Notch-1 signaling activation sustains overexpression of interleukin 33 in the epithelium of nasal polyps.

BACKGROUND: Alterations in the nasal epithelial barrier homeostasis and increased interleukin 33 (IL-33) expression contribute to the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). AIMS: As Notch-1 signaling is crucial in repair processes of mucosa, the current study assessed Notch-1/Jagged-1 signaling and IL-33 in the epithelium of nasal polyps biopsies from allergic (A-CRSwNP; n = 9) and not allergic (NA-CRSwNP; n = 9) subjects by immunohistochemistry. We also assessed, in a model of nasal epithelial cells, the effects of stimulation of Notch-1 with Jagged-1 on the expression of IL-33 (by flow cytometry, immunofluorescence, and immunocytochemistry), Jagged-1 (by flow cytometry), and p-CREB transcription factor (by western blot analysis). RESULTS: Ex vivo (a) in normal epithelium, the expression of Notch-1 and IL-33 were higher in NA-CRSwNP than in A-CRSwNP; (b) in metaplastic epithelium, the expression of Notch-1, Jagged-1, and IL-33 were higher in NA-CRSwNP than in A-CRSwNP; (c) in hyperplastic epithelium, the expression of Notch-1, Jagged-1, and IL-33 were higher in A-CRSwNP than in NA-CRSwNP; and (d) in basal epithelial cells, no differences were observed in the expression of Jagged-1, IL-33, and Notch-1. The expression of Notch-1 significantly correlated with the expression of IL-33. In vitro, stimulation of Notch-1 with Jagged-1 induced the expression of (a) Jagged-1; (b) IL-33; and (c) p-CREB transcription factor. The inhibitor of Notch-1, DAPT, reduced all the effects of Jagged-1 on nasal epithelial cells. CONCLUSIONS: The data herein provided support, for the first time, a putative role of Notch-1/Jagged-1 signaling in the overexpression of IL-33 in the epithelium of nasal polyps from patients with CRSwNP.

Nasal packing in sphenopalatine artery bleeding: therapeutic or harmful?

The aim of this study is to present our management protocol of sphenopalatine artery bleeding, demonstrating that nasoendoscopic cautery (NC) was a more effective method than the nasal packing, in terms of shorter inpatient stay and reduced complications rate. We present ten posterior epistaxis not resolved by nasal packing. Tabotamp® was placed in the area of sphenopalatine foramen and/or in those parts of the posterior nasal cavity, where it was suspected that bleeding origins. In two cases, the bleeding was resolved in this way, instead eight cases needed of subperiosteal cauterization of sphenopalatine artery by Dessi bipolar forceps (MicroFrance®). 4 of these 8 patients evidenced a remarkable bleeding removing nasal packing (Hb before-nasal packing = 15 ± 0.69 versus Hb after-nasal packing = 13.3 ± 0.81; t student = 2.94; p value = 0.025). These four patients showed a deviation of the nasal septum ipsilateral to epistaxis, and according our experience, a traumatism of sphenopalatine area can be caused by Merocel® nasal packing in this condition. During follow-up, no recurrences of nasal bleeding have been observed in such patients. Nasal packing must be considered if posterior epistaxis is severe, but always taking into account the specific anatomy of patient and in particular septal spurs that can further compromise sphenopalatine artery. In our experience, the endoscopic endonasal cauterization of the sphenopalatine branches represented a safe and effective procedure.

Secondary septal mucocele diagnosed by MRI and CBCT and treated surgically.

