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Objectives: Children with mucopolysaccharidosis (MPS) with difficult airways may require tracheostomy, and surgery can be challenging. This review aims to study the indications, surgical aspects, postoperative complications and outcomes of tracheostomy in MPS children., Methods: A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted. Pubmed and Embase were searched for studies on tracheostomy in children with MPS. The Joanna Briggs Institute was used for quality appraisal., Results: A total of 9 studies were included. Three were retrospectives, one was prospective, and five were case series. Overall, 34 subjects who underwent a tracheostomy were included. The mean age was 11 years and the male/female ratio was 1.7. MPS II was the most common type included (16/34). The percentage of tracheotomized MPS children was 10 % (ranging from 3.5 % to 15.5 %). Indications for tracheostomy were: progressive or urgent airway obstruction unresponsive to conservative treatments, before a planned surgical procedure, and in case of failed intubation/extubation. Characteristics clinical features make surgery difficult and predispose complications such as tracheal granulations, wound infection, stomal narrowing, persistent of abundant secretions and tracheitis. Considering tracheostomy outcome, two patients underwent decannulation, but one of them required reinsertion tracheostomy after one year. The duration of follow-up was 8.4 and 9.98 years., Conclusion: Tracheostomy is an effective means of ensuring airway patency in children with MPS and is considered essentially permanent. Management can be challenging due to typical clinical features and progression of MPS. A planned multidisciplinary approach may prevent complications., Competing Interests: Declaration of competing interest No conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background & Aims: The relation between various types of plant-based diets and cancer risk is still unclear. We examined the association of the overall plant-based diet index (PDI) and healthy (hPDI) and unhealthy plant-based diet indices (uPDI) with the risk of selected digestive cancers., Methods: We used data from a network of hospital-based case-control studies including 942 oral/pharyngeal, 304 esophageal, 230 stomach, 1953 colorectal, and 326 pancreatic cancer cases. We calculated PDI, hPDI, and uPDI from a validated food frequency questionnaire. We used multivariable logistic regression models to estimate the odds ratios (OR) of selected digestive cancers across the three indices (in quintiles, Q, or tertiles, T, and in continuous)., Results: The PDI was significantly inversely associated with oral/pharyngeal (OR Q5 vs Q1 =0.63, 95% confidence interval, CI, 0.47-0.84) and esophageal cancer risk (OR T3 vs T1 =0.47, 95% CI 0.31-0.72). The inverse associations appeared stronger for the hPDI (oral cavity/pharynx: OR Q5 vs Q1 =0.52; 95% CI 0.39-0.70; esophagus: OR T3 vs T1 =0.59, 95% CI 0.39-0.91; stomach: OR T3 vs T1 =0.42, 95% CI 0.27-0.67; colorectum: OR Q5 vs Q1 =0.69; 95% CI 0.57-0.84; pancreas: OR T3 vs T1 =0.60; 95% CI 0.41-0.89). In contrast, the uPDI was directly associated with the risk of oral/pharyngeal (OR Q5 vs Q1 =1.43, 95% CI 1.06-1.94), colorectal (OR Q5 vs Q1 =2.28, 95% CI 1.86-2.81), and pancreatic cancer (OR T3 vs T1 =1.74, 95% CI 1.14-2.65). Esophageal and stomach cancer risks were non-significantly increased by 34% and 46% respectively in the highest uPDI quantile., Conclusion: A plant-based diet, especially a healthy plant-based diet, may reduce the risk of various digestive cancers, whereas an unhealthy plant-based diet may increase the risk. The quality of plant-based diets is important for digestive cancer risk evaluation and prevention., Competing Interests: Conflict of interest LSAA is a founding member and CLV a member of the International Carbohydrate Quality Consortium (ICQC). LSAA has received honoraria from the Nutrition Foundation of Italy (NFI). All other authors: no conflict of interest are reported., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The aim of this study is to investigate the prognostic role of body mass index (BMI) on survival from head and neck cancer (HNC). We performed a pooled analysis of studies included in the International Head and Neck Cancer Epidemiology consortium. We used Cox proportional hazards models to estimate the adjusted hazard ratios (HR) for overall survival and HNC-specific survival, and we stratified the results according to cancer site. The study included 10,177 patients from 10 studies worldwide. Underweight patients had lower overall survival (HR=1.69, 95% CI: 1.31-2.19) respect to those having normal weight with consistent results across the HNC sites. Overweight and obese patients had a favourable HNC-specific survival (HR=0.77 (95% CI: 0.70-0.84) and HR=0.80 (95% CI: 0.76-0.84), respectively), with heterogenous results according to HNC site. Our findings show that high BMI values at cancer diagnosis improved the survival rates in patients with HNC, especially among smokers. This association may be explained by residual confounding, reverse causation, and collider stratification bias, but may also suggest that a nutritional reserve may help patients survive HNC cancer., Competing Interests: None., (AJCR Copyright © 2024.)

Background: Aspirin intake might be inversely associated with head and neck cancer (HNC). Thus, we investigated this relationship within the International Head and Neck Cancer Epidemiology (INHANCE) consortium., Methods: Four case-control studies within the INHANCE consortium were included (2024 cases, 4196 controls). Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression and subsequently pooled with DerSimonian-Laird random-effects model. Nonlinearity of the relationship between duration of intake and HNC was modeled with fractional polynomials., Results: Aspirin was inversely associated with HNC overall (OR = 0.48; 95% CI: 0.26, 0.91). Results for laryngeal cancer were similar (OR = 0.54; 95% CI: 0.30, 0.96). Analysis on duration of intake confirmed findings for HNC overall, showing also inverse associations for oropharyngeal and laryngeal cancer., Conclusions: This study suggests that aspirin intake may reduce the risk of HNC, driven mainly by decreases in risk for laryngeal and oropharyngeal cancer., (© 2024 Wiley Periodicals LLC.)

Objective: To study the role of adenotonsillectomy (ADT) for obstructive sleep apnea (OSA) in children with mucopolysaccharidosis (MPS)., Methods: A systematic review were performed following the PRISMA guideline. PubMed and Embase were searched for studies regarding adenotonsillectomy for OSA in children with MPS. The MINOR Score were applied for quality assessment of the included studies., Results: Nineteen studies were eligible for inclusion: fifteen were retrospective and four prospective. A total of 1406 subjects were included. The samples size varied from 2 to 336, the male to female ratio is 1.2 and mean age varied from 2.4 to 11 years. Overall, 56.2 % (IC 95%: 53.6-58.8) of the included subjects underwent ADT. MPS I and II are the two most operated types. Three studies, including 50 children, reported improvement in polysomnographic parameters after surgery. Two authors described the duration of follow-up: 8.4 and 9.8 years, respectively., Conclusions: More than half of children with MPS underwent ADT for the treatment of OSA, although few evidence demonstrated improvement in term of polysomnographic parameters. The two types of MPS most involved are type I and II. Considering the disease progression and anesthetic risks, multidisciplinary management may help identify the subgroup of children with MPS who benefit from ADT for the treatment of OSA., Competing Interests: Declaration of competing interest Authors declare none., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: The aim of this review was to study the surgical management of laryngeal amyloidosis and estimate the rate of recurrence after surgery., Methods: A systematic review searching PubMed and EMBASE was performed. A qualitative synthesis of data regarding the surgical management of LA and a quantitative analysis of the recurrence rate after surgery was conducted., Results: This systematic review included 14 retrospective studies, one of whom is retrospective controlled. A total of 515 subjects were included, the mean age ranged from 43.3 to 58 years with a male-to-female ratio of 1:1.3. All cases had a localized laryngeal amyloidosis. The supraglottic region was the most affected laryngeal site and multiple sites were commonly involved. Surgical treatment consists of endoscopic excision using laser, cold or powered instruments. Open surgery is required for severe primary case or revision surgery. Surgical complications such as granulomatosis scar tissue formation, tracheostomy, laryngotracheal stenosis, pneumothorax and concomitant malignancy were developed in 17.5% of patients. The time onset to diagnosis varied from 1 months to 15 years and the duration of follow-up from 3 months to 25 years. The rate of recurrence was 28.4% (95% CI 24.5-32.6) and the timing of recurrences ranged from 3 months to 10 years., Conclusion: The recurrence rate after primary surgery for laryngeal amyloidosis is high. A tailored surgical treatment based on the disease extension and a long-term follow up are recommended., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: We analyzed the pooled case-control data from the International Head and Neck Cancer Epidemiology (INHANCE) consortium to compare cigarette smoking and alcohol consumption risk factors for head and neck cancer between less developed and more developed countries., Subjects and Methods: The location of each study was categorized as either a less developed or more developed country. We compared the risk of overall head and neck cancer and cancer of specific anatomic subsites associated with cigarette smoking and alcohol consumption. Additionally, age and sex distribution between categories was compared., Results: The odds ratios for head and neck cancer sites associated with smoking duration differed between less developed and more developed countries. Smoking greater than 20 years conferred a higher risk for oral cavity and laryngeal cancer in more developed countries, whereas the risk was greater for oropharynx and hypopharynx cancer in less developed countries. Alcohol consumed for more than 20 years conferred a higher risk for oropharynx, hypopharynx, and larynx cancer in less developed countries. The proportion of cases that were young (<45 years) or female differed by country type for some HNC subsites., Conclusion: These findings suggest the degree of industrialization and economic development affects the relationship between smoking and alcohol with head and neck cancer., (© 2022 Wiley Periodicals LLC.)

