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Importance: Metastases to the submandibular gland (SMG) from oral cavity primaries are very rare. Hence, a gland-preserving level IB dissection technique is a feasible option without compromising the lymph node yield (LNY). Objective: To assess the feasibility and noninferiority of the SMG-preserving dissection technique to the conventional en bloc removal of level IB in terms of LNY in patients with cN0 oral squamous cell carcinoma (OSCC) undergoing elective neck dissection. Design: Parallel-design, single-center, open-label, randomized controlled trial. Setting: Tertiary care health care center—Department of Otorhinolaryngology-Head & Neck Surgery, AIIMS Rishikesh. Participants: Thirty-eight (n = 38) participants with 46 (n = 46) neck dissection specimens of OSCC were randomly allocated (1:1) into gland-preserving (n1 = 23) and en bloc (n2 = 23) dissection groups. Intervention: Elective neck dissection comparing SMG-sparing level IB dissection technique versus en bloc level IB dissection. Main Outcome Measures: LNY, lymph node density, and level IB operative time in both groups were compared between groups (α <.05). Results: Median LNY (P =.543) and lymph node density (P = 1.000) in level IB did not show significant differences between the groups. LNY in level IB by gland-preserving technique is also not inferior to the conventional en bloc dissection technique (mean difference = 0.217; 95% CI: [−0.597, 1.032]; P =.593). The mean level IB operative time is significantly longer in the gland-preserving group (P <.001). Conclusions and Relevance: None of the examined SMGs were involved by the tumor. SMG-preserving technique is noninferior to the traditional technique of level IB clearance and can be used in elective neck dissections without compromising the LNY. Functional neck dissection has greatly evolved to decrease patient morbidity, and this method can be adopted in case-specific situations. Trial registration: The trial was registered in the Clinical Trials Registry—India (CTRI/2022/05/042344) on May 2, 2023, https://ctri.nic.in/. [ABSTRACT FROM AUTHOR]

The surgical management of extensive jugular foramen schwannomas presents a formidable challenge, aiming for gross total resection while minimizing complications. Here, we present a case with giant triple dumbbell-shaped jugular Foramen Schwannoma. A 45-year-old male with a one-year history of a left neck mass underwent surgery. Initial misdiagnosis of submandibular gland inflammation led to persistent symptoms despite anti-inflammatory treatment. Imaging revealed a large lesion in the left cerebellar peduncle-neck-jugular foramen region (39.6 x 26.2 x 90 mm). The combination of retrosigmoid and transcervical approach was selected. Sufficient drilling of the infralabyrinthine, retrofacial area of the mastoid with facial nerve transposition is important for the safe gross total removal of the tumor. The patient underwent a gross total removal of the tumor. Facial nerve function was preserved. Although dysphagia and hoarseness complicated postoperatively, he became able to take foods orally after the surgery. In conclusion, this case underscores the successful surgical approach for a large jugular foramen Schwannoma, emphasizing the importance of precise techniques to achieve complete tumor resection while minimizing postoperative complications. [ABSTRACT FROM AUTHOR]

Salivation is easily taken for granted, but without normal salivation, simple essential tasks such as chewing and swallowing become difficult, with consequences for quality of life, nutrition and oral health. Many important drug classes cause dry mouth as a side effect, contributing substantially to patient non-compliance. Available treatments are mostly palliative. Cannabis user complaints of dry mouth prompted a study that showed that basal salivation is likely regulated by cannabinoid CB1 receptors on neurons that innervate the submandibular gland. But what about stimulated salivation? The adjoining parotid gland releases saliva in response to olfactory or other cues and contributes a large portion of the net salivation in humans. We investigated cannabinoid regulation of stimulated salivation using functional and protein-expression studies in mice. In developing a model of stimulated salivary responses to food-related odorants in mice, we noted sex-dependent responses to food-related cues. Only male mice learned to salivate in response to the odor of peanut butter while only female mice responded to a chocolate hazelnut spread. Both males and females responded to sugar or marmite. Testing peanut butter, we found that the cannabinoid receptor agonist CP55940 (0.5 mg/kg, IP) lowered baseline salivation, as shown previously, but also prevented the odorant-induced increase in salivation. CB1 receptors are expressed in axons innervating the parotid gland, paralleling our findings in the submandibular gland. Notably, we also found that CB1 deletion impaired some responses (those to peanut butter and chocolate hazelnut spread) but not others (sugar or marmite). In mice, the CB1 antagonist SR141716 (4 mg/kg, IP) prevented a previously learned salivary response to peanut butter. We find that CB1 receptors are expressed in a subset of glomeruli in coronal sections of olfactory bulb that may serve as a site of action for scent-specific effects of CB1 receptors. We additionally observe CB1 expression in accessory olfactory bulb. In summary, we find a novel sex-dependence in responses to a subset of food-related odorant cues and that cannabinoid receptors regulate some of these responses. We propose that CB1 receptors act at the parotid gland to inhibit stimulated salivation but also in the olfactory system, where functional CB1 receptors are required for salivary responses to specific appetitive odors. [ABSTRACT FROM AUTHOR]

Introduction: Primary Sjögren syndrome (pSS) is a systemic autoimmune disease that is characterized by the infiltration of immune cells into the salivary glands. The re-establishment of salivary glands (SGs) function in pSS remains a clinical challenge. Myeloid-derived growth factor (MYDGF) has anti-inflammatory, immunomodulatory, and tissue-functional restorative abilities. However, its potential to restore SGs function during pSS has not yet been investigated. Methods: Nonobese diabetic (NOD)/LtJ mice (pSS model) were intravenously administered with adeno-associated viruses carrying MYDGF at 11 weeks of age. Salivary flow rates were determined before and after treatment. Mice were killed 5 weeks after MYDGF treatment, and submandibular glands were collected for analyses of histological disease scores, inflammatory cell infiltration, PCR determination of genes, and Western blotting of functional proteins. Furthermore, mRNA sequencing and bioinformatics were used to predict the mechanism underlying the therapeutic effect of MYDGF. Results: Treatment of NOD/LtJ mice with MYDGF alleviated pSS, as indicated by increased salivary flow rate, reduced lymphocyte infiltration, attenuated glandular inflammation, and enhanced AQP5 and NKCC1 expression. The gene expression levels of cytokines and chemokines, including Ccl12, Ccl3, Il1r1, Ccr2, Cx3cr1, Il7, Mmp2, Mmp14, Il1b, and Il7, significantly decreased after treatment with MYDGF, as determined by RNA sequencing. Meanwhile, MYDGF inhibits infiltration of macrophages (Mf) in SGs, induces polarization of M2f, and suppresses C-X3C motif ligand 1 (CX3CL1)/C-X3C motif receptor 1 (CX3CR1) axis. Conclusions: Our findings showed that MYDGF could revitalize the SGs function of pSS, inhibit infiltration of Mf, and promote M2f polarization via suppression of the CX3CL1/CX3CR1 axis, which has implications for potential therapy for pSS. [ABSTRACT FROM AUTHOR]

Previous studies have shown that the mean dose to the parotid gland stem cell rich regions (D mean,SCR) is the strongest dosimetric predictor for the risk of patient-reported daytime xerostomia. This study aimed to test whether the relationship between patient-reported xerostomia and D mean,SCR is explained by a dose-dependent reduction of saliva production. In 570 patients with head and neck cancer treated with definitive radiation therapy (RT), flow from the parotid (FLOW PAR) and submandibular/sublingual (FLOW SMSL) glands, and patient-reported daytime (XER DAY) and nighttime (XER NIGHT) xerostomia were prospectively measured before, at 6 months, and 12 months after RT. Using linear mixed effect models, the relationship of the mean dose to the parotid glands (D mean,par), D mean,SCR , non-SCR parotid gland tissue (D mean,non-SCR), submandibular glands (D mean,sub), and oral cavity (D mean,oral) with salivary flow and xerostomia was analyzed while correcting for known confounders. D mean,SCR proved to be responsible for the effect of D mean,par on FLOW PAR (P ≤.03), while D mean,non-SCR did not affect FLOW PAR (P ≥.11). To illustrate, increasing D mean,SCR by 10 Gy at a fixed D mean,non-SCR reduced FLOW PAR by 0.02 mL/min (25%) after RT. However, if the opposite happened, no change in FLOW PAR was observed (0.00 mL/min [4%]). As expected, D mean,sub was significantly associated with FLOW SMSL (P <.001). For example, increasing D mean,sub by 10 Gy reduced FLOW SMSL by 0.07 mL/min (26%) after RT. Xerostomia scores were also affected by dose to the salivary glands. D mean,SCR and D mean,oral were associated with higher XER DAY scores (P ≤.05), while D mean,sub increased XER NIGHT scores (P =.01). For example, an increase of 10 Gy in D mean,SCR raised XER DAY scores by 2.13 points (5%) after RT, while an additional 10 Gy in D mean,subs increased XER NIGHT scores by 2.20 points (6%) after RT. Salivary flow was not only associated with radiation dose, but also with xerostomia scores in line with the salivary glands' functions; ie, FLOW PAR only influenced XER DAY (P <.001, 10.92 points lower XER DAY per 1 mL/min saliva), while FLOW SMSL affected XER DAY and XER NIGHT (P ≤.004, 6.69 and 5.74 points lower XER DAY and XER NIGHT , respectively, per 1 mL/min saliva). Therefore, the observed relationships between dose and xerostomia were corrected for salivary flow. As hypothesized, D mean,SCR only increased XER DAY scores via reducing FLOW PAR , whereas the effects of D mean,oral on XER DAY and D mean,sub on XER NIGHT were independent of salivary flow. Higher SCR region dose reduced parotid gland saliva production, subsequently resulting in higher daytime xerostomia scores. Consequently, this study supports the clinical implementation of stem cell sparing RT to preserve salivary flow with the aim of reducing the risk of xerostomia. [ABSTRACT FROM AUTHOR]

