Objective:Traditional salivary gland surgery involves incisions in the visible facial and cervical regions, leaving postoperative scars that affect cosmesis. This study aims to investigate the clinical efficacy, safety, and application value of robot-assisted endoscopic resection of benign submandibular and parotid gland lesions via a postauricular approach, while clarifying its advantageous differences compared with endoscopic surgery. Methods:Clinical data of 23 patients who underwent robot-assisted endoscopic surgery via a postauricular approach（11 parotid gland cases and 12 submandibular gland cases） from January 2017 to February 2025 were retrospectively analyzed. Meanwhile, A matched control group of patients who received postauricular endoscopic surgery during the same period was selected as the control group in a 1∶1 ratio（11 parotid gland cases and 12 submandibular gland cases）. Indicators such as operation time, intraoperative blood loss, complications, and postoperative aesthetic satisfaction scores（Numeric Satisfaction Scale, NSS） were collected and compared between the two groups. The inclusion criteria were limited to benign lesions of the parotid superficial lobe（diameter ≤5 cm, without deep lobe involvement） and benign submandibular gland lesions（diameter ≤4 cm, without extension through the mylohyoid muscle）. Results:All robot-assisted surgeries were successfully completed without conversion to open surgery. In the robot group, there were 7 male patients（mean age 39.5 years） and 16 female patients（mean age 35.9 years）. For parotid gland surgeries, the mean operation time was （114.00±38.35） minutes. For submandibular gland surgeries, the mean operation time was（140.00±30.75） minutes.Temporary facial paralysis occurred in 0 of patients after robotic submandibular gland surgery （vs.8% in the endoscopic group） and 18% after robotic parotid gland surgery （vs.27 % in the endoscopic group）,all of which resolved within 1 month, with no occurrence of salivary fistula or infection. Patients had high aesthetic satisfaction（NSS scores: 8.90±1.20 for parotid surgeries and 9.00±0.70 for submandibular surgeries）. No tumor recurrence was observed during the 8-77 month follow-up period. Conclusion:Robot-assisted endoscopic salivary gland surgery via a postauricular approach is safe and feasible. With three-dimensional high-definition visualization and precise mechanical manipulation, it outperforms traditional endoscopic surgery in reducing blood loss, lowering the risk of nerve injury, and achieving long-term cosmetic outcomes. It is particularly suitable for young patients and cases with benign lesions of the parotid superficial lobe or submandibular gland that have high aesthetic demands. However, this surgical approach is not suitable for deep parotid lobe tumors, and its long-term efficacy requires verification through large-sample studies.
Humans ; Robotic Surgical Procedures/methods* ; Retrospective Studies ; Endoscopy/methods* ; Submandibular Gland/surgery* ; Parotid Gland/surgery* ; Female ; Male ; Operative Time ; Salivary Glands/surgery* ; Adult ; Middle Aged

Tricellulin, a key tricellular tight junction (TJ) protein, is essential for maintaining the barrier integrity of acinar epithelia against macromolecular passage in salivary glands. This study aims to explore the role and regulatory mechanism of tricellulin in the development of salivary gland hypofunction in Sjögren's syndrome (SS). Employing a multifaceted approach involving patient biopsies, non-obese diabetic (NOD) mice as a SS model, salivary gland acinar cell-specific tricellulin conditional knockout (Tric^CKO) mice, and IFN-γ-stimulated salivary gland epithelial cells, we investigated the role of tricellulin in SS-related hyposalivation. Our data revealed diminished levels of tricellulin in salivary glands of SS patients. Similarly, NOD mice displayed a reduction in tricellulin expression from the onset of the disease, concomitant with hyposecretion and an increase in salivary albumin content. Consistent with these findings, Tric^CKO mice exhibited both hyposecretion and leakage of macromolecular tracers when compared to control animals. Mechanistically, the JAK/STAT1/miR-145 axis was identified as mediating the IFN-γ-induced downregulation of tricellulin. Treatment with AT1001, a TJ sealer, ameliorated epithelial barrier dysfunction, restored tricellulin expression, and consequently alleviated hyposalivation in NOD mice. Importantly, treatment with miR-145 antagomir to specifically recover the expression of tricellulin in NOD mice significantly alleviated hyposalivation and macromolecular leakage. Collectively, we identified that tricellulin deficiency in salivary glands contributed to hyposalivation in SS. Our findings highlight tricellulin as a potential therapeutic target for hyposecretion, particularly in the context of reinforcing epithelial barrier function through preventing leakage of macromolecules in salivary glands.
Sjogren's Syndrome/complications* ; Animals ; Xerostomia/etiology* ; Mice ; Mice, Inbred NOD ; MARVEL Domain Containing 2 Protein/metabolism* ; Humans ; Mice, Knockout ; Disease Models, Animal ; Interferon-gamma ; Salivary Glands/metabolism* ; Tight Junctions/metabolism* ; MicroRNAs/metabolism* ; Female

