OM-85 in the prevention of respiratory infections: State-of-the-art and future perspectives in clinical practice.

Respiratory infections (RI) significantly burden patients, their families, and society. Respiratory infection recurrence (RRI) usually depends on a defect of the immune response, which can be more or less transient and/or selective. In particular, children, older people, heavy smokers, and patients with chronic diseases, characterized by an inadequate immune response, may be at risk of developing RRI. In this context, OM- 85 could represent a valuable option in the management of RRI. OM-85 is a bacterial lysate containing the extracts of some common pathogens, including Branhamella catarrhalis, Klebsiella pneumoniae, Klebsiella ozaenae, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans, and Staphylococcus aureus. Methodologically rigorous studies have documented the mechanism of action, efficacy, and safety of OM-85. OM-85 enhances the natural and acquired immune response through multifaceted mechanisms. Substantial evidence has shown that OM-85 can prevent respiratory infections, reduce the number of COPD exacerbations, and shorten the disease duration at home or in hospital. OM-85 can enhance the effectiveness of the 'flu vaccination without affecting the vaccine tolerability. The preventive use of OM-85 can reduce the use of antibiotics, contributing to contrast antibiotic resistance and saving the high cost of chronic respiratory diseases. Further studies should define the ideal candidate to OM-85 treatment.

Combined interventional sialendoscopy and intraductal steroid therapy for recurrent sialadenitis in Sjögren's syndrome: Results of a pilot monocentric trial.

OBJECTIVES: To evaluate the effectiveness of interventional sialendoscopy alone or combined with outpatient intraductal steroid irrigations in patients with sialadenitis due to Sjögren's syndrome (SS). DESIGN: A pilot therapeutic study. SETTING: ENT Clinics, Universities of Milan and Pavia. STUDY POPULATION: We included 22 patients with SS of whom 12 underwent interventional sialendoscopy followed by intraductal steroid irrigations (group A), and 10 interventional sialendoscopy alone (group B). OUTCOMES MEASURES: The following outcome measures were considered and recorded before and after the therapeutic intervention: (i) number of episodes of glandular swelling, (ii) cumulative prevalence of patients with glandular swelling assessed by the specific domain, the EULAR SS Disease Activity Index (ESSDAI), (iii) severity of pain by means of a 0-10 pain visual analogue scale (VAS), (iv) severity of xerostomia and other disease symptoms assessed by the EULAR SS Patient Reported Index (ESSPRI) and the Xerostomia Inventory questionnaire. RESULTS: The postoperative reduction in the mean number of episodes of glandular swelling was 87% (95% CI: 77-93) and 75% (95% CI: 47%-88%) in the groups A and B, respectively. The percentage of patients with glandular swelling decreased from 41.7% to 0.0% in the group A and from 30.0% to 0.0% in the group B, respectively. Most of the patients experienced a subjective clinical improvement documented by the statistically significant reductions in the postoperative mean pain VAS (group A P<.001; group B P=.004), Xerostomia Inventory (P<.001 and P=.003) and ESSPRI scores (P<.001 and P=.008). Interventional sialendoscopy followed by outpatient intraductal steroid irrigations was more effective than interventional sialendoscopy alone, when pain VAS, Xerostomia Inventory and ESSPRI scores before and after treatment were analysed together using the multivariate Hotelling T2 test (P=.0173). CONCLUSIONS: This pilot study confirms that interventional sialendoscopy with steroid duct irrigation significantly reduces the number of painful episodes of sialadenitis and improves the subjective sensation of oral dryness and other disease symptoms in patients with SS. The study results also suggest that the improvement is greater when interventional sialendoscopy is combined with a cycle of outpatient steroid ductal irrigations. Larger controlled randomised studies are certainly needed to confirm these preliminary data.

Prospective multicentre study on barbed reposition pharyngoplasty standing alone or as a part of multilevel surgery for sleep apnoea.

