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.

PDGF-BB exhibited therapeutic effects on rat model of bisphosphonate-related osteonecrosis of the jaw by enhancing angiogenesis and osteogenesis.

The mechanism and effective treatment of bisphosphonate-related osteonecrosis of the jaw (BRONJ) are still uncertain. Our previous study revealed that zoledronate (ZOL) preferentially inhibited osteoclasts formation and platelet-derived growth factor-BB (PDGF-BB) secretion, causing suppression of angiogenesis and osteogenesis in vitro. The present study aimed to elucidate whether PDGF-BB had therapeutic effects on rat model of BRONJ by enhancing angiogenesis and angiogenesis. Firstly, rat model of BRONJ was established by ZOL and dexamethasone administration, followed by teeth extraction. The occurrence of BRONJ was confirmed and detected dead bone formation by maxillae examination, micro-CT scan and HE staining (10/10). Compared to control rats (0/10), both angiogenesis and mature bone formation were suppressed in BRONJ-like rats, evidenced by enzyme-linked immunosorbent assay (ELISA) for VEGF (P < 0.01), immunohistochemistry of CD31 (P < 0.05) and OCN (P < 0.01). Moreover, in the early stage of bone healing, the number of preosteoclasts (P < 0.001) and PDGF-BB secretion (P < 0.05) were significantly decreased in bisphosphonates-treated rats, along with the declined numbers of microvessels (P < 0.05) and osteoblasts (P < 0.05). In vitro study, CCK8 assay, alizarin red S staining and western blot assay showed that mandible-derived bone marrow mesenchymal stem cells (BMMSCs) in BRONJ-like rats presented suppressed functions of proliferation, osteogenesis and angiogenesis. Interestingly, recombinant PDGF-BB was able to rescue the impaired functions of BMMSCs derived from BRONJ-like rats at more than 10 ng/ml. Then fibrin sealant with or without recombinant PDGF-BB were tamped into the socket after debridement in BRONJ rats. After 8 weeks, fibrin sealant containing PDGF-BB showed significant therapeutic effects on BRONJ-like rats (bone healing: 8/10 vs 3/10, P < 0.05) with enhancing microvessels and mature bone formation. Our study suggested that the inhibition of angiogenesis and osteogenesis, the potential mechanisms of BRONJ, might partly result from suppression of PDGF-BB secretion in the early stage of bone healing. PDGF-BB local treatment after debridement might avail the healing of BRONJ by increasing angiogenesis and osteogenesis.

[Multidisciplinary team model for patients with oral cancer and systemic diseases: an expert consensus].

Large general hospitals currently play an increasingly important role in the diagnosis and treatment for acute critical patients and difficult diseases because of the development of dual referral system and hierarchical diagnosis, as well as the formation of medical treatment alliance. Patients with oral cancers are often associated with systemic diseases, which increases the complexity of the condition. Thus, meeting the demand through the traditional single medical model is difficult. As such, a multidisciplinary team (MDT) model has been proposed and has achieved a good clinical effect. To standardize the application of this model, we organized an event in which relevant experts discussed and formulated a consensus to provide standardized suggestions on the MDT process and the diagnosis and treatment of common systemic diseases as reference for clinical practice.

Role of craniofacial surgery in oral and maxillofacial tumors involving the skull base: A retrospective analysis of 126 patients.

