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We aimed to evaluate the histopathological alterations in human salivary glands after radioactive iodine (RAI) treatment for thyroid diseases. We retrospectively selected patients with a history of RAI treatment for thyroid diseases from a database of patients who underwent surgery for oral and maxillofacial diseases and had specimens of salivary glands at Peking University School of Stomatology between December 2012 and July 2023. The patients' clinical records and histopathological slides of the salivary glands were carefully reviewed. Sixteen patients were included. Three symptomatic patients showed duct cell cytoplasmic vacuolization and increased numbers of disordered duct cell layers (3/3), severe duct stenosis and dilation (2/3), and exfoliated epithelial cells in the duct lumen (1/3). The glandular parenchyma showed severe acinar atrophy (2/2), fat content enhancement (2/2), and severe periductal fibrosis (3/3). Thirteen asymptomatic patients showed duct cell cytoplasmic vacuolization (5/13), acinar atrophy and increased fat content in the parenchyma (5/13), and periductal fibrosis (5/13). Main histopathologic changes in the salivary glands after RAI treatment for thyroid diseases are cytoplasmic vacuolization of duct cells, acinar atrophy, fat content enhancement, and periductal fibrosis. These changes were evident in symptomatic cases, and were also seen in some asymptomatic patients. [ABSTRACT FROM AUTHOR]

Precise recognition of the intraparotid facial nerve (IFN) is crucial during parotid tumor resection. We aimed to explore the application effect of direct visualization of the IFN in parotid tumor resection. Fifteen patients with parotid tumors were enrolled in this study and underwent specific radiological scanning in which the IFNs were displayed as high-intensity images. After image segmentation, IFN could be preoperatively directly visualized. Mixed reality combined with surgical navigation were applied to intraoperatively directly visualize the segmentation results as real-time three-dimensional holograms, guiding the surgeons in IFN dissection and tumor resection. Radiological visibility of the IFN, accuracy of image segmentation and postoperative facial nerve function were analyzed. The trunks of IFN were directly visible in radiological images for all patients. Of 37 landmark points on the IFN, 36 were accurately segmented. Four patients were classified as House–Brackmann Grade I postoperatively. Two patients with malignancies had postoperative long-standing facial paralysis. Direct visualization of IFN was a feasible novel method with high accuracy that could assist in recognition of IFN and therefore potentially improve the treatment outcome of parotid tumor resection. [ABSTRACT FROM AUTHOR]

Free fibula is the workhorse flap for mandibular reconstruction and is increasingly being used in pediatric patients. However, craniomaxillofacial growth and development involve interdependent processes, and it remains unknown whether mandibular reconstruction with free fibula allows symmetric growth of the midface. The study evaluated midfacial symmetry after pediatric mandibular defect reconstruction. This retrospective cohort study included pediatric patients aged ≤14 years who underwent mandibular reconstruction with free fibula flap. Postoperative computed tomography data were obtained at predefined follow-up time points. Midfacial symmetry was evaluated based on 3-dimensional (3D) cephalometry. The predictor variable was the side of the midface (affected or healthy side relative to the mandibular defect). The primary outcome variable was postoperative midfacial symmetry (at 1 week, 6 months, 1 year, 2 years, and >3 years, or after the age of 18 years), assessed in horizontal, vertical, and anteroposterior dimensions using 3D cephalometry. Another outcome variable was patient satisfaction based on a self-evaluation using visual analog scoring. Sex, age, diagnosis, and type of denture restoration. Paired t tests were performed to assess the relationship between the predictor and outcome variables, with the significance level of P <.05. A total of 13 patients were included in this study (9 males and 4 females; mean age: 12.23 ± 2.39 years). The average distance from upper first molar point (U6) to the horizontal plane on the affected side became greater than on the healthy side (difference: 0.7 ± 0.5 mm to 1.6 ± 1.4 mm, P <.05), while the average distance from pterygomaxillary fissure to coronal plane on affected side became shorter than that on the healthy side (difference: 0.6 ± 0.6 mm to 1.2 ± 1.1 mm, P <.05) from 1 year after the surgery. There were no statistically significant differences in the remaining measurements between the 2 sides (P >.05). All the patients were satisfied with their postoperative facial symmetry. There were no severe midface deformities after pediatric mandibular reconstruction with free fibula flap. Meanwhile, pediatric mandibular reconstruction and proper occlusion could promote midfacial growth and symmetry. [ABSTRACT FROM AUTHOR]

Purpose: Salivary gland carcinomas (SGCs) can be classified into more than 20 subtypes with various clinical behaviors. The present study aimed to analyze the clinical and pathological features of SGCs and evaluate their long-term prognosis.Methods: A retrospective cohort study was performed. This study investigated cases of histologically confirmed SGC at the authors' institution from January 1963 to December 2014. Data on sex, age, site, histopathological diagnosis, tumor-node-metastasis classification, postoperative radiotherapy and/or chemotherapy, local and regional recurrence, and distant metastasis (DM) were collected as covariates. The overall survival (OS) rate was analyzed as the outcome. Kaplan-Meier survival analysis and Cox multivariate analysis were used for survival analysis. The cohort was divided into 2 groups-before and after 1989. The clinicopathological characteristics of the 2 groups were compared using the χ2 test.Results: The cohort included 1,637 patients who met the admission criteria and had a male-to-female ratio of 0.9:1. The median age was 47 years (range, 8 months to 86 years). The median follow-up time was 54 months (range, 1-432 months). The majority of the tumors occurred in the parotid gland (35.3%), followed by the palate gland (25.2%). Adenoid cystic carcinoma was the most common tumor type (34.3%), and mucoepidermoid carcinoma (29%) was the second most common type. In the 1,637 patients, the neck lymph node metastasis rate was 8.7% at the first surgery, and the overall DM rate was 14.1%. The 5-, 10-, and 15-year OS rates of the 1,637 cases were 93.1%, 87.2%, and 79.3%, respectively. Comparative analysis before and after 1989 showed statistically significant differences in sex, site, histologic subtype, T classification, local and regional recurrence rate, and radiotherapy (P < .05), while no significant differences were found in age, N classification, M staging, DM, or chemotherapy.Conclusions: The OS rates of SGC have improved significantly over the past 30 years. This is attributable to an increase in the proportion of patients diagnosed at the early stage and receiving radiotherapy, as this has led to a reduction in the local and regional recurrence rate and, consequently, an improvement in the survival rates. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to investigate the clinical manifestations and pathologic appearances of the submandibular gland (SMG) in Stevens-Johnson syndrome (SJS).Study Design: Patients with autologous transplantation of SMG for treatment of severe dry eye between March 1998 and May 2018 were divided into the SJS group (70 cases) and non-SJS group (50 cases) according to the history of SJS. The SMG weight and computed tomography volume and salivary flow rate were measured. The concentration index and secretion index were estimated using scintigraphy with technetium-99m-pertechnetate. Histopathology studies of SMG tissues were conducted, and the acini parameters were measured using a digital image analyzer.Results: A decreased computed tomography volume and weight was observed in 48.57% the SJS group and 2% in the non-SJS group (P < .01). The rest whole, acid-stimulated whole, and SMG rest salivary flow rates decreased in the SJS group (P < .05). The normal SMG concentration index (37.5% vs 96.67%, P < .001) and secretion index (35% vs 96.67%, P < .001) rates were lower in the SJS group than in the non-SJS group. The glandular parenchyma was reduced, the acinar space was widened, and the fat content was increased in the SJS group.Conclusion: SMG atrophic and degenerative changes occurred in the SJS group, with a decrease in salivary secretion function in more than half of the patients. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to identify computed tomography (CT) features that differentiate basal cell adenoma (BCA) from Warthin tumor (WT).Materials and Methods: Histopathologically confirmed parotid gland tumors (57 BCAs and 83 WTs) were retrospectively reviewed. CT images were evaluated to determine location, distribution, cyst formation, size, the new vessel facing sign (VFS), and enhancement behavior including the CT attenuation of solid portions of the tumor (AST), the vessel near the tumor (AVT), and maxillary artery (AMA) on early stage 2-phase contrast CT. Tumor CT attenuation ratios (AST/AVT and AST/AMA) were calculated. Chi-square tests, independent t-tests, and receiver operating characteristic curve analysis were conducted.Results: Male:female ratio, patient age, posteroinferior location, tumor size, and presence of VFS were significantly lower for BCA than WT. The average AST/AVT was significantly higher for BCA than WT. The threshold value for AST/AVT on early stage 2-phase contrast CT was 0.72 between BCA and WT, and sensitivity and specificity were 94.7% and 98.8%, respectively, as calculated by receiver operating characteristic analysis.Conclusion: Gender ratio, age, location, size, presence of VFS, and AST/AVT value may help to differentiate BCA from WT in parotid glands on CT examination. [ABSTRACT FROM AUTHOR]

