Enhanced recovery protocol in esophagectomy, is it really worth it? A cost analysis related to team experience and protocol compliance.

Application of enhanced recovery protocols (ERP) in esophageal surgery seems to lead an advantage in terms of length of hospital staying and outcomes, but only few data exist on its cost effectiveness. Previous literature analyzed pre- and post-ERP groups, finding a cost reduction with the introduction of the pathway. We aimed to study the influence on costs of accumulating experience and compliance in an ERP group. Seventy-one patients have been treated at our institution from January 2014 to June 2017 with our ERP for Ivor-Lewis esophagectomy. Direct costs were divided into subcategories and were analyzed as a function of calendar year and compliance. Factor affecting costs were searched. Univariable analysis highlighted a significant reduction in costs over time. Increase in compliance led to a progressive cost reduction for each ERP item completed (€14 852-€11 045). While age was not found to significantly influence the cost (p = 0.341), complications seemed to nullify the effect of experience: the median was €11 507 in uncomplicated patients, and increased to €13 791 in Clavien-Dindo 3-4 (CD3-4) patients. Compliance and CD3-4 remained significant also in multivariable analysis, accomplished by quantile regression, while year of surgery lost its significance. Our results evidence how accumulating experience in ERP led to a cost reduction over time, which was mainly mediated by an increase in compliance. Indeed, compliance was the main factor in reducing ERP cost while CD3-4 complications were the most important factor in cost increasing, nullifying the benefit of compliance.

Validation of two prognostic models for recurrence and survival after radical gastrectomy for gastric cancer.

BACKGROUND: Prognostic models from Korea and Italy have been developed that predict overall survival and cancer recurrence respectively after radical gastrectomy for gastric cancer. The aim of this study was to validate the two models in independent patient cohorts, and to evaluate which factors may explain differences in prognosis between Korean and Italian patients with gastric cancer. METHODS: Patients who underwent radical gastrectomy for gastric cancer between January 2000 and December 2004 at Seoul National University Hospital and at eight centres in Italy were included. Discrimination of the models was tested with receiver operating characteristic (ROC) curves and calculation of area under the curve (AUC). Calibration was evaluated by plotting actual survival probability against predicted survival probability for the Korean nomogram, and actual against predicted risk of recurrence for the Italian score. RESULTS: Some 2867 and 940 patients from Korea and Italy respectively were included. The Korean nomogram achieved good discrimination in the Italian cohort (AUC 0·80, 95 per cent c.i. 0·77 to 0·83), and the Italian model performed well in the Korean cohort (AUC 0·87, 0·85 to 0·89). The Korean nomogram also achieved good calibration, but this was not seen for the Italian model. Multivariable analyses confirmed that Italian ethnicity was an independent risk factor for cancer recurrence (odds ratio (OR) 1·72, 1·31 to 2·25; P < 0·001), but not for overall survival (OR 1·20, 0·95 to 1·53; P = 0·130). CONCLUSION: Both prognostic models performed fairly well in independent patient cohorts. Differences in recurrence rates of gastric cancer may be partially explained by ethnicity.

Building dampness and mold in European homes in relation to climate, building characteristics and socio-economic status: The European Community Respiratory Health Survey ECRHS II.

We studied dampness and mold in homes in relation to climate, building characteristics and socio-economic status (SES) across Europe, for 7127 homes in 22 centers. A subsample of 3118 homes was inspected. Multilevel analysis was applied, including age, gender, center, SES, climate, and building factors. Self-reported water damage (10%), damp spots (21%), and mold (16%) in past year were similar as observed data (19% dampness and 14% mold). Ambient temperature was associated with self-reported water damage (OR=1.63 per 10°C; 95% CI 1.02-2.63), damp spots (OR=2.95; 95% CI 1.98-4.39), and mold (OR=2.28; 95% CI 1.04-4.67). Precipitation was associated with water damage (OR=1.12 per 100 mm; 95% CI 1.02-1.23) and damp spots (OR=1.11; 95% CI 1.02-1.20). Ambient relative air humidity was not associated with indoor dampness and mold. Older buildings had more dampness and mold (P<.001). Manual workers reported less water damage (OR=0.69; 95% CI 0.53-0.89) but more mold (OR=1.27; 95% CI 1.03-1.55) as compared to managerial/professional workers. There were correlations between reported and observed data at center level (Spearman rho 0.61 for dampness and 0.73 for mold). In conclusion, high ambient temperature and precipitation and high building age can be risk factors for dampness and mold in homes in Europe.

