CD8+ tissue-resident memory T cells are expanded in primary Sjögren's disease and can be therapeutically targeted by CD103 blockade.

OBJECTIVE: Tissue-resident memory cells (Trm) are a subset of T cells residing persistently and long-term within specific tissues that contribute to persistent inflammation and tissue damage. We characterised the phenotype and function of Trm and the role of CD103 in primary Sjogren's syndrome (pSS). METHODS: In both pSS and non-pSS sicca syndrome patients, we examined Trm frequency, cytokine production in salivary glands (SG) and peripheral blood (PB). We also analysed Trm-related gene expression in SG biopsies through bulk and single-cell RNA sequencing (scRNAseq). Additionally, we investigated Trm properties in an immunisation-induced animal model of pSS (experimental SS, ESS) mouse model and assessed the effects of Trm inhibition via intraglandular anti-CD103 monoclonal antibody administration. RESULTS: Transcriptomic pSS SG showed an upregulation of genes associated with tissue recruitment and long-term survival of Trm cells, confirmed by a higher frequency of CD8+CD103+CD69+ cells in pSS SG, compared with non-specific sialadenitis (nSS). In SG, CD8+ CD103+ Trm contributed to the secretion of granzyme-B and interferon-γ, CD8+ Trm cells were localised within inflammatory infiltrates, where PD1+CD8+ T cells were also increased compared with nSS and MALT lymphoma. scRNAseq of PB and pSS SG T cells confirmed expression of CD69, ITGAE, GZMB, GZMK and HLA-DRB1 among CD3+CD8+ SG T cells. In the SG of ESS, CD8+CD69+CD103+ Trm producing Granzyme B progressively expanded. However, intraglandular blockade of CD103 in ESS reduced Trm, reduced glandular damage and improved salivary flow. CONCLUSIONS: CD103+CD8+Trm cells are expanded in the SG of pSS and ESS, participate in tissue inflammation and can be therapeutically targeted.

Reliability of Ultrasonographic Assessment of Depth of Invasion and Tumor Thickness in Intraoral Mucosa Lesions: A Preliminary Experience.

Introduction: Despite the progress made in multidisciplinary care, there has been little improvement in the oncologic outcomes of oral cavity squamous cell carcinomas (OSCCs). In the latest edition of the TNM staging, "depth of invasion" (DOI) has recently been introduced as one of the criteria for determining the T stage, alongside other factors. DOI is widely recognized as an independent risk factor for nodal metastases and is a crucial consideration in the preoperative staging of OSCCs, along with measurements of tumor thickness (TT). While various diagnostic methods exist for assessing DOI, intraoral ultrasonography (IOUS) has gained popularity for its efficacy in evaluating OSCCs. Methods: This study sought to evaluate the diagnostic accuracy and reliability of ultrahigh-frequency ultrasound (UHFUS) in assessing oral cavity lesions compared to histopathological analysis. Results: The results revealed strong reliability in ultrasonographic measurements (ICC TT: 0.94; ICC DOI: 0.97) and distinct ultrasonographic features specific to different oral pathologies. This highlights the potential of UHFUS as a non-invasive imaging tool for precise diagnostic evaluations. Conclusions: Despite limitations such as a small sample size and focus on specific lesions, these promising results suggest that UHFUS could significantly enhance oral lesion diagnostics. Further research involving larger cohorts is necessary to validate and build upon these initial findings.

State of the Art in the Diagnosis and Assessment of Oral Malignant and Potentially Malignant Disorders: Present Insights and Future Outlook-An Overview.

Oral Potentially Malignant Disorder (OPMD) is a significant concern for clinicians due to the risk of malignant transformation. Oral Squamous Cell Carcinoma (OSCC) is a common type of cancer with a low survival rate, causing over 200,000 new cases globally each year. Despite advancements in diagnosis and treatment, the five-year survival rate for OSCC patients remains under 50%. Early diagnosis can greatly improve the chances of survival. Therefore, understanding the development and transformation of OSCC and developing new diagnostic methods is crucial. The field of oral medicine has been advanced by technological and molecular innovations, leading to the integration of new medical technologies into dental practice. This study aims to outline the potential role of non-invasive imaging techniques and molecular signatures for the early detection of Oral Malignant and Potentially Malignant Disorders.

Personalized Medicine in Oral Oncology: Imaging Methods and Biological Markers to Support Diagnosis of Oral Squamous Cell Carcinoma (OSCC): A Narrative Literature Review.

