Are statins onco- suppressive agents for every type of tumor? A systematic review of literature.

INTRODUCTION: Statins, in the role of anti-cancer agents, have been used in many types of cancers with results in some cases promising while, in others, disappointing. AREAS COVERED: The purpose of this review is to identify and highlight data from literature on the successes or failure of using statins as anti-cancer agents. We asked ourselves the following two questions:1. Could statins, which are taken mostly to reduce cardiovascular risk, guarantee a lower incidence or a better cancer disease prognosis, concerning local recurrence, metastasis or mortality?2. Does statins intake (before and/or after cancer diagnosis) improve the prognosis or increase the chemotherapeutic action when combined with other anticancer therapies? For the first question twenty-seven manuscripts have been selected, for the second one, twenty-eight. EXPERT OPINION: There are data which correlate statins with a possible tumor suppressive action among the following cancers: breast, lung, prostate and head and neck. Lastly, for gastric cancer and colorectal there is no evidence of a correlation. The onco-suppressive efficacy of statins is mainly related to the histopathological and/or molecular characteristics of the tumor cells, which have different characteristics.

Partial Horizontal Supracricoid Laryngectomy: Which Factors Impact on Post-decannulation Swallowing Outcomes? A Prospective Single-Center Experience.

Early decannulation, performed within the first ten days after supracricoid partial laryngectomy, can result in a more rapid recovery of swallowing function with a semisolid bolus in the short term, about 30 days. We selected 20 patients with squamous cell carcinoma of larynx, who underwent supracricoid laryngectomies: 10 cricohyoidopexy (CHP) and 10 cricohyoidoepiglottopexy (CHEP). Staging was pT2 (10 pts), and pT3 (10 pts). Fiberoptic endoscopic evaluation of swallowing was used to assess postoperative swallowing function after a mean of 12 and 22 days from surgery. A modified PAS score (penetration-aspiration scale) was assigned for subtotal laryngectomies. Decannulation occurred after 6.7 ± 2.1 days. Univariate analysis showed that the type of surgery (CHP or CHEP), pT, resection of one arytenoid, and decannulation time are significantly associated with the 12-day PAS score. The 22-day PAS score is significantly associated with only 3 variables: type of surgery, pT, and resection of one arytenoid. From the data presented, the factors that most delay an effective recovery of swallowing are T3 and the resection of one arytenoid. Early decannulation has been shown statistically to improve PAS score in the short term, but not in the long term.

Involvement of Substance P (SP) and Its Related NK1 Receptor in Primary Sjögren's Syndrome (pSS) Pathogenesis.

Primary Sjögren's Syndrome (pSS) is a systemic autoimmune disease that primarily attacks the lacrimal and salivary glands, resulting in impaired secretory function characterized by xerostomia and xerophthalmia. Patients with pSS have been shown to have impaired salivary gland innervation and altered circulating levels of neuropeptides thought to be a cause of decreased salivation, including substance P (SP). Using Western blot analysis and immunofluorescence studies, we examined the expression levels of SP and its preferred G protein-coupled TK Receptor 1 (NK1R) and apoptosis markers in biopsies of the minor salivary gland (MSG) from pSS patients compared with patients with idiopathic sicca syndrome. We confirmed a quantitative decrease in the amount of SP in the MSG of pSS patients and demonstrated a significant increase in NK1R levels compared with sicca subjects, indicating the involvement of SP fibers and NK1R in the impaired salivary secretion observed in pSS patients. Moreover, the increase in apoptosis (PARP-1 cleavage) in pSS patients was shown to be related to JNK phosphorylation. Since there is no satisfactory therapy for the treatment of secretory hypofunction in pSS patients, the SP pathway may be a new potential diagnostic tool or therapeutic target.

Kikuchi-Fujimoto Disease: A Distinct Pathological Entity but also an "Overlap" Autoimmune Syndrome: A Systematic Review.

