Myeloid-derived growth factor suppresses VSMC dedifferentiation and attenuates postinjury neointimal formation in rats by activating S1PR2 and its downstream signaling.

Restenosis after angioplasty is caused usually by neointima formation characterized by aberrant vascular smooth muscle cell (VSMC) dedifferentiation. Myeloid-derived growth factor (MYDGF), secreted from bone marrow-derived monocytes and macrophages, has been found to have cardioprotective effects. In this study we investigated the effect of MYDGF to postinjury neointimal formation and the underlying mechanisms. Rat carotid arteries balloon-injured model was established. We found that plasma MYDGF content and the level of MYDGF in injured arteries were significantly decreased after balloon injury. Local application of exogenous MYDGF (50 µg/mL) around the injured vessel during balloon injury markedly ameliorated the development of neointimal formation evidenced by relieving the narrow endovascular diameter, improving hemodynamics, and reducing collagen deposition. In addition, local application of MYDGF inhibited VSMC dedifferentiation, which was proved by reversing the elevated levels of osteopontin (OPN) protein and decreased levels of α-smooth muscle actin (α-SMA) in the left carotid arteries. We showed that PDGF-BB (30 ng/mL) stimulated VSMC proliferation, migration and dedifferentiation in vitro; pretreatment with MYDGF (50-200 ng/mL) concentration-dependently eliminated PDGF-BB-induced cell proliferation, migration and dedifferentiation. Molecular docking revealed that MYDGF had the potential to bind with sphingosine-1-phosphate receptor 2 (S1PR2), which was confirmed by SPR assay and Co-IP analysis. Pretreatment with CCG-1423 (Rho signaling inhibitor), JTE-013 (S1PR2 antagonist) or Ripasudil (ROCK inhibitor) circumvented the inhibitory effects of MYDGF on VSMC phenotypic switching through inhibiting S1PR2 or its downstream RhoA-actin monomers (G-actin) /actin filaments (F-actin)-MRTF-A signaling. In summary, this study proves that MYDGF relieves neointimal formation of carotid arteries in response to balloon injury in rats, and suppresses VSMC dedifferentiation induced by PDGF-BB via S1PR2-RhoA-G/F-actin-MRTF-A signaling pathway. In addition, our results provide evidence for cross talk between bone marrow and vasculature.

Surgical site infection in elderly oral cancer patients: is the evaluation of comorbid conditions helpful in the identification of high-risk ones?

PURPOSE: This study was performed to gain some knowledge on the possible relation between surgical site infection (SSI) and geriatric patients who undergo surgical treatment of oral squamous cell carcinoma and to identify the risk factors in this specific population. PATIENTS AND METHODS: A retrospective study from 2004 through 2010 at the Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine was conducted. The primary outcome variable was the presence of SSIs. Twenty-seven variables of the patients concerning general characteristics, comorbidities, disease information, and treatment options were investigated. A multivariate analysis using logistic regression was implemented to find SSI risk factors. RESULTS: The data of 376 patients (183 men, 48.7%; 193 women, 51.3%) older than 65 years with the diagnosis of oral squamous cell carcinoma were included in the present analysis. In multivariate logistic regression analysis, 6 parameters were identified for a significant and independent association with the development of SSI: body mass index (P = .0086); diabetes (P < .0001); American Society of Anesthesiologists score (P = .0127); Adult Comorbidity Evaluation-27 score (P = .0392); operation time (P = .0003); and reconstruction with pectoralis major myocutaneous flaps or free flaps (P < .0001). CONCLUSIONS: Special attention to SSIs should be given to elderly patients with oral squamous cell carcinoma. The authors advocate a preoperative evaluation of comorbidities and the selection of high-risk elderly patients for a more effective prevention of SSIs.

Transverse cervical artery anterior perforator flap for head and neck oncological reconstruction: Preliminary study.

BACKGROUND: To describe the indications, technique, and our experience in the application of the transverse cervical artery anterior perforator flap (ap-TCAF) for reconstruction of head and neck oncological defects. METHODS: From September 2016 to September 2019, 11 patients underwent surgical treatment for head neck squamous cell carcinoma and were subsequently reconstructed with ap-TCAFs. The clinical details were recorded, and the postoperative appearance and function were analyzed. RESULTS: The ap-TCAF was used to reconstruct intraoral defects in eight patients and to repair an oropharyngeal defect in one patient. In two remaining patients, the ap-TCAF was divided into two to restore defects with both an intraoral and extraoral component. The flap size ranged from 6 × 4 cm to 15 × 9 cm. All flaps healed uneventfully. There was no delayed wound healing or dysfunction at the donor site. CONCLUSIONS: The ap-TCAF is reliable with characteristics making it useful for head and neck oncological reconstruction, especially in male patients.

A novel application of superior thyroid artery perforator flaps for medium-sized intraoral reconstructions: Retrospective analysis of 12 cases.

