Submandibular Gland Research Articles

Insular Infraorbital Neurovascular Pedicle Labial Salivary Gland Transplantation for Severe Dry Eye: Anatomy Study and Case Report.

Severe dry eyes often require surgical intervention. Submandibular salivary and minor salivary gland transplantation are options for refractory dry eyes but have limitations. We innovatively designed an insular infraorbital neurovascular pedicle labial salivary gland transplantation (IINPLSGT) and validated its feasibility and safety through anatomical studies. An anatomical study was conducted on 13 red-colored latex arterial-perfused cadavers (24 sides). Two specimens (4 sides) simulated IINPLSGT. We recorded the branching patterns and courses of the infraorbital artery, infraorbital nerve, and angular artery, as well as the distribution of nerves, vessels, and salivary glands in the upper lip. Infraorbital artery and angular artery were anatomically classified. The feasibility of the IINPLSGT was validated. Otolaryngologists and ophthalmologists performed IINPLSGT, transferring the labial mucosal flap to the lower eyelid conjunctival fornix to treat severe dry eye in 1 patient. Infraorbital artery exhibited 5 potential branches, classified into 5 types based on developmental patterns. Angular artery was classified into 3 types based on the courses. Patient symptoms significantly improved postoperatively, with Schirmer I increasing from 0 mm to 6 mm, noninvasive breakup time from 0 seconds to 6 seconds, and SPEED (Standard Patient Evaluation of Eye Dryness questionnaire) score decreasing from 10.5 to 3 in the OD 1 year after surgery. No severe complications were observed. IINPLSGT is a safe and feasible method for treating severe dry eyes. The procedure is simple, with a high postoperative gland survival rate, stable secretion, and minimal complications.

Surgical treatment of dysphagia due to salivary mucocele (sialocele) in a cat

AbstractThis case report describes a 10‐year‐old, male, neutered, indoor–outdoor, domestic shorthair cat presented for hyporexia and dysphagia of 1‐month duration tentatively attributed to a recent diet modification. The cat was ultimately referred for a second opinion. Examination under sedation confirmed a small, soft, fluctuating mass in the ventral intermandibular space. A fine‐needle aspirate of the mass revealed its contents to be of the salivary gland origin. The sublingual–mandibular salivary gland on the left side was surgically resected, and the left sublingual mucocele (ranula) was marsupialised. Histopathology confirmed a sublingual sialocele of the resected gland. The cat recovered completely, and there has been no recurrence with an 18‐month follow‐up. A sublingual sialocoele is uncommonly seen in cats, but it should be on the differential diagnosis list for dysphagia in cats, especially when a sublingual mass is present.

Nicotinamide mononucleotide suppresses cellular senescence and increases aquaporin 5 expression in the submandibular gland of aged male mice to ameliorate aging-related dry mouth.

Dry mouth results from decreased saliva secretion due to aging or drug side effects. Decreased saliva secretion causes dryness in the oral cavity that makes swallowing difficult and increases the risk of aspiration pneumonia. There are few fundamental treatments for dry mouth. Here we investigated whether treatment of old mice with nicotinamide mononucleotide (NMN) improved factors associated with dry mouth. Young (16-week-old) and old (113-week-old) male mice were treated subcutaneously with saline or NMN (300mg/kg) once every two days for four weeks and saliva secretion was measured. The amount of nicotinamide adenine dinucleotide (NAD+) in salivary gland tissues was measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Gene expression in the intestinal tract and salivary glands was measured by real-time PCR. The population of cells with acetylation in the submandibular gland was quantified by immunohistological staining. SA-β-gal activity in the submandibular gland was measured to assess cell senescence. Statistical analysis was performed by one-way analysis of variance with Tukey post hoc analysis. The submandibular glands from old mice treated with NMN exhibited increased saliva secretion and NAD+ levels, which both decrease with aging. In addition, the submandibular glands from NMN-treated old mice had decreased acetylation, numbers of senescent cells, and levels of senescence-associated secretory phenotype (SASP) factors, which all increase with aging, as well as increased aquaporin5 (AQP5) mRNA expression. NMN administration may improve dry mouth by regulating cellular senescence in the submandibular gland and increasing expression of AQP5, a water channel involved in saliva secretion, to inhibit age-related decreases in saliva secretion. It is necessary to elucidate further mechanism and confirm its effectiveness in humans.

