Patient-reported outcomes after oral cancer reconstructions with radial and ulnar forearm-free flaps.

OBJECTIVES: This study aimed to evaluate patient-reported quality of life and incidence of decision regret in patients undergoing radial (RFFF) and ulnar forearm-free flaps (UFFF) reconstruction. MATERIALS AND METHODS: Patients undergoing either RFFF or UFFF were assessed with the University of Washington Quality of Life (UW-QOL) and Oral Health Impact Profile (OHIP-14) questionnaires, and the Decision Regret Scale (DRS), both before and at least 12 months post-reconstruction. RESULTS: In total, 40 RFFF and 40 UFFF were included. Harvesting time was longer in RFFF (p = 0.043), and the donor-site defect was significantly larger in RFFF than in UFFF (p = 0.044). Patients with UFFF scored better UW-QOL in the appearance, pain, activity, mood, and social functioning domains (p < 0.05). However, the RFFF group excelled in swallowing and chewing domains. The DRS score revealed a significant difference between RFFF and UFFF, with scores of 36.26 versus 27.36, respectively. Moreover, the mean DRS score reduced at 12 months compared with 6 months, significantly superior for UFFF. CONCLUSION: Oral cancer patients reconstructed with UFFF exhibited a better appearance, social domain, and mild decision regret compared with RFFF, indicating that the UFFF may contribute to improving postoperative quality of life in oral cancer patients.

Targeting PI3K/AKT/mTOR signaling to overcome drug resistance in cancer.

This review comprehensively explores the challenge of drug resistance in cancer by focusing on the pivotal PI3K/AKT/mTOR pathway, elucidating its role in oncogenesis and resistance mechanisms across various cancer types. It meticulously examines the diverse mechanisms underlying resistance, including genetic mutations, feedback loops, and microenvironmental factors, while also discussing the associated resistance patterns. Evaluating current therapeutic strategies targeting this pathway, the article highlights the hurdles encountered in drug development and clinical trials. Innovative approaches to overcome resistance, such as combination therapies and precision medicine, are critically analyzed, alongside discussions on emerging therapies like immunotherapy and molecularly targeted agents. Overall, this comprehensive review not only sheds light on the complexities of resistance in cancer but also provides a roadmap for advancing cancer treatment.

Predictive, preventive, and personalized medicine in breast cancer: targeting the PI3K pathway.

Breast cancer (BC) is a multifaceted disease characterized by distinct molecular subtypes and varying responses to treatment. In BC, the phosphatidylinositol 3-kinase (PI3K) pathway has emerged as a crucial contributor to the development, advancement, and resistance to treatment. This review article explores the implications of the PI3K pathway in predictive, preventive, and personalized medicine for BC. It emphasizes the identification of predictive biomarkers, such as PIK3CA mutations, and the utility of molecular profiling in guiding treatment decisions. The review also discusses the potential of targeting the PI3K pathway for preventive strategies and the customization of therapy based on tumor stage, molecular subtypes, and genetic alterations. Overcoming resistance to PI3K inhibitors and exploring combination therapies are addressed as important considerations. While this field holds promise in improving patient outcomes, further research and clinical trials are needed to validate these approaches and translate them into clinical practice.

