Sunny holidays before and after melanoma diagnosis are respectively associated with lower breslow thickness and lower relapse rates in Italy

Background: Previous studies have reported an association between sun exposure and improved cutaneous melanoma (CM) survival. We analysed the association of UV exposure with prognostic factors and outcome in a large melanoma cohort. Methods: A questionnaire was given to 289 (42%) CM patients at diagnosis (Group 1) and to 402 CM patients (58%) during follow-up (Group 2). Analyses were carried out to investigate the associations between sun exposure and melanoma prognostic factors and survival. Results: Holidays in the sun two years before CM diagnosis were significantly associated with lower Breslow thickness (p=0.003), after multiple adjustment. Number of weeks of sunny holidays was also significantly and inversely associated with thickness in a dose-dependent manner (p=0.007). However when stratifying by gender this association was found only among women (p=0.0004) the risk of CM recurrence in both sexes was significantly lower in patients (n=271) who had holidays in the sun after diagnosis, after multiple adjustment including education: HR=0.30 (95%CI:0.10-0.87; p=0.03) conclusions: Holidays in the sun were associated with thinner melanomas in women and reduced rates of relapse in both sexes. However, these results do not prove a direct causal effect of sun exposure on survival since other confounding factors, such as vitamin D serum levels and socio-economic status, may play a role. Other factors in sun seeking individuals may also possibly affect these results

Melanocortin-1 Receptor, Skin Cancer and Phenotypic Characteristics (M-SKIP) Project: Study Design and Methods for Pooling Results of Genetic Epidemiological Studies

Background: For complex diseases like cancer, pooled-analysis of individual data represents a powerful tool to investigate the joint contribution of genetic, phenotypic and environmental factors to the development of a disease. Pooled-analysis of epidemiological studies has many advantages over meta-analysis, and preliminary results may be obtained faster and with lower costs than with prospective consortia. Design and methods: Based on our experience with the study design of the Melanocortin-1 receptor (MC1R) gene, SKin cancer and Phenotypic characteristics (M-SKIP) project, we describe the most important steps in planning and conducting a pooled-analysis of genetic epidemiological studies. We then present the statistical analysis plan that we are going to apply, giving particular attention to methods of analysis recently proposed to account for between-study heterogeneity and to explore the joint contribution of genetic, phenotypic and environmental factors in the development of a disease. Within the M-SKIP project, data on 10,959 skin cancer cases and 14,785 controls from 31 international investigators were checked for quality and recoded for standardization. We first proposed to fit the aggregated data with random-effects logistic regression models. However, for the M-SKIP project, a two-stage analysis will be preferred to overcome the problem regarding the availability of different study covariates. The joint contribution of MC1R variants and phenotypic characteristics to skin cancer development will be studied via logic regression modeling. Discussion: Methodological guidelines to correctly design and conduct pooled-analyses are needed to facilitate application of such methods, thus providing a better summary of the actual findings on specific fields

Melanocortin-1 receptor, skin cancer and phenotypic characteristics (M-SKIP) project

Background: For complex diseases like cancer, pooled-analysis of individual data represents a powerful tool to investigate the joint contribution of genetic, phenotypic and environmental factors to the development of a disease. Pooled-analysis of epidemiological studies has many advantages over meta-analysis, and preliminary results may be obtained faster and with lower costs than with prospective consortia. Design and methods. Based on our experience with the study design of the Melanocortin-1 receptor (MC1R) gene, SKin cancer and Phenotypic characteristics (M-SKIP) project, we describe the most important steps in planning and conducting a pooled-analysis of genetic epidemiological studies. We then present the statistical analysis plan that we are going to apply, giving particular attention to methods of analysis recently proposed to account for between-study heterogeneity and to explore the joint contribution of genetic, phenotypic and environmental factors in the development of a disease. Within the M-SKIP project, data on 10,959 skin cancer cases and 14,785 controls from 31 international investigators were checked for quality and recoded for standardization. We first proposed to fit the aggregated data with random-effects logistic regression models. However, for the M-SKIP project, a two-stage analysis will be preferred to overcome the problem regarding the availability of different study covariates. The joint contribution of MC1R variants and phenotypic characteristics to skin cancer dev

End-to-side circular stapled versus side-to-side linear stapled intrathoracic esophagogastric anastomosis following minimally invasive Ivor–Lewis esophagectomy: comparison of short-term outcomes

Purpose: The search for the optimal procedure for creation of a safe gastroesophageal intrathoracic anastomosis with a lower risk of leakage in totally minimally invasive Ivor–Lewis esophagectomy (TMIIL) is ongoing. In the present study, we compared the outcomes of end-to-side (with circular stapler [CS]) and side-to-side (with linear stapler [LS]) techniques for intrathoracic anastomosis during TMIIL performed in 2 European high-volume centers for upper gastrointestinal surgery. A propensity score method was used to compare the CS and LS groups. Methods: We retrospectively evaluated patients with lower esophageal cancer or Siewert type 1 or 2 esophagogastric junction carcinoma who underwent a planned TMIIL esophagectomy, performed from January 2017 to September 2020. The anastomosis was created by a semi-mechanical technique using a LS in one center and by a mechanical technique using a CS in the other center. General features, operative techniques, pathology data, and short-term outcomes were analyzed. Statistical evaluations were performed on the whole cohort, stratifying the analyses by risk strata factors identified with the propensity scores, and on a subgroup of patients matched by propensity score. The primary endpoint of the study was the rate of anastomotic leakage in the two groups. Secondary endpoints included rates of anastomotic stricture and overall postoperative complications. Results: Considering the whole population, 256 patients were included; of those, 220 received the anastomosis with a circular stapler (CS group), and 36 received the anastomosis with a linear stapler (LS group). No significant differences by group in terms of sex, age, American Society of Anesthesiologists physical status classification, and type of neoplasm were showed. The rate of anastomotic leakage did not differ in the two groups (9.6% CS vs. 5.6% LS, p = 0.438), as well as the rate of anastomotic stricture in the 3-month follow-up (0.9% CS vs. 2.8% LS, p = 0.367). The rate of chyle leakage and of pulmonary, cardiac, and infective complications was not significantly different in the groups. After propensity score matching, 72 patients were included in the analysis. The 2 obtained propensity score matched groups did not differ for any of the clinical and pathologic variables considered for the analysis, resulting in well-balanced cohorts. The results obtained on the whole population were confirmed in the matched groups. Conclusions: The results of our study suggest that both techniques for esophagogastric anastomosis during TMIIL are feasible, safe, and effective, with comparable rates of postoperative anastomotic leakage and stricture