OBJECTIVES: The aim of this study was to demonstrate in a prospective multicentre study that Barbed Reposition Pharyngoplasty (BRP) procedure is safe and effective in management of obstructive sleep apnoea/hypopnea syndrome (OSAHS) patients. DESIGN: Prospective study. SETTING: Multicentre study. PARTICIPANTS: Patients suffering from obstructive sleep apnoea. MAIN OUTCOMES MEASURES: Values of postoperative apnoea-hypopnea index (AHI), oxygen desaturation index (ODI), epworth sleepiness scale (ESS). RESULTS: 111 Barbed Reposition Pharyngoplasty procedures standing alone or as a part of multilevel surgery for OSAHS, performed between January and September 2016, were analysed in 15 different centres. The average hospitalisation period was 2.5 ± 0.5 days. The mean patient age was 46.3 ± 10.5 years. The average body mass index at the time of the procedure was 27.9 ± 3.2, and the majority of the patients were men (83%). The mean preoperative and postoperative apnoea/hypopnea index was 33.4 ± 19.5 and 13.5 ± 10.3, respectively (P < .001). The mean preoperative and postoperative ESS score was 10.2 ± 4.5 and 6.1 ± 3.6, respectively (P < .001). The mean preoperative and postoperative ODI were 29.6 ± 20.7 and 12.7 ± 10.8, respectively (P < .001). CONCLUSIONS: Patients undergoing BRP standing alone or as part of a multilevel approach for the treatment of OSAHS have a reasonable expectation for success with minimal morbidity.

Expression of PDL-1 between primary and recurrent/metastatic head and neck squamous cell carcinoma: A bi-institutional retrospective concordance analysis (CONCORDL-1 study).

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have demonstrated efficacy in the treatment of recurrent and/or metastatic (RM) head and neck squamous cell carcinoma (HNSCC) Keynote 048 highlighted the relevance of PD-L1 Combined Positive Score (CPS) as a predictive biomarker for ICIs treatment, but challenges persist regarding ideal assessment and concordance between primary and relapsing tumor has not been determined. MATERIAL AND METHODS: This is a retrospective multicentric study that included HNSCC patients with locoregional and/or metastatic relapses after curative treatment. Histological samples of primary tumors and corresponding relapses were collected. The primary objective was to evaluate PD-L1 CPS concordance between primary and recurrent tumors, with secondary objective of exploring the impact of clinical-pathological variables. RESULTS: Out of 86 evaluated patients, 30 cases were excluded due to insufficient histological material, with a final enrollment of 56 patients. Concordance analysis revealed a 66.1% agreement in PD-L1 CPS between primary and recurrent tumors. Only 3.6% of cases exhibited a change from negative to positive PD-L1 CPS status, and 7.2% showed the reverse. Factors analyzed, including primary tumor site, treatment modality, and recurrence type, did not significantly influence PD-L1 CPS concordance level. CONCLUSION: While significant changes in PD-L1 CPS expression are rare, the study underscores the importance of confirmatory biopsies on relapse. However, reliance on archival tumor tissue for initial PDL1 assessment may be considered in cases where obtaining additional biopsies poses risks to patients or urgent therapeutic decisions are required.

Adenoid hypetrophy: definition of some risk factors.

Adenoids removed for airway obstruction and-or recurrent infections have been studied to identify a possible mechanism to explain chronicity. In this regard, macrophages may play a relevant pathogenic role as well as neutrophils during bacterial infections and eosinophils in allergic inflammation. Therefore, this study aimed at investigating some mediators as surrogate markers of inflammation in children who had to undergo to adenoidectomy. Globally, 67 children (25 females, 42 males, mean age 4.9 years), affected by persistent obstruction caused by adenoid hypertrophy were consecutively enrolled into the study. Blood samples were collected from patients and controls to determine serum CD163, Myeloperoxidase (MPO) and ECP. There were significant differences between patients and controls for serum CD163 (p less than 0.0001); MPO (p less than 0.0001); serum ECP (p less than 0.0001). This study demonstrated some risk factors for severe AH: apnoea, recurrent respiratory infections, and high serum CD163 levels.

Adenoid assessment in paediatric patients: the role of flexible nasal endoscopy.

