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Introduction. RCTs support neoadjuvant chemoradiotherapy (nCRT) followed by surgery in Locally Advanced Esophago-Gastric Junction (LA-EGJ) adenocarcinoma. However, RCTs are performed in highly controlled settings with limited representativeness of real-life patients (RLS). Aim: To compare the outcomes in RLS and clinical trial settings. Methods. The outcomes of RLS, which comprised 125 patients consequently treated for LA-EGJ adenocarcinoma between 2012 and 2017, were compared with the phase II trial (PIIS), performed on 65 patients from 2003 to 2011. Results. About half of RLS (51.2%) were treated with nCRT according to VR-protocol, 20.8% with standard-CRT according to CROSS/Al-Sarraf, 20% with CT alone. pCR was 36.8%, 28.6% and 9.1% after VR-protocol, standard-CRT, and chemotherapy respectively (p=0.082), while three-year overall survival (OS) was 58.6% (95% CI 43.2-71.1%), 32.8% (14.6-52.4%) and 44.8% (21.3-65.9%) respectively (p=0.030). With respect to PIIS, RLS had a higher proportion of cN+ (94% versus 54%; p

Poorly cohesive (PC) gastric cancer (GC) exhibits variable clinical behavior, being extremely aggressive in most cases but more indolent at times. We hypothesized that the integrative genomic and gene expression characterization of a PC GC series could help identifying molecular subtypes with potential clinical implications.64 PC GCs were assessed for alterations in 409 genes and 30 cases were subjected to transcriptomic profiling of 20,815 genes.A median of 8.2 mutations per Mb (interquartile range 6.9-10.4) was found and a tumor mutational load10 muts/Mb was significantly associated with patients' worse survival ( P =0.0024). The most frequent mutated genes were CDH1 and TP53 (each 32.8%) followed by PIK3CA (10.9%). In 15 samples (23.4%), at least 1 chromatin remodeling gene was mutated: KMT2D (5 cases); ARID1A and BAP1 (4 cases each); EZH2 , KMT2A , PBRM1 (1 case each). Eight samples (12.5%) had fusion genes involving CLDN18 gene. Gene expression profiling identified 4 different clusters: cluster A associated with epithelial to mesenchymal transition (EMT) signature; cluster B associated to proliferative signature and EMT; cluster C correlated to hedgehog signaling; cluster D showing no enrichment for any of the previous signatures. Notably, cluster A and B showed a worse prognosis compared with clusters C and D ( P =0.0095).integrated genomic and transcriptomic analysis suggest the existence of 4 molecular subtypes of PC GC with prognostic significance where EMT features are associated with a worse outcome.

Background Data on ERAS for gastrectomy are scarce, and the majority of the studies come from Eastern countries. Patients in the West are older and suffer from more advanced tumors that impair their clinical condition and often require neoadjuvant treatment. This retrospective study assessed the feasibility and safety of an Enhanced Recovery After Surgery (ERAS) protocol for gastrectomy in a Western center. Methods We conducted a single-center study of 351 patients operated for gastric cancer: 103, operated from January 2015 to December 2016, followed the standard pathway, while 248, operated from January 2017 to December 2019, followed the ERAS program. The primary outcomes considered were length of hospital stay (LOS) and direct costs. Secondary outcomes were 90-day morbidity and mortality, readmission rate, and compliance with ERAS items. A propensity score (PS) was built on confounding variables. Results Compliance with ERAS items after the program was ≥ 70%. Univariable analysis evidenced a 2-day median reduction in LOS and a median cost reduction of €826 per patient in the ERAS group. PS-based multivariable analysis confirmed a significant, 2-day decrease in median LOS and a €1097 saving after ERAS introduction. Ninety-day mortality decreased slightly in ERAS group, while complications and readmissions did not change significantly. When complications were included in the multivariable analysis, ERAS retained its significance, although the effects on LOS and cost were blunted to a median reduction of 1 day and €775, respectively. Conclusions ERAS for gastrectomy improved patients’ recovery and reduced hospital costs without changes in morbidity, mortality, or readmission.