OBJECTIVE: Here we report a case of a mucocele of the nasal septum diagnosed by MRI and cone beam CT (CBCT) 23 years after Ogston Luc surgery. METHOD: A 49-year-old man with nasal obstruction was examined by endoscopy, MRI, and CBCT. RESULTS: Endoscopy showed a smooth and soft septum swelling. MRI revealed an ovalar lesion with high-intensity content on both T1 and T2 images, and a peripheral enhancing rim after i.v. administration of contrast medium. CBCT revealed that the lesion was located in the posterior portion of the septum involving the perpendicular plate of the ethmoid, and destroying the anterior ethmoid cells on the left side but sparing the left lamina papyracea. The patient underwent endoscopic marsupialization of the lesion. CONCLUSION: A mucocele of the nasal septum is a rare occurrence. MRI and CBCT are effective and affordable diagnostic tools for this condition, enabling differentiation of mucocele from other sinonasal diseases.

Increased expression of IL-19 in the epithelium of patients with chronic rhinosinusitis and nasal polyps.

BACKGROUND: Chronic rhinosinusitis (CRS) is an inflammation of the nose and of the paranasal sinuses. The involvement of the respiratory epithelium in the mechanisms of CRS is poorly understood. AIMS: Among proteins expressed by nasal epithelial cells in CRS, IL-19 may have key functions. We here aimed to determine the expression and regulation of IL-19. METHODS: Nasal biopsies from normal subjects (n = 12), subjects with CRS but without nasal polyps (NP) (CRSsNP, n = 12) and with CRS with NP (CRSwNP, n = 15) were collected. Human Asthma Gene Array and real-time PCR were used to evaluate gene expression, western blot analysis and immunohistochemistry for protein expression. Results for IL-19 were confirmed by real-time PCR. The constitutive and stimulated (LPS, TGF ß) expression of IL-19 and cell proliferation were evaluated in a nasal epithelial cell line (RPMI 2650). RESULTS: Human Asthma Gene Array showed an increased IL-19 gene expression in NP from patients with CRS in comparison with normal subjects. Real-time PCR confirmed the IL-19 mRNA up-regulation in patients with CRSwNP and showed an up-regulation of IL-19, at lower extent, in patients with chronic rhinosinusitis without nasal polyps (CRSsNP) in comparison with normal subjects. Western blot analysis confirmed that IL-19 is increased also at protein level in patients with CRSwNP in comparison with normal subjects. In NP, IL-19 is highly expressed in the metaplastic nasal epithelium when compared to normal or hyperplastic epithelium. LPS stimulation increased IL-19 expression, and recombinant IL-19 increased cell proliferation in nasal epithelial cells. CONCLUSIONS: IL-19 is overexpressed in the epithelium in CRSwNP and increases epithelial cell proliferation.

The EBV-DNA Can be Used as a Diagnostic and Follow-up Parameter of the Rhinopharyngeal Tumors in the Non-Endemic Population of the Western Sicily.

To evaluate whether EBV-DNA can be used as a diagnostic and follow-up parameter for nasopharyngeal tumors in a non-endemic population. The study was carried out in a university hospital. A retrospective study was conducted on 40 paraffin samples of histological preparations. EB-DNA was detected by real-time PCR technique. A prospective study was also conducted on a group of 30 patients who underwent nasopharyngeal biopsy for suspected nasopharyngeal carcinoma (NPC) by comparing EBV-DNA concentrations between the histological specimen and the serum. Quantification of genomic copies of EBV-DNA in serum and detection of anti-EBV antibodies was performed. In both groups the presence of high viral load of EBV-DNA was found in nonkeratinizing squamous cell carcinomas, in three cases of lymphepitomyoma and in 4 out of 6 cases of non-differentiated non-carcinoma lymph node metastases. squamous keratinizing cells. In all cases of NPC, an antibody pattern typical of reactivations (IgGVCA+, IgG-EA+, IgG-EBNA+) and IgA-EA-D, frequently positive in cases of NPC, has been highlighted. A good correlation between the high EBV-DNA charges and the histological diagnosis was highlighted. Our study also found that the assessment of viral EBV load can also be considered in the prognostic evaluation and in the follow-up of patients with NPC.

Morbidity of salivary gland digital sialography using a non-ionic dimeric contrast medium.