TLR9 activation induces immunosuppression and tumorigenesis via PARP1/PD-L1 signaling pathway in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, and metastasis and immunosuppression are responsible for the poor prognosis of OSCC. Previous studies have shown that poly(ADP-ribose) polymerase (PARP)1 plays a key role in the pathogenesis of OSCC. Therefore, PARP1 may serve as an important research target for the potential treatment of OSCC. Here, we aimed to investigate the role of PARP1 in the tumorigenesis of OSCC and elucidate the key molecular mechanisms of its upstream and downstream regulation in vivo and in vitro. In human OSCC tissues and cells, Toll-like receptor (TLR)9 and PD-L1 were highly expressed and PARP1 was lowly expressed. Suppression of TLR9 remarkably repressed CAL27 and SCC9 cell proliferation, migration, and invasion. After coculture, we found that low expression of TLR9 inhibited PD-L1 expression and immune escape. In addition, TLR9 regulated PD-L1 expression through the PARP1/STAT3 pathway. PARP1 mediated the effects of TLR9 on OSCC cell proliferation, migration, and invasion and immune escape. Additionally, in vivo experiments further verified that TLR9 promoted tumor growth and immune escape by inhibiting PARP1. Collectively, TLR9 activation induced immunosuppression and tumorigenesis via PARP1/PD-L1 signaling pathway in OSCC, providing important insights for subsequent in-depth exploration of the mechanism of OSCC.NEW & NOTEWORTHY In this research, we took PARP1 as the key target to explore its regulatory effect on oral squamous cell carcinoma (OSCC). The key molecular mechanisms involved in its upstream and downstream regulation were elucidated in OSCC cell lines in vitro and tumor-bearing mice in vivo, combined with clinical OSCC tissues.

5-aminolevulinic acid photodynamic therapy for extensive oral leukoplakia with concomitant oral submucous fibrosis: A case report.

BACKGROUND: Oral leukoplakia and oral submucous fibrosis are potentially malignant disorders of the oral cavity, with high rates of recurrence and malignant transformation. Notably, the malignant transformation rate of oral leukoplakia with concomitant oral submucous fibrosis is significantly higher than that of oral submucous fibrosis or oral leukoplakia alone. However, the management of these conditions is not well defined. Photodynamic therapy is a minimally invasive treatment modality that effectively targets oral potentially malignant disorders, such as oral leukoplakia, erythroleucoplakia, and verrucous hyperplasia, with the advantages of being repeatable and leaving no scarring. CASE PRESENTATION: We report the case of a 42-year-old man with concomitant oral leukoplakia and oral submucous fibrosis almost involving the entire right buccal mucosa, who underwent six sessions of topical 5-aminolevulinic acid-mediated photodynamic therapy. RESULTS: Photodynamic therapy successfully eradicated whitish plaques and improved mouth opening without any adverse effects. Although photodynamic therapy failed to completely reverse the pathological changes, grading of epithelial dysplasia did not progress and clinical recurrence was not found during the 10-month follow-up. CONCLUSION: In conclusion, topical 5-aminolevulinic acid-mediated photodynamic therapy appears safe and has excellent clinical efficacy against oral leukoplakia-concomitant oral submucous fibrosis, but long-term follow-up is necessary.

Tyrosine sulphation of CXCR4 induces the migration of fibroblast in OSF.

Oral submucous fibrosis (OSF) caused by areca nut chewing is a prevalent fibrotic disease in Asia-Pacific countries. Arecoline-induced migration of fibroblasts (FBs) plays a vital role in the development of OSF. However, the specific molecular mechanisms involved remain unclear. Many studies have shown that tyrosine sulphation of chemokines can influence cell migration. Herein, we demonstrated that arecoline stimulates tyrosine sulphation of the chemokine receptor 4 (CXCR4) through the tyrosylprotein sulphotransferase-1 (TPST-1) to enhance the migration ability of FBs. Moreover, by RNA-Seq analysis, we found that the most significantly altered pathway was the EGFR pathway after the arecoline stimulation for FBs. After the knockdown of arecoline-induced EGFR expression, the tyrosine sulphation of CXCR4 was significantly decreased by the inhibition of TPST-1 induction. Finally, in human OSF specimens, TPST-1 expression was directly correlated with the expression of CXCR4. These data indicate that the arecoline-induced tyrosine sulphation of CXCR4, which is regulated by TPST-1, might be a potential mechanism that contributes to FB migration in OSF.

Lateral approach is a more aesthetical option for radical resection of BSCC: assessment of its surgical, oncological, functional, and aesthetic outcomes.

