-up with a speech therapist to improve his adaptation with the prostheses. The patient was satisfied with the prostheses and able to perform the functions of chewing, swallowing, and speech production, which helped in his social reintegration and improved his quality of life.

Evaluation of the neuromotor ability of the tongue in pediatric patients using a stereognostic examination.

BACKGROUND: The term "stereognosis" comes from neurology and describes the capacity to distinguish objects solely by touch. AIM: The aim of this research study was to compare the neuromotor ability of the tongue in patients with malocclusion and tongue dysfunction with and without superficial anesthesia on the tip of the tongue and hard palate. MATERIALS AND METHODS: The study included 132 patients aged 6-13 years. Using a spatula for speech therapy and a visual evaluation while swallowing saliva, all individuals were identified as having swallowing dysfunctions and divided into three groups: study group (children with malocclusions and tongue dysfunctions) - 44 patients, comparator group (children with malocclusions and without tongue dysfunctions) - 44 patients, and control group (children without malocclusions or tongue dysfunctions) - 44 patients. The Koczorowski methods were used for the stereognostic tests. RESULTS: Age, sex, and malocclusion were taken into account during the differential analysis. The study and comparison groups, study and control groups, and the comparator and control groups all showed statistically significant differences from one another. According to the results, tongue dysfunction affects patients' ability to coordinate their movements with their senses at a developing stage. CONCLUSION: Patients with malocclusions that are made worse by tongue dysfunctions have poorer oral stereognostic sensibility. Speech therapy and interdisciplinary specialist orthodontic treatment are required for individuals with impaired oral perception who are still in the developmental stage and have abnormal tongue position and function.

SOX9 promotes stemness in the CAL27 cell line of tongue squamous cell carcinoma.

Tongue squamous cell carcinoma (TSCC) is a prevalent form of oral malignancy, with increasing incidence. Unfortunately, the 5-year survival rate for patients has not exceeded 50%. Studies have shown that sex-determining region Y box 9 (SOX9) correlates with malignancy and tumor stemness in a variety of tumors. To investigate the role of SOX9 in TSCC stemness, we analyzed its influence on various aspects of tumor biology, including cell proliferation, migration, invasion, sphere and clone formation, and drug resistance in TSCC. Our data suggest a close association between SOX9 expression and both the stemness phenotype and drug resistance in TSCC. Immunohistochemical experiments revealed a progressive increase of SOX9 expression in normal oral mucosa, paracancerous tissues, and tongue squamous carcinoma tissues. Furthermore, the expression of SOX9 was closely linked to the TNM stage, but not to lymph node metastasis or tumor diameter. SOX9 is a crucial gene in TSCC responsible for promoting the stemness function of cancer stem cells. Developing drugs that target SOX9 is extremely important in clinical settings.

FDG PET/CT in the Diagnosis and After Sunitinib Follow-up of Synchronous Base of Tongue and Thyroid Metastases From Renal Cell Carcinoma.

ABSTRACT: Renal cell carcinoma (RCC) is a leading cause of mortality among genitourinary malignancies with limited therapeutic options. The hematogenous route, lymphatic spread, and direct invasion have been documented in RCC. Usually, metastases are regional lymph nodes, lungs, bone, liver, adrenal glands, contralateral kidney, and brain. Metastases to the rare sites such as skin, breast, head and neck were documented in the literature. In the present case, we describe the synchronous metastases to the base of the tongue and thyroid gland in RCC and the response to sunitinib therapy on 18F-FDG PET/CT.

Assessment of oral hypofunction and its association with age among Korean community-dwelling older adults.

