Prognostic role of preoperative D-dimer, fibrinogen and platelet levels in patients with oral squamous cell carcinoma.

BACKGROUND: The relationship between cancer and coagulation has been intensively studied in recent years; however, the effects of coagulation factors on oral squamous cell carcinoma (OSCC) have rarely been reported. This study aimed to investigate the relationship between preoperative D-dimer (DD), fibrinogen (FIB), platelets (PLT) and OSCC, as well as the prognostic value of DD, FIB and PLT in OSCC. METHODS: We retrospectively investigated a total of 202 patients with OSCC treated at Guanghua Hospital of Stomatology, Sun Yat-sen University. Baseline demographic and clinicopathological information as well as both preoperative and postoperative DD, FIB and PLT results were collected from each patient, and patients with primary OSCC were followed up for disease progression, death or the end of the study. The correlations between preoperative DD, FIB, PLT and other clinical features, as well as the therapeutic effect and PFS were analysed statistically, and postoperative DD and surgical parameters were also analysed. RESULTS: Preoperative DD was significantly correlated with T stage, N stage, clinical stage and relapse of OSCC (P = 0.000, 0.001, 0.000 and 0.000, respectively). Univariate Cox regression analyses showed that high preoperative DD predicted poor prognosis in patients with OSCC (HR = 2.1, P = 0.033), while FIB and PLT showed no prognostic values. Postoperative DD was significantly correlated with preoperative DD and surgical type but not the duration of surgery (P = 0.005, 0.001 and 0.244, respectively). CONCLUSION: In this study, we suggested that high preoperative DD level may serve as an indicator for synchronous neck dissection in patients with T1, 2 OSCC, and the elevated DD level might be the marker of disease progression in patient follow up.

Interaction of cancer cell-derived Foxp3 and tumor microenvironment in human tongue squamous cell carcinoma.

The forkhead transcription factor, Foxp3, has been proved essential for differentiation and activation of regulatory T cells (Tregs). Recently, Foxp3 expression in tumor cells (cancer cell-derived Foxp3) has gained increasing interest, but the function has yet to be confirmed. In the current investigation, we identified the interaction of cancer cell-derived Foxp3 and tumor microenvironment in human tongue squamous cell carcinoma(TSCC) by various in vitro methods. We detected cancer cell-derived Foxp3 was closely associated with the infiltration of Foxp3 + lymphocytes in TSCC lesions using immunohistochemical staining. The cytokines secretion (IFN-γ, TGFß, IL-2, IL-6, IL-1ß, IL-10, IL-8, IL-17, IL-23) of PBMC and differentiation of CD4 +T cells were modulated by the expression of Foxp3 in TSCC, shown by ELISA and flow cytometry. As feedback, increasing TGFß and decreasing IL-17 further up-regulated cancer cell-derived Foxp3. Furthermore, CHIP on chip assay showed that both TGFß and IL-17 decreased the number of Foxp3-binding genes in TSCC. GO and pathway analysis suggested that, treated with TGFß or Th17, Foxp3-binding genes were inclined to the negative regulation of TGFß signal pathway. Taken together, this study showed cancer cell-derived Foxp3 contributed to Tregs expansion in TSCC microenvironment with positive and negative feedbacks.

Marsupialization of mandibular cystic ameloblastoma: Retrospective study of 7 years.

BACKGROUND: This retrospective study investigated the reduction rate and speed of shrinkage after marsupialization in mandibular cystic ameloblastoma and clarified whether marsupialization is appropriate for unicystic ameloblastoma and multicystic ameloblastoma. METHODS: Sixty-three patients with mandibular cystic ameloblastoma were initially treated with marsupialization. Premarsupialization and postmarsupialization panoramic radiographs were reviewed for reduction rate and speed of shrinkage, and then were evaluated with age, sex, tumor location, and tumor type. RESULTS: The overall recurrence rate was 4.5% (2/44). The average reduction rate after marsupialization was 65.6%. No significant difference was found between unicystic ameloblastoma and multicystic ameloblastoma in reduction rate. The speed of shrinkage of unicystic ameloblastoma was significantly faster than that of multicystic ameloblastoma (P < .05). Similarly, patients with multicystic ameloblastoma had longer marsupialization periods than those with unicystic ameloblastoma (P < .05). CONCLUSION: Marsupialization is effective in reducing tumor size for both unicystic ameloblastoma and multicystic ameloblastoma. Marsupialization plus second-stage curettage is recommended as the primary treatment for mandibular cystic ameloblastoma.