BACKGROUND: The association between KFD and autoimmune diseases, not only with systemic lupus erythematosus, has been repeatedly described. OBJECTIVE: The aim of this review is to evaluate whether an overlap syndrome is present between KFD and autoimmune diseases, whether there is a chronological and a casual relationship between the pathologies. METHODS: The databases used for the overlap case search were Medline and Embase from which we extrapolated the studies of interest. The search queries used were: Kikuchi-Fujimoto Syndrome and juvenile idiopathic arthritis or systemic lupus erythematosus or Systemic Sclerosis or Antiphospholipid Syndrome or Sjogren's Syndrome. All study types were considered (n = 103). RESULTS: Total number of included studies are 43. We have shown that there is an "overlap" syndrome between KFD and other autoimmune diseases. The chronology of disease onset was variable; autoimmune disease may be "preceding" (n = 11 cases) or "simultaneous" (n = 20 cases) or "post" (n = 8 cases). Kikuchi-Fujimoto Syndrome. Also, the autoimmune disease can present with a complete clinical picture or only with the presence of autoantibodies. CONCLUSION: the different pathologies associated with KFD with different chronologies would suggest that there is an alteration of the immune system that allows the pathologies to occur in different temporal relationships.

Interpretation of the mucous plug through sialendoscopy.

OBJECTIVE: The purpose of this manuscript is to highlight the behaviour of mucus inside the ducts of the major salivary glands, in presence of typical pathologies, through images obtained with sialendoscopy. SUBJECT: The authors present and comment on some sialendoscopies that show mucous plug in the ducts of the major salivary glands. RESULTS: In primary Sjogren's syndrome, mucous plugs confirm the qualitative anomaly of the mucins and acidification saliva. Instead, salivary calculations behave like foreign bodies that generate mechanical pressure and friction on the duct walls of major salivary glands, so mucus deposits in the duct in its defence; in case of infected stone, mucous plugs are formed also with the function of protecting the ducts from the aggression of germs. During sialadenitis, there is a conflict between mucus and bacteria which explains sialendoscopic evidence such as white duct walls and mucous plugs. CONCLUSIONS: The study of the salivary ducts through sialendoscopy often confirms the clinical diagnosis or hypothesize it. During its execution, it is necessary not only to liberate the ducts of the major salivary glands but also analyse the appearance of the mucous plugs and the ductal walls as they are useful to guide the physician towards diagnosis.

Maladaptive Autophagy in the Pathogenesis of Autoimmune Epithelitis in Sjögren's Syndrome.

OBJECTIVE: Salivary gland epithelial cells (SGECs) are key cellular drivers in the pathogenesis of primary Sjögren's syndrome (SS); however, the mechanisms sustaining SGEC activation in primary SS remain unclear. We undertook this study to determine the role of autophagy in the survival and activation of SGECs in primary SS. METHODS: Primary SGECs isolated from the minor SGs of patients with primary SS or sicca syndrome were evaluated by flow cytometry, immunoblotting, and immunofluorescence to assess autophagy (autophagic flux, light chain 3 IIB [LC3-IIB], p62, LC3-IIB+/lysosome-associated membrane protein 1 [LAMP-1] staining), apoptosis (annexin V/propidium iodide [PI], caspase 3), and activation (intercellular adhesion molecule, vascular cell adhesion molecule). Focus score and germinal center presence were assessed in the SGs from the same patients to assess correlation with histologic severity. Human SG (HSG) cells were stimulated in vitro with peripheral blood mononuclear cells (PBMCs) and serum from primary SS patients in the presence or absence of autophagy inhibitors to determine changes in autophagy and epithelial cell activation. RESULTS: SGECs from primary SS patients (n = 24) exhibited increased autophagy (autophagic flux [P = 0.001]; LC3-IIB [P = 0.02]; p62 [P = 0.064]; and as indicated by LC3-IIB/LAMP-1+ staining), increased expression of antiapoptotic molecules (Bcl-2 [P = 0.006]), and reduced apoptosis (annexin V/PI [P = 0.002]; caspase 3 [P = 0.057]), compared to samples from patients with sicca syndrome (n = 16). Autophagy correlated with histologic disease severity. In vitro experiments on HSG cells stimulated with serum and PBMCs from primary SS patients confirmed activation of autophagy and expression of adhesion molecules, which was reverted upon pharmacologic inhibition of autophagy. CONCLUSION: In primary SS SGECs, inflammation induces autophagy and prosurvival mechanisms, which promote SGEC activation and mirror histologic severity. These findings indicate that autophagy is a central contributor to the pathogenesis of primary SS and a new therapeutic target.

Rupture of the Pleomorphic Adenoma of the Parotid Gland: What to Know before, during and after Surgery.