For decades, oral squamous cell carcinoma (OSCC) has been one of the most prevalent and mortal cancers worldwide. The gold standard for OSCC diagnosis is still histopathology but this narrative multidisciplinary review has the aim to explore the literature about conventional OSCC prognostic indicators related to the pTNM stage at the diagnosis such as the depth of invasion and the lymphovascular invasion associated with distant metastasis as indicators of poor life expectancy. Despite its multifactorial nature and recognizable precursors, its diagnosis at the early stages is still challenging. We wanted to highlight the importance of the screening as a primary weapon that a stomatologist should consider, intercepting all at-risk conditions and lesions associated with OSCC and its early stages. This narrative review also overviews the most promising imaging techniques, such as CT, MRI, and US-echography, and their application related to clinical and surgical practice, but also the most-investigated prognostic and diagnostic tissue and salivary biomarkers helpful in OSCC diagnosis and prognostic assessment. Our work highlighted remarkable potential biomarkers that could have a leading role in the future. However, we are still far from defining an appropriate and concrete protocol to apply in clinical practice. The hope is that the present and future research will overcome these limitations to benefit patients, clinicians, and welfare.

Safety and Aesthetics of Autologous Dermis-Fat Graft after Parotidectomy: A Multidisciplinary Retrospective Study.

(1) Background: In surgical procedures for maxillofacial tumours, it is challenging to preserve functional and cosmetic properties in the affected patients. The use of fat grafting is considered as a valuable alternative to overcome postoperative aesthetic asymmetry problems. (2) Methods: In this study, we enrolled thirty patients with parotid gland tumours in which a partial or complete parotidectomy was performed with positioning in the parotid bed of autologous dermis-fat grafts. We evaluated the satisfaction rate of the patients and the objective efficacy in solving the deformity by comparing MRI data before and after surgery. (3) Results: Twenty-six patients showed a satisfying cosmetic result with proper facial symmetry between the affected side and the healthy one. Two patients presented mild postsurgical complications such as haematomas, and two patients reported temporary weakness of the facial nerve related to the parotidectomy. (4) Conclusions: Based on the imaging data obtained via MRI before and after surgery, we can assess that the employment of fat grafts in parotidectomy surgical procedures gives good cosmetic results and does not affect the post operative management and follow up of oncologic patients.

Medication-Related Osteonecrosis of the Jaws: A Comparison of SICMF-SIPMO and AAOMS Guidelines.

(1) Background: Medication-related osteonecrosis of the jaws (MRONJ) is an adverse drug reaction characterized by progressive bone disruption and necrosis in the mandibular and/or maxillary bones. It occurs in individuals who have received antiresorptive drugs without prior radiotherapy. Since its first reported cases in the USA in 2003, extensive literature has emerged worldwide, leading to significant advancements in understanding MRONJ's pathogenesis and management. (2) Results: This article aims to compare the current national recommendations provided by the Italian Society of Maxillofacial Surgery (SICMF)/Italian Society of Oral Pathology and Medicine (SIPMO) and the American Association of Oral and Maxillofacial Surgeons (AAOMS). (3) Conclusions: Historically, the AAOMS advocated for a more conservative approach compared to the Italian guidelines. However, in their 2022 update, the AAOMS adopted a different perspective based on reported evidence, highlighting the advantages of early surgical treatment. Despite resolving some initial controversies, differences still exist between the two sets of recommendations, particularly regarding diagnosis and staging.

Metastatic Lung Cancer to the Head and Neck: A Clinico-Pathological Study on 21 Cases with Narrative Review of the Literature.

Metastases from lung cancer to the oral cavity and to the head and neck generally are very infrequent and usually manifest in advanced stages of the disease. Even more rarely, they are the first sign of an unknown metastatic disease. Nevertheless, their occurrence always represents a challenging situation both for clinicians, in the management of very unusual lesions, and for pathologists, in the recognition of the primary site. We retrospectively studied 21 cases of metastases to the head and neck from lung cancer (sixteen males and five females, age range 43-80 years; eight cases localized to the gingiva [two of these to the peri-implant gingiva], seven to the sub-mandibular lymph nodes, two to the mandible, three to the tongue, one case to the parotid gland; in eight patients, metastasis was the first clinical manifestation of an occult lung cancer) and proposed a wide immunohistochemical panel for a proper identification of the primary tumor histotype, including CK5/6, CK8/18, CK7, CK20, p40, p63, TTF-1, CDX2, Chromogranin A, Synaptophysin, GATA-3, Estrogen Receptors, PAX8, PSA. Furthermore, we collected data from previously published studies and narratively reviewed the relevant literature.

Interventions for the Prevention of Oral Mucositis in Patients Receiving Cancer Treatment: Evidence from Randomised Controlled Trials.