Background: To investigate the clinicopathologic characteristics, therapeutic methods, and prognosis of secretory carcinoma of salivary gland (SCSG). Methods: The clinicopathologic data of 13 patients with SCSG admitted to Shanxi Cancer Hospital from January 2018 to June 2023 were retrospectively analyzed, and a literature review was performed. Results: A total of eight males and five females aged 22–78 years old were enrolled, and they commonly presented with painless masses in the parotid or submandibular gland. They all underwent surgical treatment, accompanied by typical pathological examinations postoperatively. Fluorescence in situ hybridization (FISH) was conducted in seven cases, the results were all positive, and no gene fusion other than ETV6-NTRK3 was found. Two patients developed local relapse during follow-up, both of which were in the surgical area. By the end of the follow-up, 12 patients survived and one patient died. Conclusions: SCSG is a rare low-grade malignancy with a good prognosis. Pathological and immunohistochemical characteristics are the key to secretory carcinoma (SC) diagnosis, and surgical excision is the major treatment means for SCSG. Whether to perform simultaneous cervical lymph node dissection and other adjuvant therapies should be determined based on the pathological stage and the presence or absence of high-risk factors. [ABSTRACT FROM AUTHOR]

This report presents a rare case of direct invasion from a metastatic submandibular lymph node (SMLN) to submandibular gland (SMG) in a resected specimen of neck dissection (ND) of buccal mucosal squamous cell carcinoma (SCC). The patient was an 82‐year‐old woman with a clinical diagnosis of the left buccal mucosal SCC (cT4bN2bM0, Stage IVB). The tracheostomy, modified radical neck dissection, buccal mucosal cancer resection including maxillary partial resection, mandibular segmentectomy, and reconstructive surgery with a plate and a free rectus abdominis flap were performed. Pathologically, the infiltrating SCC was observed in the SMG continuous with SMLN metastasis (pT4bN3bM0). No adjuvant therapy was performed for old age and oral intake dysfunction. Contrast CT detected the multiple lung and left scapula metastases at postoperative 5 months, which made the policy of best supportive care. Finally, she died 9 months after the surgery from distant metastases. SMG involvement from direct invasion from a metastatic SMLN is relatively rare. In our case, although the patient died from distant metastases, locoregional control was achieved through curative resection of the primary tumor and ND performed as one block with reconstructive surgery. [ABSTRACT FROM AUTHOR]

This letter discusses the occurrence of tuberculosis (TB) paradoxical reactions (PRs) in patients being treated with tumor necrosis factor (TNF) inhibitors. PRs are defined as the worsening of clinical or radiological findings after the initiation of appropriate antimycobacterial therapy. The authors report 15 cases of PRs in 12 patients, with most reactions occurring long after the completion of TB treatment. The article provides a table detailing the characteristics of these cases. The report emphasizes the need for clinicians to be vigilant for delayed PR presentations in patients who have received TNF inhibitor therapy, as anti-inflammatory therapy may be more important than reintroducing antimicrobial therapy. The report also mentions the increased number of TB cases associated with TNF inhibitor therapy and the potential role of immune abnormalities in PR. [Extracted from the article]

Background: The effects of unilateral submandibular gland excision on the size of the contralateral gland are not well understood, with no human studies reported to date. This study aims to investigate the impact of unilateral submandibular gland excision on the contralateral gland's size, providing insights into compensatory mechanisms and their clinical implications. Method: This retrospective study involved patients with oral cancer who underwent unilateral submandibular gland excision and ipsilateral neck dissection at Gangneung-Wonju National University Dental Hospital between 2008 and 2023. Patients were included if they had preoperative and follow-up 3D radiological images. The contralateral submandibular gland volume was measured using 3D Slicer software on preoperative, post-operative, and follow-up radiographic data. Results: The mean volume change of the contralateral submandibular gland was 1.35 ± 2.06 cm3, with a mean change ratio of 1.18 ± 0.24. These changes were statistically significant (p = 0.006). Other factors such as age, gender, and radiotherapy did not significantly affect the volume change ratio (p > 0.05). Conclusion: The contralateral submandibular gland exhibits a statistically significant increase in volume following unilateral gland excision, indicating compensatory hypertrophy. This morphological adaptation should be considered in post-operative care and surgical planning for oral cancer patients to optimize outcomes. [ABSTRACT FROM AUTHOR]

Occasionally, obtaining an adequate or acceptable postmortem blood specimen for drug analysis is not possible due to factors such as decomposition, exsanguination, or embalming. Submandibular salivary gland tissue, one of three major types of salivary gland tissue in the oral cavity of humans, has been reported to be a viable alternative postmortem specimen for toxicological testing. In this study, we evaluated the performance of the Randox Evidence Investigator instrument and Randox DOA (Drugs of Abuse) Ultra Whole Blood Array for the semi-quantitative determination of 21 immunoassays in an alternative matrix, submandibular salivary gland tissue. We analyzed 132 submandibular salivary gland tissue specimens and compared the generated results to concomitantly collected postmortem whole blood specimen results. Oxycodone 2, meprobamate, barbiturate, benzodiazepine assay 1, zolpidem, and buprenorphine all showed perfect agreement (Cohen's kappa score = 1.00) between the submandibular salivary gland tissue results and the postmortem whole blood results; dextromethorphan, fentanyl, benzoylecgonine, methamphetamine, tricyclic antidepressants, oxycodone 1, and opiate showed an almost perfect agreement (Cohen's kappa score = 0.81–0.99); methadone, generic opioids, and amphetamine exhibited substantial agreement (Cohen's kappa score = 0.61–0.80). Tramadol demonstrated fair agreement (Cohen's kappa score = 0.41–0.60). The lowest measure of agreement was observed with cannabinoids, meeting criteria for slight agreement (Cohen's kappa score = 0.01–0.20). An application of the techniques described in this study could be implemented in postmortem toxicology laboratories as well as medical examiners offices to provide preliminary drugs of abuse test results that can be used to direct additional testing. This study highlights the successful integration of a novel specimen matrix and an "off-label" use of an established analytical technique. [ABSTRACT FROM AUTHOR]

Aims: Radiotherapy inevitably causes radiation damage to the salivary glands (SGs) in patients with head and neck cancers (HNCs). Excessive reactive oxygen species (ROS) levels and imbalanced mitochondrial homeostasis are serious consequences of ionizing radiation in SGs; however, there are few mitochondria-targeting therapeutic approaches. Glycyrrhizin is the main extract of licorice root and exhibits antioxidant activity to relieve mitochondrial damage in certain oxidative stress conditions. Herein, the effects of glycyrrhizin on irradiated submandibular glands (SMGs) and the related mechanisms were investigated. Results: Glycyrrhizin reduced radiation damage in rat SMGs at both the cell and tissue levels, and promoted saliva secretion in irradiated SMGs. Glycyrrhizin significantly downregulated high-mobility group box-1 protein (HMGB1) and toll-like receptor 5 (TLR5). Moreover, glycyrrhizin significantly suppressed the increases in malondialdehyde and glutathione disulfide (GSSG) levels; elevated the activity of some critical antioxidants, including superoxide dismutase, catalase, glutathione peroxidase, and glutathione (GSH); and increased the GSH/GSSG ratio in irradiated cells. Importantly, glycyrrhizin effectively enhanced thioredoxin-2 levels and scavenged mitochondrial ROS, inhibited the decline in mitochondrial membrane potential, improved adenosine triphosphate synthesis, preserved the mitochondrial ultrastructure, activated the proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α)/nuclear respiratory factor 1/2 (NRF1/2)/mitochondrial transcription factor A (TFAM) signaling pathway, and inhibited mitochondria-related apoptosis in irradiated SMG cells and tissues. Innovation: Radiotherapy causes radiation sialadenitis in HNC patients. Our data suggest that glycyrrhizin could be a mitochondria-targeted antioxidant for the prevention of radiation damage in SGs. Conclusion: These findings demonstrate that glycyrrhizin protects SMGs from radiation damage by downregulating HMGB1/TLR5 signaling, maintaining intracellular redox balance, eliminating mitochondrial ROS, preserving mitochondrial homeostasis, and inhibiting apoptosis. [ABSTRACT FROM AUTHOR]

