Werner Garavello

Trends in oesophageal cancer incidence and mortality in Europe

To monitor recent trends in mortality from oesophageal cancer in 33 European countries, we analyzed the data provided by the World Health Organization over the last 2 decades, using also joinpoint regression. For selected European cancer registration areas, we also analyzed incidence rates for different histological types. For men in the European Union (EU), age‐standardized (world population) mortality rates were stable around 6/100,000 between the early 1980s and the early 1990s, and slightly declined in the last decade (5.4/100,000 in the early 2000s, annual percent change, APC = −1.1%). In several western European countries, male rates have started to level off or decline during the last decade (APC = −3.4% in France, and −3.0% in Italy). Also in Spain and the UK, which showed upward trends in the 1990s, the rates tended to level off in most recent years. A levelling of rates was observed only more recently in countries of central and eastern Europe, which had had substantial rises up to the late 1990s. Oesophageal cancer mortality rates remained comparatively low in European women, and overall EU female rates were stable around 1.1–1.2/100,000 over the last 2 decades (APC = −0.1%). In northern Europe a clear upward trend was observed in the incidence of oesophageal adenocarcinoma, and in Denmark and Scotland incidence of adenocarcinoma in men is now higher than that of squamous‐cell carcinoma. Squamous‐cell carcinoma remained the prevalent histological type in southern Europe. Changes in smoking habits and alcohol drinking for men, and perhaps nutrition, diet and physical activity for both sexes, can partly or largely explain these trends.

Thyroid cancer mortality and incidence: A global overview

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.

Alcohol and tobacco use, and cancer risk for upper aerodigestive tract and liver

This study reviews the association between alcohol, tobacco, and the risk of cancers of the upper digestive and respiratory tract (i.e. oral cavity and pharynx, larynx, and esophagus) and liver. Alcohol drinking and tobacco smoking are the major risk factors for upper aerodigestive tract cancers, accounting for a large proportion (i.e. about three-quarters) of cases in developed countries. Consumption amount is the strongest alcohol-related determinant of risk, whereas the pattern of alcohol-related risk with duration is inconsistent. Both dose and duration of smoking have important effects on the risk of upper aerodigestive tract cancers. The combined exposure to alcohol and tobacco has a multiplicative effect on carcinogenesis of this tract. Alcohol and tobacco consumption are also causally related to liver cancer, although the associations are moderate and a lower fraction of neoplasms is attributable to these factors as compared with cancers of the upper aerodigestive tract. An interaction between alcohol drinking and tobacco smoking has been reported, but the issue is not adequately assessed.

Effectiveness of adenotonsillectomy in PFAPA syndrome: a randomized study.

OBJECTIVE To evaluate whether adenotonsillectomy leads to complete resolution in children with PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis) syndrome. STUDY DESIGN Thirty-nine children with PFAPA syndrome were randomized to either adenotonsillectomy (surgery group; n = 19) or expectant management (control group; n = 20). All patients were then invited prospectively to record all PFAPA episodes, and were evaluated clinically every 3 months for 18 months after randomization. RESULTS The proportion of patients experiencing complete resolution was 63% in the surgery group and 5% in the control group (P < .001). The mean (+/- standard deviation) number of episodes recorded during the study period was 0.7 +/- 1.2 in the surgery group and 8.1 +/- 3.9 in the control group (P < .001). The episodes were less severe in the surgery group. CONCLUSIONS Adenotonsillectomy is an effective treatment strategy for children with PFAPA syndrome.

Hypersaline nasal irrigation in children with symptomatic seasonal allergic rhinitis: a randomized study.

Recent evidence suggests that nasal irrigation with hypertonic saline may be useful as an adjunctive treatment modality in the management of many sinonasal diseases. However, no previous studies have investigated the efficacy of this regimen in the prevention of seasonal allergic rhinitis‐related symptoms in the pediatric patient. Twenty children with seasonal allergic rhinitis to Parietaria were enrolled in the study. Ten children were randomized to receive three‐times daily nasal irrigation with hypertonic saline for the entire pollen season, which had lasted 6 weeks. Ten patients were allocated to receive no nasal irrigation and were used as controls. A mean daily rhinitis score based on the presence of nasal itching, rhinorrea, nasal obstruction and sneezing was calculated for each week of the pollen season. Moreover, patients were allowed to use oral antihistamines when required and the mean number of drug assumption per week was also calculated. In patients allocated to nasal irrigation, the mean daily rhinitis score was reduced during 5 weeks of the study period. This reduction was statistically significantly different in the 3th, 4th and 5th week of therapy. Moreover, a decreased consumption of oral antihistamines was observed in these patients. This effect became evident after the second week of treatment and resulted in statistically significant differences during the 3th, 4th and 6th week. This study supports the use of nasal irrigation with hypertonic saline in the pediatric patient with seasonal allergic rhinitis during the pollen season. This treatment was tolerable, inexpensive and effective.

Dietary factors and oral and pharyngeal cancer risk.