Oral mucositis is a common and most debilitating complication associated with cancer therapy. Despite the significant clinical and economic impact of this condition, there is little to offer to patients with oral mucositis, and the medications used in its management are generally only palliative. Given that mucositis is ultimately a predictable and, therefore, potentially preventable condition, in this study we appraised the scientific literature to evaluate effective methods of prevention that have been tested in randomised controlled trials (RCTs). Published high-level evidence shows that multiple preventative methods are potentially effective in the prevention of oral mucositis induced by radiotherapy, chemotherapy, or both. Anti-inflammatory medications (including benzydamine), growth factors and cytokines (including palifermin), cryotherapy, laser-and-light therapy, herbal medicines and supplements, and mucoprotective agents (including oral pilocarpine) showed some degree of efficacy in preventing/reducing the severity of mucositis with most anticancer treatments. Allopurinol was potentially effective in the prevention of radiotherapy-induced oral mucositis; antimicrobial mouthwash and erythropoietin mouthwash were associated with a lower risk of development of severe oral mucositis induced by chemotherapy. The results of our review may assist in highlighting the efficacy and testing the effectiveness of low-cost, safe preventative measures for oral mucositis in cancer patients.

Increased Delay in Diagnosis, but Not Treatment, Among Patients With Oral Cancer During the COVID-19 Pandemic.

This retrospective cohort study assesses delays in diagnosis and treatment for patients with oral squamous cell carcinoma in a tertiary care university hospital in Naples, Italy.

Solitary Extrapleural Fibrous Tumor in Salivary Glands: Our Experience-Case Series and Literature Review.

(1) Background: Extrapleural solitary fibrous tumors (ESFTs) are rare oncological entities occurring in the head and neck, and even more so in the salivary glands. The clinical presentation and histologic features are usually unspecific, resulting in frequent misclassification. As an unusual tumor, ESTFs have an unpredictable clinical behavior. (2) Methods: We present two clinical cases referred to our Maxillofacial Surgery Unit for the onset of a symptomless mass involving, in one case, the parotid gland, and in the other case, the sublingual gland. (3) Results: Solitary fibrous tumors could be considered as neoplasms with intermediate biological behavior that are not entirely predictable on the basis of morphological features, as these are mostly still unknown. However, a few histologic, immunohistochemical, and imaging features, such as a hypodense signal at the T1 sequence in an MRI, or positivity for CD34, bcl2, and CD99, and the NAB2-STATS6 fusion gene, could be useful for an early differential diagnosis of ESTFs. (4) Conclusions: All patients were alive at follow-up with no evidence of disease. Surgical management should always be considered as the first choice for oncological radicality, and clinical behavior should always be defined with the help of the study of radiological and anatomopathological features.

Kabat Rehabilitation in Facial Nerve Palsy after Parotid Gland Tumor Surgery: A Case-Control Study.

Temporary facial nerve palsy after parotid tumor surgery ranges from 14 to 65%, depending on surgery, tumor type, and subsite. The study aimed to evaluate the role of Kabat physical rehabilitation in the outcomes of patients affected by severe facial nerve palsy following parotid gland surgery. The results and clinical data of two groups, Kabat and non-Kabat (control), were statistically compared. Descriptive statistics, the multiple linear regression model, difference in difference approach, and the generalized linear model were used. F-Test, Chi-square test, McFadden R-squared, and adjusted R-squared were used to assess the significance. The results showed that the House-Brackmann (HB) stage of patients who had physiotherapy performed were lower than the control group. The decrease of HB staging in the Kabat group at 3 months was -0.71 on average, thus the probability of having a high HB stage decreased by about 13% using Kabat therapy. The results are statistically significant, and indicated that when the Kabat rehabilitation protocol is performed, mainly in the cases of a high-grade HB score, the patients showed a better and faster improvement in postoperative facial nerve palsy.

Salivary miRNAs Expression in Potentially Malignant Disorders of the Oral Mucosa and Oral Squamous Cell Carcinoma: A Pilot Study on miR-21, miR-27b, and miR-181b.

(1) Background: Oral potentially malignant disorders (OPMD) represent a fundamental challenge for clinicians, considering the possibility of progression into oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC). Several studies have examined the expression of miRNAs in humans as diagnostic and prognostic biomarkers. Among these, miR-21, miR-27b, and miR-181b proved to be promising. This cohort study evaluated the different expressions of those miRNAs in the saliva of patients with OPMD and OSCC. (2) Methods: Patients with a clinical diagnosis of OPMD and/or OSCC were enrolled; saliva samples were collected; miRNAs were extracted and quantified via qRT-PCR was performed. Data were analyzed by subgroups based on the histopathological diagnosis (OSCC and the grade of OED) using the ΔΔCt method. Saliva from 10 healthy donors was used as the control. One-way ANOVA and Kruskal-Wallis tests were performed to assess the differences between groups. (3) Results: 23 patients for the OPMD group (6 with no dysplasia, 7 with low-grade, and 10 with high-grade dysplasia) and 10 with OSCC were analyzed. MiR-21 did not show any variation among groups; miR-27b was under-expressed in dysplastic lesions (p = 0.046); miR-181b was upregulated in high-grade dysplasia (p = 0.006), increasing with the degree of dysplasia, and decreasing in OSCCs. (4) Conclusions: Salivary miR-27b and miR-181b could be promising biomarkers for oral dysplasia. Further studies are needed to clarify their feasibility.

