Perineural invasion (PNI) by tumor cells is a key phenotype of highly-invasive oral squamous cell carcinoma (OSCC). Since Schwann cells (SCs) and fibroblasts maintain the physiological homeostasis of the peripheral nervous system, and we have focused on cancer-associated fibroblasts (CAFs) for decades, it's imperative to elucidate the impact of CAFs on SCs in PNI⁺ OSCCs. We describe a disease progression-driven shift of PNI^- towards PNI⁺ during the progression of early-stage OSCC (31%, n = 125) to late-stage OSCC (53%, n = 97), characterized by abundant CAFs and nerve demyelination. CAFs inhibited SC proliferation/migration and reduced neurotrophic factors and myelin in vitro, and this involved up-regulated ER stress and decreased MAPK signals. Moreover, CAFs also aggravated the paralysis of the hind limb and PNI in vivo. Unexpectedly, leukemia inhibitory factor (LIF) was exclusively expressed on CAFs and up-regulated in metastatic OSCC. The LIF inhibitor EC330 restored CAF-induced SC inactivation. Thus, OSCC-derived CAFs inactivate SCs to aggravate nerve injury and PNI development.
Schwann Cells/metabolism* ; Mouth Neoplasms/metabolism* ; Humans ; Cancer-Associated Fibroblasts/metabolism* ; Animals ; Carcinoma, Squamous Cell/metabolism* ; Neoplasm Invasiveness/pathology* ; Male ; Female ; Mice ; Cell Movement/physiology* ; Cell Proliferation/physiology* ; Cell Line, Tumor ; Leukemia Inhibitory Factor/metabolism* ; Middle Aged

Purpose To analyse the expression of aldo-keto reductase AKR1C3 in the tumour tissues of oral squa-mous carcinoma(OSCC)and the correlation of clinical prognosis of patients.Methods Immunohistochemical(IHC)staining was performed to analyze the expression characteristics of AKR1C3 in 86 cases of OSCC tumor tissues and paired paratumor normal tissue.The correlation between AKR1C3 expression and clinical prognosis was evaluated.Ka-plan-Meier survival analysis was conducted to assess the survival outcomes of OSCC patients.Univariate and multivari-ate Cox regression analyses were employed to identify prognostic factors.The findings were further validated by compar-ison with the Cancer Genome Atlas(TCGA)database.Results The expression of AKR1C3 was significantly higher in OSCC tumor tissues than in paratumor normal tissue,with higher expression observed at the invasive front relative to the tumor centers.Immunohistochemical analysis revealed high expression in both tumor cells and tumor-associated fibro-blasts,while no expression was detected in tumor-infiltrating immunocytes.The x2 test was used to compare the rela-tionship between different expression levels of AKR1C3 and clinicopathological features in OSCC,the results showed that high expression of AKR1C3 was strongly associated with higher tumour stage(P=0.001),lymph node metastasis(P=0.023),differentiation(P=0.018),worst pattern of invasion(P=0.024)and depth of invasion(P=0.012).Kaplan-Meier survival curve analysis showed high expression of AKR1C3 was associated with overall survival(P=0.004),disease-free survival(P=0.019),and metastasis-free survival(P=0.05)in OSCC patients.Cox re-gression model was performed for prognostic analysis.Univariate analysis showed that high expression of AKR1C3 in tumour cells was a high-risk factor for patients' tumour stage(P＜0.001),lymph node metastasis(P＜0.001),dif-ferentiation(P＜0.001),worst pattern of invasion(P＜0.001),depth of invasion(P＜0.001).Multivariate analy-sis further showed that high expression of AKR1C3 in tumour cells was an independent prognostic factor in OSCC pa-tients(P=0.025).Conclusion The AKR1C3 expression is closely related to the prognosis of OSCC patients,and patients with high AKR1C3 expression have a poor prognosis,suggesting that AKR1C3 plays an important role in the occurrence and development of OSCC.

Oral and maxillofacial tumors significantly impact human health,with oral squamous cell carcinoma(OSCC)being par-ticularly prevalent among head and neck tumors.At present,traditional research in this area has largely relied on genomics,pro-teomics,and transcriptomics,which involve the homogenization of tissue specimens and result in the loss of critical temporal and spatial tissue information.In contrast,spatial metabolomics,an emerging field,allows for the in-situ analysis of fresh tissue sam-ples,preserving this essential information.This article reviews the application of spatial metabolomics in OSCC research,highlight-ing its potential to enhance understanding of cancer pathogenesis directly within the tissue context.