Cavernous hemangioma in the submandibular gland is rare. A 18 year old boy presented with complaints of swelling over left submandibular region for past 4 years. MRI done and showed a well defined lobulated lesion of size 3 x 1.9 x 2.5cm in the left parapharyngeal space and posteromedial to left body and ramus of mandible. He underwent excision of the submandibular gland along with the mass through the submandibular incision without any complication. Histo-pathology report showed salivary gland parenchyma with numerous congested blood vessels in the septa with a benign lesion composed of various sized dilated blood filled cavernous spaces with haemorrhage separated by a vary thin fibrous septa in microscopic view and features suggestive of cavernous haemangioma. [ABSTRACT FROM AUTHOR]

Introduction: Salivary gland lesions are one of the most common encounters in clinical practice for the evaluation of which Fine needle aspiration cytology is a well-established technique nowadays. Owing to the heterogenicity and morphological overlap between the various categories of these salivary gland lesions, there was a need for a standardized procedure. The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) provides a standardized evidence-based reporting system and thus helpful for the management of these lesions. We have undertaken this study for evaluation of salivary gland lesions by this newly introduced grading system for predicting the malignant potential of these lesions. Materials and Methods: The present study was carried out in the Cytopathology Laboratory, Department of Pathology, P.D.U Medical College and Hospital, Rajkot, Gujarat carried out over a period of 1 year between August 2023 to July 2024. All the cases referred to the department of Pathology from the Department of Surgery, ENT, and Dental Surgery for evaluation of salivary gland lesions were included in the study. Clinical data and radiological assessment were done in all these cases. Fine needle aspiration was done. Smears are prepared and the slides were stained with H and E stain, Giemsa stain and PAP stain was used in cases where required. All the cases were categories according to MSRSGC. Result: We have received 60 salivary gland lesions for aspiration over a period of one year. The most affected age group was from 21 to 40 years. Most of the study subjects were presented with parotid swellings (73%) followed by submandibular gland (25%). As per the MSRSGC classification system, 16 cases were categorized as non-neoplastic while 44 as neoplastic lesions. Of the non-neoplastic cases, 01(2%) were grouped in category I, 15 (25%) in category II. Out of the 44 salivary gland neoplasms, 32(53%) cases were in category IVa and 4(7%) cases in category IVb, 2(3%) cases in category V, and 6(10%) cases in category VI. Conclusion: MSRSGC is a six-category scheme that is recently proposed that separates the salivary gland FNAC into distinct categories, thus increasing the specificity by limiting the number of false negative and false positive cases. [ABSTRACT FROM AUTHOR]

BACKGROUND: Calcium hydroxyapatite (CaHA) dermal filler has been increasingly used in facial aesthetic procedures. OBJECTIVE: To investigate clinical and histological changes associated with calcium hydroxyapatite (CaHA) dermal filler in the orofacial region. MATERIALS AND METHODS: Forty-eight female Wistar rats were divided into CaHA and control groups. The material was applied in the ventral tongue and the submandibular region; the animals were euthanized after 7, 30, and 90 days. RESULTS: After 7 days, yellowish nodules with a firm consistency were observed on the tongue. In 2 animals, the material migrated to the base of the tongue. Histopathological examination revealed CaHA spheres surrounded by an infiltrate, predominantly composed of macrophages. In the CaHA group, the percentage of collagen in the tongue and dermis was higher compared with the control group (p, .05) at both 30 and 90 days. The thickness of the epidermis/dermis was also higher in the CaHA group (p, .05). In 5 submandibular glands containing material, areas of edema and hyperemia were observed, along with infiltrates of neutrophils, lymphocytes, and plasma cells. Changes in the morphology of ducts and acini in adjacent regions were evident. CONCLUSION: CaHA exhibits satisfactory properties for filling and collagen biostimulation in the tested regions. Further studies are required to explore the potential for migration and the glandular alterations. [ABSTRACT FROM AUTHOR]

Thymus is a paired organ which develops during the sixth week of fetal life, attains maximum size by three years and involutes in adult life. Anatomically it is situated in superior mediastinum. Thymus can be present at ectopic sites like neck, skull base, middle ear, submandibular gland and tonsil. Ectopic Cervical Thymus (ECT) is very rare in adults and can present as a solid mass, cyst or thymoma. ECT occurs due to failure of descent during embryonic development. ECT can mimic any pathologic mass, metastatic deposit or lymph node enlargement. We report a case of ECT discovered incidentally in an adult during histopathological examination of thyroid carcinoma. In addition, we described the role of immunohistochemistry markers to confirm the various thymic components. [ABSTRACT FROM AUTHOR]

Mumps, caused by the mumps virus, is a contagious disease primarily affecting children and young adults. While typically presenting with salivary gland swelling and systemic symptoms, mumps can lead to various complications including SNHL, orchitis/ oophoritis, aseptic meningitis. Recent observations suggest atypical features in mumps cases, raising concerns of a potential outbreak in India. To discuss the etiopathogenesis and clinical presentation in cases of atypical mumps with increasing number of cases, a prospective multicentric study was conducted across five major centers - SMS Medical College Jaipur, RDBP Jaipuria Hospital, Jaipur, Shri Ashwini Saxena ENT Hospital Rewari, AIIMS Bhubaneswar and SP Medical College Bikaner, in India to evaluate patients with acute salivary gland swellings. Clinical and laboratory data were collected, including demographics, presenting symptoms, history of vaccination, imaging findings, and treatment outcomes. Patients were followed for four weeks post-treatment to monitor for delayed complications. Among 53 patients, a bimodal age distribution was observed, with peaks in early adolescents and middle-aged individuals. Vaccination status was recorded based on recall. Fever and salivary gland swelling were predominant symptoms, with a significant proportion experiencing submandibular gland involvement. Elevated serum amylase and CRP levels correlated with disease severity and prolonged symptomatic resolution. Notably, cases of sensorineural hearing loss (SNHL) and airway complications emerged as significant concerns. The study highlights a shift in mumps demographics, with higher age groups affected and increased incidence of complications like SNHL and airway compromise. International trends also suggest periodic outbreaks and evolving clinical manifestations post-COVID-19 pandemic. Factors contributing to mumps resurgence include lack of vaccination or vaccine efficacy, population immunity, and seasonal variations. India appears to be facing a potential mumps outbreak, characterized by atypical features and increased risk of complications like SNHL and airway compromise. Serum amylase and CRP serve as valuable markers for disease severity. Early recognition and management of complications are crucial, emphasizing the importance of mumps immunization to mitigate the impact of the disease. ENT specialists should remain vigilant for emerging complications, particularly SNHL, advocating for comprehensive immunization strategies. [ABSTRACT FROM AUTHOR]

Epithelioid haemangioendothelioma (EHE) is a rare vascular tumour that primarily affects the liver, lungs and bone. It is very rarely described in the head and neck region, and is exceptionally uncommon within the submandibular region. We report a very rare case of EHE originating in a lymph node within the submandibular salivary gland of a 54-year-old female patient. The tumour was resected and the patient was regularly followed up, with no recurrence of disease at 24 months postoperatively. A review of existing literature, clinical and immunohistopathological features are discussed, which highlight the diagnostic dilemma, absence of consensus for management and appropriate surveillance method associated with EHE. [ABSTRACT FROM AUTHOR]

The study aimed to determine the influencing factors, reference range, the changes of salivary gland secretion function and repeatability of measurements taken from ultrasound (US) viscoelastic imaging in the salivary glands of healthy adults. From August 2023 to October 2023, 206 healthy adults were recruited. In November 2023, 50 healthy adults were recruited for acid stimulation testing. All volunteers underwent conventional and viscoelastic US of the salivary glands. The viscoelasticity values in different regions of interest (ROI), observers, genders, ages, body mass index (BMI) groups and before and after acid stimulation were compared separately. A two-sided 95% reference range was estimated accordingly. There was no difference in the E-mean and V-mean values among different ROIs (p > 0.05). The intra-group correlation coefficient values between the different observers were all >0.908. Except for the influence of age on the E-mean value of the parotid gland, the V-mean of the parotid gland, the E-mean and V-mean of the submandibular gland were not affected by age, gender or BMI. Finally, differences were detected in the E-means and V-means of the parotid and submandibular glands before and after acid stimulation (p < 0.05). US viscoelastic imaging is a simple and reliable technique for evaluating the stiffness and viscosity of salivary glands in healthy adults. It also can be used to dynamically evaluate the changes of salivary gland secretion function. [ABSTRACT FROM AUTHOR]