Protective Effects of Helmet Type on Facial Injuries.

ABSTRACT: The compulsory use of helmet by motorcyclists has lowered the incidence of facial trauma, but there are few studies evaluating the effects of different helmet types on such injuries. The authors collected retrospective data from the medical records of 287 motorcyclists presenting facial injuries treated at the maxillofacial surgery department of the "University Magna Graecia" of Catanzaro city in South Italy between 1 January 2007 and 1 August 2018. Patients were wearing 2 types of crash helmets at the time of the trauma, full face ones or open-face ones, and were compared using the Facial Injury Severity Scale (FISS). Those wearing open-face helmet were 3 times more than those wearing full-face helmet, with a higher FISS score.The purpose of this study was to investigate the impact of Italy's compulsory helmet law on the change in helmet use and in particular if protection offered by helmets w4as different according to helmet type. The authors correlated the FISS scores among motorcyclists wearing these 2 tipologies of crash helmet.

Psychological profile and unexpected pain in oral lichen planus: A case-control multicenter SIPMO studya.

OBJECTIVES: To analyze psychological profiles, pain, and oral symptoms in patients with oral lichen planus (OLP). MATERIALS AND METHODS: 300 patients with keratotic OLP (K-OLP; reticular, papular, plaque-like subtypes), 300 patients with predominant non-keratotic OLP (nK-OLP; erythematosus atrophic, erosive, ulcerative, bullous subtypes), and 300 controls were recruited in 15 universities. The number of oral sites involved and oral symptoms were recorded. The Numeric Rating Scale (NRS), Total Pain Rating Index (T-PRI), Hamilton Rating Scales for Depression and for Anxiety (HAM-D and HAM-A), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS) were administered. RESULTS: The OLP patients, especially the nK-OLP, showed higher scores in the NRS, T-PRI, HAM-D, HAM-A and PSQI compared with the controls (p-value < .001** ). A positive correlation between the NRS, T-PRI, HAM-A, HAM-D, and PSQI was found with the number of oral symptoms and number of oral sites involved. Pain was reported in 67.3% of nK-OLP and 49.7% of K-OLP cases with poor correspondence between the site of lesions and the site of the symptoms. CONCLUSIONS: Mood disorders are frequently associated with OLP with an unexpected symptomatology correlated with the number of oral symptoms and with the extension of disease suggesting a peripheral neuropathy.

Clinical management of squamous cell carcinoma of the tongue: patients not eligible for free flaps, a systematic review of the literature.

INTRODUCTION: The management of squamous cell carcinoma (SCC) of the tongue represents the most demanding treatment planning in head and neck surgery. Ablation followed by free flap reconstruction is considered the gold standard, but not all patients are suitable for this strategy. The aim of this review is to provide a comprehensive view of surgical reconstruction possibilities in patients not eligible for free flaps. METHODS: Following PRISMA recommendations, a systematic literature review was conducted searching for original papers that investigated outcomes of patients treated by surgical ablation for tongue SCC followed by reconstruction with local or pedicled flaps. Selected papers were read and data extracted for qualitative analysis. RESULTS: Twenty articles met the inclusion/exclusion criteria. The study design was case series in sixteen papers, cohort study in the remaining four. Four different local flaps (BMM, FAMM, NLIF, SMIF) and four regional flaps have been discussed in included studies (IHF, SFIF, SCM, PMMC). CONCLUSION: The improved anatomical knowledge makes local flaps a reliable alternative to free tissue transfer in cases requiring small-/medium-sized defects. Regional flaps still represent cornerstones in reconstruction of the tongue. Ease of execution, costs-to-benefit ratio, low-rate complications, minimal donor site morbidity represent the best advantages choosing local/regional flaps.

Primary branchiogenic carcinoma: malignant degeneration of a branchial cyst, a case report.

BACKGROUND: Primary branchiogenic carcinoma (PBC) is an extremely rare and poorly documented disease developed from a brachial cleft cyst. CASE: A 51-year-old patient was referred to our unit for an upper neck mass. PBC was confirmed in accordance with Kahfif's diagnostic criteria. Prophylactic selective neck dissection was performed in a second-stage surgery to ensure the complete removal of the neoplasm. Branchiogenic origin with lymphoid tissue was confirmed in the "host cyst" after histological examination and no other tumors were found elsewhere. Regular follow up documented no relapse 12 months after surgery. CONCLUSIONS: Although rare, PBC must be suspected in presence of cervical masses, especially in patients older than 40 years. A standardized treatment algorithm still lacks, but prophylactic selective neck dissection could be considered as the first line choice after the diagnosis has been confirmed.