BACKGROUND: The purpose of this study was to introduce a modified lateral approach for combined radical resection of buccal squamous cell carcinoma (BSCC) and evaluate its surgical, oncological, functional, and aesthetic outcomes in comparison with the conventional lower-lip splitting approach. METHODS: This single-center study retrospectively reviewed 80 patients with BSCC, of which 37 underwent the lateral approach and 43 underwent the conventional approach. Surgical, functional, oncological, and aesthetic evaluations, as well as follow-ups, were recorded and compared. RESULTS: Compared to the conventional approach group, the lateral approach group had a longer surgical time (P = 0.000), but there was no significant difference in other surgical and oncological parameters. Moreover, the scar in the head and neck had a significantly discreet appearance in the lateral approach group, whose satisfaction was better than those in the conventional approach group (P = 0.000). Other oral function parameters, postoperative mouth-opening, and 3-year survival rate were not significantly different between the two groups. CONCLUSION: The lateral approach could provide superior aesthetic results while maintaining equal surgical, functional, and oncological outcomes compared to the conventional approach for radical resection of BSCC.

Long Noncoding RNA LEMD1-AS1 Increases LEMD1 Expression and Activates PI3K-AKT Pathway to Promote Metastasis in Oral Squamous Cell Carcinoma.

Background: The survival rate of oral squamous cell carcinoma (OSCC) is only 50% due to a high incidence of metastasis. Long noncoding RNAs (lncRNAs) play a crucial role in OSCC genesis and progression, although their potential role in the metastasis of OSCC remains unclear. Methods: The transcriptome of 5 metastatic and 5 nonmetastatic OSCC samples were assessed by RNA sequencing. The biological functions and regulatory mechanisms of LEMD1-AS1 in OSCC were explored by in vitro and in vivo assays. Results: We identified 487 differentially expressed mRNAs (DEmRNAs) and 1507 differentially expressed lncRNAs (DElncRNAs) in OSCC with cervical lymph node (LN) metastasis relative to the nonmetastatic samples. In addition, both LEMD1-AS1 and its cognate LEMD1 were up-regulated in metastatic OSCC compared to nonmetastatic OSCC. Gain-of-function, loss-of-function, and rescue experiments indicated that LEMD1-AS1 upregulated LEMD1 to increase OSCC migration and invasion in vitro and in vivo. Mechanistically, LEMD1-AS1 stabilized LEMD1 and increased its mRNA and protein levels, and consequently activated the PI3K-AKT signaling pathway to facilitate OSCC metastasis. Conclusions: We established the lncRNA-mRNA landscape of metastatic OSCC, which indicated that LEMD1-AS1 enhanced OSCC metastasis by stabilizing its antisense transcript LEMD1. Thus, LEMD1-AS1 is a potential biomarker for predicting metastasis, as well as a therapeutic target of OSCC.

Prognostic role of PD-L1 expression in patients with salivary gland carcinoma: A systematic review and meta-analysis.

BACKGROUND: Although programmed cell death-ligand 1 (PD-L1) has been recognized as a potential marker in several cancers, the relationship between PD-L1 expression and survival in patients with salivary gland carcinoma (SGC) has remained unclear. We aimed to evaluate the association of PD-L1 expression with clinicopathological features and prognosis in SGC patients. METHODS: The databases Ovid Medline, PubMed, Scopus, and EMBASE were searched for relevant studies that detected PD-L1 expression in SGC. The meta-analysis was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA), and the reporting recommendations for tumor marker prognostic studies (REMARK) was used to assess the quality of research eligible for this meta-analysis. Included studies were assessed using the Quality in Prognosis Studies (QUIPS) tool. Odds ratios (ORs) with 95% confidence interval (CI) were calculated to estimate the correlation between PD-L1 expression and clinicopathological features. Hazard ratios (HRs) with 95% CI were applied to assess the association between PD-L1 expression and survival outcomes of patients. RESULTS: A total of ten studies (including 952 patients with SGC) were evaluated. The meta-analysis showed that positive PD-L1 expression in SGC was significantly associated with male patients, older age, Tumor stage, lymph node metastasis, high pathological grade, and non-adenoid cystic carcinoma subtype. The pooled data demonstrated that high PD-L1 expression was associated with poor overall survival and disease-free survival. There was no significant correlation between PD-L1 expression and progression-free survival or disease-specific survival of SGC patients. CONCLUSION: According to the meta-analysis, positive PD-L1 expression may play an important role as an effective marker of poor prognosis in patients with SGC. However, large-scale, prospective investigations are still needed to confirm the findings. The assessment of PD-L1 expression may aid in the personalized management of SGC.