BACKGROUND: Due to the increasing proportion of older adults in Korea and growing interest in aging, the concepts of oral aging and oral hypofunction have recently been introduced. Thus, it is necessary to investigate the age-specific oral function levels of Korean older adults and develop expert intervention methods for healthy aging. METHODS: Dysphagia, independence of daily living, and oral hypofunction were assessed in 206 older adults living in Wonju, Gangwon State, South Korea. Subjective dysphagia was assessed through self-report questionnaires using the Dysphagia Handicap Index (DHI), the Korean version of Eating Assessment Tool-10, and the Korean version of the Modified Barthel Index. In addition, the oral hypofunction assessment items included decreased chewing ability, occlusal pressure, tongue pressure, oral dryness, and oral cleanliness. RESULTS: DHI increased significantly with age, with those in their 80 s reporting the most difficulty swallowing. Oral function in terms of chewing ability (maximum occlusal pressure and number of remaining teeth), maximum occlusal pressure, and maximum tongue pressure also declined with increasing age. While there was no significant difference in oral dryness by age, those in their 80 s had dry mouth according to the criteria of the oral moisture checking device. CONCLUSIONS: In an assessment of oral function in community-dwelling, independent Korean older adults, the number of items that were assessed as oral hypofunction increased with age. The findings can be used to standardize the oral hypofunction assessment item and develop age-based individualized intervention plans for the early management of oral health and individual oral myofunctional rehabilitation in Korean community-dwelling older adults.

Respiratory outcomes after cleft palate closure in Robin sequence: a retrospective study.

OBJECTIVES: There is a paucity of information about the possible risk factors that could identify patients with Robin sequence (RS) who are more prone to developing obstructive airway complications after palate closure. This study aimed to compare the respiratory complication rates in patients with RS and isolated cleft palate (ICP). MATERIALS AND METHODS: In this retrospective study, we reviewed the medical records of 243 consecutive patients with RS and ICP who were treated at Amsterdam University Medical Centers over the past 25 years. We collected preoperative data on previous treatment, diagnostic findings, surgical technique, weight, and presence of congenital anomalies. RESULTS: During cleft palate closure, patients with RS were older (11.9 versus 10.1 months; p = 0.001) and had a lower gestational age than those with ICP (37.7 versus 38.5 weeks; p = 0.002). Patients with RS had more respiratory complications (17 versus 5%; p = 0.005), were more often non-electively admitted to the pediatric intensive care unit (PICU) (13 versus 4.1%; p = 0.022), and had a longer hospital stay duration (3.7 versus 2.7 days; p = 0.011) than those with ICP. The identified risk factors for respiratory problems were a history of tongue-lip-adhesion (TLA) (p = 0.007) and a preoperative weight of < 8 kg (p = 0.015). Similar risk factors were identified for PICU admission (p = 0.015 and 0.004, respectively). CONCLUSIONS: The possible risk factors for these outcomes were a low preoperative weight and history of TLA. Closer postoperative surveillance should be considered for patients with these risk factors. CLINICAL RELEVANCE: Identifying risk factors for respiratory complications could provide clinicians better insight into their patients and allows them to provide optimal care for their patients.

Factors associated with age-related changes in oral diadochokinesis and masticatory function in healthy old adults.

BACKGROUND: This cross-sectional study aimed to identify factors associated with age-related changes in masticatory performance (MP) and oral diadochokinesis (ODK) and to provide normal values in healthy old adults for the diagnosis of oral frailty. METHODS: A total of 385 participants were divided into three age groups (Gr1-3): 20-64 years, 65-74 years, and ≥ 75 years. To investigate tongue-lip motor function, ODK was assessed as the number of repetitions of the monosyllables /pa/ta/ka/. Four questionnaires were used to assess subjective masticatory ability, cognitive ability, and psychological status. MP, bite force, and occlusal area were tested to assess dynamic objective masticatory function, and the number of remaining teeth and functional tooth pairs were determined to assess static objective masticatory function. Handgrip strength (HG), oral dryness, and tongue pressure (TP) were assessed to identify influencing factors. Intergroup differences were evaluated by ANOVA and the Kruskal‒Wallis test, and correlations between ODK and orofacial factors were evaluated. RESULTS: This study revealed significant age-related declines in TP, HG, and ODK, especially after 65 years of age. Factors affecting MP were posterior teeth, the Eichner index, bite force, occluding area, the Korean Mini-Mental State Examination (KMMSE) score, and ODK. Each ODK syllable was associated with different factors, but common factors associated with ODK were MP, HG, and PHQ-9 score. For the syllables /pa/ta/, the Eichner Index, TP, and oral dryness were also associated. For the syllable /ka/ in Gr3, MP, TP, HG, oral dryness, and the KMMSE score were associated. CONCLUSIONS: These results could provide practical guidelines for oral rehabilitation in old adults and contribute to improving the understanding of age-related changes in oral function and the multidimensional nature of masticatory dynamics.

