Yu Gy

125I seed implant brachytherapy-assisted surgery with preservation of the facial nerve for treatment of malignant parotid gland tumors

The surgical treatment of malignant parotid gland tumors combined with (125)I seed implant brachytherapy and preservation of the facial nerve is described. Tumor and parotid gland resection with preservation of the facial nerve was carried out in 12 patients with malignant parotid gland tumors. (125)I seeds were implanted into the target area intra- or postoperatively. The extent of regional control of the tumor was followed up, and facial nerve function was evaluated. None of the patients had tumor recurrence during the follow-up period of 50-74 months (median follow-up period, 66 months). Facial nerve function had recovered to normal by 6 months postoperatively in all patients. A limited surgical resection combined with (125)I seed implant brachytherapy is therefore considered to be an alternative treatment for local control of malignant parotid gland tumors with preservation of the facial nerve.

Epiregulin promotes migration and invasion of salivary adenoid cystic carcinoma cell line SACC-83 through activation of ERK and Akt.

Hematogenous metastasis is one of the most important factors determining the outcome of the patients with salivary adenoid cystic carcinoma (SACC). In the present study, we examined expression profile of genes in SACC cell lines to look for molecules responsible for its unique metastatic trait. A transcriptomic microarray analysis between the lower lung-metastatic rate cell line SACC-83 and the higher lung-metastatic rate cell line SACC-LM were performed, and eight genes, showed by microarray to be highly expressed in SACC-LM, were picked for validation by quantitative real-time PCR. Among the genes, the expression of epiregulin, a novel member of epidermal growth factor family, was 350-folds higher in SACC-LM than in SACC-83. Accordingly, we examined the effects of epiregulin on migration and invasion in SACC-83 as well as its targeted downstream molecules, and found that epiregulin could promote in vitro migration and invasion in SACC-83. Furthermore, epiregulin not only induced activation of both ERK1/2 and Akt, but also expression of COX-2. In addition, all these effects could be partially blocked by U0126, a specific inhibitor of mitogen-activated protein kinase kinase (MEK or MAPKK), or LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K). Conclusively, the results suggest that epiregulin may play an important role in lung metastasis of SACC.

TGF-β1 Promotes Migration and Invasion of Salivary Adenoid Cystic Carcinoma

Salivary adenoid cystic carcinoma (SACC) is one of the most common subtypes of salivary gland carcinomas and frequently metastasizes to distant organs. However, little is known about the molecular mechanisms that promote SACC metastasis. In this study, we report that transforming growth factor (TGF)-β1 was highly expressed in the highly metastatic SACC-LM cell line as compared with its parental low-metastatic SACC-83 cell line. Exogenous addition of TGF-β1 induced Smad2 phosphorylation and promoted the migration and invasion of SACC-83 cells. Consistently, the inhibition of endogenous TGF-β1 signaling in SACC-LM cells by an inhibitor specific to the type I TGF-β1 receptor (TβRI) suppressed cell migration and invasion. Moreover, we found that TGF-β1 expression was significantly increased in human primary SACC samples with metastasis. Taken together, our results suggest that TGF-β1 may play a crucial role in SACC metastasis.

Clinicopathological study of distant metastases of salivary adenoid cystic carcinoma.

Most studies of the clinicopathological characteristics and prognosis of patients with distant metastasis of salivary adenoid cystic carcinoma (SACC) have used small patient samples. To further explore this issue, a descriptive and prognostic study of 467 patients with SACC who were treated from 1963 to 2009 was conducted at a single institution. One hundred and forty-five patients (31.0%) had distant metastases. At least 20% of patients who presented with the early-stage disease and no recurrence developed distant metastasis. The overall 5-, 10-, and 20-year survival rates were 85.6%, 67.4%, and 50.4%, respectively, for patients without distant metastasis, and 69.1%, 45.7%, and 14.3%, respectively, for patients with distant metastasis. The median survival time after distant metastasis was 36 months (range 1-112 months). The prognosis was similar between patients who received treatment for metastasis and those who did not. Patients who were diagnosed with early-stage disease and without local recurrence of the primary tumours could also develop distant metastases. The biological characteristics of adenoid cystic carcinoma were different from those of squamous cell carcinoma. At present, the effectiveness of treatment for distant metastases is not ideal and further research is needed.