Purpose: The double-barrel fibula flap and vascularized iliac crest flap are both commonly used for mandibular reconstruction. The present study compared the usage and reconstruction outcomes of transplanted bone with these 2 methods.Patients and Methods: The data from 30 patients who had undergone mandibular osteotomy and reconstruction were retrospectively reviewed. Of the 30 patients, 20 received a vascularized iliac crest flap (group A) and 10 received a double-barrel fibula flap (group B). The following variables were compared between the 2 groups: volume of bone flap (VBF), volume of effective bone flap (VEBF; ie, overlap between the volume of the ideal mandible [VIM] and the VBF), usage of the bone flap (VEBF divided by the VBF), mandibular reconstruction rate (VEBF divided by the VIM), volume of needless bone flap (VNBF; ie, VBF minus VEBF; the VNBF included the volume of needless buccal bone flap [VNBBF] and the volume of needless lingual bone flap [VNLBF]), percentage of alveolar crest restoration (PACR; ie, effective bone flap width divided by ideal alveolar crest width), and height of the bone flap (HBF). The independent-samples t test and the χ2 test were used to compare the variables between the 2 groups. Statistical significance was at P ≤ .05.Results: Usage of the bone flap and the length of the mandibular defect were significantly greater in group B than in group A (P = .039 and P < .001, respectively). The VBF, VNBF, and VNLBF were significantly greater in group A than in group B (P < .001 for both). The mandibular reconstruction rate, VNBBF, PACR, HBF, and tooth implantation rate were comparable between the 2 groups.Conclusions: The double-barrel fibula flap can effectively restore the height of the alveolar crest, reconstruct longer mandibular defects, and provide a better buccal and lingual appearance compared with the vascularized iliac crest flap. Although the vascularized iliac crest flap can provide sufficient bone quantity, it must be contoured to the mandible. [ABSTRACT FROM AUTHOR]

Purpose: Shifting of the flap position after condylar reconstruction with free fibular flaps is known to occur, but its long-term effects on postoperative esthetic outcomes have not been sufficiently reported. Therefore, in this study, we evaluated the long-term morphologic stability of the free fibular flap neocondyle.Patients and Methods: This was a retrospective cohort study. The primary outcome variables were neocondyle regeneration and neocondyle position including the distance between the glenoid fossa and the initial neocondyle (Fo-Co), the distance between the glenoid fossa and the stable neocondyle (Fo-Co'), and shifting of the neocondyle (defined as the distance between the stable neocondyle and the initial neocondyle). The primary predictor variable was time. The other variables were age, gender, diagnosis, and number of fibular segments. Correlation analysis between the predictor variables and outcome variables was performed.Results: The sample was composed of 26 patients (11 male and 15 female patients) with a mean age of 31 years. Diagnosis and number of fibular segments were significantly associated with Fo-Co and Fo-Co' (P < .05). Among the 26 patients, only 11 showed neocondyle regeneration at follow-up (group A) whereas 15 did not (group B). Neocondyle regeneration was significantly associated with patient age (P < .01). Stable Fo-Co and stable time were significantly associated with neocondyle regeneration (P < .05). The mean stable time was significantly shorter in group A (3.64 ± 1.12 months) than in group B (6.67 ± 3.85 months) (P < .05), and the mean Fo-Co' was significantly shorter in group A (13.65 ± 3.94 mm) than in group B (20.68 ± 8.87 mm) (P < .05).Conclusions: The possibility of neocondyle regeneration is higher in pediatric patients than in adults. Neocondyle regeneration could result in the movement of the neocondyle toward the glenoid fossa with a shorter stable time, which could improve neocondyle repositioning. Repositioning of the neocondyle with free fibular flaps for mandibular condyle defects is a self-adaption process for temporomandibular joint function. [ABSTRACT FROM AUTHOR]

Purpose: Zygomatic complex defects after extensive maxillectomy can cause severe esthetic and functional deformities. Patient-specific titanium mesh fabricated using a computer-assisted technique is a promising method for such midface reconstruction. The aim of this study was to evaluate the application and clinical outcomes of this technique.Patients and Methods: This was a retrospective study that included 9 patients with zygomatic complex defects after extensive maxillectomy from 2015 through 2017 at the authors' institution. A 3-dimensional stereo model was obtained based on mirror images of the unaffected side to fabricate a patient-specific titanium mesh using computer-assisted design and manufacturing. Titanium mesh was used to restore the contour of the zygomatic complex with free flap reconstruction after tumor resection. Anterolateral thigh flaps were used in 8 cases and a myocutaneous fibula flap was used in 1 case. Symmetry of the zygomatic complex was evaluated by measuring the zygomatic eminence on the postoperative computed tomogram, and complications were recorded during follow-up visits. Facial symmetry was self-evaluated and scored.Results: Mean duration for follow-up was 27.3 months (range, 15 to 39 months). Mean deviation of the zygomatic eminence between the reconstructed and unaffected sides was 1.4 ± 0.5 mm. No significant difference was noted in the zygomatic eminence between the reconstructed and unaffected sides (P = .591). Titanium mesh exposure occurred in only 1 patient after radiotherapy. There were no other remarkable complications. All patients were satisfied with their postoperative facial symmetry.Conclusion: Patient-specific titanium mesh fabricated using a computer-assisted technique was an alternative option for extensive zygomatic complex reconstruction, resulting in acceptable clinical outcomes. A study with a larger sample and long-term follow-up is needed for the observation of long-term outcomes and risk of titanium mesh-related complications. [ABSTRACT FROM AUTHOR]