Oral leiomyomatous hamartoma: presentation of 3 cases and review of the literature.

Oral leiomyomatous hamartoma (OLH) is a rare lesion, with only 40 cases reported in the literature. It typically presents early in life as a nodule on the anterior maxillary alveolar tissues or the tongue. Its growth potential is limited, with few cases reaching dimensions >2.0 cm, and its microscopic composition includes an intact surface mucosa with an underlying fibrovascular stroma possessing an unencapsulated proliferation of smooth muscle fascicles. Excision is considered the definitive treatment. Here we describe the clinical, microscopic, histochemical, and immunohistochemical features and management of 3 cases of OLH and review the literature. The findings we present here can assist in performing differential diagnosis, particularly in discriminating between OLH and similar yet non-hamartomatous processes and in selecting appropriate management.

Histological evaluation of the surgical margins of oral soft tissue incisions using a dual-wavelength diode laser and an Er, Cr:YSGG laser; an ex vivo study.

OBJECTIVE: This study compared a dual-wavelength diode laser and an Er, Cr:YSGG laser in oral soft tissue incisions to determine the most effective and safest laser system at the histopathological level. METHODOLOGY: The (810 and 980 nm) dual-wavelength diode laser was used at 1.5 W and 2.5 W (CW) power settings, and the (2780 nm) Er, Cr:YSGG laser was used at 2.5 W and 3.5 W (PW) power settings. Both laser systems were used to incise the tissues of freshly dissected sheep tongue pieces to obtain the following histopathological criteria: epithelial tissue changes, connective tissue changes, and lateral thermal damage extent by optical microscopy. RESULTS: The epithelial and connective tissue damage scores were significantly higher in the dual-wavelength diode laser groups than in the Er, Cr:YSGG laser groups (P<0.001), and there was a significant difference between some groups. The extent of lateral thermal damage was also significantly higher in the diode laser groups than in the Er, Cr: YSGG laser groups (P<0.001), and there was a significant difference between groups. Group 2 (2.5 W) of the diode laser was the highest for all three criteria, while group 3 (2.5 W) of the Er, Cr:YSGG laser was the lowest. CONCLUSION: The Er, Cr:YSGG laser with an output power of 2.5 W is, histologically, the most effective and safest laser for oral soft tissue incision. The dual-wavelength diode laser causes more damage than the Er, Cr:YSGG laser, but it can be used with a low output power and 1 mm safety distance in excisional biopsy.

Oral-to-rectum microbial transmission in orthopedic patients without a history of intestinal disorders.