Targeted RNA sequencing in diagnostically challenging head and neck carcinomas identifies novel MON2::STAT6, NFATC2::NUTM2B, POC5::RAF1, and NSD3::NCOA2 gene fusions.

Although molecular tests developed for a growing list of oncogenic alterations have significantly aided in the classification of head and neck carcinomas, tumours in which prototypical histologic and immunophenotypic features are lacking or only partially developed continue to pose diagnostic challenges. Searching for known diagnostic and therapeutic targets by clinical next-generation sequencing (NGS) assays can often lead to new discoveries. We present our institutional experience in applying targeted RNA NGS in 36 head and neck carcinomas that were morphologically difficult to classify between 2016 and 2023. The patients ranged in age from 5 to 83 years (median, 64), with the majority of tumors occurring in the major salivary glands and the sinonasal tract. Overall, seven (19%) cases showed unusual gene rearrangements, including five novel alterations: MON2::STAT6 in a hard palate adenocarcinoma with mucinous features, POC5::RAF1 in apocrine intraductal carcinoma of the lacrimal gland, EWSR1::CDADC1 fusion in a basaloid carcinoma of the submandibular gland, NFATC2::NUTM2B in myoepithelial carcinoma, and NSD3::NCOA2 fusion in a peculiar high-grade carcinoma with a peritheliomatous growth pattern, and focal myogenic differentiation. Potential therapeutic actionability was identified in three cases (RAF1 and FGFR2 fusions). These findings broaden the current spectrum of gene rearrangements in head and neck carcinomas and support the utility of clinical NGS in identifying unusual, actionable alterations in diagnostically challenging cases.

Current Trends in Deep Plane Neck Lifting: A Systematic Review.

The aging neck is a prevalent aesthetic concern, with over 160,000 neck procedures performed in 2020. It is characterized by increased soft tissue laxity and displacement of cervical structures. While nonsurgical interventions like cryoablation and laser resurfacing show promise, their variable responses highlight the necessity for surgical solutions. Traditional neck lifts address superficial structures but often neglect the subplatysmal plane. Recently, deep plane neck lifts have gained attention for addressing deeper anatomical structures. This paper systematically reviews the literature on subplatysmal modifications in cervicoplasty, aiming to clarify the risks and benefits of these evolving surgical techniques. On February 20, 2024, a systematic review adhering to Preferred Reporting Items for Systematic Review and Meta-Analyses 2020 guidelines was performed. MEDLINE, PubMed, Cochrane, and Scopus databases were searched for terms related to neck rejuvenation. Independent reviewers screened titles, abstracts, and full texts, including all relevant studies. Data extracted included patient numbers, procedures, outcomes, and complications. From an initial 771 articles, 57 studies encompassing 8648 patients met inclusion criteria. The most commonly altered anatomical structures during "deep plane" neck lift (DPNL) were the submandibular gland (69.9%), digastric muscles (58.6%), and subplatysmal fat (48.6%). Postoperative complications were reported in 59.6% of studies, with nerve palsy (0.2%-12%) and hematoma (0.2%-4%) being most common. Aesthetic outcomes were less frequently reported (56% of studies); patient satisfaction ranged from 81.6% to 98.6%, while objective measures were reported in only 12% of studies. Recent surveys indicate a growing concern over excess laxity under the chin, with patients increasingly seeking neck rejuvenation. Our review found that DPNL techniques vary widely, with the submandibular gland and digastric muscles being the most frequently altered structures. Despite a general lack of standardized outcome measures, patient satisfaction was high. However, DPNL showed a higher rate of postoperative nerve palsy compared to traditional neck lift. Overall, while DPNL demonstrates potential aesthetic benefits, the increased risk necessitates thorough patient counseling and further studies for standardization and comparison.

Direct minimization of normal-tissue toxicity via an NTCP-based IMPT planning method.