Xerostomia (dry mouth) is frequently experienced by patients treated with radiotherapy for head and neck cancers or with Sjögren's syndrome, with no permanent cure existing for this debilitating condition. To this end, in vitro platforms are needed to test therapies directed at salivary (fluid-secreting) cells. However, since these are highly differentiated secretory cells, the maintenance of their differentiated state while expanding in numbers is challenging. In this study, the efficiency of three reversible thermo-ionically crosslinked gels: (1) alginate-gelatin (AG), (2) collagen-containing AG (AGC), and (3) hyaluronic acid-containing AG (AGHA), to recapitulate a native-like environment for human salivary gland (SG) cell expansion and 3D spheroid formation was compared. Although all gels were of mechanical properties comparable to human SG tissue (~11 kPa) and promoted the formation of 3D spheroids, AGHA gels produced larger (>100 cells/spheroid), viable (>93%), proliferative, and well-organized 3D SG spheroids while spatially and temporally maintaining the high expression of key SG proteins (aquaporin-5, NKCC1, ZO-1, α-amylase) for 14 days in culture. Moreover, the spheroids responded to agonist-induced stimulation by increasing α-amylase secretory granules. Here, we propose alternative low-cost, reproducible, and reversible AG-based 3D hydrogels that allow the facile and rapid retrieval of intact, highly viable 3D-SG spheroids.
Humans ; Hydrogels/chemistry* ; Acinar Cells/cytology* ; Spheroids, Cellular/cytology* ; Salivary Glands/cytology* ; Gelatin/chemistry* ; Collagen/chemistry* ; Alginates/chemistry* ; Cell Culture Techniques/methods* ; Hyaluronic Acid/chemistry* ; Cell Proliferation ; Cell Survival ; Cells, Cultured

More than 30 years of rapid development of endoscopic surgery has led to the mainstreaming of this procedure in many surgical departments in China. Since the first report on endoscopy, it has been used in salivary gland resection for more than 20 years. The overall development of endoscopic surgery indicates that its use in oral and maxillofacial surgery is still in the early exploration stage; it has not yet been maturely developed or applied. Owing to the advancement of other disciplines and corresponding widening experiences in those fields, the development of endoscopic technology in oral and maxillofacial surgery will likely achieve a leapfrogging. Learning from the general development pattern of endoscopy, this research explores the application history, current situation, and future direction of the application of endoscopy in salivary gland surgery.
Endoscopy/methods* ; Endoscopes ; Salivary Glands/surgery* ; China

OBJECTIVES: This study aims to investigate the effects of tumor-stromal fibroblasts (TSFs) on the proliferation, invasion, and migration of salivary gland pleomorphic adenoma (SPA) cells in vitro. METHODS: Salivary gland pleomorphic adenoma cells (SPACs), TSFs, and peri-tumorous normal fibroblasts (NFs) were obtained by tissue primary culture and identified by immunocytochemical staining. The conditioned medium was obtained from TSF and NF in logarithmic phase. SPACs were cultured by conditioned medium and treated by TSF (group TSF-SPAC) and NF (group NF-SPAC). SPACs were used as the control group. The proliferation, invasion, and migration of the three groups of cells were detected by MTT, transwell, and scratch assays, respectively. The expression of vascular endothelial growth factor (VEGF) in the three groups was tested by enzyme linked immunosorbent assay (ELISA). RESULTS: Immunocytochemical staining showed positive vimentin expression in NF and TSF. Results also indicated the weak positive expression of α-smooth muscle actin (SMA) and fibroblast activation protein (FAP) in TSFs and the negative expression of α-SMA and FAP in NFs. MTT assay showed that cell proliferation in the TSF-SPAC group was significantly different from that in the NF-SPAC and SPAC groups (P<0.05). Cell proliferation was not different between the NF-SPAC and SPAC groups (P>0.05). Transwell and scratch assays showed no difference in cell invasion and migration among the groups (P>0.05). ELISA showed that no significant difference in VEGF expression among the three groups (P>0.05). CONCLUSIONS TSFs may be involved in SPA biological behavior by promoting the proliferation of SPACs but has no effect on the invasion and migration of SPACs in vitro. Hence, TSF may be a new therapeutic target in SPA treatment.
Humans ; Adenoma, Pleomorphic/metabolism* ; Vascular Endothelial Growth Factor A ; Culture Media, Conditioned/metabolism* ; Fibroblasts/metabolism* ; Salivary Glands/metabolism*

Salivary gland (SG) dysfunction, due to radiotherapy, disease, or aging, is a clinical manifestation that has the potential to cause severe oral and/or systemic diseases and compromise quality of life. Currently, the standard-of-care for this condition remains palliative. A variety of approaches have been employed to restore saliva production, but they have largely failed due to damage to both secretory cells and the extracellular matrix (niche). Transplantation of allogeneic cells from healthy donors has been suggested as a potential solution, but no definitive population of SG stem cells, capable of regenerating the gland, has been identified. Alternatively, mesenchymal stem cells (MSCs) are abundant, well characterized, and during SG development/homeostasis engage in signaling crosstalk with the SG epithelium. Further, the trans-differentiation potential of these cells and their ability to regenerate SG tissues have been demonstrated. However, recent findings suggest that the "immuno-privileged" status of allogeneic adult MSCs may not reflect their status post-transplantation. In contrast, autologous MSCs can be recovered from healthy tissues and do not present a challenge to the recipient's immune system. With recent advances in our ability to expand MSCs in vitro on tissue-specific matrices, autologous MSCs may offer a new therapeutic paradigm for restoration of SG function.
Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells ; Quality of Life ; Regeneration ; Salivary Glands ; Stem Cells