AIM: Sialography is considered a low invasive procedure, due to cannulation of salivary duct orifice. The aim of this study was to evaluate the morbidity of sialography using a nonionic dimeric contrast medium. METHODS: A questionnaire was proposed to 90 patients who underwent parotid and submandibular sialography to reveal related symptoms as: pain, swelling, impairment to daily activities and taste alteration. Pain and swelling intensity was assessed using a visual analogue scale (VAS). RESULTS: Fifty-two out of ninety questionnaires were returned. Sialography was performed in 30/52 patients in the submandibular gland, 22/52 in the parotid gland. Pain during sialography was complained by 28/52 patients with a 2.4 mean VAS score. Pain after sialography, was reported by 17/52 patients with a 1.3 mean VAS score. Swelling was reported by 25/52 patients with a 2.4 mean VAS score; 48/52 patients returned immediately to daily activities; 8/52 complained different taste alterations. CONCLUSION: Main related symptoms for submandibular and parotid sialography are pain and swelling, spontaneously resolving after 24-48 hours in most of cases. The statistical analysis also demonstrated in patients who underwent submandibular sialography the onset of pain during the procedure is significantly related to an increase of pain after the examination. Thus in patients, who referred severe pain during sialography, antiinflammatory drugs are recommended to control the onset of pain after sialography.

Clarithromycin in the Management of Chronic Rhinosinusitis: Preliminary Results of a Possible Its New Use.

The aim of this study is to evaluate the efficacy and safety of prolonged therapy with low-dose clarithromycin in patients with chronic rhinosinusitis with polyps (CRSwP) after endoscopic sinus surgery (ESS). A total of 10 patients with CRSwP were identified and subjected to bilateral ESS. In post-operative patients they were treated with nasal wash with saline solution and steroid sprays (beclomethasone). During follow-up, after 30-40 days after the operation (M = 35.4 SD = +4.33), patients reported a worsening of symptoms with onset of nasal obstruction; reduction/loss of smell; headache; onset of viscous secretions and therefore all patients continued therapy with saline nasal irrigation, topical steroid therapy and started macrolide (clarithromycin 500 mg/pill: 1 pill/day for 3 days a week for 1 month). 22-item SinoNasal Outcome Test (SNOT-22) and a score to the endoscopic evaluation (endoscopic appearance score, EAS) before and after treatment were performed to evaluate efficacy of treatment. The results of the SNOT-22 and EAS showed statistically significant improvements (p < 0.05) for some parameters such as: the need to blow nose, sneezing, hyposmia, viscous mucous secretions about the SNOT-22 and reduction of secretions and edema of the nasal mucosa about the EAS. The preliminary results of our study show that the low-dose clarithromycin for a period of 1 month can improve patient complaints with CRSwP not only through the antibacterial properties but also for the immunomodulatory characteristics.

Outcomes of interventional sialendoscopy for obstructive salivary gland disorders: an Italian multicentre study.

Interventional sialendoscopy has become the predominant therapeutic procedure for the management of obstructive salivary disorders, but only a few multicentre studies of large series of patients with a long-term follow-up have been published. This Italian multicentre study involved 1152 patients (553 females; mean age 50 years) who, after at least a clinical and ultrasonographic evaluation, underwent a total of 1342 diagnostic and interventional sialendoscopies, 44.6% of which involved the parotid gland. 12% (n = 138) of patients underwent multiple treatments. The procedure was successful in 1309 cases. In 33 cases (2.4%) the procedure could not be concluded mainly because of complete duct stenosis (21 cases). Salivary stones were the main cause of obstruction (55%), followed by ductal stenosis and anomalies (16%), mucous plugs (14.5%) and sialodochitis (4.7%). Complete therapeutic success was obtained in 92.5% of patients after one or more procedures, and was ineffective in < 8%. Untoward effects (peri and postoperative complications) were observed in 5.4% of cases. Sialendoscopy proved to be an effective, valid and safe procedure in the diagnostic and therapeutic management of non-neoplastic obstructive salivary gland diseases.