Zoledronate suppressed angiogenesis and osteogenesis by inhibiting osteoclasts formation and secretion of PDGF-BB.

PURPOSE: Bisphosphonates related osteonecrosis of jaw (BRONJ) is a severe complication of systemic BPs administration, the mechanism of which is still unclarified. Recently, platelet-derived growth factor-BB (PDGF-BB) secreted by preosteoclasts was reported to promote angiogenesis and osteogenesis. This study aimed to clarify whether bisphosphonates suppressed preosteoclasts releasing PDGF-BB, and whether the suppression harmed coupling of angiogenesis and osteogenesis, which could contribute to BRONJ manifestation. METHODS AND RESULTS: Zoledronate significantly inhibited osteoclast formation by tartrate-resistant acid phosphatase (TRAP) staining and PDGF-BB secretion tested by ELISA. In line with decreasing secretion of PDGF-BB by preosteoclasts exposed to zoledronate, conditioned medium (CM) from the cells significantly induced less migration of endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) compared to CM from unexposed preosteoclasts. Meanwhile, angiogenic function of EPCs and osteoblastic differentiation of MSCs also declined when culturing with CM from preosteoclasts treated by zoledronate (PZ-CM), evidenced by tube formation assay of EPCs and alkaline phosphatase activity of MSCs. Western blot assay showed that the expression of VEGF in EPCs and OCN, RUNX2 in MSCs declined when culturing with PZ-CM compared to CM from preostoeclasts without exposure of zoledronate. CONCLUSION: Our study found that zoledronate was able to suppress preosteoclasts releasing PDGF-BB, resulting in suppression of angiogenesis and osteogenesis. Our study may partly contributed to the mechanism of BRONJ.

Distribution and significance of interstitial fibrosis and stroma-infiltrating B cells in tongue squamous cell carcinoma.

Inflammation and desmoplasia are frequently identified in the tumor microenvironment, and have been demonstrated to be effective modulators of malignant biological events. However, the mechanisms by which the inflammatory microenvironment and interstitial fibrosis interact with one another remain to be elucidated. The present study aimed to investigate the degree of inflammation and interstitial fibrosis in tongue squamous cell carcinoma (TSCC), and how this acts to affect the outcome of TSCC. Tissue samples from 93 cases of TSCC and paired tumor-adjacent non-neoplastic tongue epithelium, as well as 14 cases of epithelial dysplasia, were used. Interstitial collagen fibers were assessed using Masson's trichrome stain. Immunohistochemical identification of cancer-associated fibroblasts (CAFs) and stroma-infiltrating B cells was performed via detection of α-smooth muscle actin (SMA), vimentin, desmin and cluster of differentiation 19 (CD19). The clinicopathological significance and overall survival of the TSCC patients were statistically analyzed. Regularly distributed CAFs and CD19+ B cells were identified in the TSCC stroma, whereas no CAFs or CD19+ B cells were observed in epithelial dysplasia samples or paired tumor-adjacent non-neoplastic tongue epithelium samples. The distribution of interstitial collagen fibers and CAFs was closely associated with the tumor stage of the primary cancer, and high levels of CD19+ B cells together with low CAF infiltration were identified to be associated with favorable prognosis in TSCC. In conclusion, the inflammatory and interstitial fibrotic microenvironments coexist in TSCC, and each has specific effects on disease outcome, individually or perhaps collectively. However, it remains to be determined exactly how the microenvironments affect one another in TSCC.

Maxillary reconstruction assisted by preoperative planning and accurate surgical templates.

OBJECTIVE: Surgical reconstruction of maxilla is technically challenging and time consuming. The study reports a new method of maxillary reconstruction assisted by preoperative surgical simulation and accurate transferring templates. STUDY DESIGN: Six patients requiring maxillary reconstruction were enrolled in our study. Templates of maxillary resection, fibula cutting, and positioning were designed based on computed tomography (CT) data and fabricated via rapid prototyping technique. Resection, fibula cutting, and positioning were performed according to the templates. Accuracy was evaluated by measuring deviation, performed by superimposing preoperative planning and postoperative maxilla. RESULTS: The surgery was performed faithfully to the preoperative planning. The facial contour was satisfied. Postoperative CT scans showed high accuracy of the surgical implementation. The average central point deviation, maximum deviation, and rotation were 0.58 mm, 1.53 mm, and 6.0°, respectively. CONCLUSION: With preoperative surgical simulation and templates, maxillary reconstruction can be performed accurately.

