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Purpose: Approved systemic therapies for advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) have shown limited capacity to reduce tumor burden and no antitumor activity after progression to targeted agents (TAs). We investigated the efficacy and safety of lenvatinib in patients with previously treated advanced GEP-NETs., Patients and Methods: This was a multicenter, single-arm, open-label, phase II trial with two parallel cohorts (ClinicalTrials.gov identifier: NCT02678780) involving 21 institutions in 4 European countries. Eligible patients had histologically confirmed advanced grade 1-2 pancreatic (panNET) or GI (GI-NET) NETs with documented tumor progression after treatment with a TA (panNET) or somatostatin analogs (GI-NET). Patients were treated with lenvatinib 24 mg once daily until disease progression or treatment intolerance. The primary end point was overall response rate by central radiology review. Secondary end points included progression-free survival, overall survival, duration of response, and safety., Results: Between September 2015 and March 2017, a total of 111 patients were enrolled, with 55 (panNET) and 56 (GI-NET) patients in each cohort. The median follow-up was 23 months. The overall response rate was 29.9% (95% CI, 21.6 to 39.6): 44.2% (panNET) and 16.4% (GI-NET). The median (range) duration of response was 19.9 (8.4-30.8) and 33.9 (10.6-38.3) months in the panNET and GI-NET groups, respectively. The median progression-free survival was 15.7 months (95% CI, 14.1 to 19.5). The most common adverse events were fatigue, hypertension, and diarrhea; 93.7% of patients required dose reductions or interruptions., Conclusion: We report the highest centrally confirmed response reported to date with a multikinase inhibitor in advanced GEP-NETs, with a particularly strong response in the panNET cohort. This study provides novel evidence for the efficacy of lenvatinib in patients with disease progression following treatment with other TAs, suggesting the potential value of lenvatinib in the treatment of advanced GEP-NETs., Competing Interests: Jaume CapdevilaConsulting or Advisory Role: Bayer, Eisai, Sanofi, Exelixis, Novartis, Ipsen, Pfizer, Merck Serono, Advanced Accelerator Applications, LillySpeakers' Bureau: Bayer, Eisai, Sanofi, Novartis, Ipsen, Pfizer, Merck Serono, LillyResearch Funding: Eisai, AstraZeneca, Advanced Accelerator Applications, Novartis, Ipsen, Bayer, PfizerTravel, Accommodations, Expenses: Pfizer, Ipsen, Eisai Nicola FazioHonoraria: Novartis, Ipsen, Merck, Sanofi, Advanced Accelerator ApplicationsConsulting or Advisory Role: Novartis/Ipsen, Advanced Accelerator Applications, Pfizer, Ipsen, Merck Serono, MSD OncologyResearch Funding: Novartis, Merck Serono, Ipsen, MSDOther Relationship: Springer, Il Pensiero Scientifico Editore Carlos Lopez LopezHonoraria: Roche, Merck, Sanofi, Novartis, Pfizer, Eisai, Ipsen, Bayer, AstraZeneca, Servier, Bristol Myers Squibb, MSD Oncology, Advanced Accelerator ApplicationsConsulting or Advisory Role: Amgen, Roche, Sanofi, Merck, Servier, Pfizer, Ipsen, Bayer, Eisai, AstraZenecaResearch Funding: Amgen, Roche, Merck, Merck Sharp & Dohme, AstraZeneca Spain, Sanofi, Bayer, Ipsen, Eisai, Bristol Myers Squibb, Boehringer IngelheimTravel, Accommodations, Expenses: Roche, Pfizer, Merck, Servier, Amgen, Ipsen Alex TeuleHonoraria: Ipsen, Novartis, AAA HealthCare, PfizerConsulting or Advisory Role: AAA HealthCare Juan ValleHonoraria: IpsenConsulting or Advisory Role: Ipsen, Novartis, AstraZeneca, Merck, Agios, Pfizer, PCI Biotech, Incyte, Keocyt, QED Therapeutics, Pieris Pharmaceuticals, Genoscience Pharma, Mundipharma EDO GmbH, Wren Laboratories, Nucana, Servier, Debiopharm Group, Imaging Equipment Limited, Hutchison MediPharma, Zymeworks, Aptitude Health, Sirtex Medical, BaxterSpeakers' Bureau: Novartis, Ipsen, Nucana, Imaging Equipment Limited, Mylan, IncyteTravel, Accommodations, Expenses: Nucana, Pfizer, Lilly Nicholas ReedHonoraria: Novartis, Ipsen, Eisai, Roche, LillyConsulting or Advisory Role: Novartis, Ipsen, EisaiSpeakers' Bureau: RocheResearch Funding: Novartis, Ipsen, Exelixis, Lilly Enrique GrandeHonoraria: Pfizer, Bristol Myers Squibb, Ipsen, Roche, Eisai, Eusa Pharma, MSD, Genzyme, Advanced Accelerator Applications, Novartis, Pierre Fabre, Lexicon, Celgene, Janssen-Cilag, Astellas Pharma, AstraZeneca, Lilly, EUSA PharmaConsulting or Advisory Role: MSD, Pfizer, Ipsen, Roche, Bristol Myers SquibbResearch Funding: Roche, Pfizer, AstraZeneca, Ipsen, Molecular Templates, Lexicon, Astellas PharmaTravel, Accommodations, Expenses: Bristol Myers