OBJECTIVES: Oral and maxillofacial tumors involving the skull base (SB) are rare and complex, making treatment difficult and controversial. The purpose of the present study was to evaluate the treatment efficacy of craniofacial surgery (CFS). STUDY DESIGN: Patients who underwent CFS for these tumors between May 2000 and November 2017 were retrospectively analyzed. Clinicopathologic and treatment modality data were collected and follow-up was recorded. Kaplan-Meier and log-rank tests and Cox-regression model were used for survival analysis. RESULTS: In total, 126 patients were enrolled (70 males and 56 females; 97 malignant tumors). Squamous cell carcinoma accounted for the majority of tumors. The lip-submandibular-neck approach was most frequently applied. Through-and-through SB bone or partial dura resection was performed in 42 cases. A pathologic positive margin was found in 18 cases. Of the included patients, 80 underwent simultaneous craniofacial reconstruction. The postoperative complications rate was 11.1%. Estimated 1-year, 3-year, and 5-year overall survival rates were 78.8%, 68.2%, and 54.4% respectively; and the 1-year, 3-year, and 5-year recurrence-free survival rates were 77.4%, 66.8%, and 63.8%, respectively. Multivariate analysis indicated postoperative complications, radiotherapy, recurrence, and metastasis status had a negative impact on survival (P < .05). CONCLUSIONS: Although tumors involving the SB had various clinicopathologic characteristics, with interdisciplinary cooperation, CFS is an optimal option.

Promoted Bone Regeneration by 3D-Printed Porous Scaffolds with the Synergy of a Nanotopological Morphology and Amino Modification.

Three-dimensional (3D)-printed scaffolds have great advantages for bone repair, and the combination of physical and chemical modifications of the surface can improve deficient biological properties to promote bone regeneration. In this study, a nanotopological morphology and an amino group were introduced into scaffold surfaces in sequence by alkaline solution and amination, respectively. The surface properties and the ability for osteogenic induction were investigated. The nanotopological morphology of the surface slightly enhanced the hydrophilic property of the material, while amination obviously increased the hydrophilicity of the surface. The aminated surface improved cell adhesion and proliferation, while the nanotopological morphology was able to facilitate the spread of stem cells, pseudopod extension, and osteogenic differentiation by changing the cell skeleton. The study confirmed that a nanotopological morphology and an amino group can play synergistic roles in improving the osteogenic efficiency and hydrophilicity, which was also confirmed in vivo by showing that effective surface modification of polylactic acid scaffolds enhanced high-quality bone formation, thus demonstrating great potential for clinical applications. The results indicate that scaffolds with the synergy of a nanotopological morphology and amino modification improve the osteogenic induction ability of scaffolds.

Accelerating Bone Healing by Decorating BMP-2 on Porous Composite Scaffolds.

Although artificial polymeric scaffolds act as vital characters in bone repair, their application is limited due to their inferior bioactivity. Herein, osteoinductive poly(ε-caprolactone) (PCL) composite scaffolds were prepared by synchronously enlisting bioactive nanohydroxyapatite (nHA), bioglass (BG), and bone morphogenetic protein-2 (BMP-2), which was bound up with polydopamine (pDA). It was found that pDA deposition not only significantly enhanced hydrophilicity and cell affinity of composite scaffolds but also endowed steady immobilization of BMP-2 with long-term yet sustained release. Compared to pure PCL and PCL/nHA/BG (PHB) scaffolds, the designed PHB-pDA-BMP-2 scaffolds significantly induced the differentiation of bone marrow stromal cells toward an osteogenic lineage. Meanwhile, in vivo examinations revealed the prominent osteogenic capability of PHB-pDA-BMP-2 scaffolds, which enabled complete bone healing of calvarial bone defects in rabbits by 12 weeks. This finding indicates that the developed porous composite scaffolds hold great potential for bone regeneration.

Polydopamine-Assisted Anchor of Chitosan onto Porous Composite Scaffolds for Accelerating Bone Regeneration.

Surface function has an importance for the bioactivity of porous polymeric scaffolds. The goal of the present study is to immobilize highly bioactive chitosan (CS) onto the surface of porous composite scaffolds to accelerate bone regeneration. Porous poly(ε-caprolactone) (PCL)/bioactive glass (BG) composite scaffolds with strong anchor of CS were fabricated via mussel-inspired polydopamine (PDA) coating as a bridging layer. In vitro cell culture showed that firm immobilization of CS onto the composite scaffolds significantly enhanced protein adsorption, cell adhesion, and osteogenic differentiation compared to CS-decorated scaffolds via physical adsorption. In vivo assessments demonstrated that covalent immobilization of CS onto the surface of scaffolds obviously promoted cranial bone regeneration in comparison with the counterparts with physical adsorption of CS. The proposed method offers a feasible and effective means to fabricate artificial bioactive scaffolds for bone tissue engineering application.