Type 2 diabetes is associated with an increased prevalence of respiratory symptoms as compared to the general population.

BACKGROUND: To estimate the prevalence of respiratory symptoms in individuals with type 2 diabetes, as compared to the general population. METHODS: Between 2007 and 2010 the screening questionnaire of GEIRD (Gene Environment Interactions in Respiratory Diseases) study was administered to two samples of Verona general population, aged respectively 45-64 years and 65-84 years, and to a convenience sample of individuals with type 2 diabetes, consequently recruited at the local Diabetes Centre. Ninety-four and 165 people with type 2 diabetes, aged respectively 45-64 and 65-84 years, were compared with 676 and 591 subjects in the same age range from the general population. The influence of type 2 diabetes on respiratory symptoms was evaluated by logistic regression models, controlling for sex, age (45-54, 55-64, 65-74, 75-84 years), education level, smoking habits and heavy vehicle traffic exposure and adjusting standard errors of ORs for intra-sample correlation. RESULTS: Compared to the general population, dyspnoea limiting walking pace on level ground (grade 2 dyspnoea) was more frequently reported by people with type 2 diabetes, irrespective of age (p < 0.001), while self-reported chronic cough/phlegm was more common in those aged 45-64 years (p = 0.02). These results were confirmed by multivariable analysis: compared to their counterparts from the general population, people with type 2 diabetes aged 45-54 years showed an increased risk of reporting grade 2 dyspnoea (OR = 3.92, 95% CI 3.28-4.68) or chronic cough/phlegm (OR = 1.69, 1.60-1.78). Similar figures held significant at older ages (75-84 years), although partially blunted (dyspnoea: OR = 1.79, 1.68-1.91; chough/phlegm: OR = 1.09, 1.03-1.16). As such, the interaction between age class and type 2 diabetes was significant for both respiratory disorders. The proportion of self-reported dyspnoea among individuals with type 2 diabetes significantly increased across incremental body-mass index (BMI), from 15.4 to 25.4% and further to 41.3% respectively in normoweight, overweight and obese patients (p = 0.048). CONCLUSIONS: People with type 2 diabetes more frequently reported grade 2 dyspnoea and chronic cough/phlegm than the general population of the same age, although presenting similar smoking habits. Diabetes appears to anticipate the lung ageing process, recorded in the general population. The increased occurrence of dyspnoea at incremental BMI among individuals with type 2 diabetes may reflect both cardiovascular and respiratory impairment in this high-risk patient population.

The risk of respiratory symptoms on allergen exposure increases with increasing specific IgE levels.

BACKGROUND: The relation between IgE sensitization and allergic respiratory symptoms has usually been evaluated by dichotomizing specific IgE levels. The aim of this study was to evaluate the association between specific IgE levels and risk of symptoms on allergen-related exposure, with special reference to allergen-related asthma-rhinitis comorbidity. METHODS: We considered 6391 subjects enrolled within the European Community Respiratory Health Survey 2, having information on cat/grass/D. pteronyssinus IgE levels and symptoms on exposure to animals/pollen/dust. The risk of oculonasal/asthmalike/both symptoms was evaluated by a multinomial logistic model. RESULTS: A clear positive association was observed between specific IgE levels to cat/grass/mite and the risk of symptoms on each allergen-related exposure (test for trend with P < 0.001). This trend was particularly pronounced when considering the coexistence of asthmalike and oculonasal symptoms. Compared to non-sensitized subjects, subjects with specific IgE to cat >= 3.5 kU/l presented relative risk ratios of 11.4 (95% CI 6.7-19.2), 18.8 (8.2-42.8), and 55.3 (30.5-100.2) when considering, respectively, only oculonasal symptoms, only asthmalike symptoms, or both. A similar pattern was observed when considering specific IgE to grass/mite and symptoms on exposure to pollen/dust. Also the proportion of people using inhaled medicines or visiting a general practitioner for breathing problems in the previous year increased with increasing sum of specific IgE to cat/grass/mite. CONCLUSION: Specific IgE level is the most important predictor of allergen-related symptoms. The risk of both oculonasal/asthmalike symptoms increases with specific IgE levels, suggesting that specific IgE contributes to the 'united airways disease'.