A clinicopathologic study on basaloid squamous cell carcinoma in the oral and maxillofacial region

Basaloid squamous cell carcinoma (BSCC) is a rare distinct variant of squamous cell carcinoma (SCC). To investigate its clinical behavior and prognosis, 15 patients with BSCC in the oral and maxillofacial region were clinically analyzed and compared with 15 patients with conventional SCC matched for site, stage, gender and age. To understand its immunohistochemical features, sections for cytokeratin AE1/AE3, CK 13. CK 7, CK 8, proliferating cell nuclear antigen (PCNA) and p53 were reviewed from 12 patients with BSCC. The rate of cervical lymph node metastasis of BSCC was as high as 67% and that of distant metastasis 13%. The tumor recurrence rate was 33% and the 3-year and 5-year survival rates were 53% and 32%, respectively. For conventional SCC, the cervical lymph node metastasis rate was 27%, that of distant metastasis 7%, tumor recurrence rate was 33%, and 3-year and 5-year survival rates were 80% and 70%, respectively. In most BSCC patients (10/12) the PCNA index was over 50%. Twelve BSCC patients were diagnosed with grade II or III conventional SCC when the original records of the primary diagnosis for the 15 patients with BSCC were reviewed. The biological behavior and prognosis of BSCC are similar to those of poorly differentiated SCC.

Primate mandibular reconstruction with prefabricated, vascularized tissue-engineered bone flaps and recombinant human bone morphogenetic protein-2 implanted in situ

Several studies have validated successful mandibular reconstruction with prefabricated tissue-engineered bone flaps and recombinant human bone morphogenetic protein-2 (rhBMP-2) implanted in situ. Whether rhBMP-2 applied with the prefabrication technique enables faster ossification of mandibular defects than rhBMP-2 applied in situ is unknown. We aimed to compare mandibular reconstruction with prefabricated, vascularized tissue-engineered bone flaps with rhBMP-2 and rhBMP-2 applied in situ in primates (Rhesus monkey). We also compared the use of the carriers demineralized freeze-dried bone allograft (DFDBA) and coralline hydroxyapatite (CHA) for applying rhBMP-2. After computed tomography of the monkey head, custom meshes were made, loaded with rhBMP-2-incorporated DFDBA or CHA, and implanted in the latissimus dorsi muscle. Meanwhile, contralateral segmental mandibular defects were created, and custom meshes loaded with DFDBA, CHA, or rhBMP-2-incooperated DFDBA and CHA were implanted in situ. Thirteen weeks later, the bone flaps with rhBMP-2-incorporated DFDBA or CHA were transferred to repair segmental mandibular defects. The meshes loaded with DFDBA or CHA alone showed no bone regeneration 13 weeks after implantation in latissimus dorsi muscle. Radiography, angiography and histological analysis were used to evaluate the repair and vascularization of the implant. Segmental mandibular defects were successfully restored with prefabricated bone flaps and rhBMP-2-incorporated CHA in situ, but other segmental mandibular defects remained with rhBMP-2-incorporated DFDBA, DFDBA and CHA in situ. Moreover, mandibles reconstructed with rhBMP-2-incorporated CHA bone flaps revealed more regenerated and homogeneous bone formation than did other reconstructions. The study suggested that the prefabrication technique induced better mandibular reconstruction and bone regeneration in quantity and quality.

Primary oncocytic carcinoma of the salivary glands: A clinicopathologic and immunohistochemical study of 12 cases