Purpose: Whether the submandibular gland (SMG) can be preserved during neck dissection in the surgical treatment of oral squamous cell carcinoma (OSCC) is controversial. This study investigated the SMG involvement rate and provides a basis for preserving the SMG during neck dissection in appropriate cases of OSCC.Materials and Methods: A comprehensive systematic review was conducted on the PubMed and MEDLINE, Embase, and Cochrane Library databases for studies on SMG involvement in OSCC published before December 2017 with a data analysis technique. Predictor variables were numbers of patients and resected SMGs, primary site, and tumor, node, and metastasis stage. Outcome variables were the number of involved SMGs and mode of involvement. Other variables, namely first author, publication year, mean age, and condition of neck lymph nodes at level Ib, also were extracted. A random-effects model was used to analyze the rate of SMG involvement in OSCC.Results: Twelve studies involving 2,126 patients with OSCC who underwent neck dissection were included in the study. Fifty-two SMGs were involved, and the pooled involvement rate was 2% (I2 = 73%; 95% confidence interval [CI], 1-3). Forty-eight SMGs were involved through direct spread from the primary site or extracapsular spread of positive lymph nodes, and the pooled involvement rate was 1.9% (I2 = 72%; 95% CI, 0.9-3.1). Except for direct spread, 4 SMGs were involved through the intraglandular lymph node or carcinoma growing along Wharton ducts, and the pooled involvement rate was only 0.1% (I2 = 0%; 95% CI, 0-0.2).Conclusions: The rate of SMG involvement in OSCC is very low, and the most common mode of involvement is by direct spread. The SMG might be preserved during neck dissection in OSCC when it is unlikely to be involved through direct spread. [ABSTRACT FROM AUTHOR]

Background Submandibular gland (SMG) transplantation is a successful treatment approach for patients with severe dry eye. However, duct obstruction can occur post-transplant. Methods We studied nineteen patients with duct obstruction of transplanted SMGs, including five interventional modalities: stone removal; secretory stimulation (to mimic "internal irrigation" with substantial secretory flow); irrigation; surgical opening of stenosis and orifice reconstruction; cephalic vein bypass and Wharton's duct reconstruction. Results A solitary stone was found and removed in one patient. Duct blockages like mucus plug were cleared by secretory stimulation in three patients, and by normal saline irrigation in two grafts. In the remaining 13 patients, irrigation failed and surgical opening was performed. Orifice reconstruction succeeded in six of the eight patients, whose stenosis was near the orifice. Wharton's duct reconstruction was successful in two of the five cases where stenosis was located in the middle segment of the duct. Conclusion Transplanted SMGs obstruct for various reasons. Stone, which is easy to diagnose and treat, should be excluded first. Non-organic blockage and stenosis were semblable in clinic. Therefore, subsequent steps should be a diagnostic/therapeutic trial of secretory stimulation, followed by irrigation; failure of these interventions suggests the diagnosis of duct stenosis, necessitating surgical recanalization. [ABSTRACT FROM AUTHOR]

Background A reliable anterior facial vein (AFV, donor vein) is cardinal for the success of submandibular gland (SMG) transplantation. This study determined the impact of computed tomographic (CT) venography in identifying AFV variations for SMG transplantation. Methods CT venography was performed in consecutive patients with severe dry eye prior to SMG transplantation in order to identify disadvantageous AFV variations for vascular anastomosis, namely, AFVs that did not drain the SMG and those that did not match the superficial temporal vein (STV, recipient vein; AFV:STV caliber ratio, ≥3). The CT results were compared with the intraoperative findings for the diagnostic accuracy. Results Forty-two donors were included. Compared with the intraoperative findings, the CT results accurately identified AFV–STV caliber mismatches ( P = 1.00; sensitivity and specificity, 100%). In the identification of AFVs not draining the SMG, CT showed 94.7% sensitivity and 100% specificity ( P = 0.25). According to the CT findings, 10 contralateral SMGs with AFVs (23.8%), instead of ipsilateral donors, were selected for transplantations (conventionally ipsilateral donor was the first choice). The surgical success rate was 95.2% (40/42). Conclusion CT venography is valuable in determining disadvantageous AFV variations for anastomosis and choosing a reliable donor for SMG transplantation. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to evaluate the safety, effectiveness, and long-term gland function of endoscopy-assisted lithectomy for extraction of parotid gland calculi.Study Design: Overall, 116 consecutive patients with parotid gland calculi underwent endoscopy-assisted lithectomy at our center. The immediate safety and effectiveness were evaluated. After surgery, the patients were followed up, and gland function was analyzed on the basis of clinical manifestations and sialography.Results: Complete stone extraction was achieved in 110 cases (110 of 116 [94.8%]) by using a transoral (95 cases) or transcutaneous (15 cases) approach. At a median follow-up of 3 years, clinical outcomes were excellent in 86 cases (78.2%), fair in 16 cases (14.5%), and poor in 5 cases (4.5%). Postoperative sialographic appearance in 30 stone-free patients was categorized into 3 types: (1) normal (13 cases); (2) ectasia or stenosis in the main duct but no persistent contrast, as seen on functional films (10 cases); and (3) ectasia or stenosis in the main duct and persistent contrast evident on functional films (7 cases).Conclusions: In the absence of lithotripsy, appropriate application of various minimally invasive endoscopic procedures has confirmed safety and effectiveness for stone extraction in patients with parotid calculi. Sialography is a viable method for the evaluation of postoperative gland function. [ABSTRACT FROM AUTHOR]

While vascularized iliac crest flap is widely used for mandibular reconstruction, it is often challenging to predict the clinical outcome in a conventional operation based solely on the surgeon's experience. Herein, we aimed to improve this procedure by using computer-assisted techniques. We retrospectively reviewed records of 45 patients with mandibular tumor who underwent mandibulectomy and reconstruction with vascularized iliac crest flap from January 2008 to June 2015. Computer-assisted techniques including virtual plan, stereomodel, pre-bending individual reconstruction plate, and surgical navigation were used in 15 patients. The other 30 patients underwent conventional surgery based on the surgeon's experience. Condyle position and reconstructed mandible contour were evaluated based on post-operative computed tomography. Complications were also evaluated during the follow-up. Flap success rate of the patients was 95.6% (43/45). Those in the computer-assisted group presented with better outcomes of the mandibular contour (p = 0.001) and condyle position (p = 0.026). Further, they also experienced beneficial dental restoration (p = 0.011) and postoperative appearance (p = 0.028). The difference between postoperative effect and virtual plan was within the acceptable error margin. There is no significant difference in the incidence of post-operative complications. Thus, computer-assisted techniques can improve the clinical outcomes of mandibular reconstruction with vascularized iliac crest flap. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to investigate the clinicopathologic features of carcinoma ex pleomorphic adenoma (CXPA) and comprehensively improve an understanding of this disease.Materials and Methods: This retrospective study investigated 151 cases of histologically confirmed CXPA. Disease-specific survival, local recurrence, and regional and distant metastases were analyzed.Results: Most cases were classed as frankly invasive CXPA (135 of 151). More than half these cases (73 of 135; 54.1%) developed local recurrence; 25 (18.5%) developed cervical metastasis; 21 (15.6%) developed distant metastasis; and 60 patients (55.6%) died during follow-up. In contrast, only 1 patient in the noninvasive CXPA group (n = 10) died after treatment for lung metastasis and 1 patient developed cervical metastasis. Similarly, only 1 patient in the minimally invasive CXPA group (n = 6) died of lung metastasis and the remaining 5 patients had an uneventful recovery after treatment.Conclusions: Frankly invasive CXPA was a high-grade malignancy with an unfavorable prognosis. Elective neck dissection should be performed in cases of frankly invasive CXPA that originate in the submandibular gland. Patients with minimally invasive and noninvasive CXPA should be followed closely after primary treatment because regional or distant metastasis can occur. [ABSTRACT FROM AUTHOR]

