Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Objective:To compare the effect of temporal external fixator and digital guide plate in the immediate reconstruction of mandibular defect after segmental mandibulectomy.Methods:The clinical data of all patients who received segmental mandibulectomy and immediate mandibular reconstruction with free vascularized bone graft by a single surgical team in the Department of Oral & Maxillofacial-Head & Neck Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine from August 2016 to December 2017 were retrospectively analyzed. According to different auxiliary methods, the patients were divided into temporal external fixator (TEF) group and computer aided design-manufacture (CAD-CAM) group. The width of mandible, length of mandibular body and vertical dimension of inferior 1/3 face were measured by CT before and one month after surgery, and the difference before and after surgery was calculated to evaluate the surgical effect. SPSS 19.0 was used for statistical analysis, and the data were expressed as Mean ± SD. Independent sample t-test was used for comparison of indexes of surgical time and surgical effect evaluation between the two groups, and P<0.05 indicated statistically significant differences. Results:A total of 29 patients were enrolled, including 13 patients in TEF group, 4 males and 9 females, aged (47.7±14.5) years, including 7 ameloblastomas, 2 squamous cell carcinomas, 2 abnormal proliferation of bone fibers, 1 rhabdomyosarcoma and 1 osteosarcoma. In the CAD-CAM group, there were 16 cases, including 11 males and 5 females, aged (42.4±19.7) years, including 10 ameloblastomas, 3 squamous cell carcinomas, 1 osteoblastoma, 1 otogenic fibromyxoma and 1 osteosarcoma. The bone grafts in 29 patients were all alive, the wounds healed primarily, and the occlusal relationship and facial contour of the patients were fine. After 3 years follow-up, there were no postoperative complications and tumor recurrence. The function of the supply area was not affected. The operative time was (7.12±1.40) h in the TEF group and (4.72±1.10) h in the CAD-CAM group, and the difference between the two groups was statistically significant ( P<0.01). In the TEF group, the difference of the width of mandible, length of mandibular body and vertical dimension of inferior 1/3 face were (1.08±1.12) mm, (2.08±1.61) mm, (1.77±3.15) mm, respectively; CAD-CAM group were (0.88±1.15) mm, (0.94±1.34) mm, (0.87±1.47) mm, respectively, and there was no statistical significance between the two groups ( P>0.05). Conclusions:It took significantly longer to perform immediate mandibular reconstruction assisted by TEF than that assisted by CAD-CAM in surgery, but both groups achieved better surgical results. It is simpler and more effective to use TEF when time is urgent or technology is too limited to carry out preoperative digital design.

Objective:To compare the effect of temporal external fixator and digital guide plate in the immediate reconstruction of mandibular defect after segmental mandibulectomy.Methods:The clinical data of all patients who received segmental mandibulectomy and immediate mandibular reconstruction with free vascularized bone graft by a single surgical team in the Department of Oral & Maxillofacial-Head & Neck Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine from August 2016 to December 2017 were retrospectively analyzed. According to different auxiliary methods, the patients were divided into temporal external fixator (TEF) group and computer aided design-manufacture (CAD-CAM) group. The width of mandible, length of mandibular body and vertical dimension of inferior 1/3 face were measured by CT before and one month after surgery, and the difference before and after surgery was calculated to evaluate the surgical effect. SPSS 19.0 was used for statistical analysis, and the data were expressed as Mean ± SD. Independent sample t-test was used for comparison of indexes of surgical time and surgical effect evaluation between the two groups, and P<0.05 indicated statistically significant differences. Results:A total of 29 patients were enrolled, including 13 patients in TEF group, 4 males and 9 females, aged (47.7±14.5) years, including 7 ameloblastomas, 2 squamous cell carcinomas, 2 abnormal proliferation of bone fibers, 1 rhabdomyosarcoma and 1 osteosarcoma. In the CAD-CAM group, there were 16 cases, including 11 males and 5 females, aged (42.4±19.7) years, including 10 ameloblastomas, 3 squamous cell carcinomas, 1 osteoblastoma, 1 otogenic fibromyxoma and 1 osteosarcoma. The bone grafts in 29 patients were all alive, the wounds healed primarily, and the occlusal relationship and facial contour of the patients were fine. After 3 years follow-up, there were no postoperative complications and tumor recurrence. The function of the supply area was not affected. The operative time was (7.12±1.40) h in the TEF group and (4.72±1.10) h in the CAD-CAM group, and the difference between the two groups was statistically significant ( P<0.01). In the TEF group, the difference of the width of mandible, length of mandibular body and vertical dimension of inferior 1/3 face were (1.08±1.12) mm, (2.08±1.61) mm, (1.77±3.15) mm, respectively; CAD-CAM group were (0.88±1.15) mm, (0.94±1.34) mm, (0.87±1.47) mm, respectively, and there was no statistical significance between the two groups ( P>0.05). Conclusions:It took significantly longer to perform immediate mandibular reconstruction assisted by TEF than that assisted by CAD-CAM in surgery, but both groups achieved better surgical results. It is simpler and more effective to use TEF when time is urgent or technology is too limited to carry out preoperative digital design.