Tertiary lymphoid structures (TLSs) are formed in tissues targeted by chronic inflammation processes, such as infection and autoimmunity. In Sjögren's disease, the organization of immune cells into TLS is an important part of disease progression. Here, we investigated the dynamics of tissue resident macrophages in the induction and expansion of salivary gland TLS. We induced Sjögren's disease by cannulation of the submandibular glands of C57BL/6J mice with LucAdV5. In salivary gland tissues from these mice, we analyzed the different macrophage populations prior to cannulation on day 0 and on day 2, 5, 8,16 and 23 post-infection using multicolored flow cytometry, mRNA gene analysis, and histological evaluation of tissue specific macrophages. The histological localization of macrophages in the LucAdV5 induced inflamed salivary glands was compared to salivary glands of NZBW/F1 lupus prone mice, a spontaneous mouse model of Sjögren's disease. The evaluation of the dynamics and changes in macrophage phenotype revealed that the podoplanin (PDPN) expressing CX3CR1+ macrophage population was increased in the salivary gland tissue during LucAdV5 induced inflammation. This PDPN+ CX3CR1+ macrophage population was, together with PDPN+CD206+ macrophages, observed to be localized in the parenchyma during the acute inflammation phase as well as surrounding the TLS structure in the later stages of inflammation. This suggests a dual role of tissue resident macrophages, contributing to both proinflammatory and anti-inflammatory processes, as well as their possible interactions with other immune cells within the inflamed tissue. These macrophages may be involved with lymphoid neogenesis, which is associated with disease severity and progression. In conclusion, our study substantiates the involvement of proinflammatory and regulatory macrophages in autoimmune pathology and underlines the possible multifaceted functions of macrophages in lymphoid cell organization. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to compare the salivary gland ultrasonography(SGUS) findings in patients with primary Sjögren's Syndrome (pSS) and diabetes mellitus(DM) patients with sicca symptoms and to examine the relationship between salivary gland ultrasonography (SGUS) findings with clinical and laboratory parameters. Methods: In this study, 34 patients with pSS and 34 DM patients with sicca symptoms were included. In all patients, bilateral parotid, and submandibular gland ultrasonography (totally 272 glands) was performed by blinded rheumatologist, using the Hocevar and the Outcome Measures in Rheumatology (OMERACT) scoring system. Clinic and ultrasonographic variables were compared between groups. The association between SGUS score and disease duration was analyzed by correlation analysis. Results: Patients with pSS presented significantly higher SGUS scores than patients with DM (the Hocevar score; 20.93(± 9.65) vs. 3.82(± 3.71); p < 0.05, the OMERACT score; 5.96(± 2.30) vs. 2.07(± 1.65); p < 0.05, respectively). In patients with pSS, the submandibular gland scores were significantly higher than the parotid gland scores (right; p < 0.05 vs. left; p < 0.01) while DM patients showed significantly higher parotid gland scores (right; p < 0.05 vs. left; p < 0.05). In pSS patients, the SGUS scores were associated with disease duration (r = 0.57; r = 0.50; p < 0.05), symptom duration (r = 50; r = 0.47; p < 0.05), and the European League Against Rheumatism Sjögren's Syndrome Patient Reported Index (ESSPRI)-dryness score (r = 0.35, r = 0.36; p < 0.05). However, in DM patients, the SGUS scores are highly correlated with the ESSPRI-dryness (r = 0.74, r = 0.72; p < 0.05) and HbA1C level (r = 0.91, r = 0.86; p < 0.05). Conclusions: This study demonstrated that major salivary gland involvement was more severe and correlated with disease duration, and submandibular gland was dominantly affected in pSS. Contrarily, in DM patients, salivary gland involvement was milder, parotid dominant and related to level of dryness and HbA1C, rather than disease duration when compared to pSS, [ABSTRACT FROM AUTHOR]

Native mucus is heterogeneous, displays high inter-individual variation and is prone to changes during harvesting and storage. To overcome the lack of reproducibility and availability of native mucus, commercially available purified mucins, porcine gastric mucin (PGM) and mucin from bovine submaxillary gland (BSM), have been widely used. However, the question is to which extent the choice of mucin matters in studies of their interaction with polymers as their composition, structure and hence physicochemical properties differ. Accordingly, the interactions between PGM or BSM with two widely used polymers in drug delivery, polyethylene oxide and chitosan, was studied with orthogonal methods: turbidity, dynamic light scattering, and quartz crystal microbalance with dissipation monitoring. Polymer binding and adsorption to the two commercially available and purified mucins, PGM and BSM, is different depending on the mucin type. PEO, known to interact weakly with mucin, only displayed limited interaction with both mucins as confirmed by all employed methods. In contrast, chitosan was able to bind to both PGM and BSM. Interestingly, the results suggest that chitosan interacts with BSM to a greater extent than with PGM indicating that the choice of mucin, PGM or BSM, can affect the outcome of studies of mucin interactions with polymers. [ABSTRACT FROM AUTHOR]

Soft tissue masses are very common and may appear in the context of rheumatic diseases. They usually occur alone but may occasionally be part of the syndromes and can sometimes involve periarticular tissues. Soft tissue masses can be divided into several categories. In this article, we have categorized them into 3 different groups: (1) pseudotumors, (2) benign tumors, and (3) malignant tumors. Parotid enlargement will also be discussed in this study. The majority of Soft tissue masses are pseudotumors or benign tumors, which can be easily characterized with ultrasound, therefore, considered the first screening tool in the study of this type of lesion. If the tumor is deep or poorly accessible, or present with suspected signs of malignancy, the sonographer may suggest expanding the study with magnetic resonance imaging and/or an ultrasound-guided biopsy of the lesion. Ultrasound is also a good technique for the parotid and submandibular glands and is very useful for evaluating and monitoring Sjogren's syndrome. [ABSTRACT FROM AUTHOR]

Background: Metastatic tumors of the oro-facial tissuesare rare, with an incidence ranging between 1% and 8% of all oral malignant tumors. Generally reported with a peak of incidence in the 5–7th decades but possibly occurring at any age, metastases may represent the first sign of an occult cancer or manifest in patients with an already known history of a primary carcinoma, mostly from the lungs, kidney, prostate, and colon/rectum in males, and the uterus, breast, lung, and ovary in females. In the oro-facial tissues, the most involved sites are the oral mucosa, gingiva/jawbones, tongue, and salivary glands. Methods: A broad and deep literature review with a comprehensive analysis of the existing research on oro-facial metastases from renal-cell carcinoma (RCC) was conducted by searching the most used databases, with attention also paid to the clear-cell histological variant, which is the most frequent one. Results: Among the 156 analyzed studies, 206 cases of oro-facial metastases of renal cancer were found in patients with an average age of 60.9 years (145 males, 70.3%; 61 females, 29.6%). In almost 40% of the cases, metastasis represented the first clinical manifestation of the primary tumor, and 122 were histologically diagnosed as clear-cell renal-cell carcinoma (ccRCC) (59.2%). The tongue was involved in most of the cases (55 cases, 26.7%), followed by the gingiva (39 cases, 18.9%), mandible (35 cases, 16.9%), maxilla (23 cases, 11.1%), parotid gland (22 cases, 10.6%), buccal mucosa (11 cases, 5.3%), lips (7 cases, 3.3%), hard palate (6 cases, 2.8%), soft palate, masticatory space, and submandibular gland (2 cases, 0.9%), and lymph nodes, tonsils, and floor of the mouth (1 case, 0.4%). Among the 122 ccRCCs (84 males, 68.8%; 38 females, 31.1%), with an average age of 60.8 years and representing in 33.6% the first clinical manifestation, the tongue remained the most frequent site (31 cases, 25.4%), followed by the gingiva (21 cases, 17.2%), parotid gland (16 cases, 13.1%), mandibular bone (15 cases, 12.2%), maxillary bone (14 cases, 11.4%), buccal mucosa and lips (6 cases, 4.9%), hard palate (5 cases, 4%), submandibular gland and soft palate (2 cases, 1.6%), and lymph nodes, tonsils, oral floor, and masticatory space (1 case, 0.8%). The clinical presentation in soft tissues was mainly represented by a fast-growing exophytic mass, sometimes accompanied by pain, while in bone, it generally presented as radiolucent lesions with ill-defined borders and cortical erosion. Conclusions: The current comprehensive review collected data from the literature about the incidence, site of occurrence, age, sex, and survival of patients affected by oro-facial metastases from renal-cell carcinoma, with particular attention paid to the cases diagnosed as metastases from clear-cell renal-cell carcinoma, which is the most frequent histological variant. Clinical differential diagnosis is widely discussed to provide clinicians with all the useful information for an early diagnosis despite the effective difficulties in recognizing such rare and easily misdiagnosed lesionsTheir early identification represents a diagnostic challenge, especially when the clinical work-up is limited to the cervico–facial region. Nevertheless, early diagnosis and recently introduced adjuvant therapies may represent the key to better outcomes in such patients. Therefore, general guidelines about the clinical and radiological identification of oro-facial potentially malignant lesions should be part of the cultural background of any dentist. [ABSTRACT FROM AUTHOR]