Deviation Analyses of Computer-Assisted, Template-Guided Mandibular Reconstruction With Combined Osteotomy and Reconstruction Pre-Shaped Plate Position Technology: A Comparative Study.

BACKGROUND: Computer-assisted and template-guided mandibular reconstruction provides higher accuracy and less variation than conventional freehand surgeries. The combined osteotomy and reconstruction pre-shaped plate position (CORPPP) technique is a reliable choice for mandibular reconstruction. This study aimed to evaluate the accuracy of CORPPP-guided fibular flap mandibular reconstruction and analyze the possible causes of the deviations. PATIENTS AND METHODS: From June 2015 to December 2016, 28 patients underwent fibular flap mandibular reconstruction. Virtual planning and personalized CORPPP-guided templates were applied in 15 patients while 13 patients received conventional freehand surgeries. Deviations during mandibulectomy and fibular osteotomy, and overall and triaxial deviation of the corresponding mandibular anatomical landmarks were measured by superimposing the pre- and postoperative virtual models. RESULTS: The deviation of the resection line and resection angle was 1.23 ± 0.98 mm and 4.11° ± 2.60°. The actual length of fibula segments was longer than the designed length in 7 cases (mean: 0.35 ± 0.32 mm) and shorter in 22 cases (mean: 1.53 ± 1.19 mm). In patients without ramus reconstruction, deviations of the ipsilateral condylar head point (Co.), gonion point (Go.), and coracoid process point (Cor.) were 6.71 ± 3.42 mm, 5.38 ± 1.71 mm, and 11.05 ± 3.24 mm in the freehand group and 1.73 ± 1.13 mm, 1.86 ± 0.96 mm, and 2.54 ± 0.50 mm in the CORPPP group, respectively, with significant statistical differences (p < 0.05). In patients with ramus reconstruction, deviations of ipsilateral Co. and Go. were 9.79 ± 4.74 mm vs. 3.57 ± 1.62 mm (p < 0.05), and 15.17 ± 6.53 mm vs. 4.36 ± 1.68 mm (p < 0.05) in the freehand group and CORPPP group, respectively. CONCLUSION: Mandibular reconstructions employing virtual planning and personalized CORPPP-guided templates show significantly higher predictability, convenience, and accuracy of mandibular reconstruction compared with conventional freehand surgeries. However, more clinical cases were required for further dimensional deviation analysis. The application and exploration of clinical practice would also continuously improve the design of templates.

Platelet-Derived Growth Factor Regulates the Biological Behavior of Oral Mucosal Fibroblasts by Inducing Cell Autophagy and Its Mechanism.