Knowledge on the role of diet in tinnitus onset is mostly based on few cross-sectional studies. In 2016-2019 we conducted a hospital-based case-control study in northern Italy on 185 incident idiopathic tinnitus cases and 198 controls, providing data on dietary habits through a 37-item food-frequency questionnaire. Odds ratios (OR) for tinnitus risk were derived through unconditional multiple logistic regression models. Moderate-to-high vs. low intake of caffeine (OR, 0.49; 95% confidence interval (CI), 0.24-0.99) and butter (OR, 0.46; 95% CI, 0.23-0.93), and high vs. low intake of poultry (OR, 0.43; 95% CI, 0.23-0.81), prosciutto (OR, 0.44; 95% CI, 0.23-0.85), and legumes (OR, 0.50; 95% CI, 0.28-0.92) were inversely associated with tinnitus onset. Other food items, including cereals, red meat, fish, vegetables, and fruit did not show any statistically significant relationship. The variety of food consumed decreased the risk of tinnitus (OR for at least 20 vs. less than 16 different food items, 0.47; 95% CI, 0.24-0.90). Our findings highlight the importance of diet in tinnitus onset and confirm a potential inverse association of protein-rich food and caffeine on the incidence of tinnitus. Confirmation of our findings in longitudinal studies is necessary before proving any diet recommendations for tinnitus prevention.

Importance: To date, no systematic review has taken a meta-analytic approach to estimating the prevalence and incidence of tinnitus in the general population., Objective: To provide frequency estimates of tinnitus worldwide., Data Sources: An umbrella review followed by a traditional systematic review was performed by searching PubMed-MEDLINE and Embase from inception through November 19, 2021., Study Selection: Research data from the general population were selected, and studies based on patients or on subgroups of the population with selected lifestyle habits were excluded. No restrictions were applied according to date, age, sex, and country., Data Extraction and Synthesis: Relevant extracted information included type of study, time and location, end point, population characteristics, and tinnitus definition. The study followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline., Main Outcomes and Measures: Pooled prevalence estimates of any tinnitus, severe tinnitus, chronic tinnitus, and diagnosed tinnitus as well as incidence of tinnitus were obtained using random-effects meta-analytic models; heterogeneity between studies was controlled using the χ2 test, and inconsistency was measured using the I2 statistic., Results: Among 767 publications, 113 eligible articles published between 1972 and 2021 were identified, and prevalence estimates from 83 articles and incidence estimates from 12 articles were extracted. The pooled prevalence of any tinnitus among adults was 14.4% (95% CI, 12.6%-16.5%) and ranged from 4.1% (95% CI, 3.7%-4.4%) to 37.2% (95% CI, 34.6%-39.9%). Prevalence estimates did not significantly differ by sex (14.1% [95% CI, 11.6%-17.0%] among male individuals; 13.1% [95% CI, 10.5%-16.2%] among female individuals), but increased prevalence was associated with age (9.7% [95% CI, 7.4%-12.5%] among adults aged 18-44 years; 13.7% [95% CI, 11.0%-17.0%] among those aged 45-64 years; and 23.6% [95% CI, 19.4%-28.5%] among those aged ≥65 years; P < .001 among age groups). The pooled prevalence of severe tinnitus was 2.3% (95% CI, 1.7%-3.1%), ranging from 0.5% (95% CI, 0.3%-0.7%) to 12.6% (95% CI, 11.1%-14.1%). The pooled prevalence of chronic tinnitus was 9.8% (95% CI, 4.7%-19.3%) and the pooled prevalence of diagnosed tinnitus was 3.4% (95% CI, 2.1%-5.5%). The pooled incidence rate of any tinnitus was 1164 per 100 000 person-years (95% CI, 479-2828 per 100 000 person-years)., Conclusions and Relevance: Despite the substantial heterogeneity among studies, this comprehensive systematic review on the prevalence and incidence of tinnitus suggests that tinnitus affects more than 740 million adults globally and is perceived as a major problem by more than 120 million people, mostly aged 65 years or older. Health policy makers should consider the global burden of tinnitus, and greater effort should be devoted to boost research on tinnitus.

Objectives: To evaluate surgical approaches and outcomes of pleomorphic adenoma of parotid gland in pediatric population., Methods: A systematic search of PubMed and EMBASE was performed to identify articles reporting surgical treatment of pleomorphic adenoma of the parotid gland in children. A qualitative analysis on results was conducted., Results: Our search included 23 retrospective studies. The number of children with pleomorphic adenoma underwent surgical treatment were 330. Superficial parotidectomy is the most reported type of surgery, total parotidectomy is performed when the tumor occurs in the deep lobe or in revision surgery and limited excisions in selected case of small lesions mainly in the tail of parotid gland. The rate of recurrences after surgery ranged from 0% to 44.4%. Revision surgery was performed in all cases of recurrences. Considering major complications, transient facial paralysis was observed from 0% to 50% of cases after primary and/or revision surgery; Frey's syndrome from 0% to 14.3% of cases regardless of the type of surgeries., Conclusion: Surgical treatment of pleomorphic adenoma of parotid gland in children requires a tailored approach based on the location and extent of the tumor with the main aim of complete excision of the neoplasm. Appropriate surgical approach results in a decrease of recurrence rate and morbidity. Surgical skill is needed to reduce complication rates especially in children., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest, (Copyright © 2022. Published by Elsevier B.V.)

Background: Although a direct relationship between tinnitus or hearing difficulties and COVID-19 has been suggested, current literature provides inconsistent results, and no research has been undertaken in older adults., Methods: In November 2020, we conducted the LOST in Lombardia survey, a telephone-based cross-sectional study on a sample of 4,400 individuals representative of the general population aged ≥65 years from Lombardy region, Northern Italy. Individuals with diagnosed tinnitus and/or hearing loss were asked whether their conditions had improved or deteriorated in 2020 compared to 2019., Results: Overall, 8.1% of older adults reported a diagnosis of tinnitus and 10.5% of hearing loss. In 2020 compared to 2019, among individuals with tinnitus, those with increasing severity (5.0%) were similar to those decreasing it (5.3%). Among individuals with hearing loss, more people reported an increase (13.6%) than a decrease (3.2%) in their disease severity. No individual with a diagnosis in 2020 of tinnitus ( n = 6) or hearing loss ( n = 13) had COVID-19. The incidence of tinnitus was lower in 2020 (rate: 14.8 per 10,000 person-years) than in previous years (rate in 1990-2019: 36.0 per 10,000 person-years; p = 0.026). There was no change in the incidence of hearing loss ( p = 0.134)., Conclusions: In this large representative sample of older adults, on average neither COVID-19 confinement nor SARS-CoV-2 infection appeared to increase the severity or incidence of tinnitus. The increased severity of hearing difficulties may totally or partially be explained by physiologic deterioration of the condition, or by a misperception due to the use of face-masks., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jarach, Lugo, Stival, Bosetti, Amerio, Cavalieri d'Oro, Iacoviello, Odone, Stuckler, Zucchi, van den Brandt, Garavello, Cederroth, Schlee, Gallus and the LOST in Lombardia Study Investigators.)