[Retracted] Long non­coding RNA MALAT1 interacts with miR­124 and modulates tongue cancer growth by targeting JAG1.

We wish to retract our research article entitled "Long non­coding RNA MALAT1 interacts with miR­124 and modulates tongue cancer growth by targeting JAG1" published in Oncology Reports 37 2087­2094, 2017. Following the publication of this article, it was drawn to our attention that this paper bore numerous similarites with an article published previously in the journal OncoTargets and Therapy. Although all the data reported in our study were original, we recognize that it was not appropriate that we should have modelled our paper on previously published articles as a template on which to base the writing of our paper. Therefore, we have agreed to follow the Editor's recommendation that this paper be retracted from the publication. All the named authors agree to this retraction. We sincerely apologize to the Editor and the readership of the Journal for our action, and regret any inconvenience this has caused. [the original article was published in the Oncology Reports 37: 2087­2094, 2017; DOI: 10.3892/or.2017.5445].

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.

Synergistic effects of ischemic preconditioning and immediate post-conditioning in the protection against ischemia/reperfusion injury in rabbit submandibular glands.

Submandibular gland autotransplantation is an effective approach for treating severe keratoconjunctivitis sicca. However, ischemia/reperfusion (I/R) injury, which inevitably occurs during transplantation, is involved in the hypofunction and structural damage that occur early after transplantation. Therefore, it is critical to identify effective strategies to ameliorate I/R injury in submandibular glands. In this study, we investigated the ability of immediate post-conditioning combined with ischemic preconditioning to attenuate I/R injury. We observed that after I/R injury, the level of reactive oxygen species was increased, inflammatory response was strengthened, and severe apoptosis had occurred. In addition, the salivary flow rate was greatly decreased. However, the pathogenesis of I/R injury was significantly ameliorated by ischemia post-conditioning or ischemia preconditioning treatments. In addition, the combination of ischemia preconditioning and post-conditioning achieved synergistic protective effects against I/R injury compared with ischemia preconditioning or ischemia post-conditioning alone. The secretion function was restored in the combination group. Furthermore, the combination treatment involved the same mechanisms of ischemia preconditioning or ischemia post-conditioning, including suppression of the inflammatory reaction and neutrophil accumulation, attenuation of oxidation stress, and inhibition of apoptosis. In conclusion, the combination of ischemia preconditioning and ischemia post-conditioning treatment is a simple and effective approach for treating I/R injury in submandibular glands.

[Relationship between interleukins in the saliva and oral cavity cancer].

Saliva is being attached great importance for its application in illness diagnosis and have more advantage on the diagnose in oral cavity cancer (OCC). Studies have showed that interleukin (IL) in the saliva could be used as a potential biomarker for OCC diagnosis. Moreover, they have a close connection with tumor genesis, invasion, and metastasis in OCC. Therefore, we reviewed research progress on the relationship between salivary interleukins and OCC.

Microvascular Submandibular Gland Transplantation for Severe Keratoconjunctivitis Sicca: A Single-Institution Experience of 61 Grafts.