Background To assess the prognosis and morbidity between supraomohyoid neck dissection (SOND) and modified radical neck dissection (MRND) for oral squamous cell carcinoma (OSCC) in patients with a clinically node-negative neck (cN0). Patients and methods This prospective randomized study began in June 1999, and patient accrual concluded in May 2010. The cN0 neck was confirmed on clinical palpation by senior doctors. Ultimately, there were 322 patients recruited into the study. Results Patient demographics were well balanced between the two groups. There were 10 patients in the SOND group and 21 patients in the MRND group who developed nodal recurrence without associated local recurrence or distant metastasis. The 3-year neck control rate (NCR) rate was 92.6% for the SOND group and 87.5% for the MRND group (in favor of SOND, P = 0.108). There was no significant difference between the SOND group and the MRND group in the 3-year disease-specific survival (DSS) rate (79.0% vs. 76.9%, P = 0.659). Importantly, there were significantly fewer complications in the SOND group compared with the MRND group (13.0% vs. 21.9%, P = 0.040). The disease-free survivors in the SOND group also reported better pain relief ( P = 0.013) and shoulder function ( P < 0.001) than those in the MRND group one year after treatment. Conclusions We recommend SOND as a priority treatment for cN0 OSCC patients. [ABSTRACT FROM AUTHOR]

Purpose: To assess the clinical effects of endoscopy-assisted sialolithectomy for submandibular hilar calculi. Materials and Methods: The present study was undertaken in 70 patients with symptomatic stones in the hilum of submandibular glands who underwent endoscopy-assisted sialolithectomy from December 2005 through March 2011 in the Peking University School and Hospital of Stomatology. The operative data were analyzed retrospectively. All patients were followed periodically postoperatively. Submandibular gland function was investigated by postoperative symptoms, clinical examinations, sialography, and scintigraphy. Results: Submandibular stones were successfully removed in 65 patients, with a success rate of 92.9%. Temporary lingual nerve injury occurred in 1 patient. Two patients developed ranulae and underwent an uneventful sublingual gland excision. During a mean follow-up of 23 months (range, 6 to 55 mo), 52 of 65 patients were symptom free, whereas 11 patients complained of occasional swelling of the affected gland at mealtimes and 2 patients developed a recurrent stone. Thirty patients underwent postoperative sialography. The sialographic appearances included 4 types: 1) approximately normal; 2) the main duct was significantly dilated at the hilum, but no persistent contrast was seen on the functional film; 3) the main duct was significantly dilated in the hilar region, and persistent contrast was seen at the dilated hilum of the functional film; 4) the main duct was dilated or strictured, and persistent contrast was seen on the functional film. Three of the 4 patients who underwent scintigraphy exhibited good function. Conclusions: Sialoendoscopy-assisted sialolithectomy is a safe and effective gland-preservation technique for patients with hilar stones of the Wharton''s duct. [Copyright &y& Elsevier]

Abstract: We have evaluated transplantation of reduced submandibular glands for the treatment of severe keratoconjunctivitis sicca. Thirty-four rabbits were allocated into three groups: dry eye (controls, n =10), transplantation of whole submandibular glands (n =12), and transplantation of reduced submandibular glands (n =12). Outcome measures included the results of Schirmer''s test and the Rose Bengal test, and histological examination of the cornea and the transplanted gland. Volume of tears significantly increased after transplantation of the whole gland, but did not change after transplantation of the reduced gland compared with dry eyes induced preoperatively. Neither transplantion group had keratoconjunctivitis sicca postoperatively. There were no histological abnormalities in the transplanted tissues. The results that the surgical technique of using reduced submandibular glands for transplantation was feasible, and that the secretion from the reduced gland was similar to that from a normal lacrimal gland. In conclusion, transplantation of a reduced submandibular glands is feasible in the treatment of keratoconjunctivitis sicca. [Copyright &y& Elsevier]

Purpose: Autologous microvascular submandibular gland (SMG) transfer is an effective treatment for severe keratoconjunctivitis sicca (KCS). However, epiphora (excessive tear secretion) may occur after the successful transfer of whole submandibular gland because tear secretion level is closely related to the size of the transferred gland. The aim of this study was to investigate the microanatomy of SMG to explore the possibility of partial SMG transfer to prevent postoperative epiphora. Materials and Methods: Sixty intact and histologically normal human SMGs from patients with benign tumor of the mandible who underwent vascularized mandibular reconstruction and removal of the SMG for anastomosis of the blood vessels were included in the study. SMGs were perfused with methacrylate to form resin casts of blood vessels and ducts. The length and diameter of the blood vessels and ducts in the casts were measured using a sliding caliper. The numbers of lobules, distribution of arteries, veins, and ducts, as well as the relationship among them, were analyzed. Results: The resin cast of the gland showed a treelike structure, with the vessels gradually dividing into multiple branches. The arteries, veins, and ducts run in parallel and were roughly divided into 3 levels: from the stem extending into the main branches (level I), into the narrower secondary branches (level II), and then the secondary branches subsequently divided into terminal branches (level III). The structures of the blood vessels and ducts were similar at each level in the lobules. In the vein casts, communicating vessels were found between the anterior facial vein and the concomitant vein of the facial artery. Conclusion: The characteristic treelike structure of the SMG vascular and ductal system may provide useful information for partial gland transfers. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the relationship between the ducts of the submandibular gland (SMG) and sublingual gland (SLG) and discuss its clinical application relating to SMG radiologic examinations and transfer. Materials and Methods: The microanatomy of the SMG and SLG was investigated by use of 30 adult cadavers through anatomic dissection by use of a microscope. The relationship between the SMG and SLG ducts was observed and recorded during operations of microvascular autologous SMG transfer in 63 cases of severe keratoconjunctivitis sicca. Results: There were 3 patterns of SLG and SMG duct anatomic variation: 1) The SMG and SLG have their own respective ducts that secrete separately at the orifices of the ducts in the floor of the mouth. 2) The SLG has a major duct that joins the duct of the SMG. 3) The SLG only has many fine ducts (7-15) that secrete in the floor of the mouth. Conclusions: The anatomy of the ducts of the SMG and SLG is quite complicated. More attention should be paid to the anatomy of the ducts during surgery or imaging procedures related to the SMG. [Copyright &y& Elsevier]

