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Primary Sjögren’s Syndrome (pSS) is a multi-system autoimmune disease that involves the exocrine glands. Lymphocytes infiltrate the gland tissue, leading to anatomical modification and hypofunction. Even if the prognosis of pSS is favorable, quality of life is typically reduced due to the diverse manifestations of the disease. The aim of this study is to compare the salivary metabolomes of pSS with healthy controls (HCs). Seven cases were selected from a cohort of pSS patients, and six age- and sex-matched HCs were recruited from a cohort of volunteers. Whole unstimulated saliva was collected for NMR analysis. Our metabolomic analysis focused on 360 ms total echo 1D 1H NMR CPMG spectra. Metabolites detected with CPMG NMR spectra were assigned through 2D NMR spectra (COSY, TOCSY, and HSQC). About 50 metabolites were detected and assigned. Unsupervised exploratory PCA returned partial clustering, and PLS-DA improved the separation between pSS and HCs, highlighting a pool of metabolites distinctly describing each group. Despite the limited number of samples, the presented preliminary data are promising. PLS-DA indicated well-defined group separation, suggesting that the application of 1H-NMR metabolomics is suitable for the study of pSS.

Systemic sclerosis is a connective tissue disease. Skin involvement of the mouth and hand may compromise function and quality of life. Autologous fat grafting has been described as a specific treatment of these clinical features. We report the results of our prospective study designed to treat and prevent skin complications in systemic sclerosis. We treated 25 patients with mouth and/or hand involvement (microstomia, xerostomia, skin sclerosis, Raynaud’s phenomenon and long-lasting digital ulcers) with autologous fat grafting, according to the Coleman’s technique, around the mouth and/or at the base of each finger. The surgical procedures were repeated in each patient every 6 months for a total of two or three times. Clinical data were collected before the first surgery and again 6 months after each surgical procedure. Pain, skin thickness, saliva production and disability were assessed with validated tests. Overall we performed 63 autologous fat grafting sessions (either on the mouth, on the hands or on both anatomical areas). Results at 6 moths after the last session included improvement of xerostomia evaluated with a sialogram, reduction of the skin tension around the mouth and, in the hands, reduction of the Raynaud phenomenon as well as skin thickness. Pain was reduced while the perception of disability improved. Digital ulcers healed completely in 8/9 patients. Our results confirm the efficacy and safety of autologous fat grafting for the treatment of skin complications and digital ulcers due to systemic sclerosis. In addition, the patients’ subjective well-being improved. Level of evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Antiresorptive and antiangiogenic therapy, as well as target therapy agents (such as drugs for immunotherapy, immunomodulators, enzyme or protein inhibitors), are widely administered in several life-threatening oncological and hematological diseases. Medication-related osteonecrosis of jaws (MR-ONJ) is an adverse effect which incidence is strongly related to primary disease history, therapy management and duration, systemic co-morbidities treatments, dental and oral health control. A previously reported case series described a 10-year (2007-2016) single-center raw incidence of 47 MR-ONJ cases in a cohort of 1663 patients treated with antiresorptive drugs (2.8%). The significant positive effect of a dental and oral health prevention protocol was appreciated by splitting the cohort into two timeframes, 2007-2010 and 2011-2016. During the first period, dental evaluation and treatment were not implemented and MR-ONJ incidence was 4.9%; in the second one, the incidence dropped (1.9%), suggesting the value of the applied protocol. Between February 2020 and February 2021, 184 onco-hematological new patients were referred for comprehensive dental, oral health evaluation and treatment. Including subjects already in follow-up, overall 313 patients were in charge. In 12 months, MR-ONJ occurred in 5 cases (incidence 1.6%). Altogether, 11 MR-ONJ cases were treated in the considered timeframe, of which 6 were previously diagnosed. Following staging, treatment options ranged from conservative to surgical therapy, depending on extension, drug history, primary disease prognosis, and patient feasibility.