Simple Summary: In vivo microdialysis applied to rat submandibular glands showed that an increase in the norepinephrine and serotonin levels in the dialysate was primarily dependent on their release from the nerve endings. Either infusion of imipramine into interstitial fluids in rat submandibular glands through a dialysis probe or intraperitoneal administration of imipramine significantly and dose-dependently increased both norepinephrine and serotonin concentrations in the interstitial fluids. Xerostomia induced by antidepressants such as imipramine has long been thought to be due to their anticholinergic effects. However, even antidepressants with low anticholinergic effects may have a high incidence of xerostomia. In salivary glands, norepinephrine activates alpha-adrenergic receptors in blood vessels and beta-adrenergic receptors in acinar cells, respectively, causing a decrease in the blood flow and an increase in the protein secretion, resulting in the secretion of viscous saliva with low water content and high protein content. A previous study demonstrated that perfusion of the submandibular glands of rats with serotonin significantly decreased saliva secretion. The results of the present study revealed the following: (1) that norepinephrine and serotonin, but not epinephrine nor dopamine, were detected in the interstitial fluids in rat submandibular glands; (2) that norepinephrine and serotonin concentrations in the dialysate was 4.3 ± 2.8 nM and 32.3 ± 19.6 nM at stable level, respectively; (3) that infusion with imipramine, a reuptake inhibitor of norepinephrine and serotonin, significantly and dose-dependently increased both norepinephrine and serotonin concentrations in the dialysate; and (4) that intraperitoneal administration of imipramine significantly increased both norepinephrine and serotonin concentrations in the dialysate. These results suggested that one of the mechanisms of xerostomia induced by reuptake inhibitors of norepinephrine and serotonin involves the activation of adrenergic and serotonin receptors in the salivary glands, respectively. [ABSTRACT FROM AUTHOR]

Botulinum toxin can be used for various purposes to enhance neck aesthetics, addressing concerns such as platysmal bands, optimizing the cervicomental angle, preventing worsening of horizontal neckline and decolletage lines during aging, submandibular gland hypertrophy, and hypertrophied superior trapezius muscle. Understanding the anatomy of muscles such as the trapezius, platysma, and submandibular gland is crucial for achieving desirable outcomes with botulinum toxin administration. Techniques for injecting botulinum toxin into these muscles are discussed, emphasizing safety and efficacy. Specific injection points and methods are detailed for treating platysmal bands, optimizing the cervicomental angle, addressing submandibular gland hypertrophy, and managing hypertrophied superior trapezius muscle. Careful consideration of anatomical landmarks and potential complications is essential for successful botulinum toxin injections in these areas. [ABSTRACT FROM AUTHOR]

In Sjögren's disease (SjD), the salivary glandular epithelial cells can induce the chemotaxis of B cells by secreting B-cell chemokines such as C-X-C motif chemokine ligand 13 (CXCL13). Syndecan-1 (SDC-1) is a major transmembrane heparan sulfate proteoglycan (HSPG) predominantly expressed on epithelial cells that binds to and regulates heparan sulfate (HS)-binding molecules, including chemokines. We aimed to determine whether SDC-1 plays a role in the pathogenesis of SjD by acting on the binding of HS to B-cell chemokines. To assess changes in glandular inflammation and SDC-1 concentrations in the submandibular gland (SMG) and blood, female NOD/ShiLtJ and sex- and age-matched C57BL/10 mice were used. In the SMG of NOD/ShiLtJ mice, inflammatory responses were identified at 8 weeks of age, but increased SDC-1 concentrations in the SMG and blood were observed at 6 weeks of age, when inflammation had not yet started. As the inflammation of the SMG worsened, the SDC-1 concentrations in the SMG and blood increased. The expression of the CXCL13 and its receptor C-X-C chemokine receptor type 5 (CXCR5) began to increase in the SMG at 6 weeks of age and continued until 12 weeks of age. Immunofluorescence staining in SMG tissue and normal murine mammary gland cells confirmed the co-localization of SDC-1 and CXCL13, and SDC-1 formed a complex with CXCL13 in an immunoprecipitation assay. Furthermore, NOD/ShiLtJ mice were treated with 5 mg/kg HS intraperitoneally thrice per week for 6–10 weeks of age, and the therapeutic effects in the SMG were assessed at the end of 10 weeks of age. NOD/ShiLtJ mice treated with HS showed attenuated salivary gland inflammation with reduced B-cell infiltration, germinal center formation and CXCR5 expression. These findings suggest that SDC-1 plays a pivotal role in the pathogenesis of SjD by binding to CXCL13 through the HS chain. [ABSTRACT FROM AUTHOR]

BACKGROUND Hypertrophied submandibular glands provide a bulky contour to the lower face. Botulinum neurotoxin injection methods are commonly used for facial contouring; however, no studies have suggested injection points because of the lack of delicate anatomical information on the submandibular gland. OBJECTIVE The aim of this study was to determine the optimal injection site for botulinum neurotoxin injections in the submandibular gland. MATERIALS AND METHODS Anatomical considerations when injecting botulinum neurotoxin into the submandibular gland were determined using ultrasonography. The thickness of the submandibular gland, its depth from the skin surface, and the location of the vascular bundle were observed bilaterally in 42 participants. Two cadavers were dissected to measure the location of the submandibular gland corresponding to the ultrasonographic observation. RESULTS The thickest part of the submandibular gland measured 11.1262.46 in width with a depth of 4.6360.76. At the point where it crosses the line of the lateral canthus, it measured 5.53 6 1.83 in width and 8.73 6 1.64 in depth. CONCLUSION The authors suggest optimal injection sites based on external anatomical landmarks. These guidelines aim to maximize the effects of botulinum neurotoxin therapy by minimizing its deleterious effects, which can be useful in clinical settings. [ABSTRACT FROM AUTHOR]

Purpose: To identify the biodistribution and diagnostic performance of a novel fibroblast activation protein (FAP) targeted positron emission tomography (PET) tracer, [68Ga]Ga-DOTA-GPFAPI-04, in patients with solid tumors in a head-to-head comparison with [18F]F-FDG. Methods: Twenty-six patients histologically proven with cancers of nasopharyngeal (n = 5), esophagus (n = 5), gastro-esophagus (n = 1), stomach (n = 7), liver (n = 3), and colorectum (n = 5) were recruited for [68Ga]Ga-DOTA-GPFAPI-04 and [18F]F-FDG PET/CT scans on consecutive days. The primary endpoint was the diagnostic efficacy, with the histological diagnosis and the follow-up results selected as the gold standard. The secondary endpoint was the background uptake pattern. Two experienced nuclear medicine physicians who were blinded to the gold standard results while having essential awareness of the clinical context reviewed the images and labeled lesions by consensus for subsequent software-assisted lesion segmentation. Additionally, background organs were automatically segmented, assisted by artificial intelligence. Volume, mean, and maximum standard uptake values (SUVmean and SUVmax) of all segmentations were recorded. P < 0.05 was deemed as statistically significant. Results: Significant glandular uptake of [68Ga]Ga-DOTA-GPFAPI-04 was detected in the thyroid, pancreas, and submandibular glands, while moderate uptake was observed in the parotid glands. The myocardium and myometrium exhibited 2–3 times higher uptake of the radiotracer than that of the background levels in blood and liver. A total of 349 targeted lesions, consisting of 324 malignancies and 25 benign lesions, were segmented. [68Ga]Ga-DOTA-GPFAPI-04 is more sensitive than [18F]F-FDG, especially for abdominopelvic dissemination (1.000 vs. 0.475, P < 0.001). Interestingly, [18F]F-FDG demonstrated higher sensitivity for lung metastasis compared to [68Ga]Ga-DOTA-GPFAPI-04 (0.845 vs. 0.682, P = 0.003). The high glandular uptake made it difficult to delineate lesions in close proximity and masked two metastatic lesions in these organs. Conclusion: Despite prominent glandular uptake, [68Ga]Ga-DOTA-GPFAPI-04 demonstrates favorable diagnostic performance. It is a promising probe scaffold for further development of FAP-targeted tumor theranostic agents. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to ascertain the diagnostic efficacy of routine 68Ga-PSMA imaging conducted 1 h post-injection, in conjunction with delayed imaging performed 3 h post-injection, for differentiating between benign and malignant lesions in prostate cancer (PCa) patients. Methods: A retrospective assessment was undertaken on 44 prostate cancer patients who had undergone both routine and delayed 68Ga-PSMA PET/CT scans. Variations in SUVmax and SUVmean values in normal organs, primary prostate cancer sites, metastatic sites, and benign lesions were analyzed. Pathological examination and extended follow-ups were used to confirm all lesions. Results: The study encompassed 44 patients, presenting 35 primary prostate cancer lesions, 44 metastatic lesions, and 30 benign lesions. Delayed imaging (3 h post-injection) demonstrated a decreasing trend in the SUVmax and SUVmean for the liver, blood, and spleen. Conversely, an increasing trend was observed for the parotid, lacrimal, and submandibular glands. For primary lesions, the SUVmax and SUVmean values were 17.63 ± 9.61 and 9.77 ± 5.18 during routine imaging, and 25.09 ± 15.11 and 14.05 ± 8.02 (P < 0.001) during delayed imaging. A comparable increase in SUVmax and SUVmean was seen in the delayed images for metastatic lesions when juxtaposed with routine images. Nevertheless, benign lesions displayed a decrease in SUVmax and SUVmean during delayed imaging when set against routine imaging (SUVmax: 3.56 ± 1.49 vs 2.93 ± 1.47, P = 0.001; SUVmean: 1.99 ± 0.87 vs 1.65 ± 0.87, P = 0.003). Conclusion: Imaging using 68Ga-PSMA PET/CT at 3 h post-injection manifested a higher uptake and target-to-background uptake in most malignant prostate cancer lesions, but a diminished uptake in benign lesions. This observation can assist clinicians in distinguishing non-specific PSMA uptake in prostate cancer patients based on PSMA PET/CT image. [ABSTRACT FROM AUTHOR]