Objective: The aim was to evaluate a semirigid endoscopic technique for diagnosis and management of sialolithiasis. Study design: Diagnostic and interventional sialendoscopic procedures were performed in 90 patients with sialoliths (78 submandibular glands and 12 parotid glands). Results: Owing to its extreme flexibility and rigidity, the endoscope can be introduced easily into the ductal system. Sialoliths with a round or irregular shape were detected by endoscopy in all cases, including 84 radiopaque and 6 radiolucent stone cases. Of the 78 cases with sialoliths in the submandibular (Wharton''s) duct, 14 were present in the hilum of the main duct, 34 in the premolar region of the duct, 24 in the molar region of the duct, and 6 in both the premolar and the molar regions of the duct. Among these cases, we could remove the stones intraductally in 44 cases by endoscopy alone. Additionally, 6 cases were treated with basket retrieval and endoscopic-assisted surgery, and the remaining 27 were treated with endoscopic-assisted surgery. Of the 12 cases of sialoliths in the parotid (Stensen''s) duct, 9 were treated with basket retrieval and 1 with basket-capturing and open surgery via a buccal incision. In total, 87 of 90 cases were successfully treated, with (n = 34) or without (n = 53) endoscopic-assisted surgery. These patients were stone free at their last follow-up (3 to 30 months). Conclusions: The semirigid endoscope permits a better visualization of sialoliths and coexisting obstructive pathologies. With minimally invasive procedures, most stones in the main duct of the salivary gland can be removed using either an intraductal or an extraductal approach. [Copyright &y& Elsevier]

Summary: The ability of near infrared spectroscopy (NIRS) to predict vascular compromise in vascular free flaps postoperatively has been assessed, and the extent of regional tissue oxygen saturation (rSO2) after fibular flap transplantation was investigated quantitatively. To validate the sensibility and precision of the technique, the following methods were used. (1) Forearm vessel obstructive tests were conducted in four healthy volunteers. (2) Measurement and analysis of bilateral rSO2 at the mandibular body and ramus were performed in 40 healthy volunteers by NIRS in the morning and afternoon. (3) Measurement and analysis of rSO2 in transplanted fibular flaps for 41 cases with mandibular reconstruction were performed by NIRS at postoperative days 1–6. The results were: NIRS had high sensibility and precision in monitoring rSO2 of living tissues. No significant difference in the values of rSO2 was found across different times or areas in the normal mandible. However, rSO2 in the transplanted fibular flaps was reduced compared to the value on the control side. rSO2 decreased gradually 4–12 hours postoperatively. After that period, rSO2 increased gradually and approached the value of the control side at 20h after the operation. It can be concluded that NIRS is a reliable noninvasive method for monitoring blood circulation in transplanted tissues, particularly for buried flaps. [Copyright &y& Elsevier]

Objective: To investigate the clinicopathologic features of eosinophilic hyperplastic lymphogranuloma (Kimura’s disease) in the parotid gland. Study design: The hematoxylin and eosin sections and clinical data of 60 patients with eosinophilic hyperplastic lymphogranuloma (Kimura’s disease), including with parotid involvement, were reviewed. Results: Of 60 cases of eosinophilic hyperplastic lymphogranuloma (average age, 42 years; average disease duration, 5.8 years), 35 cases (58%) were clinically seen to involve swelling of the parotid region. Parotid specimens were available in 21 cases and showed different microscopic changes. In mildly affected parotid samples, the histological features included infiltration of lymphocytes and eosinophils around the ducts of the interlobular connective tissues. In the moderately involved glands, the infiltrated area was enlarged and contained lymphoid follicles, resulting in adjacent acinar atrophy that was particularly obvious around the salivary ducts. In severe lesions, most acini were lost and only a few ducts remained. All cases with parotid involvement showed more severe pathological changes in the subcutaneous connective tissues and/or local lymph nodes. The parotid lesions often surrounded a central intraglandular lymph node with characteristic features of the disease; however, the salivary parenchyma was left alone. Nerve fibers affected by inflammatory lymphocytes and eosinophils were seen in 38/60 (63%) cases of eosinophilic hyperplastic lymphogranuloma (Kimura’s disease) examined in this study. Conclusions: Eosinophilic hyperplastic lymphogranuloma (Kimura’s disease) does not show primary parotid involvement, but instead, pathological changes in the parotid gland are a result of disease spread from the intraparotid lymph nodes and adjacent soft tissues. In addition, our observations suggest that the pruritus often associated with the disease may be due to nerve infiltration by lymphocytes and eosinophils. [Copyright &y& Elsevier]

Abstract: We used a model of allografts of submandibular glands in miniature swine to test the requirements of immunosuppressants for the survival of such grafts. Animals in the first group (n =6) were given no immunosuppressant, and the submandibular glands were rejected within 7 days. Those in the low-dose group (n =4) were treated with a low dose of cyclosporine, methylprednisolone, and azathioprine. The allografts were rejected on days 15, 17, 19, and 20. The animals in the high-dose group (n =6) were treated with a high dose of cyclosporin, methylprednisolone, and azathioprine. Three allografts were rejected, on days 35, 48, and 60. One animal died from anaesthetic problems on day 30 after transplantation, and there were no signs of rejection in the allograft. The other two allografts survived for 100 days with secretory function and no signs of rejection. After we discontinued the immunosuppression on day 100, the two remaining allografts were rejected on days 121 and 128. Blood tests and biopsy specimens of the heart, lung, liver, and kidneys were normal in all animals that were given immunosuppressants. To our knowledge, this study is the first to describe long-term survival of allografted submandibular glands with secretory function in miniature swine. [Copyright &y& Elsevier]

To investigate the expression and secretion of epidermal growth factor (EGF) in major and minor salivary gland tissues of human subjects and to examine the potential influence of sex and age on EGF expression and secretion. Saliva samples from the oral cavity at rest and after citric acid stimulation, as well as serum samples, were collected from 150 healthy subjects, and the concentrations of EGF were measured with enzyme-linked immunosorbent assay (ELISA) and compared. The expression of EGF mRNA and protein in normal salivary gland tissues was measured by real-time polymerase chain reaction (RT-PCR), Western blot (WB), and immunohistochemistry (IHC). The EGF concentration in acid-stimulated saliva was significantly higher than that in resting saliva (P < 0.001), and significantly higher than that in serum (P < 0.001). No sex difference was observed in EGF levels of whole saliva and serum, whereas the EGF levels in saliva and serum were decreased with age (P < 0.001 and P < 0.001, respectively). The EGF concentration and compound secretion rate (CSR) in resting submandibular glands saliva were significantly higher than those in resting parotid glands saliva (P = 0.002 and P < 0.001, respectively). The EGF was expressed in all major and minor salivary glands and ranked in order of submandibular, parotid, sublingual, and labial glands. All salivary glands have the function of secreting EGF, and the submandibular gland is the main source of salivary EGF. Aging is a factor influencing the expression and secretion of EGF. • EGF is expressed in major and minor salivary glands. • The submandibular gland shows the highest level of EGF expression, followed by the parotid gland. • The positive immunohistochemical expression of EGF is located in serous acini. • The EGF concentration in saliva is higher than that in serum. • EGF levels in saliva are decreased with age. [ABSTRACT FROM AUTHOR]

