Tert-expressing cells contribute to salivary gland homeostasis and tissue regeneration after radiation therapy.

Salivary gland homeostasis and regeneration after radiotherapy depend significantly on progenitor cells. However, the lineage of submandibular gland (SMG) progenitor cells remains less defined compared with other normal organs. Here, using a mouse strain expressing regulated CreERT2 recombinase from the endogenous Tert locus, we identify a distinct telomerase-expressing (TertHigh) cell population located in the ductal region of the adult SMG. These TertHigh cells contribute to ductal cell generation during SMG homeostasis and to both ductal and acinar cell renewal 1 year after radiotherapy. TertHigh cells maintain self-renewal capacity during in vitro culture, exhibit resistance to radiation damage, and demonstrate enhanced proliferative activity after radiation exposure. Similarly, primary human SMG cells with high Tert expression display enhanced cell survival after radiotherapy, and CRISPR-activated Tert in human SMG spheres increases proliferation after radiation. RNA sequencing reveals upregulation of "cell cycling" and "oxidative stress response" pathways in TertHigh cells following radiation. Mechanistically, Tert appears to modulate cell survival through ROS levels in SMG spheres following radiation damage. Our findings highlight the significance of TertHigh cells in salivary gland biology, providing insights into their response to radiotherapy and into their use as a potential target for enhancing salivary gland regeneration after radiotherapy.

Botulinum toxin type a blocks aquaporin 5 trafficking by decreasing synaptosomal-associated protein 23 in submandibular acinar cells.

The trafficking of aquaporin 5 (AQP5) is critical for salivary secretion. Synaptosomal-associated protein 23 (SNAP23) is an important regulator in the process of membrane fusion. However, the role of SNAP23 on AQP5 trafficking has not been explored. Botulinum toxin type A (BoNT/A) is a bacterial toxin that effectively treats sialorrhea. We previously reported that BoNT/A induced AQP5 redistribution in cultured acinar cells, but the mechanism remained unclear. In this study, SNAP23 was predominantly localized to the plasma membrane of acinar cells in the rat submandibular gland (SMG) and colocalized with AQP5 at the apical membrane of acinar cells. In stable GFP-AQP5-transfected SMG-C6 cells, the acetylcholine receptor agonist carbachol (CCh) induced trafficking of AQP5 from intracellular vesicles to the apical membrane. Furthermore, SNAP23 knockdown by siRNA significantly inhibited CCh-induced AQP5 trafficking, whereas this inhibitory effect was reversed by SNAP23 re-expression, indicating that SNAP23 was essential in AQP5 trafficking. More importantly, BoNT/A inhibited salivary secretion from SMGs, and the underlying mechanism involved that BoNT/A blocked CCh-triggered AQP5 trafficking by decreasing SNAP23 in acinar cells. Taken together, these results identified a crucial role for SNAP23 in AQP5 trafficking and provided new insights into the mechanism of BoNT/A in treating sialorrhea and thereby a theoretical basis for clinical applications.

A mechanogenetic role for the actomyosin complex in branching morphogenesis of epithelial organs.

The actomyosin complex plays crucial roles in various life processes by balancing the forces generated by cellular components. In addition to its physical function, the actomyosin complex participates in mechanotransduction. However, the exact role of actomyosin contractility in force transmission and the related transcriptional changes during morphogenesis are not fully understood. Here, we report a mechanogenetic role of the actomyosin complex in branching morphogenesis using an organotypic culture system of mouse embryonic submandibular glands. We dissected the physical factors arranged by characteristic actin structures in developing epithelial buds and identified the spatial distribution of forces that is essential for buckling mechanism to promote the branching process. Moreover, the crucial genes required for the distribution of epithelial progenitor cells were regulated by YAP and TAZ through a mechanotransduction process in epithelial organs. These findings are important for our understanding of the physical processes involved in the development of epithelial organs and provide a theoretical background for developing new approaches for organ regeneration.

Tlx1 regulates acinar and duct development in mouse salivary glands.