Benign paroxysmal positional vertigo is a rare vestibular disorder in the pediatric population. It is a vestibulopathy characterized by brief attacks of vertigo, which occur after specific movements. This review aims to provide the current evidence regarding benign paroxysmal positional vertigo in children. This is a narrative review of the available literature on benign paroxysmal positional vertigo in children. The studies were retrieved from systematic searches on PubMed and by cross referencing. Few studies have focused on pediatric benign paroxysmal positional vertigo, and most are retrospective non-controlled studies that include a small number of children. The vast majority of cases of benign paroxysmal positional vertigo in children have been reported to be secondary. The most frequent forms involve the posterior canal and the horizontal canal. The diagnosis is based on positional maneuvers, respectively the Dix-Hallpike maneuver, which reveals a torsional upbeating nystagmus; and the supine roll test, which reveals a geotropic, horizontal nystagmus. The treatment consists of physical repositioning maneuvers: the Semont or the modified Epley maneuver for benign paroxysmal positional vertigo involving the posterior canal and the Gufoni or the Barbecue maneuver in case of the horizontal canal. Benign paroxysmal positional vertigo in children can be resistant to treatment and repetitive positional maneuvers may be necessary, particularly for children with vestibular migraine or benign paroxysmal vertigo of childhood, who have a statistically significant major risk of having recurrences compared to patients who do not. Benign paroxysmal positional vertigo in children is a rare but well-recognized clinical entity. It is diagnosed by positional testing and treated by repositioning maneuvers. Wide awareness and education among pediatric providers and otolaryngologists are needed in order to avoid a delay in identification and treatment.

Objectives: To determine the impact of adenotonsillectomy for treatment of severe obstructive sleep apnea (OSA) in children without comorbidities., Methods: A systematic review was performed to identify studies regarding adenotonsillectomy for treatment of children with severe sleep apnea. Polysomnographic parameters were considered as metric of cure and the number of patients of persistent apnea was calculated. Quality of evidence was graded using OCEBM (Oxford Center for Evidence Based Medicine) and MINORS (Methodological Index for Nonrandomized Studies) scores., Results: The systematic review included nine studies. Five studies were prospective and four retrospectives. No one was controlled. The number of subjects with severe OSA included was 499 with a prevalence of male. The mean age varied from 4.3 to 8.2. The follow-up period ranges from 1 to 23 months. The criteria for considering severe OSA ranges from AHI or RDI ≥10 to ≥30. All the trials have found a statistically significant reduction of postoperative AHI or RDI values in patients who had undergone adenotonsillectomy for severe OSA. The AHI and RDI improving varied from 57.7% to 93.3%. All the studies documented persistent OSA after adenotonsillectomy. The number of residual OSA considering AHI≥5 varied from 30 to 55.5%, in case of AHI ≥1 from 60 to 90.6%., Conclusion: To the best of our knowledge, this is the first review regarding the effectiveness of adenotonsillectomy for severe OSA in otherwise healthy children. Adenotonsillectomy is partially effective in the treatment of severe OSA in children without comorbidities. However, it reduces the severity of OSA determining a significant reduction of polysomnographic parameters. These results suggest a clinical and polysomnographic follow-up after surgery in order to manage the residual mild and moderate OSA., (Copyright © 2020. Published by Elsevier B.V.)

Introduction: Smell and taste loss are characteristic symptoms of SARS-CoV-2 infection. The aim of this study is to investigate the prevalence and risk factors associated with olfactory and gustatory dysfunctions in coronavirus disease (COVID-19) patients., Methods: We conducted an observational, retrospective study on 376 patients with documented SARS-CoV-2 infection admitted to the San Gerardo Hospital in Monza, Italy, from March to July 2020. All patients answered a phone questionnaire providing information on age, sex, smoking status, and clinical characteristics. Adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated through logistic regression models including relevant covariates., Results: The prevalence of olfactory and gustatory dysfunctions in COVID-19 patients was 33.5 and 35.6%, respectively. Olfactory dysfunctions were significantly directly associated with current smoking and history of allergy, the multivariable ORs being 6.53 (95% CI 1.16-36.86) for current smokers versus never smokers, and 1.89 (95% CI 1.05-3.39) for those with an allergy compared to those without any allergy. Respiratory allergy in particular was significantly associated with olfactory dysfunctions (multivariable OR 2.30, 95% CI 1.02-5.17). Significant inverse associations were observed for patients aged 60 years or more (multivariable OR 0.33, 95% CI 0.19-0.57) and hospitalization (multivariable OR 0.22, 95% CI 0.06-0.89). Considering gustatory dysfunctions, after allowance of other variables a significant direct association was found for respiratory allergies (OR 2.24, 95% CI 1.03-4.86), and an inverse association was found only for hospitalization (OR 0.21, 95% CI 0.06-0.76)., Conclusion: Our study indicates that current smoking and history of allergy (particularly respiratory) significantly increase the risk for smell loss in COVID-19 patients; the latter is also significantly associated to taste loss. Hospitalization has an inverse association with the risk of olfactory and gustatory dysfunctions, suggesting that these may be symptoms characteristics of less severe SARS-CoV-2 infection., (© 2021 S. Karger AG, Basel.)

Introduction: Tinnitus is a symptom and not a disease in its own right. A number of medical conditions are known to increase the risk of developing tinnitus. Most known risk factors are otological or neurological, but general health and lifestyle can also precipitate the condition. Understanding these modifiable risk factors can help to identify vulnerable groups and can inform preventive actions to reduce likelihood of developing tinnitus. Smoking, alcohol consumption, body mass index (BMI) and caffeine intake are all lifestyle risk factors hypothesized to be related to tinnitus. Nonetheless, research findings in support of those relationships are somewhat mixed., Methods: A systematic review was conducted to identify all relevant studies on the specific risk factors. Findings were summarized using a narrative synthesis and meta-analysis, where possible., Results: Overall 384 studies were included, mostly using cross-sectional designs. Findings indicated significantly increased risk of tinnitus among current (based on 26 studies) and ever smokers (based on 16 studies) and among obese people (based on seven studies), but no effect of alcohol consumption (based on 11 studies). With respect to caffeine intake or coffee drinking, only three studies examined this risk factor and so we were unable to draw conclusions., Conclusion: Our results contribute to quantifying the relationship between tinnitus and specific lifestyle-related risk factors, and we highlight some of the gaps and inconsistencies across published studies., Competing Interests: Conflict of interest None declared., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The considerable differences in food consumption across countries pose major challenges to the research on diet and cancer, due to the difficulty to generalise and reproduce the dietary patterns identified in a specific population., Methods: We analysed data from a multicentric case-control study on oesophageal squamous cell carcinoma (ESCC) carried out between 1992 and 2009 in three Italian areas and in the Canton of Vaud, Switzerland, which included 505 cases and 1259 hospital controls. Dietary patterns were derived applying LCA on 24 food groups, controlling for country membership, and non-alcoholic energy intake. A multiple logistic regression model was used to derive odds ratio (ORs) and corresponding 95% CIs for ESCC according to the dietary patterns identified, correcting for classification error., Results and Conclusion: We identified three dietary patterns. The 'Prudent' pattern was distinguished by a diet rich in fruits and vegetables. The 'Western' pattern was characterised by low consumption of these food groups and higher intakes of sugar. The 'Lower consumers-combination pattern' exhibited a diet poor in most of the nutrients, preferences for fish, potatoes, meat and a few specific types of vegetables. Differences between Italy and Switzerland emerged for pattern sizes and for specific single food preferences. Compared to the 'Prudent' pattern, the 'Western' and the 'Lower consumers-combination' patterns were associated with an increased risk of ESCC (OR=3.04, 95% CI=2.12-4.38 and OR=2.81, 95% CI=1.65-4.76)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Alcohol is a well-established risk factor for head and neck cancer (HNC). This study aims to explore the effect of alcohol intensity and duration, as joint continuous exposures, on HNC risk., Methods: Data from 26 case-control studies in the INHANCE Consortium were used, including never and current drinkers who drunk ≤10 drinks/day for ≤54 years (24234 controls, 4085 oral cavity, 3359 oropharyngeal, 983 hypopharyngeal and 3340 laryngeal cancers). The dose-response relationship between the risk and the joint exposure to drinking intensity and duration was investigated through bivariate regression spline models, adjusting for potential confounders, including tobacco smoking., Results: For all subsites, cancer risk steeply increased with increasing drinks/day, with no appreciable threshold effect at lower intensities. For each intensity level, the risk of oral cavity, hypopharyngeal and laryngeal cancers did not vary according to years of drinking, suggesting no effect of duration. For oropharyngeal cancer, the risk increased with durations up to 28 years, flattening thereafter. The risk peaked at the higher levels of intensity and duration for all subsites (odds ratio = 7.95 for oral cavity, 12.86 for oropharynx, 24.96 for hypopharynx and 6.60 for larynx)., Conclusions: Present results further encourage the reduction of alcohol intensity to mitigate HNC risk.

