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 explore the clinical application pathway of the CT generative adversarial networks (CTGANs) algorithm in mandibular reconstruction surgery, aiming to provide a valuable reference for this procedure.Methods:A clinical exploratory study was conducted, 27 patients who visited the Department of Oral and Maxillofacial Surgery, Xiangya Hospital of Central South University between January 2022 and January 2024 and required mandibular reconstruction were selected. The cohort included 16 males and 11 females, with the age of (46.6±11.5) years; among them, 7 cases involved mandibular defects crossing the midline. The CTGANs generator produced 100 images, and the mean squared error (MSE) was calculated for differences between any two generated images. Preoperative cone-beam CT data from 5 patients were used to construct a labeled test database, divided into groups: normal maxilla, normal mandible, diseased mandible, and noise (each group containing 70 cross-sectional images). The CTGANs discriminator was used to evaluate the loss values for each group, and one-way ANOVA and intergroup comparisons were performed. Using the self-developed KuYe multioutcome-option-network generation system (KMG) software, the three-dimensional (3D) completion area of the mandible under cone-beam CT was defined for the 27 patients. The CTGANs algorithm was applied to obtain a reference model for the mandible. Virtual surgery was then performed, utilizing the fibular segment to reconstruct the mandible and design the surgical expectation model. The second-generation combined bone-cutting and prebent reconstruction plate positioning method was used to design and 3D print surgical guides, which were subsequently applied in mandibular reconstruction surgery for the 27 patients. Postoperative cone-beam CT was used to compare the morphology of the reconstructed mandible with the surgical expectation model and the mandibular reference model to assess the three-dimensional deviation.Results:The MSE for the CTGANs generator was 2 411.9±833.6 (95% CI: 2 388.7-2 435.1). No significant difference in loss values was found between the normal mandible and diseased mandible groups ( P>0.05), while both groups demonstrated significantly lower loss values than the maxilla and noise groups ( P<0.001). All 27 patients successfully obtained mandibular reference models and surgical expectation models. In total, 14 162 negative deviation points and 15 346 positive deviation points were observed when comparing the reconstructed mandible morphology with the surgical expectation model, with mean deviations of -1.32 mm (95% CI:-1.33- -1.31 mm) and 1.90 mm (95% CI: 1.04-1.06 mm), respectively. Conclusions:The CTGANs algorithm is capable of generating diverse mandibular reference models that reflect the natural anatomical characteristics of the mandible and closely match individual patient morphology, thereby facilitating the design of surgical expectation models. This method shows promise for application in patients with mandibular defects crossing the midline.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by the highest mortality among carcinomas. The pathogenesis of PDAC requires elevated autophagy, inhibition of which using hydroxychloroquine has shown promise. However, current realization is impeded by its suboptimal use and unpredictable toxicity. Attempts to identify novel autophagy-modulating agents from already approved drugs offer a rapid and accessible approach. Here, using a patient-derived organoid model, we performed a comparative analysis of therapeutic responses among various antimalarial/fungal/parasitic/viral agents, through which econazole (ECON), an antifungal compound, emerged as the top candidate. Further testing in cell-line and xenograft models of PDAC validated this activity, which occurred as a direct consequence of dysfunctional autophagy. More specifically, ECON boosted autophagy initiation but blocked lysosome biogenesis. RNA sequencing analysis revealed that this autophagic induction was largely attributed to the altered expression of activation transcription factor 3 (ATF3). Increased nuclear import of ATF3 and its transcriptional repression of inhibitor of differentiation-1 (ID-1) led to inactivation of the AKT/mammalian target of rapamycin (mTOR) pathway, thus giving rise to autophagosome accumulation in PDAC cells. The magnitude of the increase in autophagosomes was sufficient to elicit ER stress-mediated apoptosis. Furthermore, ECON, as an autophagy inhibitor, exhibited synergistic effects with trametinib on PDAC. This study provides direct preclinical and experimental evidence for the therapeutic efficacy of ECON in PDAC treatment and reveals a mechanism whereby ECON inhibits PDAC growth.

Objective: To summarize the clinical anatomical features and surgical technique of the submental artery perforator flap (SMAPF), and to evaluate the outcome and value of the flap for oral cavity reconstruction after cancer ablation. Methods: A total of 56 patients with oral cancer were included in this study. The modified SMAPF excluded the anterior belly of the digastric muscle and submental fatty tissue. The primary sites of malignancy were buccal mucosa (n=24), tongue (n=21), mandibular gingiva (n=6), mouth floor (n=3), soft palate (n=2). Results: The flap size varied from 3 cm×5 cm to 5 cm×12 cm. Four flaps presented mild venous congestion, which was salvaged with conservative measures such as acupuncture and blood letting. Overall flap survival rate was 100%. The SMAPF with septocutaneous perforator was used in 49 cases and with musculocutaneous perforator in seven cases. External jugular vein and internal jugular vein provides venous drainage were applied in half cases respectively. All the patients showed a good recovery of tongue mobility and mouth opening with a follow-up of 3-41 months. Local recurrence was detected in one patient 4 months after operation. Conclusions The SMAPF is a reliable flap for oral cavity reconstruction with outstanding functional and aesthetic outcomes.