TAK1-regulated expression of BIRC3 predicts resistance to preoperative chemoradiotherapy in oesophageal adenocarcinoma patients.

BACKGROUND: About 20% of resectable oesophageal carcinoma is resistant to preoperative chemoradiotherapy. Here we hypothesised that the expression of the antiapoptotic gene Baculoviral inhibitor of apoptosis repeat containing (BIRC)3 induced by the transforming growth factor ß activated kinase 1 (TAK1) might be responsible for the resistance to the proapoptotic effect of chemoradiotherapy in oesophageal carcinoma. METHODS: TAK1 kinase activity was inhibited in FLO-1 and KYAE-1 oesophageal adenocarcinoma cells using (5Z)-7-oxozeaenol. The BIRC3 mRNA expression was measured by qRT-PCR in 65 pretreatment frozen biopsies from patients receiving preoperatively docetaxel, cisplatin, 5-fluorouracil, and concurrent radiotherapy. Receiver operator characteristic (ROC) analyses were performed to determine the performance of BIRC3 expression levels in distinguishing patients with sensitive or resistant carcinoma. RESULTS: In vitro, (5Z)-7-oxozeaenol significantly reduced BIRC3 expression in FLO-1 and KYAE-1 cells. Exposure to chemotherapeutic agents or radiotherapy plus (5Z)-7-oxozeaenol resulted in a strong synergistic antiapoptotic effect. In patients, median expression of BIRC3 was significantly (P<0.0001) higher in adenocarcinoma than in the more sensitive squamous cell carcinoma subtype. The BIRC3 expression significantly discriminated patients with sensitive or resistant adenocarcinoma (AUC-ROC=0.7773 and 0.8074 by size-based pathological response or Mandard's tumour regression grade classifications, respectively). CONCLUSIONS: The BIRC3 expression might be a valid biomarker for predicting patients with oesophageal adenocarcinoma that could most likely benefit from preoperative chemoradiotherapy.

House dust-mite allergen exposure is associated with serum specific IgE but not with respiratory outcomes.

Exposure to house dust has been associated with asthma in adults, and this is commonly interpreted as a direct immunologic response to dust-mite allergens in those who are IgE sensitized to house dust-mite. Mattress house dust-mite concentrations were measured in a population-based sample of 2890 adults aged between 27 and 56 years living in 22 centers in 10 countries. Generalized linear mixed models were employed to explore the association of respiratory symptoms with house dust-mite concentrations, adjusting for individual and household confounders. There was no overall association of respiratory outcomes with measured house dust-mite concentrations, even in those who reported they had symptoms on exposure to dust and those who had physician-diagnosed asthma. However, there was a positive association of high serum specific IgE levels to HDM (>3.5 kUA /l) with mattress house dust-mite concentrations and a negative association of sensitization to cat with increasing house dust-mite concentrations. In conclusion, there was no evidence that respiratory symptoms in adults were associated with exposure to house dust-mite allergen in the mattress, but an association of house mite with strong sensitization was observed.

Adult eczema in Italy: prevalence and associations with environmental factors.

BACKGROUND: Studies on the prevalence of eczema and atopic dermatitis (AD), and on the factors associated with these diseases, have been mostly performed in children, whereas studies on adult populations are lacking. OBJECTIVES: To determine the prevalence of eczema and AD in the Italian adult population, and to investigate risk factors associated with the disease. METHODS: A postal screening questionnaire was administered to 18 357 randomly selected subjects aged 20-44 years in the Gene-Environment Interaction in Respiratory Diseases study, which involved seven centres distributed across northern, central and southern Italy. The questionnaire included items on the occurrence of doctor-diagnosed eczema, asthma and hay fever, socio-demographic characteristics and environmental exposures. RESULTS: In all, 10 464 (57.0%) subjects responded to the questionnaire. The prevalence of current eczema was 8.1% (95% CI: 7.6-8.7%), while the prevalence of eczema with asthma and/or hay fever (EAH), which was adopted as proxy of AD, was 3.4% (95% CI: 3.1-3.8%). About 60% of the subjects with current eczema reported the onset of the disease in adulthood. In multi-variable models, the prevalence of eczema was significantly associated with female sex, older age, living close to industrial plants, high levels of heavy traffic near home and living in central-southern Italy. CONCLUSIONS: Eczema and EAH are highly prevalent in Italian young adults, especially in women. Our results suggest that adult onset is not unusual, and that environmental factors may influence the occurrence of eczema and EAH.