The enrichment of oral taxa in the gut has recently been reported as a notable alteration in the microbial balance in patients with intestinal disorders. However, translocation in populations without such diseases remains controversial. In this study, we examined 49 pairs of tongue and rectal samples collected from orthopedic patients without a history of intestinal disorders to verify the presence of oral taxa in the rectal microbiota. The bacterial composition of each sample was determined using 16S rRNA gene sequencing and amplicon sequence variant (ASV) analysis. Although the bacterial compositions of the tongue and rectal microbiota were distinctly different, tongue ASVs were detected in 67.3% of the participants and accounted for 0.0%-9.37% of the rectal microbiota. Particularly, Streptococcus salivarius, Fusobacterium nucleatum, and Streptococcus parasanguinis were abundant in the rectal microbiota. According to the network analysis, tongue taxa, such as S. salivarius and S. parasanguinis, formed a cohabiting group with Klebsiella pneumoniae and Alistipes finegoldii in the rectal microbiota. The total abundance of tongue ASVs in the rectal microbiota was significantly higher in participants with older age, hypertension, and proton pump inhibitor (PPI) use. Our study presents an extensive translocation of oral taxa to the rectum of a population without intestinal disorders and suggests that aging, hypertension, and PPI use are associated with an increased abundance of oral taxa and potential pathogenic bacteria in the rectal microbiota.

Predictive value of TCM tongue characteristics for chemotherapy-induced myelosuppression in patients with lung cancer.

This study aimed to investigate the clinical predictors, including traditional Chinese medicine tongue characteristics and other clinical parameters for chemotherapy-induced myelosuppression (CIM), and then to develop a clinical prediction model and construct a nomogram. A total of 103 patients with lung cancer were prospectively enrolled in this study. All of them were scheduled to receive first-line chemotherapy regimens. Participants were randomly assigned to either the training group (n = 52) or the test group (n = 51). Tongue characteristics and clinical parameters were collected before the start of chemotherapy, and then the incidence of myelosuppression was assessed after treatment. We used univariate logistic regression analysis to identify the risk predictors for assessing the incidence of CIM. Moreover, we developed a predictive model and a nomogram using multivariate logistic regression analysis. Finally, we evaluated the predictive performance of the model by examining the area under the curve value of the receiver operating characteristic, calibration curve, and decision curve analysis. As a result, a total of 3 independent predictors were found to be associated with the CIM in multivariate regression analysis: the fat tongue (OR = 3.67), Karnofsky performance status score (OR = 0.11), and the number of high-toxic drugs in chemotherapy regimens (OR = 4.78). Then a model was constructed using these 3 predictors and it exhibited a robust predictive performance with an area under the curve of 0.82 and the consistent calibration curves. Besides, the decision curve analysis results suggested that applying this predictive model can result in more net clinical benefit for patients. We established a traditional Chinese medicine prediction model based on the tongue characteristics and clinical parameters, which could serve as a useful tool for assessing the risk of CIM.

Tongue reflex for speech posture control.

Although there is no doubt from an empirical viewpoint that reflex mechanisms can contribute to tongue motor control in humans, there is limited neurophysiological evidence to support this idea. Previous results failing to observe any tonic stretch reflex in the tongue had reduced the likelihood of a reflex contribution in tongue motor control. The current study presents experimental evidence of a human tongue reflex in response to a sudden stretch while holding a posture for speech. The latency was relatively long (50 ms), which is possibly mediated through cortical-arc. The activation peak in a speech task was greater than in a non-speech task while background activation levels were similar in both tasks, and the peak amplitude in a speech task was not modulated by the additional task to react voluntarily to the perturbation. Computer simulations with a simplified linear mass-spring-damper model showed that the recorded muscle activation response is suited for the generation of tongue movement responses that were observed in a previous study with the appropriate timing when taking into account a possible physiological delay between reflex muscle activation and the corresponding force. Our results evidenced clearly that reflex mechanisms contribute to tongue posture stabilization for speech production.

Magnetic resonance imaging accuracy in assessing depth of invasion in tongue squamous cell carcinomas and predicting cervical nodal metastasis.