PURPOSE: Keratoconjunctivitis sicca (KCS) is a relatively common disease that results in discomfort, tear film instability, visual impairment, and ocular surface damage. Artificial tear substitutes may be suitable for the treatment of mild KCS, but no effective treatment currently exists for severe KCS. Therefore, this study evaluated the effectiveness of autologous microvascular submandibular gland transplantation in the treatment of severe KCS. PATIENTS AND METHODS: A total of 61 eyes (56 patients) with severe KCS were treated with autologous submandibular gland transplantation from June 2002 to June 2017. The cephalic vein or the great saphenous vein was applied to solve the problem of unmatched veins. RESULTS: In 53 cases (53 of 56, 94.6%), 58 glands (58 of 61, 95.1%) were transplanted successfully. The mean Schirmer I test value improved from 0.78 ± 0.84 mm preoperatively to 18.83 ± 5.72 mm in the stable period after transplantation. Epiphora (14 of 58, 24.14%) was the most common complication of this procedure. Other postoperative complications included venous thrombosis (6 of 61, 9.84%), local infection (2 of 58, 3.45%), xerostomia (2 of 53, 3.77%), duct fistula (1 of 58, 1.72%), sialolithiasis (1 of 58, 1.72%), and ranula (1 of 58, 1.72%). CONCLUSIONS: Autologous microvascular submandibular gland transplantation is a credible and effective solution for severe KCS.

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.

Does the Surgery-First Approach Produce Better Outcomes in Orthognathic Surgery? A Systematic Review and Meta-Analysis.

PURPOSE: The surgery-first approach (SFA) in orthognathic surgery, performed without presurgical orthodontic treatment, has gained attention, but the results remain controversial. The purpose of this study was to assess the current evidence on stability, efficacy, and surgical results of SFA versus conventional 3-stage method (CTM) orthognathic surgery. MATERIALS AND METHODS: A comprehensive search in PubMed and Web of Science was conducted. A systematic review and cumulative meta-analysis of all comparative studies were performed to assess the 2 strategies (SFA and CTM) using a random- or a fixed-effects model. Outcomes included treatment duration, postoperative stability, surgical movement, and postoperative occlusion. RESULTS: Ten nonrandomized controlled studies including 513 patients were identified. Compared with CTM, patients in the SFA group benefited from shorter total treatment duration (weighted mean difference [WMD], -5.25; 95% confidence interval [CI], -8.21 to -2.29; P = .0005), similar postoperative stability of the mandible (WMD, 0.35 mm; 95% CI, -0.24 to 0.94; P = .55) and maxilla (WMD, 0.13 mm; 95% CI, -0.35 to 0.60; P = .60), similar surgical movements, and other surgical results. CONCLUSIONS: SFA offers an efficient alternative to CTM with shorter total treatment duration, similar postoperative stability, and other surgical results but longer postoperative orthodontic time.

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.

Long non-coding RNA MALAT1 interacts with miR-124 and modulates tongue cancer growth by targeting JAG1.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long non-coding RNA (lncRNA), was the earliest discovered to be correlated with cancer and contributes to the initiation and development of several types of tumors. Dysregulation of MALAT1 expression is frequently observed in many types of cancer such as gastric cancer, esophageal squamous cell carcinoma and glioma. To date, the role of MALAT1 and the underlying mechanisms in tongue cancer development remain unclear. In the present study, we studied the influence of MALAT1 on tongue cancer cell lines and clinical tongue cancer samples so as to detect its function and the underlying mechanism. In the present study, lncRNA-MALAT1 was specifically upregulated in tongue cancer cell lines and overexpression promoted tongue cancer cell growth by targeting miR-124. Knockdown of MALAT1 suppressed the growth and invasion of human tongue cancer cells and inhibited metastasis in vitro and in vivo. In addition, miR-124-dependent jagged1 (JAG1) regulation was required for MALAT1-induced tongue cancer cell growth. Our data revealed that MALAT1 inhibited tongue cancer cell growth and metastasis through miR-124-dependent JAG1 regulation. In conclusion, we revealed that MALAT1 may play an oncogenic role by increasing proliferation and metastasis of tongue cancer and is a potential therapeutic target in human tongue cancer.

Risk factors and prognosis for salivary gland adenoid cystic carcinoma in southern china: A 25-year retrospective study.