Neoadjuvant concurrent chemoradiotherapy for locally advanced esophageal cancer in a single high-volume center.

BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) is now considered the standard of care by many centers in the treatment of both squamous cell carcinoma (SCC) and adenocarcinoma of the esophagus. This study evaluates the effectiveness of a neoadjuvant CRT protocol, as regards pathological complete response (pCR) rate and long-term survival. METHODS: From 2003 to 2011, at Upper G.I. Surgery Division of Verona University, 155 consecutive patients with locally advanced esophageal cancers (90 SCC, 65 adenocarcinoma) were treated with a single protocol of neoadjuvant CRT (docetaxel, cisplatin, and 5-fluorouracil with 50.4 Gy of concurrent radiotherapy). Response to CRT was evaluated through percentage of pathological complete response (pCR or ypT0N0), overall (OS) and disease-related survival (DRS), and pattern of relapse. RESULTS: One hundred thirty-one patients (84.5 %) underwent surgery. Radical resection (R0) was achieved in 123 patients (79.3 %), and pCR in 65 (41.9 %). Postoperative mortality was 0.7 % (one case). Five-year OS and DRS were respectively 43 and 49 % in the entire cohort, 52 and 59 % in R0 cases, and 72 and 81 % in pCR cases. Survival did not significantly differ between SCC and adenocarcinoma, except for pCR cases. Forty-nine patients suffered from relapse, which was mainly systemic in adenocarcinoma. Only three out of 26 pCR patients with previous adenocarcinoma developed relapse, always systemic. CONCLUSIONS: This study suggests that patients treated with the present protocol achieve good survival and high pCR rate. Further research is necessary to evaluate whether surgery on demand is feasible in selected patients, such as pCR patients with adenocarcinoma.

Systematic review of central pancreatectomy and meta-analysis of central versus distal pancreatectomy.

BACKGROUND: Central pancreatectomy (CP) is a parenchyma-sparing surgical procedure that enables the removal of benign and/or low-grade malignant lesions from the neck and proximal body of the pancreas. The aim of this review was to evaluate the short- and long-term surgical results of CP from all published studies, and the results of comparative studies of CP versus distal pancreatectomy (DP). METHODS: Eligible studies published between 1988 and 2010 were reviewed systematically. Comparisons between CP and DP were pooled and analysed by meta-analytical techniques using random- or fixed-effects models, as appropriate. RESULTS: Ninety-four studies, involving 963 patients undergoing CP, were identified. Postoperative morbidity and pancreatic fistula rates were 45·3 and 40·9 per cent respectively. Endocrine and exocrine pancreatic insufficiency was reported in 5·0 and 9·9 per cent of patients. The overall mortality rate was 0·8 per cent. Compared with DP, CP had a higher postoperative morbidity rate and a higher incidence of pancreatic fistula, but a lower risk of endocrine insufficiency (relative risk (RR) 0·22, 95 per cent confidence interval 0·14 to 0·35; P < 0·001). The risk of exocrine failure was also lower after CP, although this was not significant (RR 0·59, 0·32 to 1·07; P = 0·082). CONCLUSION: CP is a safe procedure with good long-term functional reserve. In situations where DP represents an alternative, CP is associated with a slightly higher risk of early complications.

Asthma incidence can be influenced by climate change in Italy: findings from the GEIRD study-a climatological and epidemiological assessment.

An association between climatic conditions and asthma incidence has been widely assumed. However, it is unclear whether climatic variations have a fingerprint on asthma dynamics over long time intervals. The aim of this study is to detect a possible correlation of the Summer North Atlantic Oscillation (S-NAO) index and the self-calibrated palmer drought severity index (scPDSI) with asthma incidence over the period from 1957 to 2006 in Italy. To this aim, an analysis of non-stationary and non-linear signals was performed on the time series of the Italian databases on respiratory health (ISAYA and GEIRD) including 36,255 individuals overall, S-NAO, and scPDSI indices to search for characteristic periodicities. The ISAYA (Italian Study on Asthma in Young Adults) and GEIRD (Gene Environment Interactions in Respiratory Diseases) studies collected information on respiratory health in general population samples, born between 1925 and 1989 and aged 20-84 years at the time of the interview, from 13 Italian centres. We found that annual asthma total incidence shared the same periodicity throughout the 1957-2006 time interval. Asthma incidence turned out to be correlated with the dynamics of the scPDSI, modulated by the S-NAO, sharing the same averaged 6 year-periodicity. Since climate patterns appear to influence asthma incidence, future studies aimed at elucidating the complex relationships between climate and asthma incidence are warranted.