Many factors contribute to a successful total knee arthroplasty, and postoperative coronal lower limb alignment has always been a focus of joint surgeons. Previous researches have suggested that neutral alignment can bring higher prosthesis survival rate and better knee function. However, the theory has been challenged in recent years.In this article, the author introduces the axis, alignment and osteotomy of total knee arthroplasty briefly and reviews the studies on the neutral alignment and kinematic alignment of recent years in order to provide some advice for the clinical operation.

Objective To evaluate the clinical repair effects of the reconstruction of different vermilion tubercle after primary cleft lip repair.Methods According to the tight lip deformity and dif ferent degrees of defect of the vermilion tubercle and exposing the gums and the crown of the anterior incisors,178 patients after primary repair of the cleft lip from Department of Oral and Maxillofacial Surgery of Xiangya Hospital,Central South University were classified into the tight lip deformity and four grades of whistling deformities.According to different deformities and defects,the different operative techniques were used as follows:classic Abbé flap and modified Abbé flap were used for tight lip deformity;the bilateral advanced myomucosal flaps of lip were used for the grade Ⅰ;modified Abbé flap was used for repairing the grade Ⅱ and the grade Ⅲ whistling deformities;for grade Ⅳ whistling deformity,we mainly used classic Abbé flap.The follow-up after operation was performed,all patient's Cupid's bow,Cupid's bow peak,the vermilion tubercle and the height and width of the upper lip were observed.The scarring of the upper lip was also observed.Results The follow-up after operation was performed from six months to ninteen years,all the 187 patient's anatomical structures of the upper lip were nearly normal after recovery.The all patients showed an obvious Cupid's bow,Cupid's bow peak,the vermilion tubercle and the height and width of the upper lip.The relation of the upper lip and lower lip was harmonious.The scarring of the upper lip was not obvious 2 years after operation.Conclusions The different repair methods are chosen to repair different deformity and defect that has an important clinical value.

BACKGROUND:Fast track surgery, also cal ed enhanced recovery after surgery, is a series of optimal measures adopted during the perioperative period on the basis of evidence-based medicine, to reduce the physical and mental trauma brought to the patient and accelerate their recovery. It has become the research focus of orthopedic clinic as the surgery and anesthesia skil s are improved a lot in recent years, especial y the articular surgery, which has been widely used in clinics. OBJECTIVE:To summarize the clinical study of the application of optimal measures in joint replacement surgery both at home and abroad in recent years. METHODS:The first author searched related articles in PubMed and Chinese Journal Ful-text Database from January 1997 to September 2016. The key words were“joint replacement, enhanced recovery after surgery, multi-mode analgesia, diet management, steroid hormones”. 81 articles were found at last and one monograph was included. RESULTS AND CONCLUSION:(1) We found that the recovery plan reduced the hospital stays of the patients from 4-12 days to 1-3 days, including pre-operative health education, shortening fasting and water-depriving duration before surgery, super-anesthesia before surgery and do not place catheter;adopting general anesthesia and appropriate adductor canal to relieve the pain, and stopping bleeding using tranexamic acid during operation;multi-mode analgesia, faster function exercise after anesthesia recovery, and drinking water in early phase after surgery during the perioperative period of joint replacement surgery conducted by the cooperation of surgeon, anesthetist, nurse and nutritionist. There were no significant improvements of postoperative complications rate and rehospitalization rate. (2) The research found that, enhanced recovery after surgery is suitable for most of the patients receiving joint replacement surgery, including those in advanced age, combined heart and lung disease before surgery, type 2 diabetes and smoking and drinking before surgery.

Objective:To introduce a new style of platysma myocutaneous flap and to evaluate its application value in the restoration of oral-maxiofacial defects.Methods:Platysma myocutaneous flap with apron incision was used for the restoration of oral-maxiofacial defects after oral lesion ablation in 15 cases from January,2014 to September,2015.The platysma muocutaneous flap was harvested with a U shaped apron incision.The skin above the flap pedicle was preserved.The platysma pedicle was widened to ensure the flap survival.All the patients were followed up form 4 to 33 months.Results:Of the 15 platysma myocutaneous flaps,12 survived completely and 3 had partial flap necrosis.The total survival rate of the flaps at the recipient site of buccal mucosa,tongue and alveolar was 8/9,1/3 and 3/3 respectively.Additionally,there were 2 cases of disturbed wound healing in the neck.Except for 1 case of carcinoma of gingiva which had apparent cervical scar and 1 case of tongue carcinoma which had limited tongue mobility,the other cases showed a satisfactory recovery of oral-maxillofacial contour and fucnction.Conclusion:Compared with the traditional platysma myocutaneous flap,the platysma myocutaneous flap with apron incision can provide a larger skin paddle,and is suitable for the restoration of small and medium sized buccal mucosa and alveloar defects,but not for tongue defect.