Excessive salt consumption is one of the leading causes of high blood pressure. Worldwide salt intake largely exceeds the WHO recommended amount. This study aimed to evaluate the prevalence of high salt consumers and the effectiveness of a short-term workplace educational intervention among health workers. An online survey, assessing daily salt consumption through the MINISAL-SIIA questionnaire, was sent to the 4911 health workers employed by the University Hospital of Verona, Italy. Health workers who had a high (total score ≥ 10) or moderate (total score = 8/9) salt consumption associated with obesity or arterial hypertension were invited to undergo a medical examination and a short individual counselling session. A total of 1665 health workers (34.0%) completed the online questionnaire; 40.9% and 12.6% had moderate and high salt intake, respectively. High salt intake was more prevalent in men, current and past smokers, and obese and overweight subjects. In 95 participants completing the clinical phase, median daily salt consumption decreased from 10 (p25–p75 8–11) to 7 g (6–8) (p < 0.001), systolic blood pressure from 130 (120–140) to 120 (120–130) mmHg and weight from 78 (62–87) to 75 (62–86) kg. More than half of health workers had an excessive salt intake. However, a brief educational intervention in the healthcare working setting can substantially reduce unhealthy dietary habits, fostering weight loss and blood pressure control. Studies with a longer follow-up are needed to evaluate the persistence over time of these effects.

BACKGROUNDPatients with coronavirus disease 2019 (COVID-19) develop pneumonia generally associated with lymphopenia and a severe inflammatory response due to uncontrolled cytokine release. These mediators are transcriptionally regulated by the JAK/STAT signaling pathways, which can be disabled by small molecules.METHODSWe treated a group of patients (n = 20) with baricitinib according to an off-label use of the drug. The study was designed as an observational, longitudinal trial and approved by the local ethics committee. The patients were treated with 4 mg baricitinib twice daily for 2 days, followed by 4 mg per day for the remaining 7 days. Changes in the immune phenotype and expression of phosphorylated STAT3 (p-STAT3) in blood cells were evaluated and correlated with serum-derived cytokine levels and antibodies against severe acute respiratory syndrome-coronavirus 2 (anti-SARS-CoV-2). In a single treated patient, we also evaluated the alteration of myeloid cell functional activity.RESULTSWe provide evidence that patients treated with baricitinib had a marked reduction in serum levels of IL-6, IL-1β, and TNF-α, a rapid recovery of circulating T and B cell frequencies, and increased antibody production against the SARS-CoV-2 spike protein, all of which were clinically associated with a reduction in the need for oxygen therapy and a progressive increase in the P/F (PaO2, oxygen partial pressure/FiO2, fraction of inspired oxygen) ratio.CONCLUSIONThese data suggest that baricitinib prevented the progression to a severe, extreme form of the viral disease by modulating the patients' immune landscape and that these changes were associated with a safer, more favorable clinical outcome for patients with COVID-19 pneumonia.TRIAL REGISTRATIONClinicalTrials.gov NCT04438629.FUNDINGThis work was supported by the Fondazione Cariverona (ENACT Project) and the Fondazione TIM.

Objectives Peritoneal carcinomatosis is the most frequent site of metastases in patients with gastric cancer. Current standard treatment is palliative systemic chemotherapy with very poor prognosis. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) resulted in long-term benefits in selected patients. Among patients with peritoneal carcinomatosis, a distinctive subset is oligometastatic disease which is characterized by low metastatic burden. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a recent technique of intraperitoneal chemotherapy used in combination with systemic chemotherapy with promising results. Methods PIPAC VER-One is a prospective, randomized, multicenter phase III clinical trial that aims to evaluate the effectiveness of the use of PIPAC in combination with systemic chemotherapy in patients with gastric cancer and synchronous positive peritoneal cytology and/or limited peritoneal metastases (peritoneal cancer index [PCI] ≤6). Patients will be randomized into two arms: arm A (control) treated with standard systemic chemotherapy and arm B (experimental) treated with a bidirectional scheme including PIPAC and systemic chemotherapy. Results Primary endpoint is the secondary resectability rate. Secondary endpoints are: overall survival (OS), pregression-free survival (PFS), disease-free survival (DFS), histological response assessed both on primary tumor and peritoneal lesions, quality of life (QoL), complication rate (CTCAE v5), and incremental cost-effectiveness ratios (ICER). Conclusions The role of PIPAC in multimodal treatment for oligometastatic gastric cancer will be investigated in this trial.