OBJECTIVE: To explore the effect of platelet-derived growth factor (PDGF) on oral mucosal fibroblast autophagy and further elucidate the molecular mechanism by which PDGF-BB regulates the biological behavior of oral mucosal fibroblasts by inducing autophagy. METHODS: Primary oral mucosal fibroblasts were isolated and cultured by the tissue block and trypsin methods and identified by indirect immunofluorescence vimentin detection. We detected the autophagy marker Beclin-1 and fibrosis marker Col-I of the primary oral mucosal fibroblasts at different time points after stimulating the fibroblasts with different PDGF-BB concentrations by Western blotting and determined the best experimental concentration and stimulation time of PDGF-BB. Then, indirect immunofluorescence, Western blotting, and quantitative real-time polymerase chain reaction (PCR) were used to detect the effect of PDGF-BB on the expression of autophagy-related and fibrotic proteins before and after 3-methyladenine (3-MA) intervention. Additionally, the effect of 3-MA on the proliferation and migration of primary oral mucosal fibroblasts stimulated by PDGF-BB was detected by the MTT method and a scratch experiment. The effect of PDGF-BB on Beclin-1 and phosphatidylinositol-3 kinase class 3 (PI3KC3) interaction was detected by co-immunoprecipitation. RESULTS: The results demonstrated that PDGF-BB could induce autophagy of the oral mucosal fibroblasts, showing a certain time and dose correlation. It induced cell autophagy through Beclin-1 and PI3KC3 interaction to promote the proliferation, migration, conversion, and collagen synthesis of the fibroblasts. However, 3-MA inhibited the combination of Beclin-1 and PI3KC3 and weakened the fibroblasts' proliferation, migration, conversion, and collagen synthesis activities. CONCLUSION: Overall, PDGF-BB induces autophagy through the Beclin-1 pathway to regulate the biological behavior of oral mucosal fibroblasts.

PDGF-BB induces conversion, proliferation, migration, and collagen synthesis of oral mucosal fibroblasts through PDGFR-ß/PI3K/ AKT signaling pathway.

OBJECTIVE: To explore the pathogenesis of oral submucosal fibrosis (OSF) by analyzing the impact of Platelet Derived Growth Factor (PDGF)-BB on oral mucosal fibroblasts (FB) and PDGFR-ß/Phosphoinositide 3-kinase (PI3K)/serine/threonine protein kinase (AKT) signaling pathway. METHODS: The isolated and purified oral mucosal fibroblasts were divided into four groups: the control group (CON, 10% FBS DMEM), the PDGF-BB group (40 ng/ml PDGF-BB), the PDGF-BB+IMA group (40 ng/ml PDGF-BB and 60 µmol/L IMA), and the PDGF-BB+LY294002 group (40 ng/ml PDGF-BB and 48 µmol/L LY294002). Primary human FB cells were isolated and cultured for detecting the effects of PDGF-BB on α-smooth muscle actin (α-SMA) by indirect immunofluorescence. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, Thiazolyl Blue Tetrazolium Bromide (MTT) method and scratch test were used to detect the proliferation and migration of FB. Western blots were used to detect the synthesis of type I collagen (Col I) and the expression of PDGFR-ß/PI3K/AKT signaling pathway-related proteins. The effects of PDGFR-ß inhibitor and PI3K inhibitor were observed. RESULTS: Compared with group CON, group IMA, and group LY294002, α-SMA was upregulated in group PDGF-BB (p< 0.05), with higher OD490 nm value (p< 0.05), narrower average scratch width, and higher relative cell migration rate (p< 0.05). The expression levels of Col I, p-PDGFR-ß, p-PI3K, and p-AKT were higher in group PDGF-BB (p< 0.05). CONCLUSIONS: PDGF-BB induces FB to transform into myofibroblasts (MFB) through the PDGFR-ß/PI3K/AKT signaling pathway, and promotes the proliferation, migration, and collagen synthesis.

Oral submucous fibrosis transforming into squamous cell carcinoma: a prospective study over 31 years in mainland China.

