Background Diabetes is related with increased cancer mortality across multiple cancer types. Its role in lung cancer mortality is still unclear. We aim to determine the prognostic value of fasting plasma glucose (FPG) and diabetes mellitus in patients with locally advanced non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy. Methods One-hundred seventy patients with stage III NSCLC received definitive concurrent chemoradiotherapy from 2010 to 2014. Clinico-pathological data and clinical outcome was retrospectively registered. Fifty-six patients (33%), met criteria for type 2 diabetes mellitus (T2DM) at baseline. The prognostic value of FPG and other clinical variables was assessed. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method and Cox proportional models and log-rank test were used. Results With a median follow-up of 36 months, median PFS was 8.0 months and median OS was 15.0 months in patients with FPG ≥7 mmol/L compared to 20 months (HR 1.13; 95% CI 1.07–1.19, p < 0.001) and 31 months (HR 1.09; 95% CI 1.04–1.15; p < 0.001) respectively, for patients with FPG < 7 mmol/L. In the multivariate analysis of the entire cohort adjusted by platinum compound and comorbidities, high levels of FPG as a continuous variable (HR 1.14; 95% CI 1.07–1.21; p < 0.001), the presence of comorbidity (HR 1.72; 95% CI 1.12–2.63; p = 0.012), and treatment with carboplatin (HR 1.95; 95% CI 1.26–2.99; p = 0.002) were independent predictors for shorter OS. In additional multivariate models considering non-diabetic patients as a reference group, diabetic patients with poor metabolic control (HbA1c > 8.5%) (HR 4.53; 95% CI 2.21–9.30; p < 0.001) and those receiving insulin (HR 3.22; 95% CI 1.90–5.46 p < 0.001) had significantly independent worse OS. Conclusion Baseline FPG level is an independent predictor of survival in our cohort of patients with locally advanced NSCLC treated with concurrent chemoradiotherapy. Studies in larger cohorts of patients are warranted to confirm this relevant association. Electronic supplementary material The online version of this article (10.1186/s12885-019-5370-5) contains supplementary material, which is available to authorized users.

Double pigtail for preventing ascending cholangitis after endoscopic ultrasonographyguided choledochoduodenostomy with lumen-apposing metal stentThe present case is a good example of how the new biliary lumen-apposing metal stent (LAMS), specially designed for endoscopic ultrasonography (EUS)-guided biliary drainage, can be totally occluded by food impaction. This can be prevented by placing a pigtail stent within the LAMS.A patient with unresectable pancreatic cancer causing obstructive jaundice after a failed endoscopic retrograde cholangiopancreatography (ERCP) underwent EUS-guided choledochoduodenostomy from the duodenal bulb, using the Hot AXIOS System (Xlumena Inc., Mountain View, CA, USA). A specific biliary diabolo-shaped lumen-apposing metal stent (inner diameter, 6 mm; length 8 mm) was successfully placed. After initial clinical improvement, the patient again had cholangitis and relapse of the obstructive jaundice. Computed tomography (CT) scan revealed a well-positioned stent and air inside the common bile duct (CBD). Upper endoscopy confirmed the suspicion of an occluded biliary LAMS. Cholangiogram was carried out revealing a quantity of food inside the CBD (Fig. 1). Cleaning of the stent was achieved using mechanical devices (sphincterotome, balloon extractor, grasping forceps) and energic Serum saline physiological (SSF) irrigation. After redirection of the guidewire using an ERCP catheter, a 10-Fr double-pigtail stent was inserted through the LAMS in order to avoid occlusion of its lumen with solid food (Fig. 2; Video S1).Although there are sufficient data on the use of LAMS in pancreatic collections, to date, only a few case reports have been published regarding the use of this new dedicated biliary self-expanding metal stent (SEMS) in EUS-guided biliary drainage. 1-5 It appears very attractive to use routinely after a failed ERCP, but despite its potential advantages, we should be cautious until more data are available. The potential risk of ascending cholangitis after biliary transmural drainage using biliary LAMS must be kept in mind. Placing a double-pigtail plastic stent within this stent (to avoid self-occlusion) could be helpful.

Disclosure declarations: M.C.U.C. has a patent for Breast Cancer Classifier: US Patent No. 9,631,239 with royalties paid, is an advisory member of Veracyte and receives research funding from NanoString Technologies. MD receives honoraria from Myriad Genetics and is a consultant and advisory board member of GTx, Radius Health, Orion Pharma, Lilly, Agile and Astrazeneca, has received funding from Pfizer (Inst) and Radius Health (Inst) and has been payed expenses from Pfizer and Myriad Genetics. HT reports a grant from Bayer. JMB reports grants from Cancer Research UK, during the conduct of the study; grants from Medivation; grants and non-financial support from AstraZeneca, Merck Sharp & Dohme, Puma Biotechnology, Clovis Oncology, Pfizer, Janssen-Cilag, Novartis, and Roche, outside the submitted work. The rest of authors declare no potential conflicts of interests. Statement of translational relevance:Our study shows that neoadjuvant treatment with short and longer-term aromatase inhibitors (AI) in primary estrogen receptor (ER+) positive breast cancer (BC) exerts comparable impact on changes in intrinsic subtypes between baseline and surgery. However, neoadjuvant AI treatment beyond 2 weeks leads moreResearch.