Adenoid hypertrophy is the most common cause of nasal obstruction in paediatric patients. Over the years, various methods to assess the adenoid size were proposed such as the posterior rhinoscopy and the radiological examination of the nasopharynx. Nasal endoscopy was introduced for children in the 80's, and nowadays this is a known and diffuse method in routine practice. The purpose of this article is to describe the personal experience in the assessment of the adenoid size in children, with a particular regard to the flexible nasal endoscopy, and to analyse the literature reports. The personal technique is described in performing nasal endoscopy in paediatric patients, reporting advantages and possible disadvantages of the procedure. A retrospective analysis was conducted on 6036 children since 1999 to 2010. In most cases children fully collaborated to complete the exam. No major or minor complications (such as nose bleedings or other traumatic injuries) were observed. No topical intranasal decongestant, local or general anaesthesia were used in our series. In our opinion, nasal endoscopy in children is a reliable, safe, accurate, easily tolerated and dynamic diagnostic method to assess the adenoid size.

Management of anaplastic thyroid carcinoma spread over the trachea with mediastinal extension.

INTRODUCTION: We report a case of treatment of anaplastic thyroid carcinoma spread over the trachea with mediastinal extension. METHODS: Case report and review of the world literature concerning the treatment of anaplastic thyroid carcinoma are presented. DISCUSSION: The role of surgery in treatment of anaplastic carcinoma remains controversial. Our case we underlined two questions: the appropriateness of the surgery options with extra-thyroid spread and the better surgery approach to anaplastic thyroid carcinoma interesting the mediastinum controlling the great vessels of the neck. Even if curative resection cannot be achieved, surgical resection can immediately reduce the tumor bulk to facilitate the efficacy of post-operative radiotherapy and/or chemotherapy and to achieve a good local control to avoid the need of a subsequent palliative tracheostomy. Tumor upper mediastinal involvement made mandatory to open the sternum in order to allow a more complete resection of the macroscopic mass. The mini-sternotomy represents a valuable alternative that allows reduction in surgical trauma increasing patient's comfort. CONCLUSION: The complete resection of the tumor mass without scarifying vital structures can lead to some prolonged survival. Even if complete resection cannot be achieved, surgical resection can immediately reduce the tumour bulk and achieve good local control of the disease to avoid the palliative tracheotomy.

Synchronous Parotid (Mammary Analog) Secretory Carcinoma and Acinic Cell Carcinoma: Report of a Case.

Mammary analogue secretory carcinoma (MASC) is a recently described low-grade salivary gland malignancy with histologic, immunohistochemical and molecular similarities to secretory carcinoma of the breast, including a specific t(12;15)(p13;q25) resulting in an ETV6-NTRK3 gene fusion. Ultrasound and magnetic resonance imaging frequently document a macrocystic structure. The main differential diagnosis of secretory carcinoma is with low grade acinic cell carcinoma (AciCC). The two can be differentiated with immunohistochemical stains for S100, mammaglobin, carbonic anhydrase VI and DOG-1; the identification of the specific translocation can help to characterize non-typical cases. We report a unique case of synchronous MASC and AciCC presenting in a parotid gland and discuss the implications of the correct identification of the two tumors.

New frontiers and emerging applications of 3D printing in ENT surgery: a systematic review of the literature.

3D printing systems have revolutionised prototyping in the industrial field by lowering production time from days to hours and costs from thousands to just a few dollars. Today, 3D printers are no more confined to prototyping, but are increasingly employed in medical disciplines with fascinating results, even in many aspects of otorhinolaryngology. All publications on ENT surgery, sourced through updated electronic databases (PubMed, MEDLINE, EMBASE) and published up to March 2017, were examined according to PRISMA guidelines. Overall, 121 studies fulfilled specific inclusion criteria and were included in our systematic review. Studies were classified according to the specific field of application (otologic, rhinologic, head and neck) and area of interest (surgical and preclinical education, customised surgical planning, tissue engineering and implantable prosthesis). Technological aspects, clinical implications and limits of 3D printing processes are discussed focusing on current benefits and future perspectives.

The supraclavicular artery island flap (SCAIF) in head and neck reconstruction: an Italian multi-institutional experience.