Tlx1 encodes a transcription factor expressed in several craniofacial structures of developing mice. The role of Tlx1 in salivary gland development was examined using morphological and immunohistochemical analyses of Tlx1 null mice. Tlx1 is expressed in submandibular and sublingual glands but not parotid glands of neonatal and adult male and female C57Bl/6J (Tlx1+/+ ) mice. TLX1 protein was localized to the nuclei of terminal tubule cells, developing duct cells and mesenchymal cells in neonatal submandibular and sublingual glands, and to nuclei of duct cells and connective tissue cells in adult glands. Occasionally, TLX1 was observed in nuclei of epithelial cells in or adjacent to the acini. Submandibular glands were smaller and sublingual glands were larger in size in mutant mice (Tlx1-/- ) compared to wild-type mice. Differentiation of terminal tubule and proacinar cells of neonatal Tlx1-/- submandibular glands was abnormal; expression of their characteristic products, submandibular gland protein C and parotid secretory protein, respectively, was reduced. At 3 weeks postnatally, terminal tubule cells at the acinar-intercalated duct junction were poorly developed or absent in Tlx1-/- mice. Granular convoluted ducts in adult mutant mice were decreased, and epidermal growth factor and nerve growth factor expression were reduced. Along with normal acinar cell proteins, adult acinar cells of Tlx1-/- mice continued to express neonatal proteins and expressed parotid proteins not normally present in submandibular glands. Sublingual gland mucous acinar and serous demilune cell differentiation were altered. Tlx1 is necessary for proper differentiation of submandibular and sublingual gland acinar cells, and granular convoluted ducts. The mechanism(s) underlying Tlx1 regulation of salivary gland development and differentiation remains unknown.

Transcriptomic analysis of the submandibular gland under psychological stress condition.

BACKGROUND: Psychological stress is associated with changes in salivary flow and composition. However, studies to show the effect of psychological stress on the transcriptome of the salivary gland are limited. This study aims to perform a transcriptomic analysis of the submandibular gland under psychological stress using a chronic restraint stress model of rats. METHODS: Sprague-Dawley rats were divided into stress groups and control groups. Psychological stress was induced in the stress group rats by enclosing them in a plastic tube for 4 h daily over 6 weeks. RNA sequencing was performed on RNA extracted from the submandibular gland. The differentially expressed genes were identified, and the genes of interest were further validated using qRT-PCR, immunofluorescence, and western blot. RESULTS: A comparison between control and stress groups showed 45 differentially expressed genes. The top five altered genes in RNA sequencing data showed similar gene expression in qRT-PCR validation. The most downregulated gene in the stress group, FosB, was a gene of interest and was further validated for its protein-level expression using immunofluorescence and western blot. The genesets for gene ontology cellular component, molecular function, and KEGG showed that pathways related to ribosome biosynthesis and function were downregulated in the stress group compared to the control. CONCLUSION: Psychological stress showed transcriptomic alteration in the submandibular gland. The findings may be important in understanding stress-related oral diseases.

Differentiation of submandibular sialadenitis based on apparent diffusion coefficient.

OBJECTIVES: This study aimed to quantify the submandibular gland in suppurative sialadenitis, primary Sjögren's syndrome (pSS) and radiation-induced sialadenitis using the apparent diffusion coefficient (ADC) for differential diagnosis. SUBJECTS AND METHODS: This retrospective study included 16 patients with suppurative sialadenitis (n = 9), pSS (n = 3) and radiation-induced sialadenitis (n = 4) who underwent magnetic resonance imaging between June 2006 and May 2022. The ADC of the submandibular glands in each state was calculated, and the differences were analysed using a one-way analysis of variance and Tukey's post hoc test. Receiver operating characteristic curves were used to assess the ability of the ADC to distinguish each condition. Statistical significance was set at p < 0.05. RESULTS: The mean ADC value (×10-3 mm2/s) ± standard deviation in the control (non-affected side of the suppurative sialadenitis group), suppurative sialadenitis, pSS and radiation-induced groups were 0.94 ± 0.16, 1.24 ± 0.16, 1.33 ± 0.13 and 1.5 ± 0.12, respectively (p < 0.001). The diagnostic value for distinguishing each group was ≥0.75. CONCLUSION: ADC values are useful for quantitatively assessing and distinguishing submandibular glands in suppurative sialadenitis, primary Sjögren's syndrome and radiation-induced sialadenitis.

Oncologic outcomes of the most prevalent major salivary gland cancers: retrospective cohort study from single center.