The emergency caused by Covid-19 pandemic raised interest in studying lifestyles and comorbidities as important determinants of poor Covid-19 prognosis. Data on tobacco smoking, alcohol consumption and obesity are still limited, while no data are available on the role of e-cigarettes and heated tobacco products (HTP). To clarify the role of tobacco smoking and other lifestyle habits on COVID-19 severity and progression, we designed a longitudinal observational study titled COvid19 and SMOking in ITaly (COSMO-IT). About 30 Italian hospitals in North, Centre and South of Italy joined the study. Its main aims are: 1) to quantify the role of tobacco smoking and smoking cessation on the severity and progression of COVID-19 in hospitalized patients; 2) to compare smoking prevalence and severity of the disease in relation to smoking in hospitalized COVID-19 patients versus patients treated at home; 3) to quantify the association between other lifestyle factors, such as e-cigarette and HTP use, alcohol and obesity and the risk of unfavourable COVID-19 outcomes. Socio-demographic, lifestyle and medical history information will be gathered for around 3000 hospitalized and 700-1000 home-isolated, laboratory-confirmed, COVID-19 patients. Given the current absence of a vaccine against SARS-COV-2 and the lack of a specific treatment for -COVID-19, prevention strategies are of extreme importance. This project, designed to highly contribute to the international scientific debate on the role of avoidable lifestyle habits on COVID-19 severity, will provide valuable epidemiological data in order to support important recommendations to prevent COVID-19 incidence, progression and mortality.

To provide an up-to-date overview of recent trends in mortality from oral and pharyngeal cancer, we analyzed death certification data for 61 countries worldwide provided by the World Health Organization in 2010-2015, and, for selected most populous countries, over the period 1970-2016. For 12 largest countries, we analyzed incidence derived from Cancer Incidence in Five Continents in 1960-2012 for all oral and pharyngeal cancers and by subsites. In 2015, male age-standardized (world population) death rates per 100,000 were 5.03 in the European Union (EU), 8.33 in the Russian Federation, 2.53 in the United States (USA), and 3.04 in Japan; corresponding rates in women were 1.23, 1.23, 0.82, and 0.76. Male mortality decreased over the last decades in several European countries, with earlier and sharper declines in southern Europe; conversely, mortality was still increasing in a few eastern European countries and the United Kingdom. Mortality in men also decreased in Argentina, Australia, and Hong Kong, while it leveled off over more recent calendar years in Brazil, Japan, Mexico, the Republic of Korea, as well as in Australia and the USA. Female mortality slightly rose in various European countries. Overall incidence trends in the largest countries were broadly consistent with mortality ones, but oropharyngeal cancer incidence rose in many countries. Changes in tobacco and alcohol exposure in men over the last decades likely explain the favorable trends in oral and pharyngeal cancer mortality and incidence observed in selected countries worldwide, while increased human papillomavirus infection is likely responsible for the rise in oropharyngeal cancer incidence., (© 2020 UICC.)

The methods traditionally used to identify a posteriori dietary patterns are principal components, factor and cluster analysis. The aim of our study is to assess the relationship between dietary patterns derived with latent class analysis (LCA) and oral/pharyngeal cancer risk (OPC), highlighting the strengths of this method compared to traditional ones. We analyzed data from an Italian multicentric case-control study on OPC including 946 cases and 2,492 hospital controls. Dietary patterns were derived using LCA on 25 food groups. A multiple logistic regression model was used to derive odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for OPC according to the dietary patterns identified. We identified four dietary patterns. The first one was characterized by a high intake of leafy and fruiting vegetable and fruits (Prudent pattern), the second one showed a high intake of red meat and low intake of selected fruits and vegetables (Western pattern). The last two patterns showed a combination-type of diet. We labeled "Lower consumers-combination pattern" the cluster that showed a low intake of the majority of foods, and "Higher consumers-combination pattern" the one characterized by a high intake of various foods. Compared to the "Prudent pattern", the "Western" and the "Lower consumers-combination" ones were positively related to the risk of OPC (OR = 2.56, 95% CI: 1.90-3.45 and OR = 2.23, 95% CI: 1.64-3.02). No difference in risk emerged for the "Higher consumers-combination pattern" (OR = 1.28, 95% CI: 0.92-1.77)., (© 2019 UICC.)

Background: Tobacco use is a well-established risk factor for head and neck cancer (HNC). However, less is known about the potential impact of exposure to tobacco at an early age on HNC risk., Methods: We analyzed individual-level data on ever tobacco smokers from 27 case-control studies (17,146 HNC cases and 17,449 controls) in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using random-effects logistic regression models., Results: Without adjusting for tobacco packyears, we observed that younger age at starting tobacco use was associated with an increased HNC risk for ever smokers (OR <10 years vs. ≥30 years : 1.64, 95% CI: 1.35, 1.97). However, the observed association between age at starting tobacco use and HNC risk became null after adjusting for tobacco packyears (OR <10 years vs. ≥30 years : 0.97, 95% CI: 0.80, 1.19). In the stratified analyses on HNC subsites by tobacco packyears or years since quitting, no difference in the association between age at start and HNC risk was observed., Conclusions: Results from this pooled analysis suggest that increased HNC risks observed with earlier age at starting tobacco smoking are largely due to longer duration and higher cumulative tobacco exposures., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Dysphagia after uncomplicated thyroidectomy is commonly reported and it includes a broad spectrum of swallowing complaints. Though various causes have been hypothesized, it remains not completely understood., Methods: A systematic review was performed to identify studies concerning dysphagia post uncomplicated thyroid surgery. A qualitative analysis of data extracted was conducted., Results: We have included 16 studies of which 15 are prospective and one are retrospective. The number of subjects varied from 12 to 254, the mean age from 39 to 54 years with an overall prevalence of females. The duration of the follow-up ranges from 1 month to 4 years. All the included trials documented postoperative dysphagia, 12 of which have detected it in the early postoperative period. Considering long-term follow-up period, 12 studies reported an overall improvement of swallow symptoms. The instrumental findings revealed non-specific alterations of swallowing., Conclusions: Dysphagia after uncomplicated thyroidectomy can arise early in the postoperative period resolving spontaneously in the first year. Diagnostic methods failed to identify the physio pathological mechanism of swallow alteration leaving this condition still unclear. Since these symptoms can reduce patient's quality of life, we suggest an appropriate education before thyroid surgery.