Daily air pollution has been linked with mortality from urban studies. Associations in rural areas are still unclear and there is growing interest in testing the role that air pollution has on other causes of death. This study aims to evaluate the association between daily air pollution and cause-specific mortality in all 8092 Italian municipalities.Natural, cardiovascular, cardiac, ischemic, cerebrovascular, respiratory, metabolic, diabetes, nervous and psychiatric causes of death occurred in Italy were extracted during 2013-2015. Daily ambient PMWe estimated a positive association between PMShort-term exposure to particulate matter was associated with mortality from nervous diseases. Mortality from metabolic diseases was associated with NO

Background and Objective: Guided bone regeneration allows new bone formation in anatomical sites showing defects preventing implant rehabilitation. Material and Methods: The present case series reported the outcomes of five patients treated with customized titanium meshes manufactured with a digital workflow for achieving bone regeneration at future implant sites. A significant gain in both width and thickness was achieved for all patients. Results: From a radiographic point of view (CBTC), satisfactory results were reached both in horizontal and vertical defects. An average horizontal gain of 3.6 &plusmn, 0.8 mm and a vertical gain of 5.2 &plusmn, 1.1 mm. Conclusions: The findings from this study suggest that customized titanium meshes represent a valid method to pursue guided bone regeneration in horizontal, vertical or combined defects. Particular attention must be paid by the surgeon in the packaging of the flap according to a correct method called the &ldquo, poncho&rdquo, technique in order to reduce the most frequent complication that is the exposure of the mesh even if a partial exposure of one mesh does not compromise the final outcome of both the reconstruction and the healing of the implants.

Background Although pathological complete response (pCR) after multimodal treatment for esophageal cancer is associated to the best prognosis, recurrence may occur in 20–40% of cases. The present study investigated the recurrence pattern and predictive factors of recurrence after pCR in patients with esophageal cancer. Methods In this study, 427 patients received preoperative treatment for either esophageal squamous cell carcinoma (SCC) or adenocarcinoma at Verona University Hospital between 2000 and 2018. Of these, 145 patients (34%) achieved a pCR. Long-term prognosis, recurrence pattern, and risk factors for relapse in pCR patients were analysed. Results During a median follow-up of 52 months, 37 relapses (25.5%) occurred, mostly at distant level (n = 28). Nearly all locoregional relapses (8/9) were detected in SCC cases. The 5-year overall survival and cancer-related survival were 71.7% (95% confidence interval [CI] 62.6–78.9%) and 77.5% (95% CI 68.5–84.2%) respectively. Male sex, higher body mass index, and cT4 were significant risk factors for recurrence at univariate analysis. The multivariate analysis confirmed the role of cT4 as predictor of recurrence only in SCCs. Conclusions Esophageal cancer recurs in about one-fourth of pCR cases. A fair number of local recurrences occurs in SCCs, but the main problem is the systemic disease control. According to our analysis, SCCs patients with cT4 stage have an increased risk to recur, so they should be managed differently by a personalized approach in terms of adjuvant treatment and follow-up.

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

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing pandemic coronavirus disease 2019 (COVID-19). The majority of patients with COVID-19 have a good prognosis, but variable percentages in different countries develop pneumonia associated with lymphocytopenia and severe inflammatory response due to uncontrolled release of cytokines. These immune mediators are transcriptionally regulated by JAK-STAT molecular pathways, which can be disabled by small molecules. Here, we provide evidences on the efficacy of baricitinib, a JAK1/JAK2 inhibitor, in correcting the immune abnormalities observed in patients hospitalized with COVID-19. Indeed, we demonstrate a significant reduction in serum levels of interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)α, a rapid recovery in circulating T and B cell frequencies and an increased antibody production against SARS-CoV-2 spike protein in baricitinib-treated patients. Moreover, treated patients underwent a rapid reduction in oxygen flow need and progressive increase in the P/F. Our work provides the basis on developing effective treatments against COVID-19 pathogenesis using on-target therapy.