Primary salivary gland squamous cell carcinoma (SCC) is a very rare malignancy, and such a tumor with sialolithiasis is even rarer. Here, we report a case of 68-year-old man with primary salivary SCC and sialolithiasis. A cystic lesion with a salivary stone was found in the submandibular gland, lined by atypical epithelium with focal invasive focus. The atypical epithelium was positive for cytokeratin 5/6 and p40, and focally positive for p63, cytokeratin 14 and periodic acid-Schiff (PAS) stain. S-100 protein, calponin, α-smooth muscle actin, SOX10 and androgen receptor were negative and no mucin-containing cells were found on PAS with diastase and Alcian blue staining. The Ki-67 labeling index was relatively high. P53 was mostly negative, and no pathogenic TP53 mutations were detected. The diagnosis of primary salivary gland SCC was made. In our review including the present case, the speculated cause of primary salivary gland SCC was squamous metaplasia and dysplasia due to chronic irritation by a salivary stone. Although no cases with recurrence or distant metastasis were identified, more cases and long-term follow-up are needed. [ABSTRACT FROM AUTHOR]

This retrospective analysis investigated the impact of interventional sialendoscopy in the management of sialolithiasis. The study included 118 patients who underwent sialoendoscopic intervention under general anesthesia for sialolithiasis between August 2015 and November 2022. Demographic and clinical parameters were collected, and preoperative imaging findings were reviewed. The majority of cases presented with submandibular gland (SMG) sialolithiasis (70.3%) compared to parotid gland (PG) sialolithiasis (29.7%). Swelling and pain were the most common complaints among patients. Stone size was not found to be a significant factor in treatment success, while stone localization and ductal stenosis played crucial roles. Stone fragmentation was achieved using Holmium:YAG (Ho/YAG) laser and pneumatic lithotripsy, with an average surgical duration of approximately 1.8 hours for SMG sialolithiasis and 1.5 hours for PG sialolithiasis. Combined approaches were employed in cases where stones were located anterior to the hilum. Treatment success rates were comparable between Ho/YAG laser and pneumatic lithotripsy. The study highlights the importance of preoperative imaging and suggests that interventional sialendoscopy, with its organ-preserving techniques, offers an effective approach for sialolithiasis management. Further research examining stone localization and ductal pathology is needed to optimize treatment selection and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Lymphoepithelial carcinoma of the submandibular gland is an extremely rare condition; therefore, no clear clinical features or established treatment is available for this. A 58-year-old Japanese man who came to our hospital with the complaint of swelling of the left submandibular region was diagnosed with stage IVa, T4aN2bM0 lymphoepithelial carcinoma of the submandibular gland. We also examined the relationship between the tumor and Epstein-Barr virus by Epstein-Barr virus encoded ribonucleoprotein in situ hybridization. The patient was treated by performing segmental mandibulectomy, neck dissection, mandibular reconstruction, and adjuvant chemoradiotherapy. After 2 years of treatment, good progress has been observed in the patient without any signs of recurrence. Here, we have reported the treatment of a patient with lymphoepithelial carcinoma of the submandibular gland using literature review.

Botulinum toxin can be used for various purposes to enhance neck aesthetics, addressing concerns such as platysmal bands, optimizing the cervicomental angle, preventing worsening of horizontal neckline and decolletage lines during aging, submandibular gland hypertrophy, and hypertrophied superior trapezius muscle. Understanding the anatomy of muscles such as the trapezius, platysma, and submandibular gland is crucial for achieving desirable outcomes with botulinum toxin administration. Techniques for injecting botulinum toxin into these muscles are discussed, emphasizing safety and efficacy. Specific injection points and methods are detailed for treating platysmal bands, optimizing the cervicomental angle, addressing submandibular gland hypertrophy, and managing hypertrophied superior trapezius muscle. Careful consideration of anatomical landmarks and potential complications is essential for successful botulinum toxin injections in these areas.

Plunging ranula is the extravasation of saliva from the sublingual gland caused by trauma or obstruction of the duct, extending through a defect in the mylohyoid muscle into the submandibular gland. The prevalence of plunging ranula is estimated to be about 2.6 per 100,000 cases with mostly unilateral lesions. Bilateral plunging ranula are rare, with only a few cases reported. This case report describes an 11-year-old boy who was diagnosed with bilateral plunging ranula by radiologic examination of ultrasound and CT scan. The patient underwent extirpation surgery with the result of ranula on histopathologic examination. Six-month follow-up after extirpation, the patient was asymptomatic and no sign of recurrence.

The aim of the study was to assess the involvement of submandibular gland in oral cancer patients undergoing neck dissection. This study reviewed the records and pathologic specimens of patients who were clinically and histopathologically diagnosed as having oral cavity squamous cell carcinoma, from the year 2018 to 2023. A total of 332 patients were included. These patients underwent surgery with primary tumor resection and neck dissection. Pathologic metastasis to submandibular gland was then evaluated. Histopathological data showed that submandibular gland was involved in only 10 cases. Out of these cases, involvement of level IA &B lymph nodes was found in 9 of the cases. Direct extension of primary tumor to submandibular gland was noted in advanced stages (stage IV). Most common primary site for involvement of SMG was buccal mucosa (six patients), with significant correlation with LVI, ENE, DOI and WPOI (p value < 0.05). This study demonstrates that the incidence of submandibular gland metastasis in oral cavity (SCC) is extremely rare. Its involvement is either through direct extension from a primary lesion or in advanced disease. Thus, patients with early-stage oral SCC with preoperative N0 neck, may be candidates for preservation of the submandibular gland. [ABSTRACT FROM AUTHOR]

Abstract Background & aim: The knowledge of the biochemical composition of salivary stones (sialoliths) is necessary for their aetiology and formation mechanism. A small number of studies have investigated sialoliths' elemental composition and clinical symptoms, probably due to the unknowingness and uncertainties of their formation. The purpose of this study was to determine the occurrence, physicochemical characteristics and clinical symptoms of salivary stones (sialoliths). Methods: This is a semi-experimental study that was conducted in Shiraz medical centers in 2023. Sialoliths' physical properties (colour, size, weight and hardness) and elemental composition (using an SEM-EDS) after non-randomly collecting from available samples in Shiraz health centres in 2022 for 9 months were determined. The target population included male and female patients of different age ranges. Statistical tests of Shapiro-Wilk and Mann-Whitney were applied to identify the data normality and find significant differences between the distribution of elements and individual factors, respectively. Results: Salivary stones comprised white to light brown colours and a 1 to 40 mm size range, with a mean weight of 0.65 g and hardness of 2 to 4. Salivary stones dominantly constitute oxygen (O), carbon (C), calcium (Ca), phosphorus (P), sodium (Na) and chlorine (Cl), respectively (98%). No significant difference was found between the distribution of elements and the individual factors (gender and age). A strong positive correlation between Ca and P (r = 0.86) and a good positive correlation between Ca and P with sialoliths' physical parameters (35 < r < 0.60) reflected that Ca and P comprise biomineral phases similar to carbonated calcium phosphates. Conclusion: The results of the present study provided a good insight into sialoliths' elemental composition, physicochemical properties and clinical symptoms. The high weight percentage of O, C, Ca and P suggested phosphorated carbonate compounds. Ca and P were two important explanatory factors for the weight and size of salivary stones. Also, age and gender were not considered the main factors controlling elements in sialoliths.