We reviewed data from six cohort studies and approximately 40 case-control studies on the relation between selected aspects of diet and the risk of oral and pharyngeal cancer. Fruit and vegetables were inversely related to the risk: the pooled relative risk (RR) for high vegetable consumption was 0.65 from three cohort studies on upper aerodigestive tract cancers and 0.52 from 18 case-control studies of oral and pharyngeal cancer; corresponding RRs for high fruit consumption were 0.78 and 0.55. beta-carotene, vitamin C and selected flavonoids have been inversely related to the risk, but it is difficult to disentangle their potential effect from that of fruit and vegetables. Whole grain, but not refined grain, intake was also favorably related to oral cancer risk. The results were not consistent with reference to other foods beverages, and nutrients, but it is now possible to exclude a strong relation between these foods and oral and pharyngeal cancer risk. In western countries, selected aspects of diet may account for 20-25% of oral and pharyngeal cancer, and the population attributable risk increases to 85-95% when tobacco and alcohol consumption are also considered.

Alcohol drinking and esophageal squamous cell carcinoma with focus on light-drinkers and never-smokers - A systematic review and meta-analysis

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.

A meta-analysis of alcohol drinking and oral and pharyngeal cancers. Part 1: Overall results and dose-risk relation

Alcohol consumption, together with tobacco, is the best recognised risk factor for oral and pharyngeal cancers (OPC), but several important aspects of this association need to be further explored. In order to provide up to date and more precise quantification of the association between alcohol drinking and OPC risk, we conducted a meta-analysis of available data. We performed a PubMed search of articles published up to September 2009, and we identified 43 case-control and two cohort studies presenting results for at least three categories of alcohol drinking, including a total of 17,085 OPC cases. We derived meta-analytic summary estimates using random-effects models, and taking into account correlation between estimates. We also performed a dose-risk analysis using non-linear random-effects meta-regression models. The pooled relative risk (RR) was 1.21 (95% confidence interval, CI, 1.10-1.33) for <or=1 drink per day, and rose to 5.24 (95% CI, 4.36-6.30) for heavy alcohol drinking (>or=4 drinks per day). The dose-risk analysis resulted in RR of 1.29 for 10g ethanol/day, 3.24 for 50g ethanol/day, 8.61 for 100g ethanol/day, and 13.02 for 125g ethanol/day. This meta-analysis provides more precise evidence of a gross excess of OPC risk for heavy alcohol drinkers. It also indicates an increased risk for moderate doses, i.e., <or=1 drink or 10g ethanol/day.

Flavonoids and the Risk of Oral and Pharyngeal Cancer: A Case-Control Study from Italy

The intake of flavonoids has been inversely related to the risk of various common neoplasms, but scanty data exist on oral and pharyngeal cancer. We used data from a case-control study conducted in Italy between 1992 and 2005 to examine the relationship between flavonoid intake and oral and pharyngeal cancer risk. The study included 805 cases with incident, histologically confirmed oral and pharyngeal cancer, and 2,081 hospital controls admitted for acute, nonneoplastic conditions. We have applied data on food and beverage content of six major classes of flavonoids, on dietary information collected through a validated food-frequency questionnaire. The odds ratios (OR) were calculated using multiple logistic regression models, conditioned on study center, sex, and age. After adjustment for education, tobacco, alcohol, body mass index, and non–alcohol energy intake, ORs for the highest versus the lowest quintile of intake were 0.51 [95% confidence intervals (95% CI), 0.37-0.71] for flavanones, 0.62 (CI, 0.43-0.89) for flavonols, and 0.56 (95% CI, 0.40-0.78) for total flavonoids. No significant association emerged for isoflavones (OR, 0.90), anthocyanidins (OR, 0.86), flavan-3-ols (OR, 0.84), and flavones (OR, 0.75). The ORs were consistent across strata of age, sex, education, body mass index, tobacco, and alcohol. After allowance for vegetable and fruit consumption, the inverse relations with total flavonoids and flavanones remained significant, whereas that with flavonols became nonsignificant. None of the associations were significant after further allowance for vitamin C, probably on account of the high collinearity between these compounds. (Cancer Epidemiol Biomarkers Prev 2007;16(8):1621–5)

Flavonoids and risk of squamous cell esophageal cancer

The relation between 5 classes of flavonoids (flavanones, flavan‐3‐ols, flavonols, flavones and anthocyanidines) and esophageal cancer was investigated using data from a case‐control study conducted between 1992 and 1997 in 3 areas of northern Italy. The study included 304 cases (275 men, 29 women) with a first diagnosis of squamous‐cell carcinoma of the esophagus and 743 controls (593 men, 150 women) with no history of cancer, admitted for acute illnesses, unrelated to tobacco and alcohol consumption, to major hospitals of the areas under surveillance. Dietary habits were investigated using a validated food frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals (CI) were computed after allowance for age, sex, study centre, years of education, alcohol drinking, tobacco smoking, body mass index and energy intake. An inverse association emerged between flavanone intake and esophageal cancer risk (OR = 0.38 for the highest vs. the lowest quintile, 95% CI = 0.23–0.66). The inverse relation between flavanones and esophageal cancer tended to be stronger in those who drank ≥6 drinks/day. In conclusion, this study suggests that flavanone intake is inversely associated with esophageal cancer risk and may account, with vitamin C, for the protective effect of fruit, especially citrus fruit, on esophageal cancer.