A randomized clinical trial showed that trastuzumab, added to traditional chemotherapy, significantly improved overall survival in human epidermal growth factor receptor 2 (HER2)-overexpressing metastatic gastric cancer patients. This population-based study aimed at evaluating both the clinical and economic impact of trastuzumab in a real-world setting. By using the healthcare utilization databases of Lombardy, Italy, a cohort of patients newly diagnosed with metastatic gastric cancer during the period 2011&ndash, 2016 was selected. Among these, patients initially treated with either trastuzumab-based chemotherapy or standard chemotherapy alone were followed up until death, migration in other regions or June 2018. Overall survival and average cumulative costs were estimated and compared between the two treatment arms. Among the 1198 metastatic gastric cancer patients who started therapy within six months after metastasis detection, 87 were initially treated with trastuzumab-based chemotherapy and 1111 with standard chemotherapy. Median overall survival and restricted mean survival were 10.2 and 7.4 months, and 14.9 and 11.4 months, respectively, in the two treatment arms. The adjusted hazard ratio of death was 0.73 (95% CI 0.57&ndash, 0.93). The average per capita cumulative healthcare costs were, respectively, EUR 39,337 and 26,504, corresponding to an incremental cost-effectiveness ratio of EUR 43,998 for each year of survival gained. Our study shows that adding trastuzumab to conventional chemotherapy is effective and cost-effective.

Prophylactic drain in gastrectomy for cancer is still widely used, although some evidence has disputed this practice and spreading enhanced recovery protocol has been pushing towards surgical simplification. This study aimed at assessing the impact of drain placement on important clinical outcomes, evaluating the results of randomised controlled trials (RCTs), or cohort studies whenever information provided by the former was scarce. PubMed, PMC, Cochrane Library, CNKI and Wanfang databases were searched from January 1990 to February 2019, both for RCTs and cohort studies comparing use or avoidance of prophylactic drain in gastric cancer patients undergoing gastrectomy. All RCTs and cohort studies were rated according to Jadad score and Newcastle-Ottawa-Scale, respectively. Meta-analysis was separately performed on RCTs and cohort studies. The following clinical outcomes were considered: anastomotic leak, reoperation rate, additional drain procedure, length of stay, postoperative morbidity, postoperative mortality, readmission rate and drain related complications. Overall, 3 RCTs (330 patients) and 7 cohort studies (2897 patients) were included. Seven studies came from Eastern Countries. Meta-analysis on RCTs evidenced that drain avoidance halves overall morbidity (RR = 0.47, 95%CI 0.26–0.86, p = 0.014) and slightly reduces length of stay (SMD -0.24, 95%CI -0.51–0.03, p = 0.083). Only one postoperative death occurred in the drain group. The other outcomes were either not reported or reported just by one RCT each. Meta-analysis on cohort studies, despite higher statistical power, did not highlight any significant difference. This meta-analysis showed that prophylactic drain avoidance can reduce morbidity and length of stay, while not significantly affecting other major surgical outcomes.

Aim investigate factors influencing the choice of neoadjuvant treatment type in the real world, analyzing our single high-volume center experience. Background & Methods The neoadjuvant chemoradiotherapy is the standard of care for esophageal cancer [1-2]. This consensus stems from the results of CCT performed on highly selected patients. However, the best treatment for non-selected patients remains unclear. In our clinical practice the treatment considered the goal standard is a TCF with 50GyRT [3-4-5], which showed an R0 resection rate of 88% and 5 y OS of 43%, better than CROSS trial. Despite these results, since 2012 not all patients underwent the same ideal treatment. We analyzed a real life patients group, that from the oncological point of view, they would be treated with our protocol in an intention to treat setting. Results From 2012 to 2017, 244 patients were treated. Analyzing retrospectively our data, it emerges that we have chosen the therapeutic strategy based on patient's characteristics: those aged over 75 yrs or with severe comorbidities were addressed to a “weakened” treatment: 37 with chemotherapy, 24 with radiotherapy and 55 with concomitant chemoradiotherapy different from our protocol. 125 with our protocol. Further selection involved lymph node status and patients with lymph node involvement (>N2 were referred to chemotherapy. The results confirmed that the protocol achieves better results in pathological response (pT0N0 in protocol 40,8% vs 18.2% in standard chemoradiotherapy – p value Conclusion Chemoradiotherapy is currently the gold standard of treatment but it cannot be consider the only treatment, especially for real life patients, less ideal but still requiring treatment. Clinical trials are certainly useful in providing information on highly selected patients, but clinical practice must consider patients whose conditions require tailored treatment.