BACKGROUND: The preoperative diagnosis of salivary gland cancer (SGC) is crucial for the application of appropriate treatment, particularly involving the extension of the resection. METHODS: Retrospective search of medical database identified 116 patients treated surgically with malignant tumors of salivary gland between 2010 and 2020. Analysis included the demographical data, clinical course, type of surgical and adjuvant treatment, histology type and margin status, perivascular invasion (LVI), perineural invasion (PNI), metastatic lymph nodes (LN). Facial nerve function, recurrence-free and overall survival were evaluated. Adequate statistics were used for data analysis. RESULTS: The final cohort included 63 SGC patients, with adenoid cystic carcinoma the most common pathological type (27%, n = 17), followed by adenocarcinoma (17.4% n = 11). T1 and T2 patients accounted for majority cases (n = 46). The lymph node metastases were confirmed with the histopathology in 31.7% (n = 20). Distant metastases were observed in 4.8% of cases (n = 3). 38% (n = 24) of SGC were treated selectively with surgery, 49.2% (n = 31) had postoperative radiotherapy and 15.9% (n = 10)-radio-chemotherapy. The final facial nerve function was impaired in 38% of patients. Mean overall survival (OS) for all patients was 108.7 (± 132.1) months, and was the most favorable for acinar cell carcinoma (118.9 ± 45.4) and the poorest for squamous cell carcinoma (44 ± 32). Cox regression analysis of disease-free survival and OS identified significant association only with patients' age over 65 years, the hazard ratio of 7.955 and 6.486, respectively. CONCLUSIONS: The efficacy of treatment modalities for SGC should be verified with regard to the histopathological type, but also the patients' age should be taken into account.

Novel decision tree models predict the overall survival of patients with submandibular gland cancer.

BACKGROUND: While the accurate prediction of the overall survival (OS) in patients with submandibular gland cancer (SGC) is paramount for informed therapeutic planning, the development of reliable survival prediction models has been hindered by the rarity of SGC cases. The purpose of this study is to identify key prognostic factors for OS in SGC patients using a large database and construct decision tree models to aid the prediction of survival probabilities in 12, 24, 60 and 120 months. MATERIALS AND METHODS: We performed a retrospective cohort study using the Surveillance, Epidemiology and End Result (SEER) program. Demographic and peri-operative predictor variables were identified. The outcome variables overall survival at 12-, 24-, 60, and 120 months. The C5.0 algorithm was utilized to establish the dichotomous decision tree models, with the depth of tree limited within 4 layers. To evaluate the performances of the novel models, the receiver operator characteristic (ROC) curves were generated, and the metrics such as accuracy rate, and area under ROC curve (AUC) were calculated. RESULTS: A total of 1,705, 1,666, 1,543, and 1,413 SGC patients with a follow up of 12, 24, 60 and 120 months and exact survival status were identified from the SEER database. Predictor variables of age, sex, surgery, radiation, chemotherapy, tumor histology, summary stage, metastasis to distant lymph node, and marital status exerted substantial influence on overall survival. Decision tree models were then developed, incorporating these vital prognostic indicators. Favorable consistency was presented between the predicted and actual survival statuses. For the training dataset, the accuracy rates for the 12-, 24-, 60- and 120-month survival models were 0.866, 0.767, 0.737 and 0.797. Correspondingly, the AUC values were 0.841, 0.756, 0.725, and 0.774 for the same time points. CONCLUSIONS: Based on the most important predictor variables identified using the large, SEER database, decision tree models were established that predict OS of SGC patients. The models offer a more exhaustive evaluation of mortality risk and may lead to more personalized treatment strategies.

Evaluation of submandibular and parotid salivary glands by ultrasonography in patients with diabetes.

BACKGROUND: Microvascular complications of diabetes mellitus (DM) include oral manifestations and complications, including xerostomia, reduced salivary flow, susceptibility to infection, periodontal disease and salivary gland enlargement. OBJECTIVE: The present study aims to evaluate B-mode ultrasonography (USG) parameters such as size, volume and echogenicity of the submandibular and parotid salivary glands on both sides, shear-wave elastography (SWE) value and colour Doppler properties in patients with DM and healthy control groups. METHODS: In total, 160 right and left submandibular glands and 160 right and left parotid glands of 80 patients, 40 patients (20 type 1 DM, 20 type 2 DM) and 40 healthy control group, between the ages of 18-70 were examined by USG. Echogenicity, parenchyma internal structure, margin and dimensional measurements (antero-posterior length, supero-inferior length, medio-lateral length and volume) and colour Doppler with 'ML 6-15-D Matrix Array (4-15 MHz)' probe, shear-wave elastography '9L-D (2-8 MHz)' probe was investigated. RESULT: Statistically significant difference was observed in echogenicity in the right submandibular gland, echogenicity in the right parotid gland, margin characteristics, parenchymal homogeneity and colour Doppler characteristics between the type 1 DM, type 2 DM and control groups (p < .05). It was observed that the size, volume and SWE values of both submandibular and parotid glands were higher in the DM patient group than in the control group. Higher values were observed in type 2 DM compared to type 1 DM in the patient group. CONCLUSION: USG is an effective imaging technique in investigating the effects of diabetes on the submandibular and parotid salivary glands.