The supraclavicular artery island flap (SCAIF) is a thin and pliable pedicled flap that is easy and quick to harvest. Thanks to its particular features and high reliability, it is best indicated for the elderly or most fragile patients. SCAIF is very versatile, as it can be used for reconstruction of oral cavity, oropharynx, hypopharynx, facial and cervical skin and tracheostomal defects. We began using this flap in four Italian tertiary referral centres, with several indications, both as first treatment and as salvage surgery. The aim of the study was to demonstrate the easy reproducibility of the flap among four different centres. A series of 28 patients underwent head and neck reconstructions with SCAIF with no recorded complications during flap harvesting. After the very first cases, harvesting time was approximately 45 minutes; 24 patients had successful flap integration at the recipient site, while the remaining 4 suffered from partial flap necrosis, two of whom needed revision surgery. Other minor complications were reported at the recipient site, always at the most distal and most delicate portion of the flap. Donor site was always closed primarily, with only three cases of partial suture dehiscence. We only selected the most fragile patients for SCAIF reconstruction, such as the elderly or those with one or more comorbidities; for this reason, we reported some serious systemic complications and one intraoperative death. SCAIF is an easy reproducible flap, with multiple possible indications. Its use as an alternative to free flaps in the head and neck region is nowadays under discussion. Its use should be encouraged among head and neck surgeons thanks to its various advantages.

From CT scanning to 3D printing technology: a new method for the preoperative planning of a transcutaneous bone-conduction hearing device.

SUMMARY: The aim of the present study was to assess the feasibility and utility of 3D printing technology in surgical planning of a transcutaneous bone-conduction hearing device (Bonebridge®) (BB), focusing on the identification of the proper location and placement of the transducer. 3D printed (3DP) models of three human cadaveric temporal bones, previously submitted to CT scan, were created with the representation of a topographic bone thickness map and the sinus pathway on the outer surface. The 3DP model was used to detect the most suitable location for the BB. A 3DP transparent mask that faithfully reproduced the surface of both the temporal bone and the 3DP model was also developed to correctly transfer the designated BB area. The accuracy of the procedure was verified by CT scan: a radiological marker was used to evaluate the degree of correspondence of the transducer site between the 3DP model and the human temporal bone. The BB positioning was successfully performed on all human temporal bones, with no difficulties in finding the proper location of the transducer. A mean error of 0.13 mm was found when the transducer site of the 3DP model was compared to that of the human temporal bone. The employment of 3D printing technology in surgical planning of BB positioning showed feasible results. Further studies will be required to evaluate its clinical applicability.

Markers of chemoradiation resistance in patients with locally advanced head and neck squamous cell carcinoma, treated by intra-arterial carboplatin and concurrent radiation.

The onset of chemo- and/or radio-resistance in tumour cells is one of the main causes of failure of integrated treatment protocols combining intra-arterial administration of platinum derivatives and radiotherapy, and is associated with recurrent disease and/or distant metastases. In the present study, the expression of a series of markers of chemo- and/or radio-resistance was investigated in 21 patients with advanced squamous cell carcinoma of the head and neck treated with combined intra-arterial carboplatin and radiotherapy. The results were correlated with local response to treatment, recurrence and overall and disease-free survival. In non-responders or in patients presenting recurrence, caspase 8 was significantly (p 0.05) under-expressed while p-Gp (p 0.035) and MDR-3 (p 0.049) were significantly over-expressed. Tumours with unfavourable outcome more frequently over-expressed two or more anti-apoptotic factors (p-53, BCL-2, BCL-x) (p 0.01). Patients with shorter overall survival, significantly overexpressed p53 (p 0.04), LRP (p 0.038) and a larger number of trans-membrane transport proteins compared with those who survived more than one year (p 0.013). Finally, patients with the shortest disease-free survival presented over-expression of p53 (p 0.027) and BCL-x (p 0.023). Further studies are necessary to confirm the possibility, in a future perspective, of using a panel of markers of chemo- and radio-resistance to identify those patients potentially sensitive to the treatment and to avoid patients at high risk of resistance from being submitted to ineffective and toxic treatment protocols.

Interventional sialendoscopy for radioiodine-induced sialadenitis: quo vadis?