End-to-side circular stapled versus side-to-side linear stapled intrathoracic esophagogastric anastomosis following minimally invasive Ivor–Lewis esophagectomy: comparison of short-term outcomes

Purpose: The search for the optimal procedure for creation of a safe gastroesophageal intrathoracic anastomosis with a lower risk of leakage in totally minimally invasive Ivor–Lewis esophagectomy (TMIIL) is ongoing. In the present study, we compared the outcomes of end-to-side (with circular stapler [CS]) and side-to-side (with linear stapler [LS]) techniques for intrathoracic anastomosis during TMIIL performed in 2 European high-volume centers for upper gastrointestinal surgery. A propensity score method was used to compare the CS and LS groups. Methods: We retrospectively evaluated patients with lower esophageal cancer or Siewert type 1 or 2 esophagogastric junction carcinoma who underwent a planned TMIIL esophagectomy, performed from January 2017 to September 2020. The anastomosis was created by a semi-mechanical technique using a LS in one center and by a mechanical technique using a CS in the other center. General features, operative techniques, pathology data, and short-term outcomes were analyzed. Statistical evaluations were performed on the whole cohort, stratifying the analyses by risk strata factors identified with the propensity scores, and on a subgroup of patients matched by propensity score. The primary endpoint of the study was the rate of anastomotic leakage in the two groups. Secondary endpoints included rates of anastomotic stricture and overall postoperative complications. Results: Considering the whole population, 256 patients were included; of those, 220 received the anastomosis with a circular stapler (CS group), and 36 received the anastomosis with a linear stapler (LS group). No significant differences by group in terms of sex, age, American Society of Anesthesiologists physical status classification, and type of neoplasm were showed. The rate of anastomotic leakage did not differ in the two groups (9.6% CS vs. 5.6% LS, p = 0.438), as well as the rate of anastomotic stricture in the 3-month follow-up (0.9% CS vs. 2.8% LS, p = 0.367). The rate of chyle leakage and of pulmonary, cardiac, and infective complications was not significantly different in the groups. After propensity score matching, 72 patients were included in the analysis. The 2 obtained propensity score matched groups did not differ for any of the clinical and pathologic variables considered for the analysis, resulting in well-balanced cohorts. The results obtained on the whole population were confirmed in the matched groups. Conclusions: The results of our study suggest that both techniques for esophagogastric anastomosis during TMIIL are feasible, safe, and effective, with comparable rates of postoperative anastomotic leakage and stricture

Brain microstructural and metabolic alterations detected <i>in vivo</i> at onset of the first demyelinating event

In early multiple sclerosis, a clearer understanding of normal-brain tissue microstructural and metabolic abnormalities will provide valuable insights into its pathophysiology. We used multi-parametric quantitative MRI to detect alterations in brain tissues of patients with their first demyelinating episode. We acquired neurite orientation dispersion and density imaging [to investigate morphology of neurites (dendrites and axons)] and 23Na MRI (to estimate total sodium concentration, a reflection of underlying changes in metabolic function). In this cross-sectional study, we enrolled 42 patients diagnosed with clinically isolated syndrome or multiple sclerosis within 3 months of their first demyelinating event and 16 healthy controls. Physical and cognitive scales were assessed. At 3 T, we acquired brain and spinal cord structural scans, and neurite orientation dispersion and density imaging. Thirty-two patients and 13 healthy controls also underwent brain 23Na MRI. We measured neurite density and orientation dispersion indices and total sodium concentration in brain normal-appearing white matter, white matter lesions, and grey matter. We used linear regression models (adjusting for brain parenchymal fraction and lesion load) and Spearman correlation tests (significance level P ≤ 0.01). Patients showed higher orientation dispersion index in normal-appearing white matter, including the corpus callosum, where they also showed lower neurite density index and higher total sodium concentration, compared with healthy controls. In grey matter, compared with healthy controls, patients demonstrated: lower orientation dispersion index in frontal, parietal and temporal cortices; lower neurite density index in parietal, temporal and occipital cortices; and higher total sodium concentration in limbic and frontal cortices. Brain volumes did not differ between patients and controls. In patients, higher orientation dispersion index in corpus callosum was associated with worse performance on timed walk test (P = 0.009, B = 0.01, 99% confidence interval = 0.0001 to 0.02), independent of brain and lesion volumes. Higher total sodium concentration in left frontal middle gyrus was associated with higher disability on Expanded Disability Status Scale (rs = 0.5, P = 0.005). Increased axonal dispersion was found in normal-appearing white matter, particularly corpus callosum, where there was also axonal degeneration and total sodium accumulation. The association between increased axonal dispersion in the corpus callosum and worse walking performance implies that morphological and metabolic alterations in this structure could mechanistically contribute to disability in multiple sclerosis. As brain volumes were neither altered nor related to disability in patients, our findings suggest that these two advanced MRI techniques are more sensitive at detecting clinically relevant pathology in early multiple sclerosis