Respiratory health and endotoxin: associations and modification by CD14/-260 genotype.

Exposure to endotoxin has been associated with increased respiratory symptoms and decrements in lung function in occupational settings but little is known about the health effects of domestic exposure in adults. Here, we describe the association of respiratory disease, immunoglobulin (Ig)E sensitisation, bronchial reactivity and lung function with mattress endotoxin levels in adults, and determine whether these associations are modified by polymorphisms in CD14. Endotoxin levels in mattress dust from a population-based sample of 972 adults were measured. Associations were examined using generalised linear mixed models, adjusting for individual and household confounders. Effect modification of these associations by CD14/-260 (rs2569190) was assessed. Mattress endotoxin levels varied from 0.1 to 402.6 EU · mg(-1). Although there was no overall association of lung function with endotoxin exposure, there was evidence that the association of forced expiratory volume in 1 s and forced vital capacity with endotoxin was modified by CD14/-260 genotype (p-value for interaction 0.005 and 0.013, respectively). There was no evidence that symptoms, IgE sensitisation or bronchial reactivity were associated with mattress endotoxin levels. In this large epidemiological study of adults, there was no evidence that mattress endotoxin level was associated with respiratory symptoms or IgE sensitisation but the association of lung function with endotoxin levels may be modified by CD14 genotype.

Trends in the prevalence of asthma and allergic rhinitis in Italy between 1991 and 2010.

The prevalence of asthma increased worldwide until the 1990s, but since then there has been no clear temporal pattern. The present study aimed to assess time trends in the prevalence of current asthma, asthma-like symptoms and allergic rhinitis in Italian adults from 1990 to 2010. The same screening questionnaire was administered by mail or phone to random samples of the general population (age 20-44 yrs) in Italy, in the frame of three multicentre studies: the European Community Respiratory Health Survey (ECRHS) (1991-1993; n = 6,031); the Italian Study on Asthma in Young Adults (ISAYA) (1998-2000; n = 18,873); and the Gene Environment Interactions in Respiratory Diseases (GEIRD) study (2007-2010; n = 10,494). Time trends in prevalence were estimated using Poisson regression models in the centres that repeated the survey at different points in time. From 1991 to 2010, the median prevalence of current asthma, wheezing and allergic rhinitis increased from 4.1% to 6.6%, from 10.1% to 13.9% and from 16.8% to 25.8%, respectively. The prevalence of current asthma was stable during the 1990s and increased (relative risk 1.38, 95% CI 1.19-1.59) from 1998-2000 to 2007-2010, mainly in subjects who did not report allergic rhinitis. The prevalence of allergic rhinitis has increased continuously since 1991. The asthma epidemic is not over in Italy. During the past 20 yrs, asthma prevalence has increased by 38%, in parallel with a similar increase in asthma-like symptoms and allergic rhinitis.

Herbal supplements in pregnancy: unexpected results from a multicentre study.

STUDY QUESTION: How common is the use of herbal supplements during pregnancy and does it adversely affect the pregnancy outcome? SUMMARY ANSWER: The use of herbal products during pregnancy is very common and daily almond oil spreading is associated with preterm birth (PTB). WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Herbal drugs are often promoted as 'natural' and 'safe' and such claims attract pregnant women. More than a quarter of Italian pregnant women consume herbs every day for at least 3 months during pregnancy. We raise an alert over the habit of daily almond oil spreading since it seems to be associated with PTB. DESIGN: A multicenter retrospective cohort study performed over a 15-month period. PARTICIPANTS AND SETTING: Seven hundred women interviewed within 3 days of childbirth, in three public hospitals in northern Italy. MAIN RESULTS AND ROLE OF CHANCE: One hundred and eighty-nine women were considered 'regular users', since they consumed herbs every day, for at least 3 months. Almond oil, chamomile and fennel were the most commonly used herbs. Both length of gestation and birthweight were affected by herb consumption. Almond oil users showed more pre-term birth (29 of 189) than non-users (51 of 511). After adjusting for multiple pregnancies, smoking, advanced age and drug intake, almond oil users maintained an increased risk to give birth <37th week (odds ratio = 2.09, 95% confidence interval: 1.08-4.08). BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION: The association between daily spreading of almond oil and PTB only raises a hypothesis that requires confirmation in larger trials devoted to this topic. The relatively small sample size did not allow the investigation of other adverse pregnancy outcomes in herb users. GENERALIZABILITY TO OTHER POPULATIONS: The population under investigation did not significantly differ from the general population attending the same hospitals. STUDY FUNDING/COMPETING INTEREST(S): No conflict of interest exists. The study has been supported by a public grant from the University of Modena and Reggio Emilia. TRIAL REGISTRATION NUMBER: None.