Sialoendoscopy: state of the art, challenges and further perspectives. Round Table, 101(st) SIO National Congress, Catania 2014.

This draft of the Official Round Table held during the 101(st) SIO National Congress is an updated review on sialoendoscopy, a technique used for diagnosis and treatment of obstructive pathologies of salivary glands in a minimally invasive fashion. This review treats many aspects of salivary gland endoscopy, starting from anatomy to deal with the more advanced surgical techniques and analyses the main decisional algorithms proposed in the literature. In addition, particular attention was directed to the current limitations of this technique and to the potential developments that sialoendoscopy could have in the near future.

The immunohistochemical peptidergic expression of leptin is associated with recurrence of malignancy in laryngeal squamous cell carcinoma.

Leptin is a peptide that plays a key role in the control of satiety, energy expenditure, food intake and various reproductive processes. In the last years, the expression of leptin had been found in malignant cells of various origins. The aim of this study is to evaluate leptin expression in human laryngeal squamous cell carcinoma (SCC) and to investigate its possible role in predicting prognosis. Leptin expression was determined by immunohistochemistry in pathological and healthy tissue specimens from 24 patients with laryngeal SCC. Specimens were stained with an anti-leptin antibody. All measurements were performed using a computer-based image analysis system and scale of staining intensity was determined. All tumoural specimens showed significant immunoreactivity for leptin compared to healthy tissues (p ≤ 0.05), but showed different immunoreactivity that was related to clinicopathological features. High leptin expression was not significantly related with TNM, histological grading (HG) or advanced (III and IV) clinical stage (p > 0.05). Recurrence of malignancy was found to be significantly related with high expression of leptin by Spearman's rank correlation test (r = 0.59; p = 0.002), Fisher's test (p = 0.017) and Kaplan- Meier product-limit estimate (Log-rank test, p ≤ 0.05). In particular, multivariate logistic regression analysis showed that recurrences were significantly related with nodal involvement, HG and leptin expression (p ≤ 0.05). These preliminary results suggest that leptin may be a valuable parameter for predicting prognosis in laryngeal SCC.

Respiration in NREM and REM sleep after upper airway surgery for obstructive sleep apnoea.

To verify whether upper airway surgery in obstructive sleep apnoea syndrome affects differently respiration in NREM and REM sleep, 22 patients were studied by polysomnography before and three months after surgical treatment. On the average, treatment improved respiration during both sleep states, but no significant interaction was found between sleep state and effect of surgical treatment. According to the response to treatment, three groups of patients were identified: the first group (N = 6), with an improvement in apnoea-hypopnoea index (AHI), percentage of sleep time spent in apnoea and hypopnoea (time in AH) and mean oxyhaemoglobin saturation (SaO2) in both NREM and REM sleep; the second group (N = 5), with an improvement in AHI only in NREM sleep, associated with improvement in mean SaO2 in both sleep states; the third group (N = 11), without any improvement in AHI and time in AH, either associated (N = 5) or not (N = 6) with an improvement in mean SaO2 in both sleep states. An increase in the percentage of hypopnoeas out of the total AHI after treatment could partly account for the apparent discrepancy between AHI and mean SaO2 behaviour in the subjects of the second group, but not in the patients of the third group who improved their mean SaO2. Mixed apnoeas occurred before surgery in six subjects; they remained numerous after surgery only in two subjects who did not show any SaO2 improvement. In conclusion, the degree of improvement in respiration after upper airway surgery was similar in every patient in NREM and REM sleep.

Head and neck carcinoma with distant metastases: a retrospective analysis of 44 cases treated with cisplatin-based chemotherapeutic regimens.