The present study aims to prospectively assess the influence of respiratory disorders on smoking cessation and re-initiation. Three population-based Italian cohorts answered a questionnaire on respiratory health and smoking habits during 1998&ndash, 2001 and after a mean follow-up (SD) of 9.1 (0.8) years. Out of 1874 current smokers and 1166 ex-smokers at baseline, 965 (51.5%) and 735 (63.0%) reported their smoking status at follow-up. From current smokers, 312 had stopped smoking at follow-up, while 86 ex-smokers had resumed smoking. People reporting asthma at baseline were more likely to stop smoking than the other subjects (48.6% vs. 31.7%), while people reporting allergic rhinitis or chronic cough/phlegm had a higher probability to resume smoking (16.7% vs. 10.5% and 20.7% vs. 10.4%, respectively). In the multivariable logistic model, smoking relapse strongly decreased with increasing abstinence duration in people without chronic cough/phlegm (OR for &ge, 7.5 years vs. &lt, 7.5 years = 0.23, 95% CI 0.20&ndash, 0.27), while no effect was detected in people with chronic cough/phlegm (p for interaction = 0.039). Smoking cessation was enhanced in asthmatic subjects, while people with allergic rhinitis or chronic cough/phlegm were at higher risk to resume smoking. Chronic cough/phlegm blunted the decrease in smoking resumption associated with longer abstinence duration.

Background: Although the Japan Clinical Oncology Group (JCOG) 9501 trial did not find that prophylactic D3 lymphadenectomy led to any survival advantage over D2 lymphadenectomy, it did find that the prognosis of subserosal and N0 gastric cancer patients improved. The aim of this retrospective observational study was to compare survival after D2 or D3 lymphadenectomy in different patient subgroups. Methods: The study considered all of the patients who underwent D2 or D3 lymphadenectomy at a high-volume center in Verona (Italy) between 1992 and 2011. After excluding patients with Bormann IV or neuroendocrine tumors, early gastric cancers, or non-curative resections, the analysis involved 301 R0 patients: 100 who underwent D2, and 201 who underwent D3 lymphadenectomy. Post-operative deaths and deaths due to recurrences were considered as terminal events in the survival analysis. Results: The D2 patients were significantly older than the D3 patients at baseline (69.8 &plusmn, 2.3 vs. 62.2 &plusmn, 10.7 years). The median number of retrieved nodes was 29 (interquartile range: 24.5&ndash, 39) after D2, and 43 (34&ndash, 52) after D3. The five-year disease-related survival rate was similar after D2 (44%, 95% confidence interval (CI) 34&ndash, 54%) and D3 (41%, 34&ndash, 48%) (p = 0.766). A Cox model controlling for sex, age, tumor site, Laur&eacute, n histology, and T and N stages showed that the risk of cancer-related death after D3 was similar to that recorded after D2 (hazard ratio 0.97, 95% CI 0.67&ndash, 1.42). There was a significant interaction between the T status and the extension of the lymphadenectomy (p = 0.012), with the prognosis being better after D2 in T2 and T4b patients, and after D3 in T3 patients. Conclusions: The findings of this study suggest that D3 lymphadenectomy is not routinely indicated for patients with advanced gastric cancer, although differences in survival after D3 across T tiers deserve further consideration.

Cancer and obesity are the two major epidemics of the 21st century. Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of death, with a five-year overall survival rate of only 8%. Its incidence and mortality have increased in recent years, and this cancer type is expected to be among the top five leading causes of cancer-related death by 2030 in the United States (US). In the last three decades, the prevalence of overweight people has boosted with a consequent increase in obesity-related diseases. Considerable epidemiologic evidence correlates overweight and obese conditions to an increased risk of several types of cancer, including PDAC. Besides being a risk factor for multiple metabolic disorders, the tumor-promoting effects of obesity occur at the local level via inflammatory mediators that are associated with adipose inflammation and metabolic or hormones mediators and microbiota dysbiosis. Although an excess of body mass index (BMI) represents the second most modifiable risk factor for PDAC with an increased cancer related-death of more than 20–40%, still little is known about the molecular mechanisms that underlie this strong association. In this review, we focused on the role of obesity as a preventable risk factor of PDAC, discussing the molecular mechanisms linking obesity to cancer initiation and progression. Moreover, we highlighted the role of obesity in defining chemoresistance, showing how a high BMI can actually reduce response to chemotherapy.