Intensity-modulated proton therapy (IMPT) planning often relies on physical dose constraints to balance tumor control and sparing of organs at risk (OARs). However, focusing solely on these dose objectives does not always minimize the normal-tissue toxicity, which is quantified as normal tissue complication probability (NTCP). NTCP is also a quantitative criterion for patient selection between proton and photon treatments. This study introduces an NTCP-based IMPT planning (NTCP-IMPT) method designed to directly minimize normal-tissue toxicity while maintaining tumor coverage. NTCP-IMPT simultaneously optimizes NTCP and dose-volume histogram (DVH)-based physical dose objectives while adhering to the minimum-monitor-unit (MMU) constraint for plan deliverability. The optimization problem is solved by the interior-point method. To assess its efficacy in reducing normal-tissue toxicity, NTCP-IMPT is compared with standard IMPT (without NTCP optimization) for four head-and-neck (HN) cancer patients in terms of physical dose quality and NTCP of xerostomia and dysphagia. Across all four patients, NTCP-IMPT plans met target dose criteria (D95%≥100% and D2%≤110%) while maintaining maximum doses to the spinal cord and brainstem comparable to standard IMPT. NTCP-IMPT also reduced mean doses to parotid glands, submandibular glands, oral cavity, and pharyngeal constrictor muscles (PCMs). Compared to the standard IMPT, NTCP-IMPT achieved average reductions in NTCP for xerostomia (grade≥2: 3.67%; grade≥3: 1.07%) and dysphagia (grade≥2: 7.54%; grade≥3: 3.72%). NTCP-IMPT effectively minimizes normal-tissue toxicity and improves the sparing of OARs associated with side effects while maintaining comparable tumor coverage compared to standard IMPT.

Functional assessment of major salivary glands using scintigraphy

To demonstrate a methodology of scintigraphy imaging interpretation considering pixel intensity values in groups of patients presenting lupus erythematosus, Sjögren’s Syndrome (SS), SS associated to systemic lupus erythematosus, parotiditis, drug-induced sialorrhea and salivary glands disease-free. Material and methods: A total of 36 salivary gland scintigraphy images that were from patients with lupus erythematosus, SS, SS combined lupus, parotiditis, and drug-induced sialorrhea were assessed. The pixel intensity of the scintigrams was also evaluated using the standardized grayscale at 8 bits, Images were analyzed under a region of interest (ROI) of 2 cm2 at maximum uptake using ImageJ. Results: Significant differences between the groups were obtained both for parotid (p=0.026) and submandibular glands (p=0.0952). Statistical significant differences were observed in post-hoc tests between Lupus combined with SS patients, for parotid and submandibular glands, when compared to normal group (p=0.04 and p=0.03 respectively). Pixel values were higher for Lupus combined with SS patients, representing a lower uptake. Conclusion: The pixel intensity assessment was able to differentiate and point to lower salivary flow rates for the systemic lupus erythematosus combined with SS patients when compared to other disorders affecting the salivary gland function.

A Rare Presentation of IgG4-Related Sinusitis With Chronic Nasal Obstruction and Headache: A Case Report and Literature Review

IgG4-related disease (IgG4-RD) is a systemic inflammatory condition characterized by tissue infiltration with IgG4-positive plasma cells and a tendency to form mass-like lesions in various organs. IgG4-related sinusitis, although a relatively rare manifestation of IgG4- RD, significantly impacts the paranasal sinuses. A 52-year-old man presented with persistent rhinorrhea, nasal obstruction, and headaches. He was diagnosed with IgG4-RD involving the bilateral nasal cavity, paranasal sinuses, submandibular glands, lacrimal glands, and parotid glands. We recently managed a case of IgG4-related sinusitis, which was successfully diagnosed and treated. This condition represents a distinct subset of chronic rhinosinusitis, with unique pathophysiological and clinical features. Accurate diagnosis and effective management of IgG4-related sinusitis require a high index of suspicion and a multidisciplinary approach.

