Hanguang Zhu

CCND1 as a predictive biomarker of neoadjuvant chemotherapy in patients with locally advanced head and neck squamous cell carcinoma.

Background Cyclin D1 (CCND1) has been associated with chemotherapy resistance and poor prognosis. In this study, we tested the hypothesis that CCND1 expression determines response and clinical outcomes in locally advanced head and neck squamous cell carcinoma (HNSCC) patients treated with neoadjuvant chemotherapy followed by surgery and radiotherapy. Methodology and Findings 224 patients with HNSCC were treated with either cisplatin-based chemotherapy followed by surgery and radiotherapy (neoadjuvant group, n = 100) or surgery and radiotherapy (non-neoadjuvant group, n = 124). CCND1 expression was assessed by immunohistochemistry. CCND1 levels were analyzed with chemotherapy response, disease-free survival (DFS) and overall survival (OS). There was no significant difference between the neoadjuvant group and non-neoadjuvant group in DFS and OS (p = 0.929 and p = 0.760) when patients treated with the indiscriminate administration of cisplatin-based chemotherapy. However, in the neoadjuvant group, patients whose tumors showed a low CCND1 expression more likely respond to chemotherapy (p<0.001) and had a significantly better OS and DFS than those whose tumors showed a high CCND1 expression (73% vs 8%, p<0.001; 63% vs 6%, p<0.001). Importantly, patients with a low CCND1 expression in neoadjuvant group received more survival benefits than those in non-neoadjuvant group (p = 0.016), however patients with a high CCND1 expression and treated with neoadjuvant chemotherapy had a significantly poor OS compared to those treated with surgery and radiotherapy (p = 0.032). A multivariate survival analysis also showed CCND1 expression was an independent predictive factor (p<0.001). Conclusions This study suggests that some but not all patients with HNSCC may benefit from neoadjuvant chemotherapy with cisplatin-based regimen and CCND1 expression may serve as a predictive biomarker in selecting patients undergo less than two cycles of neoadjuvant chemotherapy.

Experimental Study on Reconstruction of Segmental Mandible Defects Using Tissue Engineered Bone Combined Bone Marrow Stromal Cells With Three-dimensional Tricalcium Phosphate

Reconstructive procedures of segmental mandible defects often require bone graft harvesting, which results in donor site morbidity; the use of tissue-engineered bone might mitigate this problem. The aim of the present experimental pilot study was to produce three-dimensional (3D) autologous tissue-engineered constructs that combine autogenous cultivated bone marrow stromal cells with beta-tricalcium phosphate to reconstruct segmental mandible defects without donor site morbidity. Bone marrow stromal cells were isolated from a dogs caput femoris. After differentiation and proliferation in vitro, the cells were seeded into a 3D beta-tricalcium phosphate scaffold. The constructs were incubated under osteogenic culture conditions for 5 days. Segmental defects of 30 mm length were created unilaterally in the mandibles of the animals. Reconstruction was performed using the construct in three dogs and the scaffold only in three dogs as a control group. The specimens were retrieved 3 months later, and the reconstructed areas were processed for gross observation, radiographic examination, 3D computed tomographic (CT) imaging, biomechanical evaluations, and histologic observation. The construct implanted group (n = 3) showed an average height of the reconstructed area of 18.54 mm and the control group 9.16 mm (P < 0.05). Higher radiodensity was present in the construct group than in the control group, as shown by radiograph. 3D CT imaging showed nearly two-thirds absorption of the reconstructed area in the control group. The biomechanical examination of the construct and control groups showed a compression strength of 102.77 N and 42.90 N and stress of 3.504 N/mm2 and 1.930 N/mm2, which demonstrates significant difference. Histologic micrographs showed new bone formation in the scaffolds in central sections of the defects in the construct group 3 months later, with osteoblast seams, osteoclastic resorption, and cartilage formation. The construct of morphologic, 3D beta-tricalcium phosphate scaffold seeded, autologous bone marrow stromal cells ensure bone formation and vascularization throughout the procedure of mandible segmental defect reconstruction, closely resembling how tissue engineering would be used to reconstruct a segmental mandible defect in the clinical setting.