A biomarker is defined as a biological molecule found in the blood, other body fluids, or tissues that is a sign of normal or abnormal processes or a condition or disease. In cancer research, biomarkers are classified as diagnostic, prognostic, or predictive. The identification and application of biomarkers in clinical practice are important for evaluating their usefulness for clinical diagnosis, treatment and prognostic warning and for determining the biological effects of anti-cancer drugs, and they are currently one of the hottest topics in oncological translational research. Currently, translational research on biomarkers mostly focus on oncological diagnosis and molecular typing, targeted therapy, treatment protocol selection and optimization, prognostic prediction, etc. Here, we review the progress of translational research on treatments based on biomarkers in oral squamous cell carcinoma as well as the clinical application of inhibitors targeting EGFR, PD1, PI3K, WEE1, the Wnt/β-catenin pathway, the SHH pathway, and the ERK pathway. The prospect of research strategies for personalized treatments based on biomarkers in oral squamous cell carcinoma is also discussed.

Objective:To investigate the potential prognostic value of cyclin D1 expression in patients with locally advanced oral squamous cell carcinoma (OSCC) and its relationship with taxol (Docetaxel)/cisplatin plus 5-fluorouracil (TPF) induction chemothera-py. Methods:A total of 256 patients with locally advanced OSCC were selected from Shanghai Ninth People's Hospital of Shanghai Ji-ao Tong University School of Medicine between March 2008 and December 2010 as the objects of study in this prospective randomized clinical trial. The effect of TPF induction chemotherapy was investigated. Immunohistochemical staining against cyclin D1 was per-formed in the pretreatment biopsy specimen of the patients. The relationship between cyclin D1 expression and prognostic data of the TPF induction arm and control arm was analyzed. Results:Cyclin D1 expression was detected in 232 out of the 256 patients. Patients with low cyclin D1 expression showed significantly better overall survival (OS) (P=0.001), disease-free survival (DFS) (P=0.003), lo-coregional recurrence-free survival (LRFS) (P=0.004), and distant metastasis-free survival (DMFS) (P=0.001) than those with high cy-clin D1 expression. No significant differences existed in OS, DFS, LRFS, or DMFS between the patients with TPF induction chemother-apy and the control. Cyclin D1 expression levels were not predictive of the benefit from TPF induction chemotherapy in the overall pop-ulation. However, patients with nodal stage cN2 and high cyclin D1 expression, who were undergoing TPF chemotherapeutic regimen, showed significantly higher OS (P=0.024) and DMFS (P=0.024) than cN2 patients with high cyclin D1 expression but undergoing stan-dard surgical treatment. Conclusion:Cyclin D1 can be used as a prognostic biomarker for patients with locally advanced OSCC. Fur-thermore, cN2 OSCC patients with high cyclin D1 expression can receive long-term benefit from the addition of TPF induction chemo-therapy to standard surgical treatment.