The detection of salivary molecules associated with pathological and physiological alterations has encouraged the search of novel and non-invasive diagnostic biomarkers for oral health evaluation. While genomic, transcriptomic, and proteomic profiles of human saliva have been reported, its metabolic composition is a topic of research: metabolites in submandibular/sublingual saliva have never been analyzed systematically. In this study, samples of whole, parotid, and submandibular/sublingual saliva from 20 healthy donors, without dental or periodontal diseases, were examined by nuclear magnetic resonance. We identified metabolites which are differently distributed within the three saliva subtypes (54 in whole, 49 in parotid, and 36 in submandibular/sublingual saliva). Principal component analysis revealed a distinct cluster for whole saliva and a partial overlap for parotid and submandibular/sublingual metabolites. We found exclusive metabolites for each subtype: 2-hydroxy-3-methylvalerate, 3-methyl-glutarate, 3-phenylpropionate, 4-hydroxyphenylacetate, 4-hydroxyphenyllactate, galactose, and isocaproate in whole saliva, caprylate and glycolate in submandibular/sublingual saliva, arginine in parotid saliva. Salivary metabolites were classified into standard and non-proteinogenic amino acids and amines, simple carbohydrates, organic acids, bacterial-derived metabolites. The identification of a salivary gland-specific metabolic composition in healthy people provides the basis to invigorate the search for salivary biomarkers associated with oral and systemic diseases.

Background Saliva evaluation could be a possible alternative to blood and/or tissue analyses, for researching specific molecules associated to the presence of systemic diseases and malignancies. The present systematic review has been designed in order to answer to the question “are there significant associations between specific salivary biomarkers and diagnosis of systemic diseases or malignancies?”. Material and Methods The Preferred Reporting Item for Systematic Reviews and Meta-analysis (PRISMA) statement was used to guide the review. The combinations of “saliva” and “systemic diseases” or “diagnosis” or “biomarkers” or “cancers” or “carcinoma” or “tumors”, were used to search Medline, Scopus and Web of Science databases. Endpoint of research has been set at May 2019. Studies were classified into 3 groups according to the type of disease investigated for diagnosis: 1) malignant tumors; 2) neurologic diseases and 3) inflammatory/metabolic/cardiovascular diseases. Assessment of quality has been assigned according to a series of questions proposed by the National Institute of Health. Level of evidence was assessed using the categories proposed in the Oxford Center for Evidence-Based medicine (CEMB) levels for diagnosis (2011). Results Seventy-nine studies met the inclusion and exclusion criteria. Fifty-one (64%) investigated malignant tumors, 14 (17.5%) neurologic and 14 (18.5%) inflammatory/cardiovascular/metabolic diseases. Among studies investigating malignant tumors, 12 (23.5%) were scored as “good” and 11 of these reported statistically significant associations between salivary molecules and pathology. Two and 5 studies were found to have a good quality, among those evaluating the association between salivary biomarkers and neurologic and inflammatory/metabolic/cardiovascular diseases, respectively. Conclusions The present systematic review confirms the existence of some “good” quality evidence to support the role of peculiar salivary biomarkers for diagnosis of systemic diseases (e.g. lung cancer and EGFR). Key words:Salivary diagnostics, biomarkers, systemic diseases, malignant tumors, early diagnosis.

Background The purpose of this study was to evaluate whether marsupialization treatment induces changes in the histology of odontogenic keratocyst epithelium and to compare our experience with the literature. Material and Methods A retrospective revision of histological samples was performed. 5 patients with odontogenic keratocyst treated with marsupialization follow by enucleation were selected. Histologic evaluation analyzed the changes in the keratocyst epithelium after marsupialization in terms of type of keratinization, thickness of the epithelium and connective tissue, the presence of acanthosis, the presence and grade of fibrosis, the type and grade of inflammation and the presence and number of mitotic figures and daughter cysts. Results In our case series, a variation of para-keratinized into ortho-keratinized keratocyst was found in one case, and no significant increases were observed in the epithelium and capsule thickness, or even in the level of inflammation. However, we observed an increase in fibrosis and qualitative changes in inflammation type. Conclusions Minor and major histological changes were associated with reduction in cyst volume, which resulted in a simpler and less invasive cystic enucleation after marsupialization. Key words:Keratocyst, marsupialization, enucleation, histology, histological changes.