Comparative analysis of approaches to the Wharton's duct during surgery of the submandibular gland: A retrospective case-control study.

INTRODUCTION: We investigated complications and recurrence rates after surgical techniques for sialolith removal with intact and resected Wharton's duct of the submandibular gland. METHODS: The retrospective case-control analysis of a series analysed 271 surgical operations (2003-2022) for sialolithiasis performed at a hospital department of Otolaryngology-Head and Neck Surgery. The study compared two approaches: (1) pure endoscopic technique or pinpoint stone removal with Wharton's duct left intact and (2) transoral duct dissection or pinpoint stone removal technique, after which the duct was shortened. While choosing the surgical option, the size of the stone, the location of the stone, and the presence of multiple stones were taken into account. The rates of complications (lingual nerve paraesthesia, duct stenosis, drooling, and sialoadenitis), the incidence of foreign bodies, and the rate of recurrence during follow-up of ≥18 months were compared. RESULTS: 323 sialoliths were removed from 271 patients. Of these 323 calculi, 150 were removed by the first approach and 173 by the second approach. The calculi varied in diameter from 2 to 38 mm with an average diameter of 8.2 mm. For all 271 patients, the rate of recurrence was 4.8%, but 11 recurrent cases (8.7%) appeared after the first approach surgeries and 2 cases (1.4%) after the second approach surgeries (p = .03). Other variables did not show statistically significant differences. CONCLUSIONS: Surgical removal of the submandibular calculi, ending with shortening of Wharton's duct, reduces the recurrence rate for sialolithiasis but does not affect the rate of postsurgical complications.

TGF-ß1 Triggers Salivary Hypofunction via Attenuating Protein Secretion and AQP5 Expression in Human Submandibular Gland Cells.

Aging-related salivary gland degeneration usually causes poor oral health. Periductal fibrosis frequently occurs in the submandibular gland of the elderly. Transforming growth factor ß1 (TGF-ß1) is the primary driving factor for fibrosis, which exhibits an increase in the fibrotic submandibular gland tissue. This study aimed to investigate the effects of TGF-ß1 on the human submandibular gland (HSG) cell secretory function and its influences on aquaporin 5 (AQP5) expressions and distribution. We found that TGF-ß1 reduces the protein secretion amount of HSG and leads to the abundance alteration of 151 secretory proteins. Data are available via ProteomeXchange with the identifier PXD043185. The majority of HSG secretory proteins (84.11%) could be matched to the human saliva proteome. Meanwhile, TGF-ß1 enhances the expression of COL4A2, COL5A1, COL7A1, COL1A1, COL2A1, and α-SMA, hinting that TGF-ß1 possesses the potential to drive HSG fibrosis-related events. Besides, TGF-ß1 also attenuates the AQP5 expression and its membrane distribution in HSGs. The percentage for TGF-ß1-induced AQP5 reduction (52.28%) is much greater than that of the TGF-ß1-induced secretory protein concentration reduction (16.53%). Taken together, we concluded that TGF-ß1 triggers salivary hypofunction via attenuating protein secretion and AQP5 expression in HSGs, which may be associated with TGF-ß1-driven fibrosis events in HSGs.

Biofabrication, biochemical profiling, and in vitro applications of salivary gland decellularized matrices via magnetic bioassembly platforms.