Geographical variation and the determinants of domestic endotoxin levels in mattress dust in Europe.

UNLABELLED: Endotoxin exposures have manifold effects on human health. The geographical variation and determinants of domestic endotoxin levels in Europe have not yet been extensively described. To investigate the geographical variation and determinants of domestic endotoxin concentrations in mattress dust in Europe using data collected in the European Community Respiratory Health Survey follow-up (ECRHS II). Endotoxin levels were measured in mattress dust from 974 ECRHS II participants from 22 study centers using an immunoassay. Information on demographic, lifestyle, and housing characteristics of the participants was obtained in face-to-face interviews. The median endotoxin concentration in mattress dust ranged from 772 endotoxin units per gram (EU/g) dust in Reykjavik, Iceland, to 4806 EU/g in Turin, Italy. High average outdoor summer temperature of study center, cat or dog keeping, a high household crowding index, and visible damp patches in the bedroom were significantly associated with a higher endotoxin concentrations in mattress dust. There is a large variability in domestic endotoxin levels across Europe. Average outdoor summer temperature of study center, which explains only 10% of the variation in domestic endotoxin level by center, is the strongest meteorological determinant. The observed variation needs to be taken into account when evaluating the health effects of endotoxin exposures in international contexts. PRACTICAL IMPLICATIONS: The incoherent observations of the health effects of endotoxin may be partly owing to the geographical heterogeneity of endotoxin exposure. Therefore, the observed variation should be considered in further studies. Measurements of indoor endotoxin are recommended as an indicator for the level of exposures of individual domestic environments.

Lymphadenectomy for gastric cancer at European specialist centres.

BACKGROUND AND AIMS: The aim of this project was to evaluate the current practice of D2 in Europe. MATERIALS AND METHODS: In the first part of the study, 18 European high volume gastric cancer centres completed a questionnaire, designed to evaluate their preferred lymphadenectomy in a series of clinical scenarios. Surgeon compliance with international guidelines for lymphadenectomy was evaluated. In the second part, information on 381 gastrectomies performed for primary gastric cancer by participating surgeons from January to December 2015, was retrospectively collected. RESULTS: Surgical choice in clinical scenarios was affected by tumour stage and to a lesser extent, site and histotype. In particular, in early gastric cancer with diffuse histology D2 was recommended by >70% of surgeons, while this percentage dropped to 44% in intestinal histotypes. When surgeons selected a D2 dissection, the procedure was rarely fully compliant with the Japanese guidelines. In the review of gastrectomy experience an adequate number of nodes (≥15 nodes) was retrieved in 97% after D2. The number of retrieved nodes varied with median values ranging from 17 to 35 (p < 0.001) after D2. D2/D2+ was more frequently performed in mixed (80%) and diffuse (78%) cases than in intestinal cases (69%) (p = 0.016). CONCLUSIONS: Although an adequate lymphadenectomy was achieved in almost all cases in dedicated centres, there is still variation in the number of retrieved nodes. Tumor histology largely affects surgeon's choice as regards the extent of lymphadenectomy; however, the role of histology in planning surgical procedures needs to be verified in prospective trials.

Utility of Abdominal Drain in Gastrectomy (ADiGe) Trial: study protocol for a multicenter non-inferiority randomized trial.