BACKGROUND: We assessed the cases of intraoperative spillage of primary pleomorphic adenomas (PPAs) of the parotid gland in the literature, comparing them with our own cases. We aim to explain how the surgeon should manage a spillage during surgery (i.e., how to avoid spreading the contents that are coming out of the tumor). We also aim to investigate whether or not spillage is linked to a higher rate of PPA recurrence. METHODS: We collected surgical and pathological reports, taking data on capsular ruptures and the spillage of tumors. RESULTS: Intraoperative tumor spillage and tumor rupture occurred in 34/202 cases. There were three recurrences after a mean of 3.7 years (mean follow-up duration: 10.3 years). One recurrence happened to a patient who had an intraoperative tumor spillage, and two more recurrences happened to patients who did not have spillage. CONCLUSION: We believe that the real number of the events of spillage is underestimated and underreported by surgeons. Capsular rupture must always be avoided, and secure resection margins must always be pursued, independent of the type of parotidectomy being performed. Features that increase the risk of recurrence are an intraoperative rupture and the presence of satellite nodules (as recorded in the pathologist's report). In these cases, patients need a longer follow-up period.

Resilience in women with primary Sjögren's syndrome.

To assess the relationship between resilience and several diseases and individual features in primary SjÓ§gren's Syndrome (SS) patients. Resilience was assessed using the Resilience Scale (RS-14). Disease activity, damage, and reported symptoms were assessed by means of ESSDAI (EULAR Sjögren's syndrome disease activity index), SSDDI (SjÓ§gren's Syndrome Disease Damage Index) and ESSPRI (EULAR SjÓ§gren's Syndrome Patient Reported Index). EuroQol, HADS (Hospital Anxiety and Depression Scale), SF-12 (Short-form 12 health survey), FAS (Fatigue Assessment Scale), FACIT-F (Functional Assessment of Chronic Illness Therapy - Fatigue), and IPAQ (International Physical Activity Questionnaire) questionnaires were submitted to evaluate physical and mental well-being of the recruited patients. Data about the autoimmune profile, systemic manifestations, and current therapy were collected. Educational qualifications and work activities were also considered. Descriptive, correlational, and linear regression analysis were performed. 74 consecutive women with primary SS and 74 sex and age-matched healthy subjects as a control group were recruited. SS patients displayed a moderate value of resilience (median 78.5) with no significant difference compared to controls (p = 0.38). An inverse relationship was found between resilience and mood disorders such as anxiety (p = 0.038) and depression (p < 0.001). Greater resilience was associated with a better perception of the quality of life (p = 0.02) and general health (p < 0.001), as well as with less fatigue (p = 0.008) and a more physically active lifestyle (p = 0.001). No significant relationship was found neither between resilience and age, socio-demographic and disease characteristics, nor with ESSDAI (p = 0.26), ESSPRI (p = 0.83) and SSDDI (p = 0.67). This is the first study assessing resilience in a large group of unselected primary SS patients. Most resilient primary SS patients are less depressed and show a better perception of their health. Greater resilience tends to correlate with less anxiety, physical and mental fatigue, and a more active lifestyle, while no association with disease activity and duration, damage, and socio-demographic features was detected. Considering the well-known role of resilience in helping to better cope with chronic illnesses, its assessment in SS patients should not be overlooked and the possible strategies for its improvement should be better explored and further implemented.

Immunohistochemical detection of IL-17 and IL-23 improves the identification of patients with a possible diagnosis of Sjogren's syndrome.

OBJECTIVES: The diagnosis of primary Sjogren's syndrome (pSS) continues to be difficult and several patients keep symptomatic for years with different diagnoses before confirmation of pSS. Since the IL-23-IL-17 axis is involved in the etiopathogenesis of pSS we evaluated by immunohistochemistry and morphometric methods the presence of IL-17 as well as IL-23 within minor salivary glands (MSG) obtained from patients with uncertain diagnosis of pSS. MATERIALS AND METHODS: 42 patients, with symptoms attributable to pSS, and 8 patients used as a control, were enrolled for the study. Autoantibody detection, histological analysis for the presence of Germinal Centers (GC+), immunohistochemistry to detect IL-23 and IL-17 were performed. RESULTS: The detection of GC + anti-SSA and anti-SSB antibody in parallel with the detection of IL-17 and IL-23, displays only a diagnostic reinforcement value. Instead, the detection of a positive reaction for both IL-17 and IL-23 without GC + or autoantibody within minor salivary glands, as detected in 36 % of patients with uncertain diagnosis, may be hold as a sensitive and specific marker to identify those patients who are likely to evolve into pSS. CONCLUSION: we suggest to use the IL-17/ IL-23 immunohistochemical detection to improve the identification of patients with a possible diagnosis in all cases which do not fully meet the American-European criteria for pSS, in particular when the GC + are not present at histopathological analysis and anti-SSA and anti-SSB antibody are undetectable in the serum.