Purpose: To quantify gland function before and after endoscopy-assisted lithectomy for patients with parotid stones and to analyze correlations among different evaluation modalities.Materials and Methods: This study investigated 58 patients (27 men and 31 women) with a stone larger than 5 mm or multiple parotid stones who underwent successful endoscopy-assisted surgery at the authors' center from August 2007 through September 2017. Meticulous postoperative manipulations were administered routinely for 3 to 6 months to promote functional recovery of the affected gland. Gland function was evaluated preoperatively and 6 to 36 months (mean, 12 months) postoperatively by sialography, scintigraphy, and sialometry. Statistical analyses were conducted to quantify gland function recovery and to distinguish correlations among the 3 objective tests.Results: Preoperative sialograms exhibited ductal ectasia at the stone site with ductal stenosis anterior to the stone (n = 53) or duct interruption at the stone site (n = 5). Postoperative sialograms of 45 patients without stones were categorized as approximately normal (type I; n = 17); showing ectasia or stenosis of the main duct without persistent contrast on the functional film (type II; n = 16); showing ectasia or stenosis of the main duct with mild contrast retention (type III; n = 6); or showing poor ductal shape with evident contrast retention (type IV; n = 6). Scintigraphy of 23 preoperative and 12 postoperative patients and sialometry of 24 preoperative and 12 postoperative patients indicated severe preoperative impairment and postoperative improvement of gland function. Postoperatively, although no relevant differences in saliva flow rate were found between the 2 sides, scintigraphy showed lower function of the affected gland compared with the control side. Statistical data showed positive correlations among the 3 methods. Sialography intuitively reflected the ductal shape, whereas sialometry and scintigraphy were more sensitive for evaluating gland function.Conclusion: For patients with parotid stones, minimally invasive endoscopic surgery and meticulous postoperative manipulations help preserve the glands and facilitate recovery of gland function. The 3 evaluating modalities have certain positive correlations. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to describe new technology assisted by 3-dimensional (3D) image fusion of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) and contrast-enhanced CT (CECT) for computer planning of a maxillectomy of recurrent maxillary squamous cell carcinoma and defect reconstruction.Materials and Methods: Treatment of recurrent maxillary squamous cell carcinoma usually includes tumor resection and free flap reconstruction. FDG-PET/CT provided images of regions of abnormal glucose uptake and thus showed metabolic tumor volume to guide tumor resection. CECT data were used to create 3D reconstructed images of vessels to show the vascular diameters and locations, so that the most suitable vein and artery could be selected during anastomosis of the free flap. The data from preoperative maxillofacial CECT scans and FDG-PET/CT imaging were imported into the navigation system (iPlan 3.0; Brainlab, Feldkirchen, Germany). Three-dimensional image fusion between FDG-PET/CT and CECT was accomplished using Brainlab software according to the position of the 2 skulls simulated in the CECT image and PET/CT image, respectively. After verification of the image fusion accuracy, the 3D reconstruction images of the metabolic tumor, vessels, and other critical structures could be visualized within the same coordinate system. These sagittal, coronal, axial, and 3D reconstruction images were used to determine the virtual osteotomy sites and reconstruction plan, which was provided to the surgeon and used for surgical navigation.Results: The average shift of the 3D image fusion between FDG-PET/CT and CECT was less than 1 mm. This technique, by clearly showing the metabolic tumor volume and the most suitable vessels for anastomosis, facilitated resection and reconstruction of recurrent maxillary squamous cell carcinoma.Conclusions: We used 3D image fusion of FDG-PET/CT and CECT to successfully accomplish resection and reconstruction of recurrent maxillary squamous cell carcinoma. This method has the potential to improve the clinical outcomes of these challenging procedures. [ABSTRACT FROM AUTHOR]

Desmoid-type fibromatosis (DF) is a locally aggressive benign soft tissue tumor. It is rarely observed in the head and neck region and is particularly uncommon in the parotid gland. This report describes the case of a 32-month-old girl with DF of the head and neck. The tumor was resected with gross residual tumors. Recurrence occurred 3 months later and then the patient was treated with iodine-125 interstitial brachytherapy. The tumor was completely absent 6 months after brachytherapy. No recurrence was found 60 months after brachytherapy during follow-up. No severe toxicities or growth abnormalities were observed. Very-low-dose rate brachytherapy as the sole modality could be a reasonable alternative for the treatment of inoperable DF of the head and neck, which avoids the risk of cosmetic deformity caused by surgery, especially in pediatric patients. In addition, long-term follow-up is recommended. [ABSTRACT FROM AUTHOR]

Purpose: Although free fibula flaps are widely used for mandibular reconstruction, their 3-dimensional position is difficult to control during conventional surgery. We aimed to improve this process by using computer-aided design (CAD) and surgical navigation.Patients and Methods: We retrospectively reviewed 29 benign tumor patients who underwent primary unilateral mandibular reconstruction with free fibula flap. They were divided into 3 groups: group A, comprising 10 patients, underwent reconstruction based on the surgeon's experience; group B, comprising 7 patients, underwent reconstruction based on CAD; and group C, comprising 12 patients, underwent reconstruction based on CAD and surgical navigation. Condyle and gonion positions and mandibular angles were measured. Operative times were recorded.Results: Among the 17 patients who underwent condylar resection, the average condyle shift was greater in group A than in groups B and C (P < .05). The average gonion shift was greater in groups A and B than in group C (P < .05). The difference between the reconstructed and contralateral mandibular angles was greater in group A than in groups B and C (P < .05). The mean operative time did not differ among the 3 groups.Conclusions: CAD can guide mandibular angle remodeling and condyle placement. CAD and surgical navigation increase reconstruction accuracy without prolonging operative time. [ABSTRACT FROM AUTHOR]

Purpose: Orbital floor defects after extensive maxillectomy can cause severe esthetic and functional deformities. Orbital floor reconstruction using the computer-assisted fabricated individual titanium mesh technique is a promising method. This study evaluated the application and clinical outcomes of this technique.Patients and Methods: This retrospective study included 10 patients with orbital floor defects after maxillectomy performed from 2012 through 2014. A 3-dimensional individual stereo model based on mirror images of the unaffected orbit was obtained to fabricate an anatomically adapted titanium mesh using computer-assisted design and manufacturing. The titanium mesh was inserted into the defect using computer navigation. The postoperative globe projection and orbital volume were measured and the incidence of postoperative complications was evaluated.Results: The average postoperative globe projection was 15.91 ± 1.80 mm on the affected side and 16.24 ± 2.24 mm on the unaffected side (P = .505), and the average postoperative orbital volume was 26.01 ± 1.28 and 25.57 ± 1.89 mL, respectively (P = .312). The mean mesh depth was 25.11 ± 2.13 mm. The mean follow-up period was 23.4 ± 7.7 months (12 to 34 months). Of the 10 patients, 9 did not develop diplopia or a decrease in visual acuity and ocular motility. Titanium mesh exposure was not observed in any patient. All patients were satisfied with their postoperative facial symmetry.Conclusion: Orbital floor reconstruction after extensive maxillectomy with an individual titanium mesh fabricated using computer-assisted techniques can preserve globe projection and orbital volume, resulting in successful clinical outcomes. [ABSTRACT FROM AUTHOR]

Purpose The treatment of inoperable parotid gland carcinoma is challenging and controversial. The purpose of this paper was to present our experience in treating this malignancy using 125 I interstitial brachytherapy. Methods and Materials Thirteen patients with advanced carcinomas of the parotid gland were included and treated with 125 I interstitial brachytherapy in Peking University School and Hospital of Stomatology from January 2003 to December 2015. All patients were treated with 125 I interstitial brachytherapy as a sole modality for the primary tumor. Furthermore, all of them were treated with neck dissection with/without adjunctive external beam radiotherapy for the neck, simultaneously. The prescription dose of interstitial brachytherapy was 140–160 Gy. Results Median followup was 56 months (range: 8–105 months). The 2-year and 5-year local control rates were 91.7% and 58.2%, respectively. The 2-year and 5-year overall survival rates were 100% and 61%, respectively. No cervical lymph node metastasis was observed during the followup. No interstitial brachytherapy-related severe complications occurred. Facial nerve function was preserved well. Conclusions 125 I interstitial brachytherapy is a feasible and effective treatment for inoperable parotid gland carcinomas without severe complications. And neck dissection with/without external beam radiotherapy is necessary for patients with cervical metastasis or at high risk of cervical metastasis. [ABSTRACT FROM AUTHOR]