Objectives: This study aimed at re-evaluating the strength and shape of the dose-response relationship between the combined (or joint) effect of intensity and duration of cigarette smoking and the risk of head and neck cancer (HNC). We explored this issue considering bivariate spline models, where smoking intensity and duration were treated as interacting continuous exposures., Materials and Methods: We pooled individual-level data from 33 case-control studies (18,260 HNC cases and 29,844 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. In bivariate regression spline models, exposures to cigarette smoking intensity and duration (compared with never smokers) were modeled as a linear piecewise function within a logistic regression also including potential confounders. We jointly estimated the optimal knot locations and regression parameters within the Bayesian framework., Results: For oral-cavity/pharyngeal (OCP) cancers, an odds ratio (OR) >5 was reached after 30 years in current smokers of ∼20 or more cigarettes/day. Patterns of OCP cancer risk in current smokers differed across strata of alcohol intensity. For laryngeal cancer, ORs >20 were found for current smokers of ≥20 cigarettes/day for ≥30  years. In former smokers who quit ≥10  years ago, the ORs were approximately halved for OCP cancers, and ∼1/3 for laryngeal cancer, as compared to the same levels of intensity and duration in current smokers., Conclusion: Referring to bivariate spline models, this study better quantified the joint effect of intensity and duration of cigarette smoking on HNC risk, further stressing the need of smoking cessation policies., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background/objectives: To assess the association between processed meat and the risk of selected digestive tract and laryngeal cancers., Subjects/methods: We conducted a series of case-control studies between 1985 and 2007 in Italy. The studies included a total of 1475 cases of cancer of the oral cavity and pharynx, 1077 of the larynx, 716 of the esophagus, 999 of the stomach, 684 of the liver, 159 of the biliary tract, 688 of the pancreas, and a total of 9720 controls. Odds ratios (ORs), and the corresponding 95% confidence intervals (CIs), were estimated by unconditional logistic regression models, including terms for socio-demographic factors, tobacco smoking, and alcohol intake., Results: Compared to the lowest tertile of processed meat consumption, the ORs for subjects in the highest one were 1.18 (95% CI 0.98-1.43) for oral cavity and pharyngeal, 1.51 (95% CI 1.18-1.91) for esophageal, 1.19 (95% CI 0.96-1.47) for laryngeal, 0.98 (95% CI 0.81-1.18) for stomach, 0.85 (95% CI 0.51-1.40) for biliary tract, 1.20 (95% CI 0.94-1.54) for liver, and 1.46 (95% CI 1.15-1.85) for pancreatic cancers., Conclusions: Our findings support the hypothesis that high processed meat consumption increases esophageal and pancreatic cancers risk. Residual confounding by socio-demographic factors, tobacco smoking, and alcohol intake may, partly or largely, account for these associations. We found no overall association with other digestive tract and laryngeal cancers.

Purpose: To perform a comprehensive review of the literature regarding presbyphonia., Methods: We searched PUBMED through a combination of MeSH terms for articles published in the English language concerning presbyphonia., Results: Presbyphonia identifies vocal changes due to anatomical and physiological changes of the larynx occurring during the aging process. It affects about 10-20% of elderly and could negatively impact on their quality of life. The diagnosis of presbyphonia is typically a diagnosis of exclusion made in absence of other laryngeal disease with a characteristic clinic of aging voice and an instrumental pattern of presbylarynx. The treatme nt of choice for presbyphonia is speech therapy that significantly improves voice performances. In case of failure, surgical therapy should be proposed in selected patients although evidence of its benefit is scanty., Conclusions: The reviewed evidence regarding aging voice has shown that presbyphonia is considered a clinical entity that could impact the quality of life in elderly. Speech therapy is effective for improving voice performances., (© 2018. European Geriatric Medicine Society.)

Juvenile recurrent parotitis is a rare recurrent inflammation of the parotid glands occurring in children. The etiology remains obscure and the treatment is still debated. In the present study, we perform a systematic review of the literature with the purpose of identifying and discussing the treatment options emerged over the last 28 years in order to prevent recurrent episodes of parotitis. We ultimately included 24 studies. The definitions used for juvenile recurrent parotitis varied widely and none of the selected studies referred exactly to the same definition. Only one was a randomized controlled trial and it showed marked benefits with the use of Bear Bile and Huangqi, two traditional Chinese medicines. Two additional study on sialendoscopy included a control group but was not randomized. All the remaining contributions were case series or case reports. The vast majority (n = 19) of the selected studies reported on sialendoscopy. They all documented improvement of the condition following this intervention. An analysis grouping all these studies (corresponding to 336 children) showed that only 25.8% (95% Confidence Interval: 21.5-30.8) of the treated children had further recurrences. However, the only two controlled study on sialendoscopy showed a similar improvement in controls. The remaining four studies were on sialography (n = 2), on oral appliance in the specific group of children with concomitant dental malocclusion (n = 1) on ductal hydrocortisone infusion through catheter inserted in the parotid duct (n = 1). Improvements were documented in all four contributions. This systematic review of the literature did not consent us to draw definite conclusions on the most suitable treatment for juvenile recurrent parotitis. The available evidence is indeed weak and difficult to interpret because of the scarcity of randomized controlled trials, the heterogeneity of the definitions used and the high rate of spontaneous resolution. Future large and well-designed randomized controlled trials that will include children fulfilling a shared definition of the condition are warranted., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The possible role of dietary fiber in the etiology of head neck cancers (HNCs) is unclear. We used individual-level pooled data from ten case-control studies (5959 cases and 12,248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium, to examine the association between fiber intake and cancer of the oral cavity/pharynx and larynx. Odds Ratios (ORs) and their 95% Confidence Intervals (CIs) were estimated using unconditional multiple logistic regression applied to quintile categories of non-alcohol energy-adjusted fiber intake and adjusted for tobacco and alcohol use and other known or putative confounders. Fiber intake was inversely associated with oral and pharyngeal cancer combined (OR for 5th vs. 1st quintile category = 0.49, 95% CI: 0.40-0.59; p for trend <0.001) and with laryngeal cancer (OR = 0.66, 95% CI: 0.54-0.82, p for trend <0.001). There was, however, appreciable heterogeneity of the estimated effect across studies for oral and pharyngeal cancer combined. Nonetheless, inverse associations were consistently observed for the subsites of oral and pharyngeal cancers and within most strata of the considered covariates, for both cancer sites. Our findings from a multicenter large-scale pooled analysis suggest that, although in the presence of between-study heterogeneity, a greater intake of fiber may lower HNC risk., (© 2017 UICC.)

Diet and inflammation have been suggested to be important risk factors for oral and pharyngeal cancer. We examined the association between dietary inflammatory index (DII™) and oral and pharyngeal cancer in a large case-control study conducted between 1992 and 2009 in Italy. This study included 946 cases with incident, histologically confirmed oral and pharyngeal cancer, and 2,492 controls hospitalized for acute non-neoplastic diseases. The DII was computed based on dietary intake assessed by a valid 78-item food frequency questionnaire and was adjusted for nonalcohol energy intake using the residual approach (E-DII™). Logistic regression models were used to estimate odds ratios (ORs), and 95% confidence intervals (CIs), adjusted for age, sex, non-alcohol energy intake, study center, year of interview, education, body mass index, tobacco smoking, and alcohol drinking. Subjects with higher DII scores (i.e., with a more pro-inflammatory diet) had a higher risk of oral and pharyngeal cancer, the OR being 1.80 (95% CI 1.36-2.38) for the highest versus the lowest DII quartile and 1.17 (95% CI 1.10-1.25) for a one-unit increase (8% of the DII range). When stratified by selected covariates, a stronger association was observed among women (OR quartile4 v.1 3.30, 95% CI 1.95-5.57). We also observed a stronger association for oral cancers and a strong combined effect of higher DII score and tobacco smoking or alcohol consumption on oral and pharyngeal cancer. These results indicate that the pro-inflammatory potential of the diet, as shown by higher DII scores, is associated with higher odds of oral and pharyngeal cancer., (© 2017 UICC.)