BACKGROUND: To describe the indications, technique, and preliminary experience in the application of the superior thyroid artery perforator flap (STAPF) for the reconstruction of various medium-sized intraoral defects. METHODS: From September 2018 to September 2019, 12 consecutive cases of oral squamous cell carcinoma underwent reconstruction with a STAPF. Clinical details were collected, and postoperative function was analyzed. RESULTS: The venous drainage of the STAPF is variable with drainage into the internal jugular vein in six cases, into both the internal and external jugular veins in four cases, and into the external jugular vein in two cases. Ten cases were harvested as pedicled flaps, while two cases required a venous anastomosis due to inadequate length of the venous pedicle. Ten flaps survived completely, whereas two flaps had partial necrosis that ultimately resolved with secondary healing. CONCLUSIONS: STAPF is a reliable method for the reconstruction of medium-sized intraoral defects.

Management strategy in patient with familial gigantiform cementoma: A case report and analysis of the literature.

RATIONALE: Familial gigantiform cementoma (FGC) is a rare benign autosomal dominant fibrocemento-osseous lesion generally limited to the facial bones, typically in the anterior portion of the mandible; it is often associated with abnormalities of the long bones and prepubertal pathologic fractures. Owing to the small number of such patients, a uniform treatment criterion has not been established. This paper presents a patient with FGC who was treated in our department, and offers a systematic review of the patients reported in the literature. Our aim was to explore the treatment strategy for patients with FGC. PATIENT CONCERNS: Our patient, a 13-year-old boy, presented with a painless enlargement of the mandible first noted 2 years earlier. It had grown rapidly over the preceding 8 months, affecting both his appearance and ability to chew. DIAGNOSIS: Based on the pathologic, clinical, and radiographic features, FGC was diagnosed. INTERVENTIONS: Mandibuloectomy was performed. The mandibular defect was immediately reconstructed with his right vascularized iliac crest flap. At the same time, a PubMed search was conducted to identify studies reporting on other patients with FGC. OUTCOMES: A 3-dimensional computed tomography (3D-CT) scan demonstrated appropriate height of the new alveolar bone. Follow-up results showed recovery of the patient's appearance and mandibular function. He was free of recurrence at 4-year follow-up. LESSONS: FGC is a rare benign fibrocemento-osseous lesion of the jaws that can cause severe facial deformity. Incomplete removal leads to more rapid growth of the residual lesion. Therefore, extensive resection is a suitable strategy to avoid recurrence. Defects of the facial bones found intraoperatively should be repaired with resort to an appropriate donor site. However, it is important to be aware that patients with FGC always have concomitant abnormalities of skeletal metabolism and structure, as well as a vulnerability to fractures of the long bones of the lower extremity. Therefore, the optimal management strategy should include a review of treatment options for other patients as reported in the literature. An optimal protocol can not only provide sufficient high-quality bone suitable for the reconstruction of bone defects, but also minimize complications and maximize quality of life.

[Clinicopathological features of carcinosarcoma in oromaxillofacial head and neck region].

PURPOSE: To analyze the clinical features, histopathological features, treatment and prognosis of carcinosarcoma in oromaxillofacial head and neck region. METHODS: The clinical and histopathological data of 10 cases with carcinosarama were collected from database of Shanghai Ninth People's Hospital and further analyzed. RESULTS: A total of 10 cases (8 males and 2 females) of carcinosarcoma were collected and analyzed. The age of patients ranged from 20 to 81 years (mean: 44, median:45.5). The tumor size was related to the primary site. The main clinical manifestations indicated rapid increase of foreign body sensation or mass, even feeling of pain. Pathologic examination confirmed the presence of carcinoma and sarcomatoid stroma. Carcinosarcoma had low incidence and was easily misdiagnosed. Diagnosis depended on pathologic examination especially immunohistochemistry. The prognosis was poor, and 5 year survival rate was 50%. CONCLUSIONS: Diagnosis to carcinosarcoma depends on pathological examination after operation. Complete resection + free flap transplantation + postoperative radiotherapy and chemotherapy are conventional treatment.

Head and neck inflammatory myofibroblastic tumor (IMT): evaluation of clinicopathologic and prognostic features.