Objectives The aim of this cross-sectional study was to investigate the relationship between minor salivary gland (MSG) flow rates and oral dryness degrees in patients with xerostomia induced by primary Sjögren’s syndrome (pSS), IgG4-related sialadenitis (IgG4-RS), radiation therapy-induced dry mouth (RTDM), or Steven–Johnson syndrome (SJS). Design 160 patients with pSS, IgG4-RS, RTDM, or SJS and their age- and sex-matched healthy control subjects were enrolled. The whole saliva flow rates and MSG flow rates were measured in four locations, including the upper labial, lower labial, buccal, and palatal mucosae. The degree of oral dryness was assessed in patient groups using the summated xerostomia inventory (SXI). Results The flow rates of whole saliva and most MSGs in patient groups were significantly lower than the flow rates in healthy control groups ( P < 0.05). The mean relative percentage of decrease in saliva flow rates was smaller in MSGs than in whole saliva in patient groups ( P < 0.05), indicating that these disorders have less impact on MSGs. Among the four MSG locations (the upper labial, lower labial, buccal, and palatal), buccal glands showed the highest flow rates in patient groups ( P < 0.05). SXI scores were significantly higher in pSS and RTDM patients than in IgG4-RS and SJS patients ( P < 0.05). The degree of xerostomia varied among different patient groups ( P < 0.05) and there was no clear correlation between MSG flow rates and SXI scores ( P > 0.05). Conclusions MSG function is significantly reduced in pSS, RTDM, IgG4-RS, and SJS patients, but this reduction is more pronounced in the major salivary glands. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the role of ultrasonography in the diagnosis and follow-up evaluation of immunoglobulin G4-related sialadenitis. In this study, 42 patients with immunoglobulin G4-related sialadenitis underwent ultrasonography of the parotid and submandibular glands, and the sonographic appearance was compared with the pathologic findings. Post-treatment ultrasonographic appearance was compared with the pre-treatment findings in 30 patients who received immunomodulatory therapy. The ultrasonographic appearance of the affected glands was divided into five patterns: superficial hypo-echoic, multiple hypo-echoic foci, whole-gland heterogeneity, space occupying and normal echo. Histopathologic examination revealed marked lymphoplasmacytic inflammation and inter-lobular fibrosis, which were more severe in the superficial than deep portion of the affected glands. After treatment, the volume of the affected gland decreased significantly, the internal echo became more homogeneous and the superficial hypo-echoic area disappeared or was reduced. In conclusion, ultrasonography may play an important role in the diagnosis and follow-up evaluation of immunoglobulin G4-related sialadenitis. [ABSTRACT FROM AUTHOR]

Inhibitor of soluble epoxide hydrolase (t-AUCB) has been used in the experimental therapy of hypertension. This study aimed to investigate whether the secretion of submandibular glands (SMGs) altered in renal hypertensive rats, and to explore whether t-AUCB could improve the salivary secretion. 2-kidney 1-clip Sprague-Dawley rats were used as renal hypertensive animals. t-AUCB treatment was given for 1 week after 8 weeks modeling. Blood pressure, blood perfusion and the secretion of SMGs, and endothelium-dependent relaxation of external maxillary artery were measured to investigate the effects of t-AUCB on the vascular tone and the secretion of SMGs in renal hypertensive rats. SMGs were collected for histological evaluation and the internal arteries were dissected for primary endothelial cells culture. The blood perfusion and flow rate of SMGs in the renal hypertensive rats were significantly lower than those in the controls. Endothelium-dependent relaxation of the external maxillary artery and AMPK/Akt/eNOS signaling was impaired in hypertensive rats. The glandular morphology and the concentration of salivary ions did not change obviously. t-AUCB treatment ameliorated the secretion of SMGs, the blood perfusion, and the dysfunction of endothelium-dependent relaxation of the external maxillary artery by activating the AMPK/Akt/eNOS pathway in hypertensive rats. t-AUCB increases the blood perfusion through ameliorating dysfunction of endothelium-dependent relaxation of SMGs arteries and thus improves the hyposecretion of SMGs in hypertensive rats. [ABSTRACT FROM AUTHOR]

TNF-α plays an important role in the pathogenesis of salivary inflammatory diseases. Salivary dysfunction, which leads to impaired saliva secretion, can be caused by TNF-α-induced disrupted epithelial barrier. However, the signaling mechanism involved in TNF-α-modulated tight junction barrier in salivary gland remains unclear. Here, we found that TNF-α reduced transepithelial resistance (TER) and increased FITC-dextran flux in a rat submandibular cell line SMG-C6. Claudin (Cln)-3 was selectively downregulated and disrupted by TNF-α, whereas Cln-1, Cln-4, and β-catenin were not affected. Overexpression of Cln-3 retained and Cln-3 knockdown abolished the TNF-α-induced alterations. Moreover, TNF-α increased extracellular signal-regulated kinase (ERK1/2) phosphorylation and the expression of transcriptional factor slug. ERK1/2 kinase inhibitor PD98059 abrogated TNF-α-induced increase in paracellular permeability, alterations of Cln-3, and elevation of slug. Overexpression of slug decreased and slug knockdown increased Cln-3 expression. In addition, slug bind to the E-box elements of Cln-3 promoter in TNF-α-treated cells, and this response was blocked by PD98059. Furthermore, TNF-α decreased Cln-3 expression and increased slug content in cultured human submandibular gland. Taken together, our data suggest that Cln-3 plays a vital role in TNF-α-modulated paracellular permeability in submandibular epithelium and ERK1/2/slug signaling axis is involved in alteration of Cln-3 redistribution and downregulation. [ABSTRACT FROM AUTHOR]

Objectives To investigate the normal range and characteristics of saliva secretion in the minor salivary glands (MSGs). Design The flow rates of MSGs were measured in 4 anatomical locations of oral mucosa, and the relationship between MSG flow rates and whole saliva flow rates were assessed in 300 healthy subjects stratified by age and sex. An additional 30 young females were further evaluated for flow symmetry, effects of stimulation, circadian effects in MSGs, and the relationship with the flow rates of major salivary glands. Results (1) The mean saliva flow rates were 2.10 ± 0.66 (lower labial glands), 2.14 ± 0.62 (upper labial glands), 2.88 ± 0.72 (buccal glands) and 2.15 ± 0.51 (palatal glands) μl/min/cm 2 , respectively. The flow rate of buccal glands was significantly higher than the rates of SMGs in other locations ( P < 0.01). (2) 5-year-old children had the lowest MSG flow rates ( P < 0.0001) while the 10–14-year-old group had the highest ( P < 0.001). (3) MSG flow rates were independent of sex ( P > 0.05), right vs. left ( P > 0.05), and citric acid (2.5%) stimulation ( P > 0.05). (4) Only labial MSG displayed a significant secretory circadian rhythm with the highest rate in the evening ( P < 0.05). (5) A weak correlation was found between the flow rate of palatal glands and that of unstimulated whole saliva ( r = 0.195, P = 0.007). Conclusions Our findings provide a reference for functional evaluation of MSGs and for donor site selection of MSG transplantation for treatment of severe dry eye syndrome. [ABSTRACT FROM AUTHOR]