Submandibular gland transfer into the temporal fossa in patients with oral squamous cell carcinoma: A viable option to prevent radiation-induced xerostomia

Oral squamous cell carcinoma (OSCC) is associated with an important mortality and morbidity related to surgery and radiotherapy. In particular, radiation-induced xerostomia has a major impact on patient’s quality of life. Although intensity-modulated radiation therapy allowed mean dose reduction to the spared submandibular gland (SMG) in patients with head and neck squamous cell carcinoma, xerostomia is still an important sequela for patients treated for an OSCC. SMG surgical transfer into anatomical subsite receiving very low radiation doses is a promising approach to prevent xerostomia. Based on a literature review and data from our institutional cohort, we analyzed the oncological safety of SMG preservation. Then, we discussed the feasibility and relevance of SMG transfer into the temporal fossa, in order to prevent radiation-induced xerostomia in patients with OSCC

Artesunate alleviates radiation-induced submandibular gland epithelial cell damage in rats by reducing inflammation and apoptosis.

Salivary hypofunction is a common complication in patients with head and neck cancers following radiotherapy (RT). RT-induced inflammation in salivary gland cells leads to apoptosis and fibrosis. Artesunate (ART) is a bioactive compound with anti-inflammatory and anti-fibrosis properties. This study aimed to investigate the protective effects of ART on X-ray-induced injury of submandibular gland (SMG) epithelial cells in rats. Second-generation SMG epithelial cells were randomly divided into five groups: natural control group (NC), irradiated group (IR), and irradiated groups treated with ART at concentrations of 5, 10, and 20 μM. Cells were harvested 48 h postirradiation for analysis. The results demonstrated that ART attenuated the damage to AQP5, a crucial indicator of salivary gland function, as evidenced by the decreased expression of AQP5 at both mRNA and protein levels. Additionally, ART decreased the expression of inflammatory cytokines: IL-6 and TNF-α. TUNEL staining revealed reduced apoptosis in the ART groups, particularly the IR + 10 μM group. RT-PCR and Western blot analysis of apoptosis cytokines Bax/Bcl-2 and Caspase-3 confirmed these findings. Furthermore, ART inhibited the expression of NF-κB at both mRNA and protein levels. In conclusion, these results suggest that ART may reduce inflammation and apoptosis in SMG epithelial cells following radiation by inhibiting the NF-κB pathway.

Assessing the diagnostic and therapeutic value of submandibular gland elastography in patients with immunoglobulin G4-related sialadenitis.

: To investigate the utility of shear wave elastography values (SWE) in differentiating IgG4-related submandibular sialadenitis (IgG4-RSS) from healthy individuals and in monitoring the response to glucocorticoid treatment. : Patients with IgG4-RSS who underwent ultrasound between 2017 and 2023 were included. Gland size, border, internal echo pattern, vascularity, and SWE were measured. These parameters were compared with those of the healthy controls, and before and after treatment. Thirty-one glands from 16 patients were analysed. All glands had a nodular shape; the nodular hypoechoic was the most prevalent pattern, followed by the diffuse hypoechoic; the reticular was the least common. Most glands had rich vascularity, whereas two glands had minimal vascularity. The depth (mean 18 mm) and SWE (mean 3.57 m/s) were significantly higher in IgG-RSS (P=0.003 and <0.001, respectively) than in the healthy controlsNine glands from five patients were enrolled to evaluate the treatment response. After treatment, the margins became smoother and all glands showed a reduction in size, hypoechoic area, and vascularity. The mean SWE decreased from 3.56 m/s to 2.50 m/s with a significant difference between pre- and post-treatment (P= <0.001). The SWE is useful for diagnosing IgG4-RSS and assessing the effectiveness of treatment.

Clinical profile of IgG4-related disease in Japan based on the rare disease data registry

We started a registry for cases of immunoglobulin (Ig)G4-related disease (IgG4-RD) in December 2019 to clarify the clinical profile of IgG4-RD. In this study, clinical information from 854 cases registered by February 16, 2024 was analyzed from multiple perspectives. Diagnosis of IgG4-RD was made in 808 cases, comprising 638 definite, 38 probable, and 132 possible. The mean ± SD age at time of enrollment of the 808 cases was 67.9 ± 11.3 years, with 68.8% being male. The pancreas was the most frequently affected organ (49.8%), followed by the submandibular glands (46.2%) and lacrimal glands (30.6%). This study reconfirmed the pancreas and head-and-neck region as major affected areas in IgG4-RD. Clinically, submandibular adenitis and autoimmune pancreatitis often occur together in the same patient, but no association between the two organs was observed in our analysis. Regarding diagnosis, the comprehensive diagnostic criteria were most commonly used (63.6%). Storiform fibrosis and phlebitis obliterans were detected at different frequencies in different organs. In summary, this registry study identified clinical, imaging, hematologic, and pathologic findings in 808 Japanese patients with IgG4-RD. The frequency of affected organs and their characteristic pathological findings will be particularly useful for future practice.