The rarity of medical reports on the chemotherapeutic management of head and neck cancer metastatic to distant organs prompted us to review the effect of cisplatin-based regimens in this clinical setting. Out of 44 eligible patients, 10 patients (23%) achieved a CR, 16 patients (36%) has a PR, 7 (16%) no change, and 11 (25%) progressed. Patients with rhinopharyngeal carcinoma showed a 69% overall response rate, while those with other head and neck carcinomas had a 54% overall response rate. No preferential site of response was detected. The difference in mean survival of responding patients between the rhinopharyngeal group and the non-rhinopharyngeal group was statistically significant (P < 0.05). Responding patients survived longer than non responders (P < 0.05 in both groups). Interestingly, 3 patients in the rhinopharyngeal cancer group survived more than 2 years from the start of chemotherapy for metastatic disease. These data strengthen the observation that rhinopharyngeal carcinoma, even with distant metastases, responds to chemotherapy better than other carcinomas arising in the head and neck region. Moreover, although survival is still dismal, cisplatin-based systemic chemotherapy seems an effective palliative treatment for metastatic head and neck cancer.

[Surgical excision of lung neoplasms in the elderly. Immediate results]. / Chirurgia di exeresi per cancro del polmone negli anziani. Risultati immediati.

The authors have analyzed a series of 807 patients who underwent resection for Bronchogenic Carcinoma at the "I Istituto di Clinica Chirurgica" of the University of Rome "La Sapienza" since 1950. The aim of the search was to evaluate the immediate results of surgical treatment in relation to age of the patients. Seventy-one patients were < 65 years old, 91 patients were older. The incidence of post-operative complications and mortality rate (within the 30th day from surgery) was related to the following risk factors: concomitant pulmonary and extrapulmonary diseases, cigarette smoking, laboratory values (red blood cell count, protein electrophoresis, urea nitrogen, glucose), type of lung resection, extent of resection, histology and post-surgical stage. The rates of post-operative complications and mortality were 34.1% and 27.5% in elderly patients, while in younger patients they were respectively 26.3% and 16.2%. In the elderly, cigarette smoking, cardiovascular diseases, diabetes, renal failure, type of lung resection and extent of resection, were related to an increase of the post-operative complications and mortality rate. In the younger patients, the extent of resection to adjacent structures was the primary risk factor for immediate results. Screenings in elderly and early diagnosis represent the strategy to allow more conservative surgical treatments and reduction of complications and mortality.

[Brain stem auditory evoked potentials in obstructive sleep apnea syndrome]. / I potenziali evocati uditivi del tronco cerebrale nella sindrome dell'apnea ostruttiva nel sonno.

To evaluate a possible brainstem role in pathogenesis of obstructive sleep apnea syndrome, a study on brainstem auditory evoked potentials (BAEP), has been conducted. 15 OSAS patients, medium and severe form, with organic pathologies of the upper respiratory tract have been evaluated. 15 normal subjects were compared as control. All the patients were subjected to audiometry, including total liminal audiometry, timpanometry, acustic reflex, and BAEP study. BAEP evoked with trains of cliks at 11 and 51 periods/sec., showed morphological alterations and a longer central conductance of time interval (I-V interval) in only four patients. BAEP alterations noted in the OSAS-affected patients are neither constant nor specific. Therefore, the observed BAEP alterations might be due to apneas, as a consequence of the chronic hypoxic- hypercapnic status occurring in the brain-stem.

[Morphologic and ultrastructural changes of soft palate in patients who underwent palatopharyngoplasty]. / Rilievi istopatologici ed ultrastrutturali del palato molle in pazienti sottoposti ad intervento di palatofaringoplastica (PPP).

In order to clarify pathogenesis of Obstructive Sleep Apnea Syndrome (OSAS) in patients with anatomic abnormalities of upper airways, we studied soft palate and uvula of OSAS patients by means of histological and ultrastructural techniques. 38 OSAS patients, severe and moderately severe form, underwent modified Palatopharingoplasty. We evaluated only 16 OSAS patients' soft palate and uvula and observed histological changes in all of them: submucosal edema and minor salivary glandes ipertrophy and iperplasy are present. On the contrary, ultramicroscope showed normal muscle fibers. Strie Z alterations and sarcomeres disorganization, although present, have no statistical value. Very probably, ronflement and apneas determined the observed alterations through trauma on pharingeal wall. Therefore, they are not OSAS primary cause.