Salivary gland toxicity is a common adverse effect of radioactive iodine (131I) for the treatment of thyroid cancers with a prevalence ranging from 2% to 67% of the 131I exposed population. Recently, sialendoscopy has been introduced as an attractive diagnostic and therapeutic tool for management of patients with radioiodine-induced sialadenitis that is unresponsive to standard medical treatments. The objective of the current review was to assess the impact of this procedure on outcomes in patients suffering from radioiodine sialadenitis. Overall, eight studies were included and 122 patients underwent 264 sialendoscopic procedures. Duct stenosis and mucous plugs were observed in 85.7% of endoscopic findings, supporting the role of ductal obstruction in the pathophysiology of radioiodine sialadenitis. In total, 89.3% of patients experienced complete or partial resolution of sialadenitis recurrences without any major adverse events, and parotidectomy was advocated in only 1 case. However, outcomes mainly concerned subjective reports and only two clinical experiences evaluated objective measurement with dissimilar results. Limited to few studies, xerostomia and obstructive symptoms responded differently after sialendoscopy. The optimal timing of salivary gland videoendoscopy needs to be further analysed in order to define the best management of radioiodine-induced obstructive sialadenitis.

Modern management of paediatric obstructive salivary disorders: long-term clinical experience.

Recent technological improvements in head and neck field have changed diagnostic and therapeutic strategies for salivary disorders. Diagnosis is now based on colour Doppler ultrasonography (US), magnetic resonance (MR) sialography and cone beam 3D computed tomography (CT), and extra- and intracorporeal lithotripsy, interventional sialendscopy and sialendoscopy-assisted surgery are used as minimally invasive, conservative procedures for functional preservation of the affected gland. We evaluated the results of our long-term experience in the management of paediatric obstructive salivary disorders. The study involved a consecutive series of 66 children (38 females) whose obstructive salivary symptoms caused by juvenile recurrent parotitis (JRP) (n = 32), stones (n = 20), ranula (n = 9) and ductal stenosis (n = 5). 45 patients underwent interventional sialendoscopy for JRP, stones and stenoses, 12 a cycle of extracorporeal shockwave lithotripsy (ESWL), three sialendoscopy-assisted transoral surgery, one drainage, six marsupialisation, and two suturing of a ranula. Three children underwent combined ESWL and interventional sialendoscopy, and seven a secondary procedure. An overall successful result was obtained in 90.9% of cases. None of the patients underwent traditional invasive sialadenectomy notwithstanding persistence of mild obstructive symptoms in six patients. No major complications were observed. Using a diagnostic work-up based on colour Doppler US, MR sialography and cone beam 3D TC, children with obstructive salivary disorders can be effectively treated in a modern minimally-invasive manner by extracorporeal and intracorporeal lithotripsy, interventional sialendoscopy and sialendoscopy-assisted transoral surgery; this approach guarantees a successful result in most patients, thus avoiding the need for invasive sialadenectomy while functionally preserving the gland.

[Laparoscopic harvest of the jejunal free flap for cervical esophageal reconstruction]. / Il prelievo laparoscopico di un lembo libero di digiuno per la ricostruzione dell' esofago cervicale.

The jejunal free flap is a standard technique in the reconstruction of hypopharyngeal and cervical esophageal defects. Conventional harvesting of the jejunal segment is performed with midline open laparotomy, which is associated with complications including prolonged ileus, abdominal pain, wound infection or dehiscence. Laparoscopic resection of the small intestine is a well documented surgical technique. Two different methods of laparoscopic harvest of a jejunal autografts for their cervical implantation have been already described. In both cases, low complication rate and better postoperative course have been observed in the patients treated. During the last 10 years, we have performed 43 circumferential pharyngoesophageal resection for advanced hypo-pharyngeal cancer followed by reconstruction with a free flap of jejunum. All but one the jejunal segments have been harvested with conventional open laparotomy. In the last patient of this group, laparoscopic harvest of the jejunal segment has been successfully performed. In this paper, we describe the laparoscopic technique used and we compare the postoperative course of this patient with those of the patients treated with conventional technique.

Acoustic changes in voice after surgery for snoring: preliminary results.