Minimally Invasive Intraoral Approach to Submandibular Lodge.

The purpose of this study is to describe the Minimally Invasive Intraoral Approach (MIIA) performed on selected cases of abscesses and neck phlegmons of odontogenic origin when the infection has not spread beyond the inferior mandibular margin. This technique allows us to avoid cervicotomy by a direct approach to the abscess, draining it through the oral cavity. If the limits have already been crossed, then cervicotomy is necessary. The aim of the study is to show the surgical outcomes that we have achieved during a time span of two years, and to show the effectiveness of the MIIA and its results. We selected 66 patients with abscesses and neck phlegmons, from January 2018 to June 2020. Among these cases, five patients were excluded as it was not possible to recover medical records from database. The MIIA technique has been performed on 16 patients (26.2%) when a successful dental extraction and drainage of the submandibular lodge were accomplished. The patients who underwent the MIIA surgery have all perfectly healed and did not suffer from relapses during the follow-up. The results show the achievement of excellent healing, underlining the lower impact required by MIIA when compared to a more traditional approach through cervicotomy.

CXCL13 as biomarker for histological involvement in Sjögren's syndrome.

OBJECTIVES: SS is an autoimmune condition characterized by systemic B-cell activation, autoantibody production and ectopic germinal centres' formation within the salivary gland (SG). The extent of SG infiltrate has been proposed as a biomarker of disease severity. Plasma levels of CXCL13 correlate with germinal centres' activity in animal models and disease severity in SS, suggesting its potential use as a surrogate serum marker to monitor local B-cell activation. The aim of this study was to evaluate the potential role of CXCL13 as a biomarker of SG pathology in two independent SS cohorts. METHODS: 109 patients with SS were recruited at Sapienza University of Rome (Italy) (n = 60), or at Queen Elizabeth Hospital in Birmingham and Barts Health NHS Trust in London (n = 49). Both sera and matched minor SG biopsy were available. Sicca (n = 57) and healthy subjects' (n = 19) sera were used as control. RESULTS: CXCL13 serum level was higher in SS patients compared with controls. Correlations between its serum levels and a series of histomorphological parameters, including size of the aggregates and the presence germinal centres', were observed. CONCLUSION: Our data foster the use of CXCL13 to monitor the extent of local pathology in SS and its validation in longitudinal clinical studies.

Odontogenic phlegmons and abscesses in relation to the financial situation of Italian families.

BACKGROUND: In recent years, we have recorded an increase in the number of hospital admissions due to odontogenic abscesses and neck phlegmons requiring surgery. We believe that the cause may be related both to the rationalization of funding allocation procedures in public health service making access to public dental healthcare more difficult, and the financial situation of Italian families. METHODS: Fifty-five patients admitted between January 2013 and November 2017 with a diagnosis of "neck abscess" and/or "neck phlegmon" and/or "neck infection" were enrolled in this longitudinal retrospective study. RESULTS: The results of this study showed that the number of cases of abscesses and neck phlegmons with an odontogenic origin have quadrupled, with reference to gender was 31 males (56%) and 24 females (44%). The average age was 46 and most cases involved patients between 30 and 50. Eighteen patients (33%) were not EU citizens and had been living in Italy for over 5 years. These data indicate an increase in the incidence of odontogenic neck infections. The data gathered by ISTAT (Istituto Nazionale di Statistica), Eurostat Data Explorer, Fondazione Giuseppe Di Vittorio and Tecnè revealed that these outcomes are directly related to the financial difficulties Italian families are experiencing. The exclusion of essential dental assistance from public healthcare forced Italians to consult expensive private facilities that not everyone can afford. CONCLUSIONS: Connections were found between odontogenic neck infection complications and the financial difficulties Italian families are suffering from; Italians are reducing their budget for dental healthcare becoming exposed to serious neck pathologies.

Correction to: Is there a relation between sudden sensorineural hearing loss and white matter lesions?

In the original publication, fifth author's surname was incorrectly published as "Diacinto". The correct surname should read as "Diacinti".

Is there a relation between sudden sensorineural hearing loss and white matter lesions?