Background: The aberrant expression of microRNAs (miRNAs) has been associated with several diseases, including cancer, inflammatory, and autoimmune conditions. Interest in salivary miRNAs as non-invasive tools for the diagnosis of malignancies and systemic diseases is rapidly increasing. The present systematic review was developed for answering the question: “Are salivary microRNAs reliable biomarkers for diagnosis of cancer and systemic diseases?” Methods: The application of inclusion and exclusion criteria led to the selection of 11 papers. Critical appraisals and quality assessments of the selected studies were performed through the National Institute of Health “Study Quality Assessment Tool” and the classification of the Oxford Center for Evidence-Based Medicine. Results: Seven studies reported statistically significant correlations between one or more salivary miRNAs and the investigated disease. The critical analysis allowed us to classify only two studies (18.2%) as having “good” quality, the rest being scored as “intermediate” (8; 73%) and “poor” (1; 9%). Evidence exists that salivary miR-940 and miR-3679-5p are reliable markers for pancreatic cancer and that miR140-5p and miR301a are promising molecules for the salivary diagnosis of gastric cancer. Conclusions: Further studies, possibly avoiding the risk of bias highlighted here, are necessary to consolidate these findings and to identify new reliable salivary biomarkers.

Oral squamous-cell carcinoma, the most frequent malignant neoplasm of the oral cavity, has a poor 5 years survival rate. [...]

Primary Sjogren Syndrome (pSS) is a multisystem autoimmune disease which mainly involves exocrine glands, such as salivary and lacrimal. [...]

Background The etiology of traumatic ulcerative granulomas with stromal eosinophilia (TUGSE) is not clear, traumatic irritation having advocated as the most likely cause. TUGSEs are typically self-limiting slow-healing lesions of the oral mucosa with unclear pathogenesis, commonly manifesting as a rapidly developing, long-lasting ulcer. Case presentation Here we report a controversial case of a self-healing lesion of the tongue in a 57 year-old woman. A clonal T-cell proliferation and CD30 negative immunohistochemical (IHC) profile could be documented. Discussion and conclusion In view of the very peculiar clinical and histological features, a retrospective diagnosis of a TUGSE with scarce eosinophilic infiltrate (possibly in regression), displaying CD30- T-clonal proliferation was eventually rendered. The patient did not report signs of recurrence after a 3-year follow-up period.

Summary Scalp reconstruction following wide, non-melanoma skin cancer resection remains very challenging due to the anatomy of the area and the nature of the disease. We present a new reconstructive proposal for full-thickness and wide scalp defects; we term our new flap the “bat flap”. Seven patients with large squamous cell carcinomas of the scalp underwent local excision of the neoplastic lesions and defect reconstruction using bat flaps. The average defect size was 15 × 12 cm 2 . The depth of the excision was dictated by the extent of involvement of the various anatomical structures in the NMSC. The bat flap is a bilaterally based temporalis fasciocutaneus flap created by sliding the occipital part of the scalp forwards, or the anterior parietal part of the scalp backwards, depending on the position of the defect. The surgical defect in the donor area is repaired by placing split-thickness skin grafts or by placing an artificial dermis graft. No case developed any serious post-operative complication. The procedural time averaged 2 h. All patients were satisfied with their long-term postoperative outcomes. We encountered no serious post-operative complication and achieved optimal aesthetic results. The technique is oncologically safe and feasible.

The purpose of this study is to help in the choice of an appropriate reconstructive technique by reference to the dimensions of the defect, the required functional and esthetic outcomes, and retention of adequate surgical safety margins to prevent primary tumor recurrence. Material and methods A total of 158 patients were treated. We indicate how the most appropriate reconstructive method may be chosen, with reference to the size and position of the cancer and depth of tissue infiltration. Result Of all patients, 89 (56.3%) had T1 (lesions up to 2 cm long, less than 1/3). The remaining patients had T2 lesions >2 cm, from 1/3 to 2/3 of lip involvement (50 patients), T3 lesions >4 cm, more than 2/3 of lip involvement (18), and a T4 lesion > 5.5 cm with commissure involvement (1). Conclusion We share the widespread view that a surgeon who performs a reconstruction using the minimal tissue components required to close the lesion will achieve the best results. Reconstruction does not influence prognosis and overall should be oriented to the defect. Careful, clean, and safe resection of lip carcinoma, with creation of healthy margins, can be followed by functional and esthetic lip reconstruction.

Malignant epithelioid hemangioendothelioma (MEH), or high-risk epithelioid hemangioendothelioma, is a low- to intermediate-grade vascular malignancy. A few cases of MEH have been documented in the head and neck region, including the neck, thyroid gland, larynx and scalp. MEHs are extremely rare in the oral cavity. Only 31 cases of MEH in the oral cavity were described in English literature between 1975 and 2014. Further, only eleven cases were referred to MEH of the maxillary or mandibular gingiva. No gingival MEH metastases have been described in literature. We report a literature review and a case of MEH with a metastatic occurrence 4 years after surgical excision.