Targeted transcriptomic analysis of pancreatic adenocarcinoma in EUS-FNA samples by NanoString technology.

Background: Integration of transcriptomic testing into EUS-FNA samples is a growing need for precision oncology in pancreatic ductal adenocarcinoma (PDAC). The NanoString platform is suitable for transcriptome profiling in low yield RNA samples. Methods: Inclusion of patients that underwent EUS-FNA cytological diagnosis of pancreatic ductal adenocarcinoma using 19G and/or 22G needles and subsequent surgical resection. Formalin-fixed, paraffin-embedded (FFPE) cytological and surgical samples underwent RNA extraction and transcriptomic analysis using a custom 52-gene NanoString panel of stromal PDAC features. Cell type abundance was quantified in FFPE specimens and correlated. Results: 18 PDAC patients were included. Mean EUS-FNA passes was 2 + 0.7. All FFPE passed the RNA quality control for genomic analysis. Hierarchical clustering on the global gene expression data showed that genes were differentially expressed between EUS and surgical samples. A more enriched cancer-associated fibroblasts and epithelial-mesenchymal transition transcriptomic profile was observed across surgical specimens whereas immunological biomarkers were more represented in EUS-FNA samples. Cytological examination confirmed a scanty representation of CAF and more immunological cell abundance in cytological samples in comparison to surgical specimens. Conclusion: Targeted transcriptomic NanoString profiling of PDAC samples obtained by EUS-FNA is a feasible approach for pre-surgical molecular analysis although stromal CAF/EMT mRNA biomarkers are underrepresented.

EUS-guided tissue acquisition in the study of the adrenal glands: Results of a nationwide multicenter study.

BACKGROUND: There are limited data about the role of endoscopic ultrasound-guided tissue acquisition (EUS-TA), by fine needle aspiration (EUS-FNA) or biopsy (EUS-FNB), in the evaluation of the adrenal glands (AG). The primary aim was to assess the diagnostic yield and safety. The secondary aims were the malignancy predictors, and to create a predictive model of malignancy. METHODS: This was a retrospective nationwide study involving all Spanish hospitals experienced in EUS-TA of AGs. Inclusion period was from April-2003 to April-2016. Inclusion criteria: all consecutive cases that underwent EUS-TA of AGs. EUS and cytopathology findings were evaluated. Statistical analyses: diagnostic accuracy of echoendoscopist's suspicion using cytology by EUS-TA, as gold standard; multivariate logistic regression model to predict tumor malignancy. RESULTS: A total of 204 EUS-TA of AGs were evaluated. Primary tumor locations were lung70%, others19%, and unknown11%. AG samples were adequate for cytological diagnosis in 91%, and confirmed malignancy in 60%. Diagnostic accuracy of the endosonographer's suspicion was 68%. The most common technique was: a 22-G (65%) and cytological needle (75%) with suction-syringe (66%). No serious adverse events were described. The variables most associated with malignancy were size>30mm (OR2.27; 95%CI, 1.16-4.05), heterogeneous echo-pattern (OR2.11; 95%CI, 1.1-3.9), variegated AG shape (OR2.46; 95%CI, 1-6.24), and endosonographer suspicion (OR17.46; 95%CI, 6.2-58.5). The best variables for a predictive multivariate logistic model of malignancy were age, sex, echo-pattern, and AG-shape. CONCLUSIONS: EUS-TA of the AGs is a safe, minimally invasive procedure, allowing an excellent diagnostic yield. These results suggest the possibility of developing a pre-EUS procedure predictive malignancy model.

Efficacy and safety of a combination of hyaluronic acid, chondroitin sulfate, and poloxamer 407 as a submucosal injection solution for endoscopic resection: pilot study on a swine model.

BACKGROUND AND AIMS: Endoscopic resection techniques require use of submucosal injection. The aim of this study was to assess a new solution that combines hyaluronic acid, chondroitin sulfate, and poloxamer 407 for submucosal injection. METHODS: A total of 48 gastric submucosal cushions were created in fresh porcine stomachs using gelafundin (n = 16) or the new solution diluted at 50 % (n = 16), or 80 % (n = 16). The duration of mucosal elevation was measured. In an in vivo model, 10 gastric submucosal cushions were created by injecting 2 mL of the new solution at 80 % and the animal was euthanized 30 minutes after the last injection. RESULTS: Submucosal cushions with the new solution at 80 % and 50 % concentration lasted longer than with gelafundin (23.13 ±â€Š15.57, 13.1 ±â€Š6.6, 3.94 ±â€Š1.53 minutes, respectively; P  = 0.000). In the in vivo study, no damage or necrosis was observed in the mucosa or muscularis propria. CONCLUSION: The combination of hyaluronic acid, chondroitin sulfate, and poloxamer 407 produces a long-lasting submucosal cushion and does not seem to induce acute damage in the tissue making it suitable for submucosal injection.

Impact of surveillance of hepatitis b and hepatitis c in patients with inflammatory bowel disease under anti-TNF therapies: multicenter prospective observational study (REPENTINA 3).

AIMS: Assess IBD patients starting anti-TNF for the impact of preventive measures in HBV and/or HCV, and the predictive response factors to HBV vaccination. METHODS: Multicenter prospective study including 389 IBD patients. Four interventions were established: I-1) anti-HBs <100IU/L: HBV vaccination with double doses at 0-1-2months, and revaccination if titres <100IU/L (seroprotection defined as anti-HBs10-100IU/L and effective vaccination anti-HBs >100IU/L); I-2) anti-HBs >100IU/L (previous effective vaccination): monitoring levels; I-3) anti-HBc and/or HCV+: analysis every two months; I-4) HBsAg+: start anti-virals. RESULTS: I-1 and I-2) For first vaccination, effective vaccination and seroprotection were obtained in 26.4% and 43.5%, and for revaccination 31.3% and 44.4%, respectively. Predictive factors of effective vaccination were age ≤30years (OR=2.2) and being vaccinated simultaneously with anti-TNF (OR=5.2) instead of late vaccination, whereas age ≤30years (OR=2.6) and anti-TNF monotherapy (OR=2.4) were predictive for seroprotection. 80.8% of patients previously vaccinated maintained titres at 29months follow-up. The only factor related to maintaining titres was previous vaccination versus achieving effective vaccination during anti-TNF (HR=2.49); I-3 and I-4) HBV-DNA + without reactivation was detected in 7% of 29 anti-HBc. No reactivation was found in the remaining HCV (n=5) or HBsAg (n=4) patients. CONCLUSIONS: 1) Response to vaccination/revaccination is low in patients with anti-TNF. Young patients vaccinated at the beginning of anti-TNF and receiving it as a monotheraphy showed better response. 2) Long-lasting effective vaccination is greatest in patients previously vaccinated. 3) Following-up the established surveillance and/or preventive anti-viral therapy seems to be safe in HBV and HCV patients.