Summary: Objectives: Adenoid cystic carcinoma (ACC) is one of the most common malignancies of salivary glands, characterized by poor prognosis, particularly due to pulmonary metastasis. We previously reported that transforming growth factor (TGF)-β1 promoted ACC cell migration and invasion via the Smad pathway in vitro. The aim of this study was to establish the underlying mechanisms. Materials and methods: TGF-β1, phospho-Smad2 and β-catenin expression in ACC tissues derived from patients was evaluated by immunohistochemistry. The role of TGF- β1 on the invasive capacity of ACC cells was determined by transwell assays in SACC-83 cells transfected with TGF-β1 and TGF-β type II dominant-negative receptor (TβRIIDN) plasmids or silenced by TGF-β1 siRNA. Expression of the epithelial–mesenchymal transition (EMT) markers, β-catenin, E-cadherin and Nectin-1, was determined by real-time PCR and immunochemistry. In vivo investigations were performed by inoculating nude mice with the transfected ACC cells and examining metastasis in bilateral lung tissues by immunohistochemistry. Results: Overexpression of TGF-β1 and phospho-Smad2, and reduced expression of membrane β-catenin, were closely associated with lung metastasis in ACC. Furthermore, the EMT markers were downregulated. In vitro, cells transfected with TGF-β1 exhibited altered morphology and increased invasive capacity compared to TβRIIDN-transfected cells or TGF-β1 siRNA silenced cells. In vivo, mice inoculated with TGF-β1 transfected ACC cells exhibited more metastases than other cells. Conclusion: TGF-β1, phospho-Smad2 and β-catenin were significantly correlated with ACC metastasis. Blockade of TGF-β signaling by TβRIIDN or siRNA may offer potential gene therapies against pulmonary metastasis in patients with ACC. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The aim of the present study was to reveal the expression characteristics of ghrelin in human three major salivary glands and to investigate saliva and serum ghrelin level and the relation with weight and lipid indices in Chinese children. Design: Expression and distribution of ghrelin in parotid, submandibular, and sublingual glands were measured by reverse transcription-polymerase chain reaction and immunohistochemistry. Saliva and serum samples were collected from 194 Chinese children and adolescents (mean age 12.98 years). Ghrelin levels were tested by enzyme-linked immunosorbent assay. Significant differences were estimated by one-way ANOVA. Results: Ghrelin mRNA was expressed in parotid and submandibular glands, but was not detectable in sublingual glands. Ghrelin proteins were widespread in the cytoplasm of striated, intercalated and excretory ducts, as well as in serous acini of parotid and submandibular glands, but not in mucous acinar cells of sublingual glands. Saliva and serum ghrelin levels were increased along with BMI. There was positive correlation between saliva and serum ghrelin levels (r =0.534, P <0.01). Serum and saliva ghrelin levels were both significantly correlated with BMI (r =0.523, r =0.374, P <0.01, respectively), but not with blood lipid levels. Conclusions: Parotid and submandibular glands were primary sources of ghrelin produced and released in saliva. Although whether salivary ghrelin could be useful in the diagnosis of obesity remains to be determined, salivary ghrelin might be a possible alternative to serum ghrelin for predicting obesity. [Copyright &y& Elsevier]

Summary: 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 86years (median age: 61.3years). 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. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

Summary: 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. [Copyright &y& Elsevier]

Abstract: β-Adrenoceptors (β-ARs) mediate important physiological functions in salivary glands. Here we investigated the expression and function of β-AR subtypes in rabbit submandibular gland (SMG). Both β1- and β2-ARs, but not β3-AR, were strongly expressed in rabbit SMG. β1-AR proteins were widely expressed in acinar and ductal cells whereas β2-AR proteins were mainly detected in ductal cells. A [3H]-dihydroalprenolol binding assay revealed that β-AR B max was 186±11.9 fmol/mg protein and K d was 2.71±0.23 nM. A competitive binding assay with CGP 20712A, a β1-AR antagonist, indicated that the proportion of β1-AR and β2-AR was 71.9% and 28.1%, respectively. Gland perfusion with the β-AR agonist isoproterenol induced a significant increase in saliva secretion which was abolished by pretreatment with the non-selective β-AR antagonist propranolol. Pretreatment with β1- or β2-AR selective antagonists, CGP 20712A or ICI 118551, diminished isoproterenol-induced increase in saliva secretion by 71.2% and 28.8%, respectively. The expression of α-amylase mRNA was significantly stimulated by isoproterenol, which was eliminated by propranolol and CGP 20712A. Perfusion with isoproterenol decreased α-amylase protein storage in SMG and increased α-amylase activity in saliva. These alterations became less significant after pretreatment with propranolol and CGP 20712A. Our results suggest that both β1- and β2-ARs are expressed in rabbit SMG. β1-AR is the predominant subtype and may play an important role in regulating saliva and α-amylase secretion. [Copyright &y& Elsevier]

C1q/tumour necrosis factor-related protein 3 (CTRP3) plays important roles in metabolism and inflammatory responses in various cells and tissues. However, the expression and function of CTRP3 in salivary glands have not been explored. The expression and distribution of CTRP3 were detected by western blot, polymerase chain reaction, immunohistochemical and immunofluorescence staining. The effects of CTRP3 on tumour necrosis factor (TNF)-α-induced apoptosis and barrier dysfunction were detected by flow cytometry, western blot, co-immunoprecipitation, and measurement of transepithelial resistance and paracellular tracer flux. CTRP3 was distributed in both acinar and ductal cells of human submandibular gland (SMG) and was primarily located in the ducts of rat and mouse SMGs. TNF-α increased the apoptotic rate, elevated expression of cleaved caspase 3 and cytochrome C, and reduced B cell lymphoma-2 (Bcl-2) levels in cultured human SMG tissue and SMG-C6 cells, and CTRP3 further enhanced TNF-α-induced apoptosis response. Additionally, CTRP3 aggravated TNF-α-increased paracellular permeability. Mechanistically, CTRP3 promoted TNF-α-enhanced TNF type I receptor (TNFR1) expression, inhibited the expression of cellular Fas-associated death domain (FADD)-like interleukin-1β converting enzyme inhibitory protein (c-FLIP), and increased the recruitment of FADD with receptor-interacting protein kinase 1 and caspase 8. Moreover, CTRP3 was significantly increased in the labial gland of Sjögren's syndrome patients and in the serum and SMG of nonobese diabetic mice. These findings suggest that the salivary glands are a novel source of CTRP3 synthesis and secretion. CTRP3 might promote TNF-α-induced cell apoptosis through the TNFR1-mediated complex II pathway. • The expression and distribution of CTRP3 is verified in salivary glands. • CTRP3 promotes TNF-α-induced acinar apoptosis and barrier dysfunction. • CTRP3 facilitates TNF-α-increased TNFR1 expression and apoptotic complex II formation. [ABSTRACT FROM AUTHOR]