OBJECTIVE: Oral submucous fibrosis (OSF) is an oral mucous disease caused by betel quid chewing. It is controversial whether OSF can transform into oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: In this prospective study, a group of 567 patients with OSF were enrolled from 1986 to 2017 and followed-up until 2019. The cancerous information was collected and analyzed. RESULTS: OSF transformed into OSCC in 32 cases (32/567, 5.6%). The patient's age ranged from 20 to 69 years, and the average age was 52 years. The time taken for transformation ranged from 2 to 24 years, the average being 8.6 years. The cancerous transformation occurred in 18 patients (56%) from years 2 to 9, in 13 patients (41%) from years 10-19 and in 1 patient (3%) from 24 years. We analyzed the betel quid chewing habits and found all 32 patients with OSCC-chewed betel quid. Betel quid chewing was most prevalent in patients aged 40-69 years. Sixteen patients had chewed betel quid for 10-19 years (16/32, 50%) and 19 patients (60%) chewed 10-19 slices each day. The OSCC was located in the left or right buccal regions in 23 patients (23/32; 72%) and in the left or right lingual regions in 4 patients (4/32; 12%). Well, moderately and poorly differentiated squamous cell carcinoma was present in 23 patients (23/32; 72%), 4 patients (3/32; 9%), and 5 patients (5/32; 16%), respectively. CONCLUSION: Our findings supported that OSF is a real oral premalignant disorder. CLINICAL RELEVANCE: The long duration of the transformation from the OSF to OSCC suggests more frequent examinations and corresponding treatments are necessary for OSF patients.

Higher Trait Impulsivity and Altered Frontostriatal Connectivity in Betel-Quid Dependent Individuals.

Objective: Betel quid dependency (BQD) is characterized by functional and structural brain alterations. Trait impulsivity may influence substance dependence by impacting its neurobiological underpinnings in the frontostriatal circuit. However, little is known about the trait impulsivity and its neural correlates in individuals with BQD. Methods: Forty-eight participants with BQD and 22 normal controls (NCs) were recruited and scanned on a 3T MRI scanner. Barratt impulsiveness scale (BIS) was used to measure trait impulsivity: motor, attention, and no plan impulsivity. We used voxel-based morphometry (VBM) to assess the relationship between trait impulsivity and gray matter volumes. The relevant clusters identified were served as regions of interest (ROI) seeds. The whole-volume psycho-physiological interactions (PPI) analysis was used to investigate the changes of functional connectivity related to ROI seeds in the cue-reactivity task condition (BQ and control images). Results: Behaviorally, the BQD group showed significantly higher trait impulsivity including motor and no plan impulsivity than the NCs group. VBM analyses showed that motor impulsivity was negatively associated with gray matter volume of right caudate in the whole sample. No difference in gray matter volume between the two groups was observed. PPI analyses showed that there was a significantly decreased functional connectivity between the right caudate and right dorsolateral prefrontal cortex (DLPFC) when watching BQ related images than control images in individuals with BQD. Furthermore, functional connectivity between the right caudate and right DLPFC was negatively correlated with BQ dependency scores. Conclusions: Our study demonstrated the structural basis of trait impulsivity in the caudate and provided evidence for abnormal interactions within frontostriatal circuitsin individuals with BQD, which may provide insight into the selection of potential novel therapeutic targets for the treatment of BQ dependency.

Dysfunction of the Prefrontal Cortex in Betel-Quid-Dependent Chewers.

Betel quid is the fourth most popular psychoactive agent worldwide. Imaging studies have found altered brain structure in prefrontal cortex (PFC) in betel-quid dependent (BQD) chewers. However, the brain function in PFC associated with BQ use still remains unclear. The present study aimed to examine brain functional activity in PFC in individuals with BQD. This study recruited 48 participants with BQD and 22 normal controls (NCs). Both BQ-specific cue reactivity and Go/NoGo tasks were administered with functional magnetic resonance imaging (fMRI). Behavioral results showed a deficit in the choice reaction time task in BQD group. The fMRI results of the cue reactivity task suggested that, individuals with BQD exhibited responses in right ventromedial PFC, left posterior cingulate cortex (PCC), left lateral parietal lobe (LPL), left middle temporal gyrus and left visual cortex, when seeing BQ images compared with control images. In the Go/NoGo task, relative to NCs group, individuals with BQD showed higher activity in right dorsolateral PFC, right PCC and bilateral LPL between NoGo and Go trials. Across these two tasks, we consistently found disrupted function in PFC in individuals with BQD, which might lead to impaired craving and response inhibition in BQ addiction. Results of current study might shed light on the neural mechanisms involved in BQ use, which could be used as potential guidelines for diagnosis and treatment of BQ dependence.