BACKGROUND: Prophylactic use of abdominal drain in gastrectomy has been questioned in the last 15 years, and a 2015 Cochrane meta-analysis on four RCTs concluded that there was no convincing evidence to the routine drain placement in gastrectomy. Nevertheless, the authors evidenced the moderate/low quality of the included studies and highlighted how 3 out of 4 came from Eastern countries. After 2015, only retrospective studies have been published, all with inconsistent results. METHODS: ADiGe (Abdominal Drain in Gastrectomy) Trial is a multicenter prospective randomized non-inferiority trial with a parallel design. It aimed to verify whether avoiding routine use of abdominal drain is burdened with complications, particularly an increase in postoperative invasive procedures. Patients with gastric cancer, scheduled for subtotal or total gastrectomy with curative intent, are eligible for inclusion, irrespective of previous oncological treatment. The primary composite endpoint is reoperation or percutaneous drainage procedures within 30 postoperative days. The primary analysis will verify whether the incidence of the primary composite endpoint is higher in the experimental arm, avoiding routine drain placement, than control arm, undergoing prophylactic drain placement, in order to falsify or support the null hypothesis of inferiority. Secondary endpoints assessed for superiority are overall morbidity and mortality, Comprehensive Complications Index, incidence and time for diagnosis of anastomotic and duodenal leaks, length of hospital stay, and readmission rate. Assuming one-sided alpha of 5%, and cumulative incidence of the primary composite endpoint of 6.4% in the control arm and 4.2% in the experimental one, 364 patients allow to achieve 80% power to detect a non-inferiority margin difference between the arm proportions of 3.6%. Considering a 10% drop-out rate, 404 patients are needed. In order to have a balanced percentage between total and subtotal gastrectomy, recruitment will end at 202 patients for each type of gastrectomy. The surgeon and the patient are blinded until the end of the operation, while postoperative course is not blinded to the patient and caregivers. DISCUSSION: ADiGe Trial could contribute to critically re-evaluate the role of prophylactic drain in gastrectomy, a still widely used procedure. TRIAL REGISTRATION: Prospectively registered (last updated on 29 October 2020) at ClinicalTrials.gov with the identifier NCT04227951 .

Response to induction therapy in oesophageal and cardia carcinoma using Mandard tumour regression grade or size of residual foci.

BACKGROUND: Tumour regression grade (TRG) is used to evaluate responses to induction therapy in cancer of the oesophagus or cardia. This study aimed to determine whether inclusion of node category could improve the prognostic accuracy provided by TRG, and explore the prognostic value of an alternative classification based on size of residual foci and node category. METHODS: Patients with oesophageal or cardia cancer treated with neoadjuvant chemoradiotherapy followed by resection were studied. Treatment-induced response at the primary site was evaluated by TRG and by a method whereby patients were classified as having no residual cancer, minimal residual disease (MRD) or as non-responders. RESULTS: Between 2000 and 2007, 108 patients underwent resection. Disease-related survival decreased with increasing TRG in node-negative (N0) patients (P < 0.001), whereas in node-positive (N+) patients it was poor irrespective of TRG (P = 0.241). For N0 disease, 3-year survival in patients with MRD (58 (95 per cent confidence interval 26 to 80) per cent) was intermediate between that in patients with no residual cancer (85 (70 to 93) per cent) and non-responders (28 (4 to 59) per cent). Worst prognosis was for N+ disease (21 (9 to 36) per cent). CONCLUSION: Node category should be considered when evaluating response to induction therapy in oesophageal or cardia cancer. A new classification based on size of residual foci and node category seems promising.

The Gene-Environment Interactions in Respiratory Diseases (GEIRD) Project.

The role of genetic and environmental factors, as well as their interaction, in the natural history of asthma, allergic rhinitis and chronic obstructive pulmonary disease (COPD) is largely unknown. This is mainly due to the lack of large-scale analytical epidemiological/genetic studies aimed at investigating these 3 respiratory conditions simultaneously. The GEIRD project is a collaborative initiative designed to collect information on biomarkers of inflammation and oxidative stress, individual and ecological exposures, diet, early-life factors, smoking habits, genetic traits and medication use in large and accurately defined series of asthma, allergic rhinitis and COPD phenotypes. It is a population-based multicase-control design, where cases and controls are identified through a 2-stage screening process (postal questionnaire and clinical examination) in pre-existing cohorts or new samples of subjects. It is aimed at elucidating the role that modifiable and genetic factors play in the occurrence, persistence, severity and control of inflammatory airway diseases, by way of the establishment of a historical multicentre standardized databank of phenotypes, contributed by and openly available to international epidemiologists. Researchers conducting population-based surveys with standardized methods may contribute to the public-domain case-control database, and use the resulting increased power to answer their own scientific questions.