Objective:To analyze survival in patients with advanced oral cancer from prospective clinical trials. Methods:From 2008 to 2010, 256 patients with oral cancer at clinical stage III/IVA were randomly categorized into two groups. Patients in the experi-mental group received neo-adjuvant chemotherapy, surgery, and post-operative radiation, and patients in the control group underwent surgery and post-operative radiation. All patients were routinely followed-up after treatments. Survival was analyzed using Kaplan–Meier method and log-rank test, and differences were considered statistically significant at P value lower than 0.05. Results: Each group was composed of 128 patients. With the median follow-up period of 60 months, the 5-year overall survival rate was 61.7%and the disease-free survival rate was 53.9%. The overall survival rate (P=0.350) and the disease-free survival rate (P=0.160) were not sig-nificantly different between the experimental and control groups. Patients with positive pathological response to neo-adjuvant chemo-therapy exhibited significantly improved overall survival (P＜0.05). Conclusion:Radical surgery should be emphasized to improve the prognosis of oral cancer. Functional reconstruction could also improve the quality of life and survival of patients. Despite that neo-adju-vant chemotherapy could not improve the survival of patients with advanced oral cancer in entirety, it could benefit patients exhibiting positive treatment responses.

OBJECTIVETo use combined comparative genome hybridization (array-CGH) and conventional karyotype analysis to study the relationship between ultrasonographic abnormalities of fetuses and chromosomal aberrations.

METHODSOne hundred twenty two fetuses with ultrasonographic abnormalities in middle and late trimesters suspected with chromosomal abnormalities were collected between March 2012 and February 2013.

RESULTSThe pregnant women had an average age of 31 yr (22-38), among whom 35 were above the age of 35. The average gestational age was 27(+5) weeks (18-37 weeks), and the most common abnormal findings have involved heart, central nervous system and bones. Multiple malformations were found in 49 cases. The success rate of the combined methods was 100%. In 24 (19.7%) of the cases, a chromosomal abnormality was detected. Among all cases, 16 (13.1%) were detected by the combined method (12.3%). Seventeen cases (13.9%) of chromosomal abnormalities and 4 cases (3.3%) of polymorphic variation were detected by karyotype analysis, and 23 cases (8.9%) of abnormalities were detected by array-CGH. Meanwhile, 7 cases (5.7%) of abnormalities were detected by array-CGH, but the results of karyotype analysis were normal. One case (0.8%) with low level of chromosome chimerism detected by the karyotype analysis was missed by array-CGH.

CONCLUSIONThe results suggested that multiple congenital deformity of the fetus has a strong correlation with chromosomal abnormalities. For fetuses with ultrasonographic abnormalities, array-CGH can improve the detection sensitivity of the chromosomal disease.

Adult ; Chromosome Aberrations ; Chromosome Banding ; methods ; Chromosome Disorders ; diagnosis ; embryology ; genetics ; Comparative Genomic Hybridization ; methods ; Female ; Fetal Diseases ; diagnosis ; diagnostic imaging ; genetics ; Gestational Age ; Humans ; Karyotyping ; Male ; Pregnancy ; Prenatal Diagnosis ; methods ; Ultrasonography, Prenatal ; methods ; Young Adult

OBJECTIVETo investigate the expression of cytokeratin 17 (CK17) in oral squamous cell carcinoma (OSCC) as well as its clinical significance.

METHODSDetection of the mRNA level and protein expression of CK17 in the in vitro cellular carcinogenesis model of OSCC, some OSCC cell lines and tissue specimens from 30 primary OSCC patients were performed using real-time polymerase chain reaction (PCR), Western blot and immunohistochemistry, respectively.

RESULTSIncreased CK17 mRNA level was observed in the HB56 and OSC cell lines compared with the HIOEC using real-time PCR technique. Western blot showed increased CK17 protein expression in all the cell lines compared with the HIOEC. Increased CK17 mRNA and immunoreaction levels were also observed in the cancerous tissue specimens from OSCC patients compared with normal adjacent tissues (P<0.01).

CONCLUSIONThe significantly increased CK17 gene may be associated with the tumorigenesis and development of OSCC.

Adult ; Blotting, Western ; Carcinoma, Squamous Cell ; Cell Line ; Cell Line, Tumor ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Keratin-17 ; Male ; Middle Aged ; Mouth Neoplasms ; RNA, Messenger

Adult ; Chondroblastoma ; pathology ; Female ; Humans ; Male ; Mandibular Neoplasms ; pathology ; Middle Aged ; Temporomandibular Joint Disorders ; pathology