Involvement of CCR6/CCL20/IL-17 Axis in NSCLC Disease Progression

OBJECTIVES: Autocrine and paracrine chemokine/chemokine receptor-based interactions promote non-small-cell-lung-cancer (NSCLC) carcinogenesis. CCL20/CCR6 interactions are involved in prostatic and colonic malignancy pathogenesis. The expression and function of CCL20/CCR6 and its related Th-17 type immune response in NSCLC is not yet defined. We sought to characterize the role of the CCL20/CCR6/IL-17 axis in NSCLC tumor growth. METHODS: A specialized histopathologist blindly assessed CCL20/CCR6 expression levels in 49 tissue samples of NSCLC patients operated in our department. Results were correlated to disease progression. Colony assays, ERK signaling and chemokine production were measured to assess cancer cell responsiveness to CCL20 and IL-17 stimulation. RESULTS: CCL20 was highly expressed in the majority (38/49, 77.5%) of tumor samples. Only a minority of samples (8/49, 16.5%) showed high CCR6 expression. High CCR6 expression was associated with a shorter disease-free survival (P = 0.008) and conferred a disease stage-independent 4.87-fold increased risk for disease recurrence (P = 0.0076, CI 95% 1.52-15.563). Cancerous cell colony-forming capacity was increased by CCL20 stimulation; this effect was dependent in part on ERK phosphorylation and signaling. IL-17 expression was detected in NSCLC; IL-17 potentiated the production of CCL20 by cancerous cells. CONCLUSION: Our findings suggest that the CCL20/CCR6 axis promotes NSCLC disease progression. CCR6 is identified as a potential new prognostic marker and the CCL20/CCR6/IL-17 axis as a potential new therapeutic target. Larger scale studies are required to consolidate these observations

International workshop on “professionalism in the practice of medicine- where are we now?”

Abstract Medical professionalism refers to attributes, values, behaviors, responsibilities and commitments of physicians that are congruent with the public’s expectations. An international workshop on medical professionalism took place at the Dead Sea, Israel, on December 11–12, 2016. The meeting brought together local medical professionals, physicians and others, as well as international experts, to discuss definitions of professionalism and wrestle with current challenges facing the profession including its perceived status and physician satisfaction, unprofessional behavior and its relation to health care quality and patient safety, and professionalism as a learned competence. Individual medical schools reported on educational efforts to promote professionalism in their curricula. Patient complaints as an improvement mechanism were explored on a national and health plan level. I was found that complaints regarding physician behavior are rare in the Israeli context and need to be dealt with expeditiously at a local level in order to be effective tools for change. The meeting provided a venue to understand local and international strategies and mechanism for regulation and self-regulation, highlighting the role of the Israel Medical Association. A major focus of the meeting was on intergenerational differences in attitude and practice and the necessary adaptation of medicine to the digital age. We provide an overview of the topics addressed, synopsis, evaluation and lessons learned in this first-ever national meeting on medical professionalism in Israel

Additional file 1: of International workshop on “professionalism in the practice of medicine- where are we now?”

Workshop Program. (PDF 327 kb

Management of Pathogenic CDH1 Variant Carriers Within the FREGAT Network

International audienceObjective: To describe the management of pathogenic CDH1 variant carriers (pCDH1vc) within the FREGAT (FRench Eso-GAsTric tumor) network. Primary objective focused on clinical outcomes and pathological findings, Secondary objective was to identify risk factor predicting postoperative morbidity (POM).Background: Prophylactic total gastrectomy (PTG) remains the recommended option for gastric cancer risk management in pCDH1vc with, however, endoscopic surveillance as an alternative.Methods: A retrospective observational multicenter study was carried out between 2003 and 2021. Data were reported as median (interquartile range) or as counts (proportion). Usual tests were used for univariate analysis. Risk factors of overall and severe POM (ie, Clavien-Dindo grade 3 or more) were identified with a binary logistic regression.Results: A total of 99 patients including 14 index cases were reported from 11 centers. Median survival among index cases was 12.0 (7.6-16.4) months with most of them having peritoneal carcinomatosis at diagnosis (71.4%). Among the remaining 85 patients, 77 underwent a PTG [median age=34.6 (23.7-46.2), American Society of Anesthesiologists score 1: 75%] mostly via a minimally invasive approach (51.9%). POM rate was 37.7% including 20.8% of severe POM, with age 40 years and above and low-volume centers as predictors ( P =0.030 and 0.038). After PTG, the cancer rate on specimen was 54.5% (n=42, all pT1a) of which 59.5% had no cancer detected on preoperative endoscopy (n=25).Conclusions: Among pCDH1vc, index cases carry a dismal prognosis. The risk of cancer among patients undergoing PTG remained high and unpredictable and has to be balanced with the morbidity and functional consequence of PTG

Total Versus Subtotal Gastrectomy for Distal Gastric Poorly Cohesive Carcinoma

International audienc