Nasopharyngeal cancer (NPC) mortality shows great disparity between endemic high risk areas, where non-keratinizing carcinoma (NKC) histology is prevalent, and non-endemic low risk regions, where the keratinizing squamous cell carcinoma (KSCC) type is more frequent. We used the World Health Organization database to calculate NPC mortality trends from 1970 to 2014 in several countries worldwide. For the European Union (EU), the United States (US) and Japan, we also predicted trends to 2020. In 2012, the highest age-standardized (world standard) rates were in Hong Kong (4.51/100,000 men and 1.15/100,000 women), followed by selected Eastern European countries. The lowest rates were in Northern Europe and Latin America. EU rates were 0.27/100,000 men and 0.09/100,000 women, US rates were 0.20/100,000 men and 0.08/100,000 women and Japanese rates were 0.16/100,000 men and 0.04/100,000 women. NPC mortality trends were favourable for several countries. The decline was -15% in men and -5% in women between 2002 and 2012 in the EU, -12% in men and -9% in women in the US and about -30% in both sexes in Hong Kong and Japan. The favourable patterns in Europe and the United States are predicted to continue. Changes in salted fish and preserved food consumption account for the fall in NKC. Smoking and alcohol prevalence disparities between sexes and geographic areas may explain the different rates and trends observed for KSCC and partially for NKC. Dietary patterns, as well as improvement in management of the disease, may partly account for the observed trends, too., (© 2017 UICC.)

Metastatic cervical carcinoma from unknown primary is a metastatic disease in the lymph nodes of the neck without any evidence of a primary tumour after appropriate investigation. The condition is rare and definite evidence is lacking for both diagnosis and treatment. In this review of the literature, we tried to draw some clinical indications based on the few available studies. We ultimately came to the following conclusions: (1) a thorough and accurate diagnostic work-up should be systematically offered. It includes accurate inspection with fibroscopy, CT or MRI, fine needle aspiration, panendoscopy and positron emission tomography, (2) Patients with low-volume neck disease, N1 and N2a stage and without extracapsular extension on histopathological examination should receive single modality treatment. Radiotherapy and surgery may be similarly effective but, if possible, surgery (excisional biopsy, neck dissection and tonsillectomy) should be favoured because it consents a more precise staging, (3) patients with more advanced conditions require combined treatment in the form of either resection followed by adjuvant radiation (±chemotherapy) or primary chemoradiation (±post-therapy neck dissection)., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: Few studies investigated the role of diet on nasopharyngeal cancer (NPC) risk in non-endemic areas. The aim of this study was to assess the association between adherence to the traditional Mediterranean diet and NPC risk in a southern European low-risk population., Methods: We conducted a hospital-based case-control study in Italy, including 198 histologically confirmed NPC cases and 594 matched controls. Dietary habits were collected by means of a validated food-frequency questionnaire, including 83 foods, food groups, or beverages. Adherence to the traditional Mediterranean diet was assessed through a Mediterranean Diet Score (MDS), based on nine dietary components characterizing this dietary profile, i.e., high intake of vegetables, fruits and nuts, cereals, legumes, and fish; low intake of dairy products and meat; high monounsaturated to saturated fatty acid ratio; and moderate alcohol intake. We estimated odds ratios (ORs) of NPC, and the corresponding 95% confidence intervals (CIs), for increasing MDS (i.e., increasing adherence) using multiple logistic regression models, adjusted for major confounding factors., Results: As compared to MDS ≤ 4, the ORs of NPC were 0.83 (95% CI: 0.54-1.25) for MDS of 5 and 0.66 (95% CI: 0.44-0.99) for MDS ≥ 6, with a significant trend of decreasing risk (p 0.043). The corresponding population attributable fraction was 22%, indicating that 22% of NPC cases in this population would be avoided by shifting all subjects to a score ≥6., Conclusions: Our study supports a favorable role of the Mediterranean diet on NPC risk.

After a steady increase between the 1950s and the 1970s, laryngeal cancer mortality has been levelling off since the early 1980s in men from most western and southern European countries and since the early 1990s in central and eastern Europe. To update trends in laryngeal cancer mortality, we analyzed data provided by the World Health Organization over the last two decades for 34 European countries and the European Union (EU) as a whole. For major European countries, we also identified significant changes in trends between 1980 and 2012 using joinpoint regression analysis. Male mortality in the EU was approximately constant between 1980 and 1991 (annual percent change, APC=-0.5%) and declined by 3.3% per year in 1991-2012. EU age-standardized (world population) rates were 4.7/100,000 in 1990-91 and 2.5/100,000 in 2010-2011. Rates declined in most European countries, particularly over the last two decades. In 2010-11, the highest male rates were in Hungary, the Republic of Moldova, and Romania (over 6/100,000), and the lowest ones in Finland, Norway, Sweden, and Switzerland (below 1/100,000). In EU women, mortality was stable around 0.29/100,000 between 1980 and 1994 and slightly decreased thereafter (APC=-1.3%; 0.23/100,000 in 2000-01). We also considered male incidence trends for nine European countries or cancer registration areas. In most of them, declines were observed over recent decades. Laryngeal cancer mortality thus showed favourable trends over the last few decades in most Europe, following favourable changes in tobacco and, mostly for Mediterranean countries, alcohol consumption., (© 2015 UICC.)

Oral cancer, representing all the malignancies arising in the oral cavity, is the eighth most diffused neoplasm worldwide. Despite therapeutic improvements, its survival rate has not changed significantly over the past few decades, with a 5-year survival rate slightly above 50%. In this context, a search for new therapeutic strategies is mandatory. Flavonoids, polyphenolic compounds derived from plants, have a broad spectrum of biological activities, including antioxidant and anticancer. They have been proved to counteract the growth of several types of cancer through multiple mechanisms including the inhibition of cell cycle progression, apoptosis induction, and the modulation of intracellular pathways. Because of their multiple biological activities and their safe toxicological profile, flavonoids have been studied widely in the last decade as potential leads for anticancer therapy. Several studies have reported different flavonoid effects according to cancer cell type. In the present review, therefore, we have evaluated the data available on the effect of flavonoids on oral cancer, with the aim of identifying the molecular mechanisms underlying their potential anticancer properties.

In most areas of the world, thyroid cancer incidence has been appreciably increasing over the last few decades, whereas mortality has steadily declined. We updated global trends in thyroid cancer mortality and incidence using official mortality data from the World Health Organization (1970-2012) and incidence data from the Cancer Incidence in Five Continents (1960-2007). Male mortality declined in all the major countries considered, with annual percent changes around -2/-3% over the last decades. Only in the United States mortality declined up to the mid 1980s and increased thereafter. Similarly, in women mortality declined in most countries considered, with APCs around -2/-5% over the last decades, with the exception of the UK, the United States and Australia, where mortality has been declining up to the late 1980s/late 1990s to level off (or increase) thereafter. In 2008-2012, most countries had mortality rates (age-standardized, world population) between 0.20 and 0.40/100,000 men and 0.20 and 0.60/100,000 women, the highest rates being in Latvia, Hungary, the Republic of Moldova and Israel (over 0.40/100,000) for men and in Ecuador, Colombia and Israel (over 0.60/100,000) for women. In most countries, a steady increase in the incidence of thyroid cancer (mainly papillary carcinomas) was observed in both sexes. The declines in thyroid cancer mortality reflect both variations in risk factor exposure and changes in the diagnosis and treatment of the disease, while the increases in the incidence are likely due to the increase in the detection of this neoplasm over the last few decades., (© 2014 UICC.)

Aim of the Study: The odontogenic sinusitis has an incidence between 38 and 40.6%. Increased risk of maxillary sinusitis has been reported with the presence of periapical abscesses, periodontal disease, dental trauma, tooth extraction and implant placement when the sinusal membrane is perforated., Materials and Methods: A patient with odontogenic maxillary sinusitis associated with oro-nasal fistula was treated., Results: The follow-up at six months showed the complete resolution of maxillary sinusitis, palatal fistula got closed and pain symptoms disappeared., Conclusion: This case report describes a rare complication of odontogenic maxillary sinusitis: the oro-nasal fistula.