Optimizing surgical outcomes in recurrent plunging ranula: a case report

A plunging ranula is the extravasation of saliva from the sublingual gland due to trauma or ductal obstruction. The saliva tracks through fascial planes into the submandibular space. While typically originating from the sublingual gland, it rarely involves the submandibular gland. Two types are recognized: simple oral ranula and plunging ranula. Various treatment approaches exist, particularly for preventing recurrence in the plunging type. This case report presents the clinical and radiological findings along with our surgical management of a recurrent plunging ranula using a combined intraoral and extraoral approach with dual salivary gland excision utilising intraoperative ultrasonography to ensure complete excision and prevent recurrence. We present the case of a 16-year-old female with recurrent plunging ranula following incomplete excision of a sublingual ranula in the past. Initially asymptomatic after the first surgery, the patient later developed swelling in the mouth floor and neck. The recurrence was managed using a combined intraoral and extraoral approach for complete excision of the sublingual and submandibular glands, along with the cervical extension of the ranula, guided by intraoperative ultrasonography. Postoperatively, the patient showed no signs of recurrence during follow-up, with complete resolution of symptoms. The combined approach ensured thorough removal of mucus-secreting glands and cystic components, preventing recurrence. The optimal treatment for a plunging ranula involves excision of the lesion and the involved gland. Intraoperative ultrasonography aids in ensuring complete excision of all cystic components, reducing recurrence risk.

Efficacy of Submandibular Gland Excision Versus Preservation During Supraomohyoid Neck Dissection for T1, T2, and N0 Oral Squamous Cell Carcinoma

Efficacy of Submandibular Gland Excision Versus Preservation During Supraomohyoid Neck Dissection for T1, T2, and N0 Oral Squamous Cell Carcinoma

Single-Cell RNA-Seq and Histological Analysis Reveals Dynamic Lrig1 Expression During Salivary Gland Development.

The development of the salivary gland (SG) is a complex process regulated by multiple signaling pathways in a spatiotemporal manner. Various stem/progenitor cell populations and respective cell lineages are involved in SG morphogenesis and postnatal maturation. Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) has been identified as critical regulator of stem cells by virtue of its ability to restrain stem cell proliferation, indicating its potential role in the development of several maxillofacial tissues and in the regulation of the quiescence in adult tissues. This study aimed to investigate the expression pattern and functions of Lrig1 in the developing and mature murine submandibular gland (SMG). To accomplish this objective, we collected the murine SMGs at different developmental stages and examined the expression pattern and levels of Lrig1 with qRT-PCR, immunofluorescent (IF) and RNAscope staining. We observed that Lrig1 was widely distributed in both epithelial and mesenchymal cells throughout embryonic and neonatal stages, with specific localization in the more mature epithelium. Furthermore, through single-cell RNA sequencing (scRNA-Seq) and IF techniques, we confirmed that LRIG1 is highly concentrated along with SMG progenitor markers in acinar and basal cells. Additionally, transcription factors (TFs) that could regulate LRIG1 expression were predicted from JASPAR databases and their motifs were identified by the UCSC browser's BLAT tool. Gene Ontology (GO) enrichment analyses on postnatal day 5 (PN5) scRNA-Seq data also provided insights into Lrig1's functions in SG development. Finally, we also conducted in vitro experiments on a human salivary gland (HSG) cell line to assess LRIG1's impact on HSG proliferation and migration, as well as its potential upstream regulatory TFs. Taken together, our study reveals that LRIG1 plays a vital role in SG development.