Adenoid cystic carcinoma (ACC) is characterized by slow growth, frequent local recurrences, and high incidence of distant metastasis (DM). The aim of this study was to evaluate predictive factors for local-regional (LR) recurrence, DM, and survival in ACC.A retrospective review of the medical records for patients with salivary glands ACC from 1990 to 2015 was performed. The clinical parameters were assessed to identify correlations with the development of LR recurrence, DM, and survival of these patients.Among 228 patients who underwent surgery as definitive treatment, 210 (92.1%) were followed up in the study. DM was detected in 64 (30.5%) patients, LR recurrence was detected in 58 (27.6%) patients. The estimated 5, 10, and 15-year overall survival rates were 84.7%, 70.8%, and 34.0%, respectively. Multivariate analysis revealed that the presence of lymphovascular invasion and a high T classification were very strong adverse factors, which independently influenced LR recurrence, DM, and survival of ACC patients. Positive/close margin and N+ status were independent risk factors for DM and LR recurrence, respectively. Survival of ACC patents was also affected by tumor location.Presence of lymphovascular invasion and a high T classification were very strong adverse factors and independent predictors for ACC patients' prognosis, which influenced LR control, DM control, and survival.

Association between high expression of phosphorylated Akt and mammalian target of rapamycin and improved survival in salivary gland adenoid cystic carcinoma.

BACKGROUND: Previous genomic studies revealed phosphotidylinositol-3-kinase (PI3K)/Akt pathway mutation in human salivary gland adenoid cystic carcinoma (ACC). No validation of its prognostic value has been reported. METHODS: P-Akt, pan-Akt, phosphorylated-mammalian target of rapamycin (p-mTOR), PI3K, and insulin-like growth factor-1 receptor beta (IGF-1Rß) were detected on 120 salivary gland ACC/adjacent salivary gland pairs immunohistochemically and were correlated with clinicopathological data. RESULTS: Expression of cytoplasmic and nuclear p-Akt, cytoplasmic p-mTOR, nuclear pan-Akt, and nuclear IGF-1Rß were higher in ACC than in adjacent salivary glands. P-Akt, p-mTOR, PI3K, and IGF-1Rß expression were correlated with one another in both cytoplasm and nucleus. Low p-mTOR expression in both subcellular compartments was associated with locoregional recurrence, poor disease-free survival (DFS), and overall survival (OS). Low nuclear p-Akt (Ser473) and p-mTOR expression were independent predictors for poor OS and DFS, respectively. CONCLUSION: High level of Akt/mTOR activation in ACC is correlated with a significantly improved survival. P-mTOR and nuclear p-Akt are prognostic biomarkers of salivary gland ACC. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1145-1154, 2017.

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.

Is Pilocarpine Effective in Preventing Radiation-Induced Xerostomia? A Systematic Review and Meta-analysis.

PURPOSE: To evaluate the efficacy of concomitant administration of pilocarpine on radiation-induced xerostomia in patients with head and neck cancers. METHODS AND MATERIALS: The PubMed, Web of Science, Cochrane Library, and ClinicalTrials were searched to identify randomized, controlled trials studying the effect of concomitant administration of pilocarpine for radiation-induced xerostomia. Included trials were systematically reviewed, and quantifiable outcomes were pooled for meta-analysis. Outcomes of interest included salivary flow, clinician-rated xerostomia grade, patient-reported xerostomia scoring, quality of life, and adverse effects. RESULTS: Six prospective, randomized, controlled trials in 8 articles were included in this systematic review. The total number of patients was 369 in the pilocarpine group and 367 in the control group. Concomitant administration of pilocarpine during radiation could increase the unstimulated salivary flow rate in a period of 3 to 6 months after treatment, and also reduce the clinician-rated xerostomia grade. Patient-reported xerostomia was not significantly impacted by pilocarpine in the initial 3 months but was superior at 6 months. No significant difference of stimulated salivary flow rate could be confirmed between the 2 arms. Adverse effects of pilocarpine were mild and tolerable. CONCLUSIONS: The concomitant administration of pilocarpine during radiation increases unstimulated salivary flow rate and reduces clinician-rated xerostomia grade after radiation. It also relieves patients' xerostomia at 6 months and possibly at 12 months. However, pilocarpine has no effect on stimulated salivary flow rate.