Purpose: The role of dietary habits in the etiology of nasopharyngeal carcinoma (NPC) has been extensively investigated in high-incidence areas, but evidence is scanty in low-incidence populations. This study aimed to investigate the relationship between NPC risk and a wide range of food groups in the Italian population., Methods: We conducted a hospital-based case-control study in Italy on 198, histologically confirmed, NPC cases of Caucasian ethnicity, aged 18-76 years. Controls were 594 Caucasian cancer-free patients admitted to general hospitals for acute conditions. Odds ratios (ORs) and the corresponding confidence intervals (CIs) were estimated through logistic regression, adjusting for socio-demographic characteristics, tobacco smoking, alcohol drinking, and energy intake., Results: Elevated vegetable consumption was inversely related to NPC risk (OR for highest vs. lower quartile = 0.51; 95 % CI 0.29-0.90). The association was particularly strong for yellow- or red-pigmented vegetables (OR = 0.31; 95 % CI 0.18-0.54), and this effect was stronger among never smokers (OR = 0.18; 95 % CI 0.06-0.55) than among ever smokers (OR = 0.37; 95 % CI 0.19-0.71). Increased NPC risk emerged for elevated eggs consumption (OR = 2.50; 95 % CI 1.44-4.32; p-trend <0.01). No significant associations emerged between NPC risk and consumption of cereals, meat, fish, dairy products, and sweets., Conclusions: The study findings show that, also in low-risk populations, vegetable consumption is a protective factor against NPC. The stronger effect for yellow- or red-pigmented vegetables is in agreement with the inverse association reported for carotenoids intake.

Purpose: To determine the rate of recurrence following surgical treatment of thyroglossal duct cysts (TDGCs) in children., Methods: A search of electronic databases (Pubmed and MEDLINE) was performed in order to identify studies concerning surgical treatment of TGDCs in children published between 1980 and 2012. The following terms were used: "thyroglossal duct cysts", "recurrent", "recurrence", "children", "pediatric"., Results: Sixteen articles were selected with the majority published during the last decade. The total number of included subjects was 1233. The mean (95% confidence interval (CI)) rate of recurrences was 10.7% (9.1%-12.6%). Eleven studies involving 751 subjects reported the frequency of recurrences separately for primary cases. The mean (95% CI) rate of recurrences was 10.8% (8.7%-13.3%). Five studies reported separately results of surgery for secondary cases. The mean (95% CI) rate of recurrences was 20.0% (12.2%-30.8%). Eight of the sixteen studies reported data on risk factors for recurrence. The use of the Sistrunk technique is a protective factor, whereas children who experienced repeated episodes of infection prior to surgery are exposed to a higher risk of recurrence., Conclusion: Recurrences after surgery for TDGCs remain a clinically relevant issue. One of ten operated children experiences a recurrence. Available data support the use of the Sistrunk technique but further studies aimed at improving the clinical management of TDGCs are required., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: Bacterial biofilms have been detected in biopsies of the adenoid and middle ear mucosa of otitis-prone children and children with chronic middle otitis media. However, the invasiveness of biopsy makes it unsuitable for routine clinical practice, especially in pediatrics. This study aimed to investigate nasopharyngeal biofilm-producing otopathogens (BPOs) of nasopharyngeal swabs (NPS) in children with a history of nonsevere recurrent acute otitis media (RAOM) and healthy controls., Study Design: A cross-sectional study with planned data collection., Setting: University of Milan., Subjects and Methods: Transoral NPS were taken from infants and children aged 10 months to 11 years with nonsevere RAOM or healthy controls without adenoid hypertrophy. Nasopharyngeal colonization by otopathogens was assessed by means of microbiological cultures and standard bacterial identification, as well as nasopharyngeal BPOs by means of spectrophotometric analysis., Results: The study involved 113 children (56.6% males; median age 40 months; range, 10-132 months): 58 with a history of nonsevere RAOM (51.3%) and 55 controls (48.7%). Otopathogens were significantly more frequently detected in the RAOM group (24/58, 41.4%) than in controls (8/55, 14.5%; P = .003); the main pathogens were respectively Haemophilus influenzae (12/24, 50.0%) and Streptococcus pyogenes (3/8, 37.5%). Nasopharyngeal BPOs were more frequently isolated in the RAOM group (17/58, 29.3%) than in controls (6/55, 10.9%; P = .02). H influenzae (12/17, 70.6%) was confirmed as the main pathogen in the RAOM group., Conclusion: The presence of nasopharyngeal BPOs is an important factor favoring RAOM; it is therefore useful investigating biofilms even in children with nonsevere recurrences of AOM without adenoid hypertrophy.

Only limited data is available on the relationship between family history of laryngeal and other neoplasms and laryngeal cancer risk. We investigated the issue using data from a multicentre case-control study conducted in Italy and Switzerland between 1992 and 2009 including 852 cases with histologically confirmed laryngeal cancer and 1970 controls admitted to hospital for acute, non neoplastic conditions. Unconditional logistic regression models adjusted for age, sex, study center, education, tobacco smoking, alcohol drinking and number of siblings were used to estimate the odds ratios (ORs) of laryngeal cancer. The multivariate OR was 2.8 (95% confidence interval [CI], 1.5-5.3) in subjects reporting a first-degree relative with laryngeal cancer, as compared to subjects with no family history. The OR was higher when the relative was diagnosed before 60 years of age (OR = 3.5, 95% CI 1.4-8.8). As compared to subjects without family history, non-smokers, and moderate drinkers, the OR was 37.1 (95% CI 9.9-139.4) for current smokers, heavy drinkers, with family history of laryngeal cancer. Family history of colorectal (OR = 1.5, 95% CI 1.0-2.3) and kidney (OR = 3.8, 95% CI 1.2-12.1) cancer were also associated to an increased risk of laryngeal cancer, while no significant increase in risk was found for family history of cancer at all sites, excluding the larynx (OR = 1.1)., (Copyright © 2011 UICC.)

Quantification of the association between alcohol drinking and risk of esophageal squamous cell carcinoma (ESCC) is an open issue, particularly among light alcohol drinkers, never-smokers, and Asian populations, in which some high-risk polymorphisms in alcohol metabolizing genes are more prevalent. To address these issues, we conducted a systematic review and meta-analysis using 40 case-control and 13 cohort studies that reported on the risk associated with alcohol drinking for at least three levels of consumption. In studies adjusted for age, sex, and tobacco smoking, the relative risk (RR) and 95% confidence interval (CI) for the association between light alcohol drinking (≤ 12.5 g/d) and risk of ESCC was 1.38 (1.14-1.67). The association was slightly stronger in Asian countries than in other populations. The adjusted RRs (95% CIs) were 2.62 (2.07-3.31) for moderate drinking (>12.5-<50 g/d) and 5.54 (3.92-7.28) for high alcohol intake (≥50 g/d); the RRs were slightly higher in non-Asian populations. In prospective studies, the RR (95% CI) was 1.35 (0.92-1.98) for light, 2.15 (1.55-2.98) for moderate, and 3.35 (2.06-5.46) for high alcohol intakes; light drinking showed an association with ESCC in Asia (five studies) but not in other regions (three studies). Among never-smokers (nine studies), the RR (95% CI) was 0.74 (0.47-1.16) for light, 1.54 (1.09-2.17) for moderate, and 3.09 (1.75-5.46) for high intakes. This meta-analysis further corroborates the association of moderate and high alcohol intake with risk of ESCC and provides risk estimates based on multiple prospective studies. Light alcohol intake appears to be associated to ESCC mainly in studies in Asia, which suggests a possible role of genetic susceptibility factors., (Copyright © 2011 UICC.)