Assessment of the Prospective Protection of Quercetin on Irradiated Submandibular Salivary Gland in Mice

Assessment of the Prospective Protection of Quercetin on Irradiated Submandibular Salivary Gland in Mice

Management of a Huge Arteriovenous Malformation of the Tongue with the Submandibular Gland Flap: A Case Report

Management of a Huge Arteriovenous Malformation of the Tongue with the Submandibular Gland Flap: A Case Report

Androgens suppress the sialyltransferases ST3GAL1 and ST3GAL4 and modulate mucin 10 glycosylation in the submandibular gland, related to sex differences in commensal microbiota composition in mice.

Sex differences exist in the commensal microbiota that impact on multiple physiological processes in the host. Here, we examined the mechanism by which the sex differences are formed. In addition to the epithelial ductal cell, the acinar cell mass in the submandibular gland was associated with androgen-androgen receptor (AR) signaling. There was a sex difference in the formation of submandibular mucin 10 (MUC10) in SDS-PAGE. Neuraminidase treatment, which hydrolyzes terminal sialic acid, influenced the mobility shift of MUC10. Androgen-AR signaling negatively regulated St3 β-galactoside α-2,3-sialyltransferase 1 (St3gal1) and St3gal4 in the submandibular gland. There was a trend and significant sex differences in α-diversity (Shannon, p=0.09) and β-diversity (unweighted UniFrac) in oral microbiota composition, respectively. Some female-preferring bacteria including Akkermansia muciniphila can assimilate mucin by degrading terminal sialic acids. Our results indicate that androgen-AR signaling suppresses ST3GAL1 and ST3GAL4, which can influence sex differences in commensal microbiota composition.

Scanning Electron Microscopy of the Oropharyngeal Floor of Northern Bobwhite (Colinus virginianus, Linnaeus, 1758) Focusing on the Numerical and Regional Distribution of the Taste Buds

ABSTRACTThe architecture of the avian oropharynx corresponds to the feeding pattern. The present study aims to provide data on morphology, morphometry, and spatial distribution of taste buds in the oropharyngeal floor of the northern bobwhite (Colinus virginianus) using gross anatomy, morphometric, and scanning electron microscopy. The lower beak tip and tomia revealed the presence of variably‐sized dermal papillae. The prefrenular part of the oral floor had an interrupted median groove. Numerous taste buds and rostral submandibular salivary gland openings were detected alongside this groove. The tongue partially filled the oral floor. Its rostral end formed a median pointed process, the lingual nail. The dorsolateral aspects of the lingual apex and body showed hair‐like and rosette‐shaped filiform papillae of variable densities and sizes. However, these parts were devoid of taste buds. On the other hand, the surface mucosa of the lingual root presented numerous scale‐like cellular elevations and a large number of taste buds. Examination of cross sections in the lingual root suggested the presence of two groups of caudal lingual salivary glands, central and lateral. The laryngeal mound contained taste buds that protruded from the surface epithelium into the lumen. The mucosa of the pharyngeal floor contained many taste buds that appeared similar to those detected on the laryngeal mound, except for the large taste pores, excessive cellular porosity, and denser microvilli. The total proportions of the taste buds in the oral and pharyngeal floors were 34.1% and 65.81%, respectively. The proportions of taste buds were 34.1%, 57.26%, 4.27%, and 4.27% in the sublingual floor, lingual root, laryngeal mound, and pharyngeal wall, respectively. In conclusion, this study provides comprehensive data on the oropharynx of northern bobwhite and will help to understand mechanisms governing food gustation in the studied bird and other related birds.

Submandibular Sialolithiasis Associated with Sialadenitis –A Case Report

Sialadenitis, an inflammation of major salivary glands is commonly associated with the obstruction of the salivary duct due to sialolith. The submandibular gland is particularly susceptible to sialolithiasis. This case report discusses a 33 year old female patient who reported with a swelling below the tongue/floor of the mouth associated with pain for a week A comprehensive investigation has indicated the presence of multiple sialoliths. The treatment involved surgical removal of the sialoliths, accompanied by antibiotic therapy. Therefore, this case report emphasizes the presence of multiple sialoliths in a female patient.