All surgical procedures for treatment of snoring and obstructive sleep apnoea modify the anatomical structure of the upper airways and the resonance characteristics of the vocal tract; this can lead to a modification in voice quality. Purpose of this study was to evaluate the possible modifications of the fundamental frequency (F0) and of the frequency and amplitude of the first (F1) and second (F2) formants of the 5 Italian vowels after different surgical procedures for snoring, to verify if and how these operations can influence voice quality. A total of 40 snoring or obstructive sleep apnoea syndrome patients, not affected by laryngeal, pulmonary or neurologic disorders likely to alter voice production, were selected for the study. All were submitted to acoustic voice analysis prior to surgery and again 1 month after discharge. F0 was unchanged. The frequency of F1 of the vowel /a/ audio of F2 of the vowel /e/ were significantly higher, while F1 of /i/ and F2 of /o/ and /u/ were significantly lower compared to pre-operative values. The modifications in the anatomical structure and volume of the vocal tract, induced by the surgical procedures used for the treatment of snoring, can modify the values of the formants and, as a consequence, quality of the voice. This change can be detected not only by means of the acoustic analysis but also by the patient itself. For this reason, singers and all professional voice users about to undergo surgical treatment for snoring should be informed of this potential modification of the voice not only for clinical reasons but also for legal purposes.

Functional outcomes in patients reconstructed with flaps following surgery for hypopharyngeal cancer.

Following oncologic surgery for advanced cancer of the hypopharynx, primary closure of the defect of the upper aerodigestive tract is difficult to achieve. Usually locoregional or free flaps are used, the choice being determined by the extent of the surgical defect, the expertise of the surgeons and the general condition of the patient. Aim of the present study was to evaluate the functional recovery of patients who underwent surgical reconstruction, following hypopharyngeal cancer resection, with pedicled or free flaps. A retrospective analysis was conducted examining hospital records of the patients submitted to surgical treatment for hypopharyngeal cancer and reconstruction with pedicled or free flaps in the period between January 1995 and July 2004. Free flaps showed less severe complications, shorter hospital stay, less time to resume oral feeding compared with pedicled flaps. For this reason, we consider free flaps the gold standard for hypopharyngeal reconstruction, while pedicled flaps as the pectoralis major or other locoregional flaps should be used in those cases in which free flap reconstruction is not feasible or contraindicated.

Human papillomavirus and head and neck carcinomas: focus on evidence in the babel of published data.

Human papillomavirus (HPV)-associated squamous cell carcinoma of the oropharynx is a well-defined entity mostly affecting young to middle-aged male non-smokers. It is generally associated with a favourable outcome, and for this reason a less intensive therapeutic approach has been proposed for this subset of patients. The incidence of HPV-associated oropharyngeal cancers is rapidly increasing in most Western countries, but detailed epidemiological data are not available for the Italian population. Furthermore, among other head and neck regions, a smaller proportion of oral high-grade dysplasia and cancers seems to depend on HPV infection, whereas its role in laryngeal cancer is recognised as less relevant. HPV-dependent neoplastic transformation depends on the expression of viral oncogenes in the infected host cell that can only be directly documented through viral oncogene mRNA identification. The consensus on how to classify these patients from clinical and laboratory diagnostic points of view is still limited, with different approaches based on one or more diagnostic techniques including p16 immunostaining, in situ hybridisation and polymerase chain reation (PCR) amplification of viral DNA. The possibility of early diagnosis relying on the identification of HPV infection in oral and oropharyngeal exfoliated cells has so far provided unsatisfactory results, although viral persistence after treatment has been associated with risk of recurrence. Presently, sufficient data are not available to document the natural history and progression from tonsillar HPV infection to oropharyngeal cancer development, and to clearly define the modality of transmission and risk exposure, among which sexual behaviours appear to play a relevant role. The diffusion of HPV vaccination and its administration to both genders will undoubtedly dramatically modify the epidemiology of HPV-related head and neck cancers in the coming years.

Development of a novel Italian speech-in-noise test using a roving-level adaptive method: adult population-based normative data.

In recent years the increasing development of hearing devices has led to a critical analysis of the standard methods employed to evaluate hearing function. Being too far from reality, conventional investigation of hearing loss based on pure-tone threshold audiometry and on mono/disyllabic word lists, presented in quiet conditions, has been shown to be inadequate. A speech-in-noise test using a roving-level adaptive method employs target and competing signals varying in level in order to reproduce everyday life speaking conditions and explore a more complete sound range. Up to now, only few roving-level adaptive tests have been published in the literature. We conducted a rovinglevel adaptive test in healthy Italian adults to produce new normative data on a language of Latin origin.