Objective: To seek evidence supporting a role for tonsillectomy or adenotonsillectomy in the management of affected children with periodic fever with aphthous stomatitis, pharnygitis, and adenitis (PFAPA) syndrome., Study Design: A comprehensive literature search was conducted to identify all published English-language observational and randomized studies evaluating the efficacy of tonsillectomy or adenotonsillectomy on PFAPA syndrome. A combination of keywords was used to identify relevant articles., Results: A total of 15 studies including 149 treated children were found, including 13 observational noncomparative studies and 2 randomized controlled trials. The pooled rate of complete resolution emerging from the combined analysis of all treated children was 83% (95% CI, 77%-89%). A meta-analysis of the two randomized controlled trials showed homogeneity of the results (P=.37, Breslow-Day test) and a common odds ratio for complete resolution of 13 (95% CI, 4-43; P<.001)., Conclusions: Surgery appears to be a possible option for management of PFAPA syndrome. Available evidence is limited, however, and the precise role of surgery remains to be clarified. We suggest considering this option when symptoms markedly interfere with the child's quality of life and medical treatment has failed., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Oral and pharyngeal cancers are strongly related to alcohol drinking. We combined findings from all case-control and cohort studies published up to September 2009 and presented analyses by subsites, using a meta-analytic approach. Summary measures were obtained using random-effects models, and taking into account the correlation between estimates from the same study. We also performed a dose-risk analysis, using a random-effects meta-regression model. Compared to non- or occasional drinkers, the overall relative risks (RR) for light drinkers were 1.17 (95% confidence interval, CI, 1.01-1.35) for oral (nine studies) and 1.23 (95% CI, 0.87-1.73) for pharyngeal (five studies) cancer, with no significant heterogeneity between the two sites (p=0.793). RRs for heavy drinkers were 4.64 (95% CI, 3.78-5.70) for oral (17 studies) and 6.62 (95% CI, 4.72-9.29) for pharyngeal (17 studies) cancer (p of heterogeneity between the two sites=0.075). The summary RRs for heavy drinkers were 4.11 (95% CI, 2.46-6.87) for tongue (five studies), 7.76 (95% CI, 4.77-12.62) for oropharyngeal (four studies), and 9.03 (95% CI, 4.46-18.27) for hypopharyngeal (four studies) cancer. In conclusion, the alcohol-related RRs are higher for pharyngeal than for oral cancer, particularly at higher doses, while the association with cancer of the tongue was similar to that for oral cancer., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Advances in clinical treatment of head and neck squamous cell carcinoma (HNSCC) are hampered by its high infiltrative potential leading to distal metastasis. Since their ability to degrade the basal lamina and extracellular matrix, matrix metalloproteinases (MMP) have a pivotal role in tumor invasion. The overexpression and the aberrant activity of MMPs especially of MMP2 and MMP9, during HNSCC development and progression have been reported. However, up to now little is known about the mechanism of their regulation in HNSCC. It has been demonstrated that MMP2/9 expression is negative regulated by extracellular signal regulated kinase 1 and 2 (ERK1/2) in HNSCC cell lines. ERKs are protein kinases belonging to the mitogen-activated protein kinases family, and they are involved in the regulation of different cellular aspects, from apoptosis to cell proliferation and differentiation. In the present study we evaluated MMP2 and MMP9 activity by gelatine zymography in 16 tissue samples of HNSCC and their paired normal mucosa from patients undergoing surgical treatment. Moreover, ERK1/2 activation was analyzed by immunoblotting. A statistically significant decrease in the levels of activated ERK2 in cancer specimens in comparison with paired normal tissues was observed, whereas a significant increase in the activity of MMP2 was found in cancer specimens. However, the statistical analysis failed to demonstrate a correlation between the increase in MMP2 activity and the reduction of ERK1/2 activation levels. The results obtained, therefore, rule out, for the first time in an ex vivo study, the existence of a negative correlation between ERK1/2 activation and MMP2 activity.

To monitor recent trends in oral and pharyngeal cancer mortality in 38 European countries, we analyzed data provided by the World Health Organization over the period 1975-2004. Joinpoint analysis was used to identify significant changes in trends. In the European Union (EU), male mortality rates rose by 2.1% per year between 1975 and 1984, by 1.0% between 1984 and 1993, and declined by 1.3% between 1993 and 2004, to reach an overall age-standardized rate of 6.1/100,000 in 2000-2004. Mortality rates were much lower in women, and the rate in the EU rose by 0.9% per year up to 2000, and levelled off to 1.1/100,000 in 2000-2004. In France and Italy-which had the highest rates in the past-male rates have steadily declined during the last two decades (annual percent change, APC = -4.8% in 1998-2004 in France and -2.6% in 1986-2003 in Italy). Persisting rises were, however, observed in several central and eastern European countries, with exceedingly high rates in Hungary (21.1/100,000; APC = 6.9% in 1975-1993 and 1.4% in 1993-2004) and Slovakia (16.9/100,000; APC = 0.14% in 1992-2004). In middle aged (35 to 64) men, oral and pharyngeal cancer mortality rates in Hungary (55.3/100,000) and Slovakia (40.8/100,000) were comparable to lung cancer rates in several major European countries. The highest rates for women were in Hungary (3.3/100,000; APC = 4.7% in 1975-2004) and Denmark (1.6/100,000; APC = 1.3% in 1975-2001). Oral and pharyngeal cancer mortality essentially reflects the different patterns in tobacco smoking and alcohol drinking, including drinking patterns and type of alcohol in central Europe.

Background: Oral squamous cell carcinoma (OSCC) represents the sixth most diffused cancer in developed countries. Mitogen-activated protein kinases (MAPKs) are proteins which transduce a vast array of extracellular signals into intracellular responses. The role of MAPK signalling pathway in cancer is not completely understood., Materials and Methods: In this study, we attempted to specifically evaluate the activation state of MAPK in OSCC. MAPK expression and activation were analyzed by immunoblotting in thirty tissue samples of OSCC and their paired nonneoplastic perilesional tissues. On the same tissues, the activation and expression of MAPK JNK/SAPK were also evaluated by ELISA assay., Results: Analyzing the levels of phospho-ERK1/2(p44/p42), a statistically significant reduction was observed in tumors compared to normal tissues. No statistically significant difference between tumor and control tissue was found for p38MAPK or JNK/SAPK., Conclusion: These results suggest that a reduction in ERK1/2(p44/p42) phosphorylation is correlated with tumor growth in OSCC.

Objectives: To evaluate the frequency of distant metastases (DM) and to determine the ability of certain clinical and pathologic factors to predict the development of distant metastases., Design: Retrospective analysis., Setting: University hospital., Patients: A total of 1972 patients with oral, oropharyngeal, hypopharyngeal, and laryngeal squamous cell carcinomas who were treated from 1981 to 1998 and who were not diagnosed as having DM at the time of initial treatment., Main Outcome Measures: We evaluated the frequency of DM and the influence of different variables in their appearance., Results: A total of 181 patients (9.2%) (95% confidence interval, 7.9%-10.5%) developed DM. Younger age (<45 years), hypopharyngeal localization, an advanced T stage and/or N stage tumor according to the TNM staging system, high histologic grade, and locoregional control were found to be significantly associated with the risk of DM at both univariate and multivariate analyses., Conclusions: The incidence of DM in subjects with head and neck squamous cell carcinoma is relatively low. The risk of DM is influenced by age, site of primary cancer, local and/or regional extension, grading, and achievement of locoregional control.

A few studies have investigated whether the risk of laryngeal cancer depends on the types of alcoholic beverage consumed, providing conflicting results. We investigated this issue using the data from two case-control studies conducted in Italy between 1986 and 2000. These included 672 cases of laryngeal cancer and 3454 hospital controls, admitted for acute, non-neoplastic conditions, unrelated to smoking and alcohol consumption. Significant trends in risk were found for total alcohol intake, with multivariate odds ratios (ORs) of 1.12 for drinkers of 3-4 drinks/day, 2.43 for 5-7, 3.65 for 8-11, and 4.83 for > 12 drinks/day, as compared to abstainers or light drinkers. Corresponding ORs for wine drinkers were 1.12, 2.45, 3.29 and 5.91. After allowance was made for wine intake, the ORs for beer drinkers were 1.65 for 1-2 drinks/day, and 1.36 for > or = 3 drinks/day, as compared to non-beer drinkers; corresponding values for spirits drinkers were 0.88 and 1.15. This study thus indicates that in the Italian population characterized by frequent wine consumption, wine is the beverage most strongly related to the risk of laryngeal cancer.

Alcohol and tobacco, alone or in combination, are associated with an increased risk of various cancers, including those of the upper aero-digestive tract and liver. Both alcohol and tobacco use can increase the risk of cancer of the oral cavity and throat (pharynx, and their combined use has a multiplicative effect on risk. Moreover, those regions of the mouth and pharynx that are more directly exposed to alcohol or tobacco are more likely to be affected by cancer than other regions. A similar effect was found with respect to cancer of the voice box (larynx). For squamous cell carcinoma of the esophagus, alcohol and tobacco also appear to increase risk synergistically. With liver cancer, in contrast, alcohol consumption and tobaacco use appear to be independent risk factors.