Trending three-dimensional tissue engineering platforms developed via biofabrication and bioprinting of exocrine glands are on the rise due to a commitment to organogenesis principles. Nevertheless, a proper extracellular matrix (ECM) microarchitecture to harbor primary cells is yet to be established towards human salivary gland (SG) organogenesis. By using porcine submandibular gland (SMG) biopsies as a proof-of-concept to mimic the human SG, a new decellularized ECM bioassembly platform was developed herein with varying perfusions of sodium dodecyl sulfate (SDS) to limit denaturing events and ensure proper preservation of the native ECM biochemical niche. Porcine SMG biopsies were perfused with 0.01%, 0.1%, and 1% SDS and bio-assembled magnetically in porous polycarbonate track-etched (PCTE) membrane. Double-stranded DNA (dsDNA), cell removal efficiency, and ECM biochemical contents were analyzed. SDS at 0.1% and 1% efficiently removed dsDNA (< 50 ng/mg) and preserved key matrix components (sulfated glycosaminoglycans, collagens, elastin) and the microarchitecture of native SMG ECM. Bio-assembled SMG decellularized ECM (dECM) perfused with 0.1-1% SDS enhanced cell viability, proliferation, expansion confluency rates, and tethering of primary SMG cells during 7 culture days. Perfusion with 1% SDS promoted greater cell proliferation rates while 0.1% SDS supported higher acinar epithelial expression when compared to basement membrane extract and other substrates. Thus, this dECM magnetic bioassembly strategy was effective for decellularization while retaining the original ECM biochemical niche and promoting SMG cell proliferation, expansion, differentiation, and tethering. Altogether, these outcomes pave the way towards the recellularization of this novel SMG dECM in future in vitro and in vivo applications.

Sialin mediates submandibular gland regeneration ability by affecting polysialic acid synthesis.

OBJECTIVES: Sialin is a multifunctional molecule with a well-described role in physiological equilibrium regulation. The aim of this study was to elucidate the role of sialin in salivary glands regeneration. MATERIALS AND METHODS: Submandibular gland duct ligation/deligation of rat was performed to develop a rat model of submandibular gland regeneration. Phenotype changes were investigated using Western blotting and quantitative real-time polymerase chain reaction, as well as immunohistochemical staining. LV-slc17a5-RNAi vectors were injected into the submandibular glands via retroductal instillation to establish a stable sialin-knockdown model. RESULTS: Submandibular gland tissue structure could completely restore 28 days after duct deligation, when the duct had been ligated for 7 days. The expression of sialin, polysialic acid, and polysialyltransferase IV was significantly increased on Day 0 after duct deligation, and it returned to the level of the control group at Day 28. Moreover, sialin knockdown could weakened gland regeneration by reducing polysialic acid synthesis. Supplementing drinking water with polysialic acid precursors (ManNAc) in drinking water could partially rescue submandibular gland regeneration in sialin-knockdown rats. CONCLUSION: These data indicated that sialin was vital for submandibular gland regeneration which mediated the process of gland regeneration by affecting the polysialic acid synthesis.

Alteration of myoepithelial cells during botulinum toxin type A-inhibited salivary secretion.

OBJECTIVE: Intraglandular injection of botulinum toxin type A (BoNT/A) effectively treats sialorrhea. Myoepithelial cells (MECs) are essential for salivary secretion. The role of MECs in BoNT/A-inhibited salivary secretion, and its underlying mechanisms remain unknown. MATERIALS AND METHODS: BoNT/A was injected into rat submandibular glands (SMGs). At 1, 2, 4, 8, and 12 weeks postinjection, salivary flow rate of SMGs was measured. Electron microscopy, immunohistochemistry, immunofluorescence, and Western blot analysis were used to detect morphological and functional changes in MECs and chemical denervation in SMGs. RESULTS: BoNT/A temporarily decreased salivary secretion in rat SMGs and this inhibitory effect lasted 4 weeks. During the inhibitory period, MECs atrophied and expressed reduced α-smooth muscle actin (α-SMA), vimentin, and phosphorylated myosin light chain 2 (p-MLC2), suggesting that BoNT/A attenuated MEC contractility. Furthermore, BoNT/A cleaved synaptosome-associated protein 25 (SNAP-25) and decreased the expression and activity of acetylcholinesterase (AChE), indicating that BoNT/A-induced chemical parasympathetic denervation of SMGs by cleaving SNAP-25. CONCLUSIONS: BoNT/A temporarily caused MEC atrophy and decreased MEC contractility in rat SMGs, which contributed to reversible inhibition of salivary secretion. The underlying mechanisms involved temporary parasympathetic denervation caused by SNAP-25 cleavage. These findings provide new insights into the mechanisms of BoNT/A-inhibited salivary secretion.

Alteration of tight junctions during botulinum toxin type A-inhibited salivary secretion.