Owing to rarity and awareness deficiency towards inflammatory myofibroblastic tumor (IMT), we sought to review on its clinicopathological features; arising awareness to achieve early diagnosis; exploring prognostic factors and then establishing a treatment protocol. Retrospective study was performed on patients with histological proven IMT between January 2003 and December 2010. Their demographic data, clinical and histological presentations were recorded. Overall survival (OS) and progression-free-survival (PFS) were estimated via Kaplan-Meier method. Cox regression model was applied to determine the significant of prognostic factors. Logistic regression model was established to predict the probability of relapse. A total of 28 patients. Five-year PFS was 65%. Surgical margins primarily and independently determined the survival, followed by size, pseudocapsule of the lesion, intra-lesional necrosis and lastly Ki-67 and ALK overexpression. Logistic model in prediction of relapse was established, with the formula as probability of relapse = 1/(1 + e(-z)) where e = exponential function, z = constant value (3.9) + B*margin + B*size + B*immunohistochemical expression + B*pseudocapsule + B*intra-lesional necrosis. Immunohistochemical overexpression was significant if Ki-67 was strongly expressed with a conditioned ALK overexpression simultaneously. Staining intensity must be at least moderate for those ALK nuclear staining was less than 25%. Weak ALK staining intensity is only significant if nuclear staining was more than 25%. Diagnosis of IMT is achieved via exclusion. Radical resection and obtaining negative margins remains the mainstay of treatment. Both high and moderate-risk groups required post-operative radiotherapy. In low-risk group, post-operative radiotherapy was recommended if the lesion is larger than 5 cm in diameter with a conditioned ALK & Ki-67 overexpression.

Synovial sarcoma involving skull base--a retrospective analysis of diagnosis and treatment of 21 cases in one institution.

To retrospectively review the diagnosis and treatment outcomes of 21 diagnosed with synovial sarcoma (SS) extending to skull base region and identify prognostic factors for local recurrence and distant metastasis. The clinical and pathological records of 21 synovial sarcoma cases involving skull base treated at Department of Oral and Maxillofacial Surgery, Affiliated to Ninth People's Hospital, Shanghai Jiao Tong University, from 2003 to 2008 were reviewed. Parameters including clinical, radiographic, histological findings, and treatment modalities were analyzed. Prognostic factors influencing overall survival, local recurrence, and metastasis were identified. Categorical variables were compared between groups for local recurrence and distant metastasis by using 2-tailed Fisher exact test. The sample consisted of 8 males and 13 females with a median age of 23. 42.9% of cases showed skull base bone erosion with 9.5% of cases presenting intracranial tumor extension. 52.4% of cases died from recurrence or metastasis with a median survival time of 11 months. Orbital involvement, perineural and cranial invasion along with other factors were statistically significant for their impact on overall survival. Local recurrence was associated with tumors located in the infratemporal space (p=0.01), perineural invasion (p=0.001), pathological grade 3 (p=0.005), and tumor size >5 cm (p=0.008). The aggressive behavior of skull base SS and its close proximity to vital structures make the diagnosis and management a challenge. The study reported high local recurrence rates despite surgical and postoperative radiotherapy. Adjuvant chemotherapy did not seem to affect distant metastasis rates.

[Application of serum tumor markers and support vector machine in the diagnosis of oral squamous cell carcinoma].

PURPOSE: To investigate the clinical application value of serum tumor markers detection combined with support vector machine (SVM) model in the diagnosis of oral squamous cell carcinoma. METHODS: Serum levels of neuron-specific enolase (NSE), cancer antigen 242 (CA242), cancer antigen 19-9 (CA199), carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), cancer antigen 72-4 (CA724), cancer antigen 21-1 (CA211) and alpha fetoprotein (AFP) were detected with enzyme-linked immunosorbent assay (ELISA) and time-resolved fluoroimmunoassay (TRFIA) in 163 oral squamous cell carcinoma patients and 160 healthy persons. All the data was analyzed with SVM; the SVM models for diagnosis of oral squamous cell carcinoma were created, trained and validated by cross validation. RESULTS: Among the 163 oral squamous cell carcinoma patients, there were 128 males and 35 females with the male-to-female ratio of 3.66:1; the age ranged from 30 to 85 years old with a mean age of 59.3 years old; according to the primary site of tumor, 72 cases in tongue, 34 in gingiva, 22 in buccal mucosa, 15 in palatal mucosa, 13 in floor of mouth, 4 in lip and 3 in retromolar region; according to the TNM-UICC classification, there were 33 patients at stage T1, 72 at T2, 44 at T3, 14 at T4, 119 at N0, 42 at N1, 2 at N2, 159 at M0, 4 at M1, 27 at clinical stage I, 51 at stage II, 52 at III, and 33 at IV; according to the pathological differentiation grade, 109 tumors were well differentiated, 42 were moderately differentiated and 12 were poorly differentiated. Five serum tumor markers of CA211, CA199, TPA, CA724 and NSE were selected optimally to create the optimal SVM model for diagnosis of oral squamous cell carcinoma. The accuracy, specificity, sensitivity and positive predictive value of the optimal SVM model were 88.54%, 93.13%, 84.05% and 92.57%, respectively. CONCLUSION: From the results, SVM model combined with 5 optimal serum tumor markers is suggested to be used in the diagnosis of oral squamous cell carcinoma. Supported by Shanghai Leading Academic Discipline Project (Grant No.Y0203).