OBJECTIVE: The aim of this study was to evaluate magnetic resonance imaging (MRI) accuracy in assessing the depth of invasion (DOI) compared to pathological DOI in oral tongue squamous cell carcinoma (SCC) and to determine whether MRI-measured DOI can predict lymph node metastasis in the cervical region. PATIENTS AND METHODS: This retrospective study comprised 36 patients diagnosed with oral tongue SCC who underwent head and neck MRI 1-30 days before surgery and were surgically treated at King Fahad Medical City between January 2017 and November 2022. Relevant information was collected from the patients' records, and the data were analyzed to determine the radiological-histopathological correlations for the DOI and ascertain the cutoff point for nodal metastasis. RESULTS: A value for Pearson's correlation coefficient between MRI-measured and pathological DOI was 0.86, indicating that these measures were highly associated and consistent with each other. The MRI-measured DOI coronal view (CV) was slightly overestimated than the pathological DOI by 1.72 mm. The cutoff values for the MRI-measured DOI CV and pathological DOI that indicated nodal metastasis were 7.08 mm and 9.04 mm, respectively. CONCLUSIONS: Preoperative MRI is a valuable tool to accurately stage oral tongue SCC by measuring the depth of tumor invasion.

High-Performance Photodynamic Therapy of Tongue Squamous Cell Carcinoma with Multifunctional Nano-Verteporfin.

Background: The photodynamic therapy (PDT) showed promising potential in treating tongue squamous cell carcinoma (TSCC). The Food and Drug Administration approved Verteporfin (Ver) is a powerful alternative in this field for its penetrating power and high production of reactive oxygen species (ROS). However, its applications in the treatment of TSCC are still rare. Methods: Ver was loaded onto Poly (lactic-co-glycolic acid) (PLGA) nanoparticles, followed by the modification with RGD peptide as the ligand. The nanostructured was named as RPV. In vitro assessments were conducted to evaluate the cytotoxicity of RPV through the Live/Dead assay analysis and Cell Counting Kit-8 (CCK-8) assay. Using the reactive oxygen species assay kit, the potential for inducing targeted tumor cell death upon laser irradiation by promoting ROS production was investigated. In vivo experiments involved with the biological distribution of RPV, the administration with RPV followed by laser irradiation, and the measurement of the tumor volumes. Immunohistochemical analysis was used to detect the Ki-67 expression, and apoptosis induced by RPV-treated group. Systemic toxicity was evaluated through hematoxylin-eosin staining and blood routine analysis. Real-time monitoring was employed to track RPV accumulation at tumor sites. Results: The in vitro assessments demonstrated the low cytotoxicity of RPV and indicated its potential for targeted killing TSCC cells under laser irradiation. In vivo experiments revealed significant tumor growth inhibition with RPV treatment and laser irradiation. Immunohistochemical analysis showed a notable decrease in Ki-67 expression, suggesting the effective suppression of cell proliferation, and TUNEL assay indicated the increased apoptosis in the RPV-treated group. Pathological examination and blood routine analysis revealed no significant systemic toxicity. Real-time monitoring exhibited selective accumulation of RPV at tumor sites. Conclusion: The findings collectively suggest that RPV holds promise as a safe and effective therapeutic strategy for TSCC, offering a combination of targeted drug delivery with photodynamic therapy.

Prey capture kinematics of horned frogs (Anura: Ceratophryidae).

Horned frogs, members of the Ceratophryidae family, encompass a group of anurans varying in size and behavior, yet unified by morphological and behavioral traits enabling them to adopt a megalophagous diet (i.e., large prey feeding). Although the group has been the focus of numerous studies, our understanding of its feeding behavior remains limited. In this study, we characterize the feeding mechanism in five species representing the three extant genera of ceratophryid anurans, both in terrestrial and aquatic environments. We also explore the ability of Chacophrys pierottii to adjust feeding behavior based on prey type. Our findings show that all species are capable of wide mouth opening, displaying an asymmetric feeding cycle. While tongue usage is the primary method for capturing prey on land, ceratophryids may use their forelimbs to manipulate prey into their mouths, exhibiting different behavioral patterns. C. pierottii shows modulation of its feeding kinematics and is also capable of some modulation of its feeding in response to prey properties.