OBJECTIVES: Tight junctions (TJs) are involved in the regulation of salivary secretion via paracellular pathway. Botulinum toxin type A (BTXA) is widely used for the treatment of hypersecretion diseases such as sialorrhea. This study aimed to investigate the role of TJs in BTXA-inhibited secretion of the submandibular gland (SMG). MATERIALS AND METHODS: BTXA was injected into the SMGs of rats, and the same amount of saline was injected as a control. Western blot, real-time PCR, and immunofluorescence staining were used to detect the expression and distribution of TJ proteins. Paracellular permeability was evaluated using the transepithelial electrical resistance (TER) measurements and fluorescent tracer detection in BTXA-stimulated SMG-C6 cells. RESULTS: BTXA injection into the SMGs of rats led to increased expression of claudin (Cldn) -1 and Cldn3. Immunofluorescence staining showed no significant changes in the distribution of TJ proteins. In vitro, BTXA increased the TER values and significantly reduced the permeability of fluorescent tracer, suggesting that BTXA decreased the paracellular permeability. The expression levels of Cldn1, Cldn3, and Cldn4 were upregulated after BTXA treatment. CONCLUSION: The expression of TJ proteins changed in both animal models and SMG-C6 cells after BTXA treatment, which may contribute to the inhibition of salivary secretion.

Oxidative-antioxidant imbalance in chronic sialadenitis of submandibular gland in human and rat.

OBJECTIVES: This study aimed to evaluate the level of oxidative stress (OS) in human and rat chronic sialadenitis (CS) of the submandibular gland (SMG). METHOD: We collected human SMG tissues and established a rat CS model using Wharton's duct partial ligation (PL). Morphological changes in the SMG were evaluated by HE, Sirius Red, AB/PAS, TUNEL and immunohistochemical (IHC) staining. Oxidative damage and antioxidant capacity were detected by ELISA, commercial assay kits and IHC staining to evaluate their expression levels and locations in the SMG. RESULTS: Histopathological damage were observed in the human and rat CS. In rat PL group, the oxidative damage products (8-OHdG, AOPP, 8-iso-PGF2α and H2 O2 ) were significantly increased. For antioxidants, the PL group had markedly decreased T-AOC and CAT activity, but markedly increased SOD activity. 3-NT, 4-HNE and MDA expression changed during the process of CS, and antioxidant enzymes (CAT, SOD1, SOD2, GPX1 and GPX4) were mainly expressed in ducts. CONCLUSIONS: The oxidative-antioxidant imbalance of CS in human and rats was revealed, the different expression of oxidative damage during the process of CS was detected, and the different antioxidant reaction in acinar and ductal cells was demonstrated.

Prognostic factors and treatment considerations of submandibular gland carcinomas: A population-based study.

OBJECTIVES: The therapeutic regimen of submandibular gland carcinoma (SGC) has not reached consensus, especially for the neck treatment of patients with cN0. MATERIALS AND METHODS: Patients with SGC were identified from the medical database of Shanghai Ninth People's Hospital. Kaplan-Meier analysis, univariate and multivariate Cox regression were employed to evaluate the survival and independent prognostic factors. RESULTS: Two hundred and fifteen patients with SGC were retrospectively reviewed. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 71.5% and 77.8%, respectively. Multivariate analysis revealed that histological grade, cT classification, cN classification, and perineural invasion (PNI) were independent prognostic factors for DFS, while histological grade, cT classification, cN classification, and age were those for OS. The neck dissection showed no significant survival benefit for patients with cN0. Lung was the most common site of distant metastasis (16.7%). CONCLUSIONS: Histological grade, cT classification, cN classification, age, and PNI were independent prognostic factors of patient with SGC, which should be the main considerations for making therapeutic regimens. Our study also verifies the neck dissection of patient with cN0 is unnecessary, and postoperative radiotherapy (PORT) is vital for patients with pN+.

Carcinoma ex pleomorphic adenoma of the submandibular gland: A retrospective analysis of 86 patients.