Clinical analysis of Castleman disease (hyaline vascular type) in parotid and neck region

OBJECTIVE The aim of this study was to analyze a single institutions experience in clinical diagnosis, treatment, and prognosis of Castleman disease (hyaline vascular type) in the parotid and neck region. STUDY DESIGN From 2004 to 2008, a total of 10 consecutive patients with Castleman disease (hyaline vascular type) in the parotid and neck region underwent surgery were included in this retrospective study. The preoperative examinations, clinical diagnosis, surgical treatment, and prognosis were recorded and analyzed. RESULTS Of the 10 patients, 4 were males and 6 female; their age ranged from 13 to 54 years with a mean of 26.6 years. The lesion occurred in the parotid region in 3 patients, in the neck region in 5 patients, and in both the parotid and neck regions in 2 patients. Their course of disease ranged from 3 months to 48 months with a mean of 12.5 months; 70% of the patients (7 out of 10) had a course of disease of <12 months. The patients always had no obvious complaint, and the laboratory examinations were almost within the normal limits. Magnetic resonance imaging/angiography were valuable on clinical diagnosis and differential diagnosis. All patients underwent surgical removal of the masses completely. During the follow-up period, which ranged from 9 months to 60 months with a mean of 38.9 months, no recurrence of the lesion occurred, and the quality of life of each patient was good. CONCLUSIONS Castleman disease (hyaline vascular type) in the parotid and neck region is rare, with clinical manifestation and physical examination the same as benign lesions. There is no specific indication in the laboratory tests and imaging examinations; however, magnetic resonance imaging/angiography has potential value on clinical diagnosis and differential diagnosis. Surgical resection is the choice of treatment with good prognosis.

Dose Dependent Activation of Retinoic Acid-Inducible Gene-I Promotes Both Proliferation and Apoptosis Signals in Human Head and Neck Squamous Cell Carcinoma

The retinoic-acid-inducible gene (RIG)-like receptor (RLR) family proteins are major pathogen reorganization receptors (PRR) responsible for detection of viral RNA, which initiates antiviral response. Here, we evaluated the functional role of one RLR family member, RIG-I, in human head and neck squamous cell carcinoma (HNSCC). RIG-I is abundantly expressed both in poorly-differentiated primary cancer and lymph node metastasis, but not in normal adjacent tissues. Activation of RIG-I by transfection with low dose of 5′-triphosphate RNA (3p-RNA) induces low levels of interferon and proinflammatory cytokines and promotes NF-κB- and Akt-dependent cell proliferation, migration and invasion. In contrast, activation of RIG-I by a high dose of 3p-RNA induces robust mitochondria-derived apoptosis accompanied by decreased activation of Akt, which is independent of the interferon and TNFα receptor, but can be rescued by over-expression of constitutively active Akt. Furthermore, co-immunoprecipitation experiments indicate that the CARD domain of RIG-I is essential for inducing apoptosis by interacting with caspase-9. Together, our results reveal a dual role of RIG-I in HNSCC through regulating activation of Akt, in which RIG-I activation by low-dose viral dsRNA increases host cell surviral, whereas higher level of RIG-I activation leads to apopotosis. These findings highlight the therapeutic potential of dsRNA mediated RIG-I activation in the treatment of HNSCC.

Multicentric Gorham's Disease in the Oral and Maxillofacial Region: Report of a Case and Review of the Literature

Gorham’s disease, also known as massive osteolysis, Gorham-Stout syndrome, vanishing bone disease, and phantom bone disease, is a rare disease characterized by progressive osteolysis and proliferation of fibrous connective tissue similar to that of vascular malformations. It was first described by Jackson in 1838 and characterized pathologically by Gorham and Stout in 1955. It is more common in young adults with no significant gender difference and affects mainly the pelvis, humerus, and axial skeleton. There are 2 types of Gorham’s disease, monocentric and multicentric. The multicentric type has a feature of “skip lesions,” with the lesions skipping anatomic boundaries, excluding the lesions spreading along contiguous structures. To the best of our knowledge, only about 50 cases of Gorham’s disease in the oral and maxillofacial region have been reported in the English literature. Most of these lesions are monocentric and located in the mandible; others have been reported in the maxilla, zygoma, orbit, and other structures. Only 9 cases have been reported with multicentric lesions in the oral and maxillofacial region (Table 1). Here we report a new case of multicentric Gorham’s disease in the mandible, maxilla, and zygoma and describe its diagnosis and treatment.