Use of artificial intelligence to recover mandibular morphology after disease.

Mandibular tumors and radical oral cancer surgery often cause bone dysmorphia and defects. Most patients present with noticeable mandibular deformations, and doctors often have difficulty determining their exact mandibular morphology. In this study, a deep convolutional generative adversarial network (DCGAN) called CTGAN is proposed to complete 3D mandibular cone beam computed tomography data from CT data. After extensive training, CTGAN was tested on 6 mandibular tumor cases, resulting in 3D virtual mandibular completion. We found that CTGAN can generate mandibles with different levels and rich morphology, including positional and angular changes and local patterns. The completion results are shown as tomographic images combining generated and natural areas. The 3D generated mandibles have the anatomical morphology of the real mandibles and transition smoothly to the portions without disease, showing that CTGAN constructs mandibles with the expected patient characteristics and is suitable for mandibular morphological completion. The presented modeling principles can be applied to other areas for 3D morphological completion from medical images.Clinical trial registration: This study is not a clinical trial. Patient data were only used for testing in a virtual environment. The use of the digital data used in this study was ethically approved.

Application of a chimeric ALT perforator flap with vastus lateralis muscle mass in the reconstruction of the defects after radical resection of a buccal carcinoma: A retrospective clinical study.

BACKGROUND AND OBJECTIVES: Aggressive resection of buccal cancer simultaneously leaves both oral and lateral facial defects. It is unknown whether a perforator-based chimeric anterolateral thigh (ALT) flap, with a muscular component, is suitable for the reconstruction of these complicated defects. METHODS: In this retrospective study, 48 patients with a buccal carcinoma (T2 N0-1 M0), who underwent extensive surgical resection, were enrolled. Twenty-seven cases underwent reconstruction using the classical ALT perforator flap (classical group), and 21 cases used the chimeric ALT perforator flap with vastus lateralis muscle mass (chimeric group). The incidence of wound infection, lower limb extremity function, facial appearance, survival curves, and quality of life were compared between groups. RESULTS: The incidence of wound infection or effusion was lower in the chimeric group than in the classical group. The aesthetic result achieved in the chimeric group was better than in the classical group. Meanwhile, there was no significant difference in the function of the donor site between groups. CONCLUSIONS: The chimeric ALT perforator flap, with a muscular component, can reconstruct both the oral and lateral face defects accurately. It sustains the profile of the lateral face and decreases the incidence of wound infection.

The circEPSTI1/mir-942-5p/LTBP2 axis regulates the progression of OSCC in the background of OSF via EMT and the PI3K/Akt/mTOR pathway.

Oral squamous cell carcinoma (OSCC) in the background of oral submucous fibrosis (OSF) caused by areca nut chewing has a high incidence in Asia-Pacific countries. However, the molecular mechanism remains unclear. Here, we performed circRNA microarray analysis to screen the circRNA expression profiles in OSCC and OSF. We identified circEPSTI1 as a circRNA with consistent, sequential upregulation from normal buccal mucosa (NBM) to OSF to OSCC. Functionally, circEPSTI1 significantly promoted OSCC cell proliferation and invasion, as evidenced by the CCK8, colony formation, wound healing, and transwell assays with circEPSTI1 overexpression and silencing. OSCC patients with circEPSTI1high status exhibited poor prognoses. CircEPSTI1 sponged miR-942-5p and accelerated epithelial-mesenchymal transition (EMT) to increase LTBP2 expression in OSCC through phosphorylation of PI3K/Akt/mTOR signaling pathway components. Blocking the PI3K/Akt/mTOR signaling pathway with the dual PI3k/mTOR inhibitor BEZ235 reversed OSCC progression induced by overexpression of circEPSTI1 and LTBP2. Collectively, these results indicate that the circEPSTI1/miR-942-5p/LTBP2 axis affects OSCC cell proliferation and invasion via the acceleration of EMT and the phosphorylation of PI3K/Akt/mTOR signaling pathway components. CircEPSTI1 may be an independent diagnostic and prognostic marker and a potential therapeutic target for OSCC patients with OSF.

