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Bacteria normally resident in the pharynx were present in the proximal jejunal mucosa following Roux-en-Y gastric bypass surgery. After gastric bypass, there was increased secretion of HD-5 and an increase in HD-5 expressing intermediate cells and enterocytes in the crypt. The increase in HD-5 expression in the jejunal mucosa following gastric bypass surgery is likely to be secondary to exposure to orally-acquired microorganisms.

Pancreatic ductal adenocarcinoma (PDAC) is a tumor with an extremely poor prognosis, predominantly as a result of chemotherapy resistance and numerous somatic mutations. Consequently, PDAC is a prime candidate for the use of sequencing to identify causative mutations, facilitating subsequent administration of targeted therapy. In a feasibility study, we retrospectively assessed the therapeutic recommendations of a novel, evidence‐based software that analyzes next‐generation sequencing (NGS) data using a large panel of pharmacogenomic biomarkers for efficacy and toxicity. Tissue from 14 patients with PDAC was sequenced using NGS with a 620 gene panel. FASTQ files were fed into treatmentmap. The results were compared with chemotherapy in the patients, including all side effects. No changes in therapy were made. Known driver mutations for PDAC were confirmed (e.g. KRAS,TP53). Software analysis revealed positive biomarkers for predicted effective and ineffective treatments in all patients. At least one biomarker associated with increased toxicity could be detected in all patients. Patients had been receiving one of the currently approved chemotherapy agents. In two patients, toxicity could have been correctly predicted by the software analysis. The results suggest that NGS, in combination with an evidence‐based software, could be conducted within a 2‐week period, thus being feasible for clinical routine. Therapy recommendations were principally off‐label use. Based on the predominant KRAS mutations, other drugs were predicted to be ineffective. The pharmacogenomic biomarkers indicative of increased toxicity could be retrospectively linked to reported negative side effects in the respective patients. Finally, the occurrence of somatic and germline mutations in cancer syndrome‐associated genes is noteworthy, despite a high frequency of these particular variants in the background population. These results suggest software‐analysis of NGS data provides evidence‐based information on effective, ineffective and toxic drugs, potentially forming the basis for precision cancer medicine in PDAC.

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Background: Drugs targeting the RANK/RANK-ligand pathway may improve the outcome in early breast cancer, mainly due to prevention of bone metastasis. We aimed at exploring the value of RANK expression in primary breast cancer samples and its impact on the incidence of bone and visceral metastases. Methods: RANK expression was assessed in samples of 79 ER-positive/HER2-negative early breast cancer by immunohistochemistry in tissue micro array (TMA) blocks. Correlation between high and low RANK expression was done with the clinicopathological factors using Fisher's exact test and with bone metastasis free survival (BMFS), visceral metastasis free survival (VMFS) and overall survival (OS) using Kaplan Meier and Cox regression tests. Results: Median age at diagnosis was 56 years (42-85 years). RANK was highly expressed in 27 patients (34.2%) while 52 patients (65.8%) had low expression. BMFS in patients with high RANK expression was poorer than those with low expression with an 8y BMFS of 54.9% in patients with high expression versus 83.9% in the RANK low expression group (HR ¼ 2.93, 95%CI: 1.36 to 6.30, p ¼ 0.006). RANK expression was similarly associated with more visceral metastases with 8y VMFS of 54.5% versus 83.8% respectively (HR ¼ 3.20, 95%CI: 1.47 to 6.99, p ¼ 0.004). Moreover, OS was worse in cases with high RANK expression with 8y OS of 70.0% versus 90.2% respectively (HR ¼ 2.79, 95%CI: 1.20 to 6.49, p ¼ 0.017). In the multivariate analysis, high RANK expression was still an independent predictor for bone metastasis (HR ¼ 2.43, 95%CI: 1.10 to 5.37, p ¼ 0.028) and visceral metastasis (HR ¼ 2.69, 95%CI: 1.21 to 6.0, p ¼ 0.016). Conclusions: RANK expression in the primary ERþ/HER2-breast cancer samples is associated with more bone and visceral metastasis denoting inherent aggressiveness of this subgroup of patients rather than organ tropism. Further research is still needed to confirm these results.Legal entity responsible for the study: Centre Léon Bérard. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.98P Customized or randomized trials for relapsed refractory pediatric Burkitt lymphomas? A retrospective analysis of two clinical cases with comprehensive molecular profiling: Possible explanation for different treatment outcomes after similar targeted therapies

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