Purpose To analyse the expression of aldo-keto reductase AKR1C3 in the tumour tissues of oral squa-mous carcinoma(OSCC)and the correlation of clinical prognosis of patients.Methods Immunohistochemical(IHC)staining was performed to analyze the expression characteristics of AKR1C3 in 86 cases of OSCC tumor tissues and paired paratumor normal tissue.The correlation between AKR1C3 expression and clinical prognosis was evaluated.Ka-plan-Meier survival analysis was conducted to assess the survival outcomes of OSCC patients.Univariate and multivari-ate Cox regression analyses were employed to identify prognostic factors.The findings were further validated by compar-ison with the Cancer Genome Atlas(TCGA)database.Results The expression of AKR1C3 was significantly higher in OSCC tumor tissues than in paratumor normal tissue,with higher expression observed at the invasive front relative to the tumor centers.Immunohistochemical analysis revealed high expression in both tumor cells and tumor-associated fibro-blasts,while no expression was detected in tumor-infiltrating immunocytes.The x2 test was used to compare the rela-tionship between different expression levels of AKR1C3 and clinicopathological features in OSCC,the results showed that high expression of AKR1C3 was strongly associated with higher tumour stage(P=0.001),lymph node metastasis(P=0.023),differentiation(P=0.018),worst pattern of invasion(P=0.024)and depth of invasion(P=0.012).Kaplan-Meier survival curve analysis showed high expression of AKR1C3 was associated with overall survival(P=0.004),disease-free survival(P=0.019),and metastasis-free survival(P=0.05)in OSCC patients.Cox re-gression model was performed for prognostic analysis.Univariate analysis showed that high expression of AKR1C3 in tumour cells was a high-risk factor for patients' tumour stage(P＜0.001),lymph node metastasis(P＜0.001),dif-ferentiation(P＜0.001),worst pattern of invasion(P＜0.001),depth of invasion(P＜0.001).Multivariate analy-sis further showed that high expression of AKR1C3 in tumour cells was an independent prognostic factor in OSCC pa-tients(P=0.025).Conclusion The AKR1C3 expression is closely related to the prognosis of OSCC patients,and patients with high AKR1C3 expression have a poor prognosis,suggesting that AKR1C3 plays an important role in the occurrence and development of OSCC.

Oral and maxillofacial tumors significantly impact human health,with oral squamous cell carcinoma(OSCC)being par-ticularly prevalent among head and neck tumors.At present,traditional research in this area has largely relied on genomics,pro-teomics,and transcriptomics,which involve the homogenization of tissue specimens and result in the loss of critical temporal and spatial tissue information.In contrast,spatial metabolomics,an emerging field,allows for the in-situ analysis of fresh tissue sam-ples,preserving this essential information.This article reviews the application of spatial metabolomics in OSCC research,highlight-ing its potential to enhance understanding of cancer pathogenesis directly within the tissue context.

Objective:To investigate the precise reconstruction method of anterior maxillary defect with fibula musculocutaneous flap assisted by digital surgical technology.Methods:The clinical data of the patients with anterior maxillary defect repaired by fibular free flap from January 2014 to January 2020 in Nanjing Stomatological Hospital were analyzed retrospectively. Mimics 23.0 software was used to perform computer virtual surgery using preoperative CT data of patients. Then the design of the focal osteotomy guide plate, fibular plastic guide plate and fibular reduction guide plate as well as the surgical plan was completed. The navigation registration point was designed by the Accunavi-A navigation system. The surgical guide plates were 3D printed. During the operation, the fibular musculocutaneous flap was harvested to cover the defect after resection of the anterior maxillary lesion with the assistance of the surgical guide plate and navigation technology. The facial appearance and function were followed up after operation.Results:A total of 12 cases, 9 males and 3 females, aged from 33 to 56 years, were included. There were 5 cases of gingival carcinoma, 4 cases of ameloblastoma, 1 case of chondrosarcoma, 1 case of mucoepidermoid carcinoma and 1 case of odontogenic myxoma. The size of the defect after resection was 5 cm×4 cm-6 cm×5 cm. In 12 patients, the focal osteotomy guide plate and fibula plastic guide plate were designed accurately, and the fibular reduction guide plate was successfully placed with accurate navigation and no displacement during the operation. The position of transplanted fibula was consistent with the normal maxillary position. The length of fibula was 8 -10 cm, and the size of the fibular free flap was 5 cm× 4 cm-6 cm×5 cm. All fibular musculocutaneous flaps survived. The patients were followed up for 1 to 72 months, with an average of 24.5 months. The patients had clear pronunciation, no oral and nasal reflux during diets, and presented in good facial appearance. No tumor recurrence occurred in 12 patients during follow-up.Conclusions:It is an accurate and feasible method to repair the anterior maxilla defect with fibula free flap assisted by digital surgical technology. The function of oral and nasal closure and speech was well maintained. A satisfactory facial appearance was obtained.