PURPOSE: Sudden sensorineural hearing loss (SSNHL) has similarities to conditions with vascular etiologies such as myocardial infarction and cerebral stroke. Thus, it could be considered as an early sign of a vascular disease and not only a specific local condition. Chronic hypoperfusion in the brain districts leads to a chronic ischemic damage, called cerebral small vessel disease (CSVD), detectable with brain magnetic resonance imaging (MRI). METHODS: The authors used CSVD to establish the presence of vascular risk factors in individuals with SSNHL and used the Fazekas score scale to classify them. RESULTS: Our study showed that individuals with SSNHL aged between 48 and 60 years have 26% more probability to have a Fazekas score higher than 1 compared to the general population. Individuals younger than 28 years showed a statistically significant negative correlation to have a Fazekas score higher than 0. The higher is the Fazekas score, the less is the probability of hearing recovery. The medium hearing-recovery probability is 46%. This decreases by 16% for every increase of score in the Fazekas scale. In the present study, the recovery probability decreased from 80% in individuals younger than 48 years with a score of 0 to 14% in individuals with a Fazekas scores of 3 and 4. CONCLUSIONS: The authors assessed a higher prevalence of CSVD compared to the general population in patients aged between 48 and 60 years with SSNHL. Moreover, they assessed that the presence of CSVD is related to a decreased probability of recovery, as it has already been demonstrated for stroke.

Antibiotic and Anticoagulation Therapy in Lemierre's Syndrome: Case Report and Review.

Lemierre's syndrome is a rare and fatal disease and is also known as the forgotten disease to describe the rarity of this syndrome in the antibiotic era. However, in the last 20 years, the incidence of this disease has been increasing. Authors report a case of Lemierre's syndrome with extensive venous thrombosis involving right internal jugular veins with extension to the sigmoid and lateral sinus and also review the literature on the use of anticoagulant therapy in Lemierre's syndrome. A computerized Medline study was carried out through the use of PUBMED: using the Medical Subject Headings terms 'Lemierre Syndrome/diagnosis' and words 'Lemierre's syndrome and anticoagulation'. From this, authors found 64 articles from 2002 to January 2018 with a total of 165 patients. The purpose of our review is to emphasize that antibiotic therapy should be started immediately, while anticoagulant therapy should be started in selected cases. Anticoagulation should be carried out in absence of any contraindication or presumed risk following clinical anticoagulation guidelines and only in patients with poor clinical response despite antibiotics therapy, predisposing thrombophilia and intracranial thrombosis.

Alpha-synuclein in salivary gland as biomarker for Parkinson's disease.

Estimates of the accuracy of clinical diagnosis of Parkinson's disease (PD) range between 46% and 90%, the accuracy of diagnosis dependent on prolonged clinical observation and clinical response to levodopa. For this reason, we need reliable diagnostic biomarkers. The cardinal hallmark of PD is alpha-synuclein aggregation in the brain. Demonstrating pathological alpha-synuclein in live patients would be useful for identifying and monitoring PD patients. By autopsy studies and in vivo studies, the presence of alpha-synuclein has been demonstrated even outside the central nervous system and the gastro-enteric tract appears to be the most promising candidate tissue for biopsy-taking and the esophagus and salivary glands appear to be the area with the highest concentration of alpha-synuclein. The purpose of our study is to conduct a review to determine the utility of salivary gland biopsy for the histological diagnosis of PD. A computerized medline study was carried out through the use of pubmed: using the MeSH terms: 'salivary gland biopsy for PD', 'PD and dysphagia', 'alpha-synuclein and salivary gland'. We found 9 articles about minor salivary glands and submandibular gland biopsy for diagnosis of PD. According to the results of this review, the submandibular gland biopsy is the test with the increased sensitivity and specificity compared to the biopsy of the minor salivary glands (sensitivity: 0.85 and 0.37 respectability and specificity: 0.96 and 0.94 respectively). New studies are necessary on a wider population to confirm these results.

Nasopharyngeal angiofibroma in an elderly female patient: A rare case report.

'Juvenile' nasopharyngeal angiofibroma, which accounts for <1% of all head and neck neoplasms, occurs predominantly in males between 10 and 18 years of age. The small number of patients older than 30 years confirms that presentation after this age is exceptional. Only rare cases of nasopharyngeal angiofibroma in female patients have been documented to date, and some authors believe that sex chromosome studies are indicated in such cases. The pathogenesis of nasopharyngeal angiofibroma remains unknown, but it has been hypothesized that it is a testosterone-dependent tumor. We herein report a particularly rare case of a 68-year-old woman diagnosed with nasopharyngeal angiofibroma and describe the diagnostic and therapeutic workup. This case describes, to the best of our knowledge, the oldest patient reported in the literature.