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Antonello A.,Veneto Institute of Oncology IOV IRCSS | Ishaq S.,Birmingham City University | Ishaq S.,St. Georges University | Zanatta L.,Santa Maria del Prato Hospital | And 3 more authors.
Surgical Endoscopy and Other Interventional Techniques | Year: 2016

Background: Currently there are three main treatment options for Zenker’s diverticulum (ZD): surgery, rigid endoscopy and flexible endoscopy. After primary success, recurrence can be as high as 19 % for surgery, 12.8 % for rigid endoscopy and 20 % for flexible endoscopy. Flexible endoscopy may represent an ideal treatment option for recurring ZD. The aims of this paper are to evaluate the efficacy and safety of flexible endotherapy for recurring ZD after surgery and/or endoscopic stapling and to compare the treatment outcome between naive and recurring patients. Methods: Data on patients that underwent flexible endotherapy for ZD between January 2010 and January 2015 were collected. Patients were divided into those with recurrences after surgery and/or endoscopic stapling and those who did not have previous treatments. Dysphagia, regurgitation, and respiratory symptom severity before the procedure were graded. The outcome parameters were: complications, symptom improvement after the first treatment, number of treatment sessions, rate of complete remission and relapses. These parameters were then compared between patients groups. Results: Twenty-five recurring patients were included. Treatment was carried out successfully in all patients. Two adverse events occurred; they were successfully managed conservatively. After the first treatment, there was a significant reduction in dysphagia, regurgitation and respiratory symptoms scores. The median number of treatments was 1 (IQR 0.25, range 1–3): symptom remission was achieved in 84 % patients and partial improvement in 16 %. Relapsing symptoms occurred in 20 % patients; they were successfully managed with an additional treatment session. Results were compared with data on 34 consecutive naive patients treated within the same time span; no differences of the outcome parameters were revealed. Conclusions: Flexible endotherapy for ZD recurrences after surgery and endoscopic stapling appears to be safe and effective, and its efficacy and safety profile seems to be comparable between recurring and naive patients. © 2015, Springer Science+Business Media New York.

Battaglia G.,Veneto Institute of Oncology IOV IRCSS | Antonello A.,Veneto Institute of Oncology IOV IRCSS | Realdon S.,Veneto Institute of Oncology IOV IRCSS | Cavallin F.,Veneto Institute of Oncology IOV IRCSS | And 3 more authors.
Surgical Endoscopy and Other Interventional Techniques | Year: 2016

Background: 50 % of esophageal cancers are inoperable at the time of diagnosis, and around 15 % involve the cervical esophagus. The hypopharynx is often involved by these malignancies as well. Palliation of cervical esophageal malignancies through stent insertion is considered limited due to technical challenges, poor patient tolerance and high complication rate. The aim of this study is to review our experience with stent insertion in the cervical segment of the esophagus and to evaluate outcome differences between stent insertions involving or sparing the hypopharynx. Methods: We retrospectively reviewed data on 69 consecutive patients that underwent stent insertion for malignant strictures in the cervical esophagus at our Department. Patients were divided according to involvement or sparing of the lower hypopharynx. Dysphagia severity was measured with the Mellow–Pinkas scale before the procedure and on monthly follow-ups. Any complication and its management were recorded. The main outcome parameters were as follows: dysphagia improvement, rate of successful dysphagia palliation (i.e., a reduction of the score to 0 or 1 after stent insertion) and complication rate. Multivariable analysis was carried out to assess the influence of patient- and procedure-related factors on the outcome of the procedure. Results: Stent insertion was achieved in 100 % patients. At 4 weeks, dysphagia score improved from a median of 3–0 (p < 0.001), and a successful palliation was achieved in 76.8 % patients. The 30-day mortality rate was 14.5 %. Successful palliation throughout the follow-up was achieved in 72.9 % of the surviving patients. Complications occurred in 31.9 % patients. Dilation before stent insertion was associated with a less efficient short-term dysphagia palliation (OR 6.77, 95 % CI 1.46–31.29, p = 0.02). Conclusions: Stent insertion is a safe and effective palliative treatment for malignant cervical esophageal strictures. Results are consistent even in patients with hypopharyngeal lesions. Dilation should be avoided before stent insertion. © 2015, Springer Science+Business Media New York.

Pinton L.,University of Padua | Solito S.,University of Padua | Damuzzo V.,University of Padua | Francescato S.,University of Padua | And 9 more authors.
Oncotarget | Year: 2016

The expansion of myeloid derived suppressor cells (MDSCs), a suppressive population able to hamper the immune response against cancer, correlates with tumor progression and overall survival in several cancer types. We have previously shown that MDSCs can be induced in vitro from precursors present in the bone marrow and observed that these cells are able to actively proliferate in the presence of activated T cells, whose activation level is critical to drive the suppressive activity of MDSCs. Here we investigated at molecular level the mechanisms involved in the interplay between MDSCs and activated T cells. We found that activated T cells secrete IL-10 following interaction with MDSCs which, in turn, activates STAT3 phosphorylation on MDSCs then leading to B7-H1 expression. We also demonstrated that B7-H1+ MDSCs are responsible for immune suppression through a mechanism involving ARG-1 and IDO expression. Finally, we show that the expression of ligands B7-H1 and MHC class II both on in vitro-induced MDSCs and on MDSCs in the tumor microenvironment of cancer patients is paralleled by an increased expression of their respective receptors PD-1 and LAG-3 on T cells, two inhibitory molecules associated with T cell dysfunction. These findings highlight key molecules and interactions responsible for the extensive cross-talk between MDSCs and activated T cells that are at the basis of immune suppression.

Realdon S.,Veneto Institute of Oncology IOV IRCSS | Antonello A.,Veneto Institute of Oncology IOV IRCSS | Arcidiacono D.,Venetian Institute of Molecular Medicine | Arcidiacono D.,University of Padua | And 8 more authors.
European Journal of Nutrition | Year: 2016

Purpose: While adherence to the World Cancer Research Fund (WCRF) guidelines on lifestyle and cancer was recently proven to be associated with an increased risk of esophageal cancer, no investigation has yet been carried out on its role on Barrett’s esophagus (BE) development and its progression to esophageal adenocarcinoma (EAC). The primary aim of this study was to evaluate the role of adherence to WCRF lifestyle recommendations in BE onset and progression. The secondary aim was to investigate the association between disease progression and specific aspects of diet and lifestyle. Methods: Established risk factors for BE and EAC development and adherence to WCRF guidelines were assessed in 107 consecutive patients undergoing an upper gastrointestinal endoscopy for symptoms suggesting gastroesophageal reflux (GERD) and a suspected diagnosis of BE/dysplasia on BE. Patients were divided according to histology: those with GERD without metaplasia, with non-dysplastic BE, with low-grade dysplasia, with high-grade dysplasia or with early EAC. The four groups were expressed as an ordered categorical variable of disease progression. An ordered logit model was estimated to identify the independent predictors of disease progression. Results: Adherence to WCRF guidelines was identified as independent protective factor (OR 0.51, 95 % CI 0.37–0.67) of disease progression. Disease progression was associated with reduced adherence to guidelines on physical activity (from 48.2 to 5.3 %, p = 0.001), sedentary habits (from 33.3 to 0 %, p = 0.03), fruit consumption (from 37.0 to 5.6 %, p = 0.02) and processed meat consumption (from 51.9 to 10.5 %, p = 0.002). Conclusion: Adherence to WCRF guidelines has a protective factor in BE onset and its evolution to EAC. © 2015, Springer-Verlag Berlin Heidelberg.

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