[Influence of mandibulotomy approaches on oral function following radical resection of tongue carcinoma].

OBJECTIVE: This study aimed to compare the influences of postoperative oral function in patients with median or paramedian mandibulotomy during the radical resection of tongue carcinoma and to provide evidence for the choice of osteotomy location for mandibulotomy. METHODS: The clinical data of 126 patients who underwent combined radical neck dissection with mandibulectomy and glossectomy followed by simultaneous reconstruction were analyzed retrospectively. The patients were divided into two groups according to the position of mandibulotomy: median mandibulotomy group (median group, n=60) and paramedian mandibulotomy group (paramedian group, n=66). The fourth edition of the University of Washington Quality of Life Questionnaire (UW-QOL) was used to compare the differences in oral functions, such as swallowing, mastication, and speech, between the two groups during regular follow-up. SPSS 24.0 software package was used for statistical analysis, and P<0.05 was considered statistically significant. RESULTS: Six months after the operation, no significant differences in swallowing, mastication, and speech functions were found between the median and paramedian groups. However, the swallowing and speech functions in the paramedian group were better than those in the median group 1 year after the operation (P<0.05), whereas no statistical difference in mastication function was observed between the two groups. CONCLUSIONS: Evaluation of the postoperative oral function results showed that paramedian mandibulotomy was a better surgical approach than median mandibulotomy. Paramedian mandibulotomy is worth prioritizing in the radical resection of tongue carcinoma.

Reconstruction for Various Subtypes of Unilateral Buccal Defects After Oncologic Surgery by Using Personalized Anterolateral Thigh Flaps.

PURPOSE: Radical resection of buccal carcinoma frequently leads to intraoral or through-and-through buccal defects. Anterolateral thigh (ALT) flaps can be harvested to reconstruct different buccal defect subtypes. The purpose of this study was to investigate clinical outcomes after the application of personalized ALT flaps for the precise reconstruction of unilateral buccal defects. MATERIALS AND METHODS: Patients with primary unilateral buccal carcinoma who underwent tumor ablation and simultaneous reconstruction of personalized ALT flaps from January 2015 to January 2018 were enrolled in this retrospective case series. Buccal defects were classified into 4 subtypes. Demographic features, defect range and reconstructive method, and perioperative characteristics were reviewed and recorded. Quality of life and mouth opening were assessed by the University of Washington Quality-of-Life questionnaire and interincisal distance (IID), respectively, during follow-up. Descriptive statistics were calculated for each study variable. RESULTS: Four types of ALT flaps were harvested and used to reconstruct different buccal defects in 146 patients. Of the 193 skin paddles applied, 189 survived, and few recipient- and donor-site complications were observed. One hundred eight patients were assessed with the University of Washington Quality-of-Life questionnaire and followed until 12 months postoperatively. Our results showed that physical, functional, social, and emotional domain scores increased steadily during the follow-up period. Ninety-eight patients showed improvements in mouth opening when the IID before the operation was compared with the IID at 3 and 6 months postoperatively. CONCLUSIONS: A personalized ALT flap is a suitable choice for reconstructing unilateral buccal defects after oncologic surgery given its high success rate, customizable and flexible design, low complication rate, and satisfactory esthetic and functional results.