Oncocytic carcinoma (OC) of salivary gland origin is an extremely rare proliferation of malignant oncocytes with adenocarcinomatous architectural phenotypes, including infiltrative qualities. To help clarify the clinicopathologic and prognostic features of this tumor group, herein, we report 12 OC cases arising from the salivary glands, together with follow-up data and immunohistochemical observations. There were 10 males and 2 females with an age range of 41 to 86 years (median age: 61.3 years). Most occurred in the parotid gland (10/12) with one in the palate and one in the retromolar gland. The tumors were unencapsulated and often invaded into the nearby gland, lymphatic tissues and nerves. The neoplastic cells had eosinophilic granular cytoplasm and round vesicular nuclei with prominent red nucleoli. Ultrastructural study, PTAH, and immunohistochemistry staining confirmed the presence of numerous mitochondria in the cytoplasm of oncocytes. Cellular atypia and pleomorphism varied in the current series. Double nuclei and mitoses were observed in some cases, while one case that showed mild cellular pleomorphism but had local invasion following local recurrence was also identified as an OC. Of the 11 cases with follow-up information, 7 cases had local recurrence. Regional or distant metastases were found in 6 and 4 cases, respectively. Five-year disease-specific survivals were 54.9%. In summary, OC of salivary gland origin is a high-grade tumor, often with local recurrence, regional or distant metastasis, diagnosis of which based on a combination of clinical and histopathological features. Immunohistochemistry for mitochondria is considered as a practical and helpful adjuvant diagnosis. Complete surgical excision is the treatment of choice while the role of radiotherapy or chemotherapy is controversial, and careful follow-up is necessary.

Functional Vanilloid Receptor-1 in Human Submandibular Glands

Vanilloid receptor-1 (VR1) was originally found in the nervous system. Recent evidence indicates that VR1 is also expressed in various cell types. We hypothesized that VR1 exists in the human submandibular gland (SMG) and is involved in regulating salivary secretion. VR1 mRNA and protein were expressed in human SMGs and a human salivary intercalated duct cell line. VR1 was mainly located in serous acinar and ductal cells, but not in mucous acinar cells. Capsaicin, an agonist of VR1, increased intracellular free calcium, enhanced phosphorylation of extracellular signal-regulated kinase, and induced the trafficking of aquaporin 5 (AQP5) from the cytoplasm to the plasma membrane. These effects were abolished by pre-treatment with the VR1 antagonist capsazepine. Furthermore, capsaicin cream applied to the skin covering the submandibular area increased salivary secretion. These findings indicated that a functional VR1 is expressed in the human SMG and is involved in regulating salivary secretion by mediating AQP5 trafficking.

Diagnosis and treatment of epithelial salivary gland tumours in children and adolescents.

In a series of 2,871 epithelial salivary gland neoplasms managed in the Peking University School of Stomatology between 1974 and 1999, 86 arose in children <16 years of age (52 parotid, 12 submandibular gland, 2 sublingual gland, and 20 minor salivary gland). Considerable delay was encountered in diagnosis (benign 24 months and malignant 16 months). In this group of children, 46 tumours (53%) proved to be malignant, with an incidence in the parotid, submandibular, sublingual, and minor salivary glands of 31/52 (60%), 2/12, 0/2, and 13/20 (65%), respectively. Sixty-six of 86 neoplasms (77%) occurred in children between 10 and 16 years of age. Only six neoplasms were encountered in children of 5 years or younger, four of which were high-grade malignant tumours. Benign tumours were successfully treated by local excision with only one recurrence. Of 46 malignant neoplasms, 8 were treated palliatively; of the remainder 8 were lost to follow-up and 2 patients died of their disease.

Effects of Phenylephrine on Transplanted Submandibular Gland

Autotransplantation of the submandibular gland is a potential treatment for severe kerato-conjunctivitis sicca. However, one of the major barriers to this procedure is that secretions from the transplanted gland decrease shortly after the operation, which may lead to obstruction of Wharton’s duct, or even to transplantation failure. Using a rabbit model, we investigated whether phenylephrine could improve the secretion from the transplanted gland. We found that phenylephrine treatment significantly reversed the decrease in salivary secretion after transplantation, enhanced the expressions of α1A-, α1B-, and α1D-adrenoceptor mRNA, and ameliorated atrophy of acinar cells. Furthermore, phenylephrine also induced translocation of aquaporin-5 from the cytoplasm to the apical membrane, and increased the levels of phospho-ERK1/2, ERK1/2, phospho-PKCζ, and PKCζ in the transplanted gland. These results indicate that phenylephrine treatment moderates structural injury and improves secretory function in the transplanted submandibular gland through promoting α1-adrenoceptor expression and post-receptor signal transduction.