Background: A fine needle aspiration biopsy has been established as a safe, minimally invasive procedure in evaluation of salivary gland lesions. The complex overlapping cytomorphology of these lesions are challenging for pathologists, hence the introduction of an evidence-based system, the Milan System of Reporting Salivary Gland Cytopathology, to improve overall patient care. The study was taken up to reclassify salivary gland lesions from previous FNA biopsies in order to determine sensitivity, specificity, positive and negative predictive values of FNA, and evaluate the risk of malignancy of the various categories of the Milan system. Methodology: This was a 6-year retrospective descriptive study in a tertiary medical center. All salivary gland FNA cases were reviewed by two pathologists, and re-classified into the six categories of the Milan System. The number of false positive, false negative, true positive and true negative cases were obtained by comparing with the final histopathology diagnosis, and the risk of malignancy per category were calculated. Results: A total of 76 cases were reviewed and the overall average of the two readers diagnostic accuracy were 85.02% (95% CI: 84.50-85.60%), sensitivity and specificity were 80.77% (95% CI: 79.90-81.60%) and 86.19% (95% CI: 85.70-86.70%), respectively; positive and negative predictive values were 62.16% (95% CI: 60.70-63.60%) and 94.17% (95% CI: 94.00-94.40%), respectively. Conclusion The Milan System category with highest risk of malignancy was Malignant (Category VI – 100%). FNAB is still a reliable tool for clinicians, and use of the Milan System of Reporting Salivary Gland Cytopathology is beneficial in increasing efficacy of communication among clinicians to improve patient care.
Cytology ; Salivary Glands

Background: The Milan System for Reporting Salivary Gland Cytopathology (MSRGC) aims to increase the overall effectiveness of salivary gland FNAB by defining six general diagnostic categories with corresponding Rates of Malignancies (ROM). This study aims to use this system to categorize salivary gland FNAB in the Philippine General Hospital and stratify ROM per category. Methodology: In this study a total of 326 cases have been collected and reviewed, of which 154 (47.2%) had either surgical or clinical follow-up. The cases were assigned a Milan category by 3 cytopathologists blinded from the original diagnoses and from each other’s readings. Results: The overall sensitivity, specificity, PPV, and NPV in detecting neoplasm is at 71.6%, 90.9%, 88.3%, and 76.9%, respectively. On the other hand, the sensitivity, specificity, PPV, and NPV in detecting malignancy is at 52%, 92.9%, 59.1%, and 90.7%, respectively. The computed ROM is as follows: Category I 7.89%, Category II 9.43%, Category III 20%, Category IVa 10.53%, Category IVb 60%, Category V 75%, and Category VI 100%. Conclusion The overall diagnostic utility of salivary gland FNAB, as well as the computed ROM per diagnostic category are comparable to internationally published literature. This study also validates the MSRSGC as a valuable tool in stratifying ROM in salivary gland lesions.
Cytology ; Salivary Glands

Stem/progenitor cells are important for salivary gland development, homeostasis maintenance, and regeneration following injury. Keratin-14⁺ (K14⁺) cells have been recognized as bona fide salivary gland stem/progenitor cells. However, K14 is also expressed in terminally differentiated myoepithelial cells; therefore, more accurate molecular markers for identifying salivary stem/progenitor cells are required. The intraflagellar transport (IFT) protein IFT140 is a core component of the IFT system that functions in signaling transduction through the primary cilia. It is reportedly expressed in mesenchymal stem cells and plays a role in bone formation. In this study, we demonstrated that IFT140 was intensively expressed in K14⁺ stem/progenitor cells during the developmental period and early regeneration stage following ligation-induced injuries in murine submandibular glands. In addition, we demonstrated that IFT140⁺/ K14⁺ could self-renew and differentiate into granular duct cells at the developmental stage in vivo. The conditional deletion of Ift140 from K14⁺ cells caused abnormal epithelial structure and function during salivary gland development and inhibited regeneration. IFT140 partly coordinated the function of K14⁺ stem/progenitor cells by modulating ciliary membrane trafficking. Our investigation identified a combined marker, IFT140⁺/K14⁺, for salivary gland stem/progenitor cells and elucidated the essential role of IFT140 and cilia in regulating salivary stem/progenitor cell differentiation and gland regeneration.
Animals ; Carrier Proteins/metabolism* ; Cell Differentiation ; Keratin-14/metabolism* ; Mice ; Osteogenesis ; Salivary Glands/metabolism* ; Stem Cells

Breast/pathology* ; Humans ; Salivary Gland Neoplasms/pathology* ; Salivary Glands/pathology*