OBJECTIVES: To evaluate the prognostic and locoregional metastatic features of carcinoma ex pleomorphic adenoma of submandibular gland (SMG-CXPA) and improve the understanding of this uncommon condition. PATIENTS AND METHODS: We retrospectively reviewed patients who were diagnosed with SMG-CXPA. The survival data of SMG-CXPA patients were statistically analyzed using Cox regression and Kaplan-Meier method. The associations between cervical metastasis and clinicopathological parameters were evaluated using chi-squared test. Additionally, two different histological categories (histological grade and invasiveness) and their combination were evaluated with the Kaplan-Meier method and receiver operating characteristic curves. RESULTS: In total, 86 patients were diagnosed: 38 clinically node-negative, 31 pathologically node-negative, and 17 node-positive patients. Clinical tumor stage and histological grade were two independent prognostic factors for SMG-CXPA. There were significant correlations between sex, tumor size, clinical tumor stage, clinical lymph node stage, histological grade, invasiveness, malignant components, perineural invasion, and no specific criteria exist for the clinical outcome. CONCLUSION: SMG-CXPA is a high-grade malignancy with an unfavorable prognosis. Elective neck dissection should be performed in SMG-CXPA patients with a risk of locoregional metastasis. Histological grade seems to be a more valuable predictor of lymph node involvement than invasiveness.

Assessment of Dimensional Changes in Submandibular Glands in Head-Neck Radiotherapy Patients by Ultrasonography.

OBJECTIVES: The present study investigated the dimensional changes in the submandibular glands following radiotherapy using ultrasonography. METHODS: Twenty-three patients planned to receive head-neck radiotherapy were included in this study. The anteroposterior, superoinferior, mediolateral length, and volumes of 46 submandibular glands were measured by ultrasonography at 3 different time periods (before radiotherapy and in the second and sixth months after the radiotherapy onset) and evaluated in terms of dimensional changes and the effect of the radiation dose on these changes. The data were statistically analyzed using repeated measures analysis of variance (ANOVA) and 2-factor repeated measures ANOVA. RESULTS: Before radiotherapy and in the second and sixth months after the radiotherapy onset, mean anteroposterior length of the submandibular glands was 32.39 ± 4.55, 30.38 ± 4.80, and 31.50 ± 3.68 mm, respectively; mean superoinferior length was 9.96 ± 1.54, 8.76 ± 1.26, and 9.08 ± 1.01 mm, respectively; mean mediolateral length was 24.66 ± 3.77, 22.03 ± 3.73, and 21.76 ± 4.01 mm, respectively; and mean volume was 4.21 ± 1.01, 3.08 ± 0.77, and 3.32 ± 0.63 cm3 , respectively. Moreover, there were significant differences in the anteroposterior (P < .01), superoinferior (P < .001), and mediolateral lengths (P < .001), as well as the volumes (P < .001) of the submandibular glands measured at the 3 different time periods. CONCLUSION: In the second and sixth months after the radiotherapy onset, the sizes of the submandibular glands were markedly reduced, but it partially recovered to normal as more time elapsed after radiotherapy.

Value of High-Frequency Ultrasonography in the Qualitative and Semi-Quantitative Assessment of Immunoglobulin G4-Related Submandibular Sialadenitis.

OBJECTIVE: To assess the value of high-frequency ultrasonography in the evaluation of immunoglobulin G4-related submandibular sialadenitis (IgG4-SS). METHODS: Thirty-four submandibular glands in 17 patients with IgG4-SS were retrospectively enrolled, as well as 34 submandibular glands in 17 healthy control subjects. Qualitative ultrasonic features including submandibular gland size, border, echogenicity, and vascularity were reviewed. Two different scoring systems (0-16 and 0-48, respectively) were used for semi-quantitative analysis of imaging features. Comparison of both qualitative and semi-quantitative ultrasonic analysis were made between patients with IgG4-SS and healthy controls. Spearman correlation was used to explore relationships between variables. RESULTS: The submandibular glands with IgG4-SS presented with enlarged size, rough border, increased vascularity, and abnormal echogenicity (All P < .05). The most common echogenicity pattern for IgG-SS was diffuse hypoechoic foci pattern (44.1%), followed by superficial hypoechoic pattern (20.6%), tumor-like pattern (14.7%), and diffuse hypoechogenicity pattern (11.8%). Most IgG4-SS glands presented linear hyperechogenicity in parenchyma (91.2%). Based on both scoring system, scores of IgG4-SS were significantly higher than those of the controls (All P < .05). Association analysis of both scoring systems showed positive correlation of scores with vascularity in the gland parenchyma (All P < .05). CONCLUSION: The ultrasonic features of IgG4-SS comprise enlarged gland, rough border, increased vascularity, and abnormal echogenicity, which correlate with its pathological characteristics. The most common echogenicity pattern for IgG4-SS was diffuse hypoechoic foci pattern. Semi-quantitative analysis systems could be useful in the assessment of IgG4-SS. Ultrasound is a potential, valuable, and non-invasive tool for the diagnosis and evaluation of IgG4-SS.