Localization of the atrial natriuretic factor in the human inferior turbinates. An immunohistochemical study.

In man, the architecture of the turbinates is able to modify some of the physiochemical characteristics of the air inhaled. These modifications depend on the nervous system and on the action of neurotransmitters such as vasoactive intestinal peptide. Substance P, calcitonin gene-related peptide and other neuropeptides. As atrial natriuretic factor has been detected in the trachea and lung, the present immunohistochemical study was carried out to establish the presence and localisation of the atrial natriuretic factor on the inferior turbinates of the human being. The findings show atrial natriuretic factor to be present in the serous epithelial cells and in some cells of the tonaca propria near the sinusoids and the arteriovenous shunts and the acinar cells of the glands. Atrial natriuretic factor, therefore, could play a part in the stratification of mucus on the luminal surface and also regulate the blood flow of the capillaries, modifying, in this way, the physiochemical features of the air inhaled.

[Otoneurological findings in a case of congenital central hypoventilation syndrome (Ondine's curse)]. / Rilievi otoneurologici in un caso di sindrome da ipoventilazione centrale congenita (Maledizione di Ondine).

The authors report a case of congenital central hypoventilation syndrome (CCHS) studied from the otoneurological point of view. Emphasis is placed on the numerous alterations in the electronystagmograph and auditory potentials. The results obtained confirm the hypothesis that such patients are subject to CNS alterations, suggesting that the disease pathogenesis derives from an alteration in the mechanism of central chemoreceptor stimuli integration.

[The surgical treatment of obstructive sleep apnea syndrome]. / La terapia chirurgica nella sindrome dell'apnea ostruttiva nel sonno (OSAS).

Studies concerning the anatomical abnormalities of upper airways in patients affected by Obstructive Sleep Apnea Syndrome (OSAS) allowed the corrective surgical treatments in this syndrome. To provide an improvement or a definitive recovery of OSAS, various surgical treatments, i.e. functional nasal surgery, palatal surgery [Partial resection of palate (RPP), Uvulopalatopharingoplasty (UPPP), Palatopharingoplasty (PPP), modified Palatopharingoplasty (modified PPP)], mandibular and base tongue surgery, have been performed in order to obtain an enlargement of upper airways. It has been reported that in RPP, UPPP, PPP and modified PPP partial or total uvula and soft palate resection is conduct; in our research we performed modified PPP. 44 OSAS patients, severe or moderately severe form (polisomnographic diagnosis), underwent surgical treatment: 5 patients underwent functional nasal surgery; 9 patients underwent modified PPP; 29 patients underwent nasal and palatal surgery; only 1 patient underwent base tongue surgery. 32 patients underwent polisomnographic records after surgery (two months later) and we evaluated Apnea Index (I.A.) and a SaO2 low (nadir) with statistic tests. The results have been positive. Therefore, we have now 7 normal, 2 mild form, 7 moderate form, 3 moderately severe form and 13 severe form OSAS patients. If, on the one hand, all these surgical treatments can be considered a good way of therapy, on the other, only tracheostomy represents today the unfailing surgical therapy.

[Otolaryngologic disorders caused by esophageal reflux]. / Molestias otorrinolaringológicas del reflujo gastro-esofágico.

The authors through an accurate analysis of the literature make a synthesis of the most recent knowledge about the correlation existing between the distal and proximal gastroesophageal reflux (GER) and a series of common otolaryngologic symptoms whose aetiology is doubtful, in order to explain its most significative physiopathological and clinic aspects. The diagnostic modalities able to reveal the presence of the correlation and the adequacy therapy to cure the disease are also discussed.