OBJECTIVEThis study aimed to investigate the value of carbon nanoparticles as lymph node tracers in neck dissection for cN0 lingual squamous cell carcinoma patients.

METHODSNinety-six patients with cN0 lingual squamous cell carcinoma were recruited to undergo surgical treatment were randomly divided into two groups, namely, the carbon nanoparticle-labeled group (the experimental group, 50 cases) and the control group (46 cases). Carbon nanoparticle suspension was injected into the submucosal layer around the site of the primary tumor at three or four points (0.1 mL for each point) 12 h before surgery. Supraomohyoid neck dissection (SOHND, Levels Ⅰ to Ⅲ) or comprehensive neck dissection (CND, Levels Ⅰto Ⅴ) were performed based on the size and location of the primary tumor. All the lymph nodes were dissected and separated from the ex vivo surgical specimens for histopathological evaluation. The number, size, location, and pathological result of all the lymph nodes were compared between the two groups. Statistical analyses were conducted by SPSS 19.0 software.

RESULTSA total of 1 137 lymph nodes were detected in 31 SOHND patients. The average number of lymph nodes detected in the experimental group was (43.79±19.23) /case, which was significantly higher than that in the control group [(30.82±8.77) /case] (P=0.019). Level Ⅲ covered the largest number of lymph nodes in the two groups. However, the number and proportion of lymph nodes found in Level Ⅱ of the experimental group were significantly higher than those of the control group (P=0.000). A total of 3 938 lymph nodes were detected in 65 CND patients. The average number of lymph nodes detected in the experimental group [(66.67±20.02) /case] was larger than that in the control group [(53.03±20.98) /case] (P=0.026). The difference in the lymph node location between the two groups was not statistically significant (P=0.354). In the two neck dissection methods, both the proportion of minute lymph nodes and the accuracy of the detected lymph nodes in the experimental group were significantly larger than those in the control groups (P=0.000). Compared with the control group, more metastases were proven by the carbon nanoparticle-labeled lymph nodes (P=0.000) in the experimental group.

CONCLUSIONSCarbon nanoparticles as lymph node tracers in patients with cN0 lingual squamous cell carcinoma undergoing neck dissection can increase the number of detected lymph nodes, especially the minute nodes. Such nanoparticles can further ensure the thoroughness of neck dissection and the accuracy of clinicopathological stage.

Carbon ; Carcinoma, Squamous Cell ; Humans ; Lymph Nodes ; Lymphatic Metastasis ; Nanoparticles ; Neck ; Neck Dissection ; Otorhinolaryngologic Neoplasms ; Thyroid Neoplasms

Objective To investigate the management of difficult recipient vessel preparation in microsurgical reconstruction for oral and maxillofacial defects with free flaps and to assess the clinical outcome.Methods A total number of 739 patients with oral and maxillofacial defects underwent consecutive free flap reconstruction with 761 free flaps from May,2012 to May,2015.There were 37 patients who could not find or lack of proper recipient vessels for microvascular anastomosis during operation.Among them,22 were recurrent oral cancer after tumor ablation,10 of them undrewent post-operative radiotherapy;5 were second primary oral cancer,7 diagnosed with osteoradionecrosis,and 3 suffered from oral and maxillofacial defect and deformity caused by trauma or inflammation.Forty free flaps including 23 anterolateral thigh flaps (ALT),10 fibular flaps and 7 radial forearm flaps were harvested.Methods and techniques used during the operation,instant patency rate after anastomosis,the overall survival rate of free flaps,and post-operative complications were recorded.Results Ninety-one anastomoses were performed between 87 pairs of vessels in 37 patients.Fifty recepient vessels were located on ipsilateral side of neck,and the most frequently used recipient vessels were those preserved or not being damaged in former operation and radiation,former transferred free flap vascular pedicles and residual ends of the ligated vessels.Thirty-seven recepient vessels were found on the contralateral side of neck.Thirty-one cases of long-pedicle flap harvesting,2 cases of vein and artery grafting,4 cases of vessel transposition,5 cases of phleboplasties,9 cases of end-to-side anastomoses,and 1 case of flow-through technique were applied in recipient vessels preparation alone or in combination.The patency rate of anastomosis during operation was 100％ and the overall survival rate of free flaps was 97.5％.Conclusion Recurrent oral cancer after tumor ablation,second primary oral cancer,osteoradionecrosis and deformity caused by trauma and inflammation are the main reasons of unsuitable recipient vessel conditions in microsurgical reconstruction for oral and maxillofacial defects.Methods including long-pedicle flap harvesting,venous grafting,vessel transposition,phleboplasty,end-to-side anastomosis and flow-through technique applied alone or in combination are still reliable choices for management of neck difficult recipient vessel preparation and anastomosis.