PAX6 is well known as a transcription factor that drives eye development in animals as widely divergent as flies and mammals. In addition to its localization in eyes, PAX6 expression has been reported in the central nervous system, the pancreas, testes, Merkel cells, nasal epithelium, developing cells of the inner ear, and embryonic submandibular salivary gland. Here we show that PAX6 also appears to be present in the mechanosensory neuromasts of the lateral line system in paedomorphic salamanders of the genus Eurycea. Using immunohistochemistry and confocal microscopy to examine a limited number of larvae of two species, listed by the United States of America's federal government as threatened (E. nana) or endangered (E. rathbuni), we found that anti-PAX6 antibody labeled structures that were extranuclear, and labeling was most intense in the apical appendages of the hair cells of the neuromast. This extranuclear localization raises the possibility of an as yet undescribed function for PAX6 as a cytoskeleton-associated protein. [ABSTRACT FROM AUTHOR]

Background: Mycoplasma pneumoniae (MP) is a significant respiratory pathogen leading to community-acquired pneumonia (CAP), especially in children. Up to 30% of confirmed MP cases can develop dermatological symptoms, with Mycoplasma pneumoniae-induced rash and mucositis (MIRM) being a distinct clinical entity marked by mucous membrane inflammation, with or without skin lesions. Methods: This case report describes a 7-year-old girl admitted with fever, stomatitis, conjunctivitis, and skin lesions. On the second day, a painful neck enlargement was observed, with ultrasound confirming bilateral submandibular salivary gland inflammation and elevated serum amylase levels. The patient later developed pneumonia, confirmed via chest X-ray and pleural ultrasound. MP infection was confirmed via specific IgM antibodies and PCR in a throat swab. Results: The patient was diagnosed with MIRM and was treated with clarithromycin, amoxicillin with clavulanic acid, and methylprednisolone, resulting in a full recovery. Conclusions: This case highlights a unique presentation of MIRM with salivary gland inflammation, not previously described in pediatric mycoplasmal infections. [ABSTRACT FROM AUTHOR]

Intranodal palisaded myofibroblastoma (IPM) is a rare benign tumor of the lymph nodes, particularly in inguinal lymph nodes. IPM originating from the submandibular gland lymph nodes is rarely encountered in clinical practice. Herein, we report the case of a 31-year-old male patient with IPM of the submandibular gland region and describe in detail magnetic resonance imaging findings and pathology. Magnetic resonance imaging detected a heterogeneous lesion with a hypointense rim on T2-weighted imaging with specificity in the left submandibular gland region. This case report will contribute to the accumulation of experience in the diagnosis of this disease. [ABSTRACT FROM AUTHOR]

Aim: The aim of the present study is to show how sodium nitrite alters the histology of submandibular salivary glands and livers of Albino rats, as well as how chlorogenic acid may have therapeutic benefits. Methods: A sample size of thirty male Sprague Dawley Albino rats weighing between 100 and 150 g (5-6 weeks old) was randomly allocated into 3 equal groups. Group I: rats were used as controls and were given phosphate buffer solution, whereas Group II: rats were given an 80 mg/kg sodium nitrites (SN) daily dissolved in distilled water. The rats in Group III were given a daily dose of 80 mg/kg SN dissolved in distilled water and after 6 hours each rat received 50 mg/mL freshly prepared chlorogenic acid (CGA) every other day. For 12 weeks, all treatment modalities will be administered orally, every day. After the experiment, all rats were euthanized. Samples from salivary glands and livers were processed and stained with H&E and interleukin 6 (IL 6). Malondialdehyde (MDA) and superoxide dismutase (SOD) enzymes were detected using an ELISA assay. Results: Groups III had nearly comparable findings to Group I regarding histological pattern with normal submandibular glands and livers features. Group III salivary gland treated with CGA exhibited higher SOD levels (20.60±4.81 U/g) in comparison to the SN group, and lower MDA levels (111.58±28.28 nmol/mg) in comparison to the SN treated samples. In comparison to the SN group, CGA treatment significantly reduced MDA levels in liver samples (167.56±21.17 nmol/mg) and raised SOD (30.85±6.77 U/g). Conclusions: Chlorogenic acid has a protective effect against salivary gland and liver toxicity induced by SN in rats. This was mediated via the anti-inflammatory and antioxidative properties of CGA and the restoration of oxidant/antioxidant balance in rat salivary gland and liver. [ABSTRACT FROM AUTHOR]

Background: Although low-level laser therapy (LLLT) is a widely used noninvasive treatment because of photobiomodulation effects, its application for xerostomia remained uncertain. Tight junctions (TJs), mainly composed of claudins, occludin, and ZO family members, are crucial structures that determine material transport through paracellular pathway in salivary gland epithelial cells. This work aimed to investigate whether LLLT affected salivary secretion through epithelial TJs. Methods: Transepithelial electrical resistance (TER) measurement and paracellular permeability assay were applied to evaluate paracellular permeability in submandibular gland (SMG)-C6 cells after irradiation with 540 nm green light. Immunofluorescence and western blot were used to detect the expression of TJ proteins. Quantitative phosphoproteomics were performed to explore possible intracellular signals. Results: We found that irradiation with 540 nm green light significantly decreased TER values while increased paracellular transport in SMG-C6 cells. 540 nm green light-induced redistribution of claudin-1, -3, and -4, but not occludin or ZO-1. Moreover, above phenomena were abolished by preincubation with capsazepine, an antagonist of transient receptor potential vanilloid subtype 1. Notably, irradiation with 540 nm green light on the skin covering the whole submandibular gland regions promoted salivary secretion and attenuated lymphocytic infiltration in 21-week-old non-obese diabetic mice (n = 5 per group), a xerostomia animal model for Sjögren's syndrome. Through in-depth bioinformatics analysis and expression verification, ERK1/2 and EphA2 served as potential canonical and noncanonical signals underlying 540 nm green light. Conclusions: Our findings uncovered the novel therapeutic effects of 540 nm green light on xerostomia through regulation on the expression and distribution of TJs. [ABSTRACT FROM AUTHOR]

The morphology of the major and minor glands in the Persian squirrel (Sciurus anomalus) is crucial for understanding this mammal's biological and ecological relationships. This study aimed to compare the macro- and microanatomies of the major and minor salivary glands in Persian squirrels. Five euthanized adult Persian squirrels were used for this investigation. The macroscopic and microscopic evaluations were carried out after dissection, and tissue samples were fixed and slides prepared. Afterward, specific staining methods were used for the histochemical study. The results of this investigation indicated that Persian squirrels, as pets and wild rodents, have several minor salivary glands, including caudal buccal, lingual, palatine, and palatoglossal salivary glands. The rostral buccal region and labial region of the Persian squirrel were sectioned serially, but there were no salivary secretory units in these regions. The parotid gland was completely acinar serous, the submandibular salivary gland was branched tubuloacinar seromucous, and the sublingual gland was tubuloacinar seromucous. In addition, in this research, the two parts of the sublingual gland, monostomatice, and polystomatic parts, were completely determined. The striated, intercalated, interlobar, and excretory ducts composed the ductal system of the major salivary glands in Persian squirrels. The interlobar septa between the lobules contained blood vessels and interlobar ducts. The myoepithelial cells were seen around the secretory units of all major salivary glands. In conclusion, it can be noticed that the major and minor salivary glands of the Persian squirrel had been scattered in the oral cavity, such as the palatine, tongue, and buccal regions, and the secretory units of these glands were different from other rodents due to the difference in nutrition of the Persian squirrel. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