Objective:To investigate the precise reconstruction method of anterior maxillary defect with fibula musculocutaneous flap assisted by digital surgical technology.Methods:The clinical data of the patients with anterior maxillary defect repaired by fibular free flap from January 2014 to January 2020 in Nanjing Stomatological Hospital were analyzed retrospectively. Mimics 23.0 software was used to perform computer virtual surgery using preoperative CT data of patients. Then the design of the focal osteotomy guide plate, fibular plastic guide plate and fibular reduction guide plate as well as the surgical plan was completed. The navigation registration point was designed by the Accunavi-A navigation system. The surgical guide plates were 3D printed. During the operation, the fibular musculocutaneous flap was harvested to cover the defect after resection of the anterior maxillary lesion with the assistance of the surgical guide plate and navigation technology. The facial appearance and function were followed up after operation.Results:A total of 12 cases, 9 males and 3 females, aged from 33 to 56 years, were included. There were 5 cases of gingival carcinoma, 4 cases of ameloblastoma, 1 case of chondrosarcoma, 1 case of mucoepidermoid carcinoma and 1 case of odontogenic myxoma. The size of the defect after resection was 5 cm×4 cm-6 cm×5 cm. In 12 patients, the focal osteotomy guide plate and fibula plastic guide plate were designed accurately, and the fibular reduction guide plate was successfully placed with accurate navigation and no displacement during the operation. The position of transplanted fibula was consistent with the normal maxillary position. The length of fibula was 8 -10 cm, and the size of the fibular free flap was 5 cm× 4 cm-6 cm×5 cm. All fibular musculocutaneous flaps survived. The patients were followed up for 1 to 72 months, with an average of 24.5 months. The patients had clear pronunciation, no oral and nasal reflux during diets, and presented in good facial appearance. No tumor recurrence occurred in 12 patients during follow-up.Conclusions:It is an accurate and feasible method to repair the anterior maxilla defect with fibula free flap assisted by digital surgical technology. The function of oral and nasal closure and speech was well maintained. A satisfactory facial appearance was obtained.

Objective: To analyze the clinical characters and surgical treatment of primary parapharyngeal space (PPS) tumors. Methods: A total of 23 cases of primary PPS tumors which were treated from November 2011 to December 2017 were included for the retrospective analysis in this study. Results: Twenty-three cases of patients with primary PPS tumors were analyzed in this study. Surgical approach was as follows: transcervial approach applied in 7 cases, transparotid approach in 4 cases, transoral approach in 2 cases, transmandibular approach in 4 cases, and the combined approaches on 6 cases. Besides, among 7 cases with upper PPS tumor, we applied the surgical navigation system in the surgery of 3 cases. The mean surgery duration of these cases, 3.5 h, was shorter than unused ones, while the mean maximum size (MMS) of tumors, 5.7 cm, was also larger. So far, 23 cases had no recurrence and metastasis. The most frequent histopathological type of all the cases was pleomorphic adenoma (8 cases), followed by Schwannoma (5 cases). With an 8-to-72-months follow up, 23 cases had no recurrence, metastasis or death. Conclusions Surgical resection is preferred in the treatment of PPS tumors. In the upper PPS tumor cases, the surgical navigation system could reduce the operative duration significantly and is more suitable for larger tumors.

Surgical resection with adequate margins is an essential component of the treatment for patients with oral squamous cell carcinoma (OSCC). A distance of 5 mm or more between healthy tissue to the tumor front is generally accepted as a safe margin. It is very important for surgeons to precisely evaluate the resection area of tumor both pre- and intra-operatively and try to achieve a safe margin, which will result in a decreased risk of local recurrence. The relationship of surgical margin status to patients' prognosis, and factors which will affect surgical margin distance demand are discussed in this paper. We recommend that adequate margins evaluation should take consideration of many factors such as anatomical location, depth of tumor invasion, pattern of tumor invasion, mucosal dysplasia grade and so on. With the development of molecular biology, surgical margin study at molecular level can give us a new strategy to evaluate its adequacy.

OBJECTIVETo assess the safety and the accuracy of surgical navigation technology in the resection of severe ankylosis of the mandibular condyle with the middle cranial fossa.

METHODSThe CT scan data was transferred to a Windows-based computer workstation, and the patient' s individual anatomy was assessed in multiplanar views at the workstation. In the operation, the patient and the virtual image were matched by individual registration with the reference points which were set on the skull bone surface and the teeth. Then the real time navigation can be performed.

RESULTSThe acquisition of the data sets was uncomplicated, and image quality was sufficient to assess the operative result in three cases. The operations were performed successfully with the guidance of real-time navigation. The application of surgical navigation have enhanced the safety and the accuracy of the surgery for bony ankylosis of temporomandibular joint.

CONCLUSIONSThe application of surgical navigation can improve the accuracy and safety of surgical excision of the ankylosed skull base tissue.

Anatomic Landmarks ; anatomy & histology ; Ankylosis ; surgery ; Humans ; Skull ; diagnostic imaging ; surgery ; Surgery, Computer-Assisted ; methods ; Temporomandibular Joint ; surgery ; Temporomandibular Joint Disorders ; surgery ; Tomography, X-Ray Computed