CD19(+)IL-10(+) regulatory B cells affect survival of tongue squamous cell carcinoma patients and induce resting CD4(+) T cells to CD4(+)Foxp3(+) regulatory T cells.

OBJECTIVES: Increase of regulatory T cells (Tregs) in the tumor microenvironment predicts worse survival of patients with various types of cancer including tongue squamous cell carcinoma (TSCC). Recently, the cross-talk between Tregs and regulatory B cells (Bregs) has been shown in several tumor models. However the relevance of Bregs to tumor immunity in humans remains elusive. Our objective was to investigate the distribution and function of Bregs in TSCC microenvironment. MATERIALS AND METHODS: Double staining (Bregs: IL10/CD19 and Tregs: Foxp3/CD4) was performed on tissue sections of 46 TSCC, 20 metastasis lymph nodes, and tumor adjacent normal tissue. Flow cytometry analysis was used to detect the Bregs from magnetic bead-sorted B cells after co-culture with TSCC cell lines, and Tregs from sorted CD4(+)CD25(-) T cells after co-culture with stimulated B cells. RESULTS: The immunohistochemical (IHC) results showed that the frequency of Bregs/CD19(+) B in TSCC (0.80±0.08%) was significantly higher than adjacent normal tissue (0.52±0.04% p<0.01). And the increase of Bregs in TSCC microenvironment was related to Tregs and predicts worse survival in patients. Cytological experiments indicated that frequency of Bregs increased after co-culture with TSCC cell line and that the induced B cells converted CD4(+)CD25(-) T cells into Tregs. CONCLUSION: The increased expression of Bregs in the TSCC microenvironment plays a significant role in the differentiation of resting CD4(+) T cells and influenced the prognosis of TSCC patients.

Genome-wide analysis of cancer cell-derived Foxp3 target genes in human tongue squamous cell carcinoma cells.

The forkhead transcription factor Foxp3 is essential for differentiation and activation of regulatory T cells (Tregs), and used to be regarded as specific transcription factor of Tregs. In recent years, Foxp3 expression in tumor cells (cancer cell-derived Foxp3) has gained great interest, but its function and molecular mechanisms remain incompletely understood. In the present study, we detected dynamic nuclear translocation of Foxp3 in TSCC cells using immunofluorescent staining. Then we performed a genome-wide analysis of Foxp3 in TSCC cells using a combination of ChIP-on-chip and whole-genome microarray assays. We also compared Foxp3 biding sites in TSCC cells with the known binding sites in human Tregs to show the differences in transcriptional regulation profile. Results indicate that Foxp3 in TSCC cells has distinct biological functions compared with that in Tregs. Cancer cell-derived Foxp3 directly regulates the transcription of genes that affect certain internal biological processes of TSCC cells, and indirectly influences the extracellular microenvironment. This study reveals the relationship between direct and indirect targets genes of Foxp3 in TSCC cells and provide molecular basis of cancer cell-derived Foxp3 function.

Sialoendoscopic management of submandibular gland obstruction caused by intraglandular foreign body.

OBJECTIVE: Submandibular gland obstruction caused by foreign body is relatively uncommon. We discuss the diagnosis and management of foreign body-induced submandibular sialadenitis by an illustrative case report and review of the literature. STUDY DESIGN: We report a case of a patient who suffered from obstructive submandibular sialadenitis caused by an intraglandular fish bone, indicating the benefits of sialoendoscopy in diagnosis and treatment of such diseases. A search of the Medline database (from 1967 to February 2011) for foreign body-caused submandibular sialadenitis was performed. RESULTS: The clinical outcome was satisfactory during a 14 months' follow-up, with no evidence of recurrence. Literature review showed that obstructive submandibular sialadenitis originating from a foreign body is relatively rare, and successful removal of an intraglandular foreign body with gland preservation had never been reported before. CONCLUSIONS: Sialoendoscopy can be served as an organ-preserving approach for diagnosis and treatment of foreign body-induced obstructive salivary diseases.