Immediate Reconstruction of Soft Palate Defects After Ablative Surgery and Evaluation of Postoperative Function: An Analysis of 45 Consecutive Patients

PURPOSE The aim of the present study was to estimate the effect of different defect sizes and flaps used on the postoperative soft palate functional outcomes. PATIENTS AND METHODS The study included 45 consecutive patients who were treated by 3 different reconstructive flaps for their soft palate defect. Postoperative speech and swallowing functions were assessed to measure the relationships between the defect size and postoperative function of the soft palate, the different flap reconstructions, and postoperative function. The 1-way analysis of variance test was computed. P < .05 was considered significant. RESULTS The postoperative evaluation revealed that both speech and swallowing functions were normal or near normal in patients with type II defects, but they were poor in the patients with type III and IV defects. No significant changes in postoperative soft palate function using different flap sizes for the same defect type were found. CONCLUSIONS The study results have confirmed that the size of the defect, rather than the type of the flap, will have the most critical influence on soft palate postoperative function. A defect size of 50% or less will have a better outcome than defect sizes greater than 50%.

Clinical management of peripheral ameloblastoma.

Peripheral ameloblastoma is a rare epithelial odontogenic tumor, limited to the soft tissues of the gingiva or oral mucosa. Peripheral ameloblastoma represents approximately 2% to 10% of all ameloblastomas. It is always considered to be benign, but occasionally it may be locally aggressive or with malignant potential. In this article, we report 3 new cases of benign peripheral ameloblastoma and further discuss the clinical management of this disease.

Tongue reconstruction with tongue base island advancement flap.

AbstractReconstruction of a medium-sized defect of the tongue remains a challenge if aesthetic impairment is to be avoided. In this study, 19 tongue base island advancement flaps were developed to reconstruct medium-sized defects after the tongue squamous cell carcinoma ablations: 13 cases were T1N0M0, and 6 cases were T2N0∼1M0. The largest size amounts to 5.4 × 4.8 cm (length × width), with a mean of 4.6 × 4.4 cm. The tongue base island advancement flap reduces the volume of the tongue base without causing function impairment of the tongue. All patients recovered with good objective and subjective speech and swallowing and aesthetics. No patient developed local recurrence or lymphatic metastasis. The technique of tongue base advancement flap is ideal for functional and aesthetic repair of medium-sized tongue defects after cancer ablation.

Gorham disease in the maxilla.

Gorham disease is a rare condition that is characterized by the proliferation of thin-walled vascular channels associated with regional osteolysis. The exact etiology of Gorham disease is unknown. The diagnosis of Gorham disease is based on clinical, radiological, and histological features after excluding osteolysis, which is secondary to other pathologic processes. Those pathologic processes include congenital, metabolic, neoplastic, and immunologic etiologies and infections. The appearance of the disease in the craniofacial region often involves the mandible. In the reported literature (English language only), there is 1 reported case of the disease located in the maxilla alone. In this study, we present another case of Gorham disease that presents in the maxilla of a 37-year-old man.

Clinical Application of the Dorsalis Pedis Free Flap for Reconstruction of Oral Cancer Defects

PURPOSE The purposes of this study were to evaluate the clinical application and efficacy of the dorsalis pedis fasciocutaneous flap in the reconstruction of oral cavity defects and to assess the associated donor-site morbidity. PATIENTS AND METHODS From September 2009 to December 2012, 7 patients with associated oral cavity defects resulting from tumor resection underwent reconstruction with a dorsalis pedis fasciocutaneous flap. Surgical anatomy and harvesting procedure of the dorsalis pedis flap are described. Special consideration was given to the associated donor-site morbidity. RESULTS All flaps survived without any complications. All 7 flaps were based on the dorsalis pedis artery and the greater saphenous vein for perfusion and drainage respectively. In all 7 cases, the donor site was closed with a full-thickness skin graft, with no associated healing complications or functional deficit of the foot. The resulting scar was well hidden in the lower extremity. CONCLUSIONS The dorsalis pedis fasciocutaneous flap is a thin and pliable flap sharing many similarities with the radial forearm flap, thus making it ideal for intraoral reconstruction. Proper intraoperative and postoperative care of the donor site can result in minimal morbidity, as shown in this study. This flap may provide an ideal alternative to the radial forearm free flap, with the added advantages of a well-hidden scar and a high level of patient satisfaction.