MicroRNA-23b-3p has been demonstrated to act as a safeguard against several autoimmune diseases. However, its role in Sjögren's syndrome (SS) remains unclear. In order to investigate its role in SS, we administered agomiR-23b-3p or agomiR-NC to non-obese diabetic (NOD) mice via tail vein weekly for 6 weeks. The study examined the saliva flow rate, histological changes in submandibular glands, and levels of autoantibodies. Additionally, the levels of several cytokines, cell apoptosis, and NF-κB signaling were evaluated. The protective effect of miR-23b-3p was confirmed in a cell model. The results demonstrated that miR-23b-3p overexpression improved salivary flow rates, inhibited lymphocyte infiltration, reduced cytokine levels, and suppressed cell apoptosis in NOD mice. Moreover, NF-κB signaling was inactivated following miR-23b-3p overexpression. In a cellular model of SS, overexpression of miR-23b-3p protected submandibular gland epithelial cells exposed to IFN-γ against apoptosis and inflammation by targeting SOX6. The study concludes that miR-23b-3p alleviates SS by targeting SOX6 and inhibiting the NF-κB signaling pathway. The miR-23b-3p/SOX6 axis represents a promising avenue for the development of novel therapeutic strategies for SS. • MiR-23b-3p was downregulated in a spontaneous animal model for SS. • MiR-23b-3p attenuated SS in mice by modulating Th1/Th17/Treg cells and cell apoptosis. • MiR-23b-3p overexpression inhibited the NF-κB pathway in NOD mice. • MiR-23b-3p exerted its protective effect by targeting SOX6 in vitro. [ABSTRACT FROM AUTHOR]

Background: Ziwan and Taoren (ZT) is a classic medicine pair in the formula of Mai Dong Di Shao Decoction, has been used to treat primary Sjogren's syndrome (pSS) for more than 20 years. But its action mechanism is still unknown. This study is aimed to reveal the potential mechanism of ZT treated pSS and discover its active compounds of ZT and therapeutic target for pSS. Methods: Firstly, the potential pathways of ZT for pSS treatment were predicted through network pharmacology and GO and KEGG enrichment analysis. Secondly, the inter-structural relationships between active compounds of ZT and target proteins were visualized using molecular docking techniques. Finally, efficacy and mechanism were conducted through in vivo experiments, such as water intake, spleen index, hematoxylin-eosin staining pathological changes, ELISA, Western Blot analysis, and immunofluorescence staining. Results: Nine active compounds were extracted from network pharmacology, including quercitrin, luteolin, kaempferol, β-sitosterol, isorhamnetin, galangin, hederagenin, diosmetin and gibberellin 7. Seven disease targets were identified: RELA, TP53, AKT1, interleukin (IL) 6, MAPK1, ESR1, IL10; with RELA being the most core target. KEGG and GO enrichment analysis indicated that ZT may act through the TLR/NF-κB/RELA inflammatory mechanism process. preliminary results of molecular docking showed that ZT's active compounds bind well to the RELA (p65) receptor. In vivo results demonstrated that a high dose of ZT significantly improved water intake and reduced lymphocytes infiltration in submandibular gland pathology in NOD mice. The expression content of AQP5 and vasoactive intestinal peptide in the submaxillary gland was significantly increased, while levels of inflammatory factors such as tumor necrosis factor-α, IL-6, and IL-1β along with protein expressions including toll-like receptor4, p-p65 and p-IKKα/β in NF-κB pathway were reduced. Conclusions: The ZT treatment exhibits a promising efficacy in mitigating dryness symptoms of pSS, potentially attributed to its capacity for suppressing the TLR/NF-κB inflammatory signaling pathway. [ABSTRACT FROM AUTHOR]

To determine the indications for neck dissection in the management of parotid, submandibular or minor salivary gland cancers depending on the clinical situation: i.e., clinical lymph node involvement (cN+) or not (cN0); low or high risk of occult nodal metastasis; diagnosis of malignancy before, during or after surgery. The French Network of Rare Head and Neck Tumors (REFCOR) formed a steering group which drafted a narrative review of the literature published on Medline and proposed recommendations. The level of adherence to the recommendations was then assessed by a rating group according to the formal consensus method. In cN+ salivary gland cancer, ipsilateral neck dissection is recommended. In cN0 salivary gland cancer, ipsilateral neck dissection is recommended, except for tumors at low risk of occult nodal metastasis. If definitive pathology reveals a high risk of occult nodal involvement, additional neck treatment is recommended: ipsilateral neck dissection or elective nodal irradiation. The rate of occult lymph node involvement, and therefore the indication for elective neck dissection, depends primarily on the pathologic grade of the salivary gland cancer. [ABSTRACT FROM AUTHOR]

The objective of our study was to evaluate early and late macroscopic and histological changes associated with the use of polycaprolactone dermal filler (PCL) in the orofacial region. Forty-eight female Wistar rats were divided into the PCL group and the control group. The material was applied to the ventral tongue and submandibular region, and the animals were euthanized at three time points—24 h, and 30 and 90 days. In the PCL group, yellowish nodules were observed on the tongue at all experimental time points. At the 24 h mark, the histological analysis revealed the presence of the PCL and a predominance of lymphocytes, plasma cells, and neutrophils. At 30 and 90 days, macrophages and multinucleated giant cells predominated around the PCL spheres. Collagen density in the dermis was higher in the PCL group when compared to the control at 30 and 90 days. In the submandibular glands, an inflammatory process similar to that observed at other sites was noted, with no alterations in acinar or ductal morphology. The results of this study highlight the effectiveness of PCL as a collagen biostimulator. Nevertheless, the development of nodular lesions on the tongue signals the potential risk of complications in mobile anatomical structures. [ABSTRACT FROM AUTHOR]

Background: Hyposalivation is treated using oral cholinergic drugs; however, systemic side effects occasionally lead to discontinuation of treatment. We aimed to investigate the effects of transdermal pilocarpine on the salivary gland skin on saliva secretion and safety in rats. Methods: Pilocarpine was administered to rats orally (0.5 mg/kg) or topically on the salivary gland skin (5 mg/body). Saliva volume, the number of sweat dots, and fecal weight were measured along with pilocarpine concentration in plasma and submandibular gland tissues. Results: Saliva volume significantly increased 0.5 h after oral administration and 0.5, 3, and 12 h after topical administration. Fecal weight and sweat dots increased significantly 1 h after oral administration; however, no changes were observed after topical application. The pilocarpine concentration in the submandibular gland tissues of the topical group was higher than that in the oral group at 0.5, 3, and 12 h of administration. Conclusions: Pilocarpine application to salivary gland skin persistently increased salivary volume in rats without inducing sweating or diarrhea. Transdermal pilocarpine applied to the skin over the salivary glands may be an effective and safe treatment option for hyposalivation. [ABSTRACT FROM AUTHOR]

Background and Objectives: Tonsillitis is common in children and is predominantly caused by viruses and, less frequently, by bacteria such as group A beta-hemolytic streptococcus. The treatment primarily involves supportive care; however, the overuse of antibiotics remains a concern due to rising antibiotic resistance. Probiotics, particularly Lactobacillus strains, have been shown to modulate immune responses, offering a potential alternative treatment. Materials and Methods: Our prospective single-arm, open-label study included 98 pediatric patients aged 5–15 years with recurrent throat and tonsil infections, from October 2022 to January 2023. Patients received lozenges containing heat-killed Lactobacillus helveticus MIMLh5. Monthly follow-ups involved a comprehensive ear, nose, and throat examination, throat cultures, and recording the frequency of infections and antibiotic use. Data were analyzed using SPSS 29.0, with statistical significance set at p < 0.05. Results: After three months, significant reductions were observed in the occurrences of nose and throat infections (p < 0.001), enlarged submandibular glands (p < 0.001), and positive throat cultures (p < 0.001). Antibiotic and corticosteroid prescriptions also significantly decreased (p < 0.001). Among children aged 5–10 years, significant improvements were noted in throat and tonsil infections (p < 0.001) and positive throat cultures (p = 0.012). Overall, there was a substantial reduction in school days missed (p < 0.001). Conclusions: The use of paraprobiotic Lactobacillus helveticus MIMLh5 lozenges significantly reduced the incidence of recurrent throat and tonsil infections in children, decreased the need for antibiotics and corticosteroids, and improved overall clinical outcomes without adverse effects. These findings support the use of paraprobiotic supplements as a safe and effective preventive measure for pediatric throat and tonsil infections. [ABSTRACT FROM AUTHOR]

This article explores the use of 18F-choline-PET/CT imaging for non-FDG-avid salivary gland cancer. Salivary gland tumors are rare and have diverse characteristics. While cross-sectional imaging with contrast-enhanced CT or MRI is the standard for initial staging, FDG-PET has also been used. However, some tumors do not show high FDG uptake, so the study aimed to assess the potential of the non-FDG tracer 18F-choline. The study included five patients with malignant salivary gland tumors and found promising results. Choline-PET was found to be somewhat superior to FDG-PET for salivary gland cancer, especially for low-grade tumors and adenoid cystic carcinoma. However, the high background uptake of choline affected the evaluation of the primary tumor. The authors concluded that more specific radiopharmaceuticals are needed for certain types of primary salivary gland carcinoma. [Extracted from the article]