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Cisplatin is the most common drug in first-line chemotherapy against solid tumors. We and others have previously used the nematode Caenorhabditis elegans to identify genetic factors influencing the sensitivity and resistance to cisplatin. In this study, we take advantage of C. elegans to explore cisplatin effects on mitochondrial functions and investigate cisplatin-induced neurotoxicity through a high-resolution semi-automated system for evaluating locomotion. Firstly, we report that a high-glucose diet sensitizes C. elegans to cisplatin at the physiological level and that mitochondrial CED-13 protects the cell from cisplatin-induced oxidative stress. Additionally, by assessing mitochondrial function with a Seahorse Analyzer, we observed a detrimental additive effect of cisplatin and glucose in mitochondrial respiration. Secondly, since we previously found that catechol-O-methyltransferases (involved in dopamine degradation) were upregulated upon cisplatin exposure, we studied the protective role of the FDA-approved drug dopamine against cisplatin-induced neurotoxicity. To implement the use of the Tierpsy Tracker system for measuring neurotoxicity in C. elegans, we showed that abnormal displacements and body postures in cat-2 mutants, which have the dopamine synthesis pathway disrupted, can be rescued by adding dopamine. Then, we used such a system to demonstrate that dopamine treatment protects from the dose-dependent neurotoxicity caused by cisplatin.

577 Background: HER-2 low has emerged as a potential new entity in breast cancer (BC). Data of this subset is still limited and prognostic results are controversial, suggesting HER2-low does not represent a distinct biological subtype. HER2-low account for up to 50% of BC, representing a potential therapeutic target with encouraging results in the metastatic setting. Hence, we pretend to analyze clinical characteristics of this subset to elucidate commented points. Methods: Confirmed HER2-negative BC patients (p) diagnosed between 2006-2017 were retrospectively reviewed in a single center study, in ICO-Badalona. HER2-positive and in situ carcinomas were excluded, and p were classified as HER2-low and HER2-0. The prevalence of HER2-low versus HER2-0 among p, originally scored as HER2-negative, was measured. Demographics and clinicopathological characteristics were examined and compared via medical charts/electronic health records. We aim to describe HER2-0/HER2-low populations, and explore its prognostic impact, using Kaplan-Meyer and Cox regression models. Results: From 1451 infiltrating HER2-negative BC p, 87% were hormone receptor (HR)-positive vs 13% triple negative (TNBC). Overall, 43% were HER2-0 and 57% HER2-low (61% IHC 1+ and 39% IHC 2+). Comparing HER2-0 vs HER2-low, the latest showed significant higher proportion of ER-positive (80% vs 91.7%, p = < 0.001) and PR-positive (69.3% vs 79.1%, p = < 0.001) cases, but there were no differences between HER2-low 1+ vs 2+. HER2-0 exhibited higher proportion of TNBC p (20% vs 8.3%, p = 0.001), grade III tumors (28.8% vs 23.5%, p = 0.036) and higher Ki67 median value (26.47% vs 23.88%, p = 0.041). No significant differences were observed in median age at diagnosis, menopausal status, clinical stage, clinical nodal status, histological subtype, time to recurrence, time to local recurrence and overall survival (OS). HER2-low presented longer time to distant recurrence (TDR) compared to HER2-0 (67.8 vs 54.1 months, p = 0.015) and better BC-related OS (19.2 vs 16.3 years, p = 0.033). However, in the multivariate analysis, considering HER2, ER, PR, histological grade and nodal status, PR showed the strongest association with longer TDR (HR: 0.69; 95%CI 0.54-0.89, p = 0.004); and positive nodal status was the strongest factor related to worse BC-related OS (HR: 2.97; CI 2.10-4.21, p = 0.000). No statistical differences in TDR and BC-related OS were observed between HER2 1+ vs 2+ populations. Conclusions: HER2-low was significantly associated to HR-positive disease whereas TNBC, histological grade III and higher Ki67% were more represented in HER2-0 group. Although HER2-0 was related to worse TDR and BC-related OS, these findings could be explained by the presence of an enriched population in worse prognostic features, as suggested by multivariate analysis. New therapies for HER2-0 disease are an unmet medical need.

Cisplatin is the most common drug in first-line chemotherapy against solid tumors. We and others have previously used the nematode Caenorhabditis elegans to identify genetic factors influencing the sensitivity and resistance to cisplatin. In this study, we use C. elegans to explore cisplatin effects on mitochondrial functions and investigate cisplatin-induced neurotoxicity through a high-resolution system for evaluating locomotion. Firstly, we report that a high-glucose diet sensitizes C. elegans to cisplatin at the physiological level and that mitochondrial CED-13 protects the cell from cisplatin-induced oxidative stress. Additionally, by assessing mitochondrial function with a Seahorse Analyzer, we observed a detrimental effect of cisplatin and glucose in mitochondrial respiration. Secondly, since catechol-O-methyltransferases (involved in dopamine degradation) are upregulated upon cisplatin exposure, we studied the protective role of dopamine against cisplatin-induced neurotoxicity. To implement the use of the Tierpsy Tracker system for measuring neurotoxicity, we showed that abnormal displacements and body postures in cat-2 mutants, which have the dopamine synthesis disrupted, can be rescued by adding dopamine. Then, we demonstrated that dopamine treatment protects from the dose-dependent neurotoxicity caused by cisplatin.