Squibb, Roche/Genentech, Pfizer, Janssen-Cilag, Ipsen Rocio Garcia-CarboneroHonoraria: Ipsen, Roche, Sanofi, Servier, Novartis, Pfizer, Merck, PharmaMar, Advanced Accelerator Applications, Bristol Myers Squibb, AstraZeneca, Lilly, Boehringer Ingelheim, Gilead Sciences, Sysmex, Pierre Fabre, Midatech Pharma, Advanz Pharma, HMP, Bayer, MSDConsulting or Advisory Role: Ipsen, Novartis, Pfizer, HMP, Advanced Accelerator Applications, Bayer, PharmaMar, Merck, MSD, Pierre FabreResearch Funding: Pfizer, Bristol Myers Squibb, MSDTravel, Accommodations, Expenses: Roche, Merck Paula J FonsecaOther Relationship: Ipsen Jorge HernandoSpeakers' Bureau: Eisai, Ipsen, Roche, Acraf, Advanced Accelerator ApplicationsTravel, Accommodations, Expenses: Ipsen, Novartis, Advanced Accelerator Applications, Roche, AstraZeneca, Eisai Francesca SpadaConsulting or Advisory Role: Ipsen, Novartis, Advanced Accelerator ApplicationsSpeakers' Bureau: Ipsen, Novartis, Advanced Accelerator ApplicationsTravel, Accommodations, Expenses: Ipsen, Novartis, Advanced Accelerator Applications Vicente AlonsoConsulting or Advisory Role: Amgen, Sanofi/Regeneron, Ipsen, Servier, Merck SeronoTravel, Accommodations, Expenses: Merck Serono, Roche, Novartis, Amgen, Sanofi/Regeneron, Ipsen, Servier Alfredo BerrutiConsulting or Advisory Role: Janssen-Cilag, Astellas Pharma, AmgenSpeakers' Bureau: Janssen-Cilag, Astellas PharmaResearch Funding: Astellas Pharma, Janssen-CilagTravel, Accommodations, Expenses: Janssen-Cilag, Sanofi, Sanofi Adelaida La CastaTravel, Accommodations, Expenses: Amgen, Roche, MSD Oncology Sevilla IsabelConsulting or Advisory Role: Ipsen, Pfizer, AmgenSpeakers' Bureau: Ipsen, PharmaMar, Sanofi, AAA HealthCareTravel, Accommodations, Expenses: Ipsen Patrizia KumpResearch Funding: Bristol Myers SquibbTravel, Accommodations, Expenses: Ipsen Pablo GajateConsulting or Advisory Role: Ipsen, Roche, EisaiSpeakers' Bureau: IPSEN, Pfizer, Novartis, EisaiTravel, Accommodations, Expenses: Ipsen, Pfizer Ignacio MatosSpeakers' Bureau: MSDResearch Funding: ESMO Angela LamarcaConsulting or Advisory Role: EISAI, Nutricia, Ipsen, QED Therapeutics, RocheSpeakers' Bureau: Merck, Ipsen, Pfizer, Novartis, Incyte, Advanced Accelerator ApplicationsResearch Funding: Ipsen, RocheTravel, Accommodations, Expenses: Abbott Nutrition, Ipsen, Pfizer, Celgene, Novartis, Advanced Accelerator Applications, Sirtex Medical, Bayer, Delcath Systems, Mylan, NanoString Technologies Toni IbrahimConsulting or Advisory Role: EISAI, Novartis, SanofiTravel, Accommodations, Expenses: Ipsen, Pharmamar, NovartisNo other potential conflicts of interest were reported.

Faecal microbiota transplantation (FMT) is an important therapeutic option for Clostridium difficile infection. Promising findings suggest that FMT may play a role also in the management of other disorders associated with the alteration of gut microbiota. Although the health community is assessing FMT with renewed interest and patients are becoming more aware, there are technical and logistical issues in establishing such a non-standardised treatment into the clinical practice with safety and proper governance. In view of this, an evidence-based recommendation is needed to drive the practical implementation of FMT. In this European Consensus Conference, 28 experts from 10 countries collaborated, in separate working groups and through an evidence-based process, to provide statements on the following key issues: FMT indications; donor selection; preparation of faecal material; clinical management and faecal delivery and basic requirements for implementing an FMT centre. Statements developed by each working group were evaluated and voted by all members, first through an electronic Delphi process, and then in a plenary consensus conference. The recommendations were released according to best available evidence, in order to act as guidance for physicians who plan to implement FMT, aiming at supporting the broad availability of the procedure, discussing other issues relevant to FMT and promoting future clinical research in the area of gut microbiota manipulation. This consensus report strongly recommends the implementation of FMT centres for the treatment of C. difficile infection as well as traces the guidelines of technicality, regulatory, administrative and laboratory requirements., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

With the ultimate objective in contributing to the improvement of the quality control of drinking water and to facilitate the checking of its compliance with the respective regulations, an inventory of analytical techniques used in water supply companies in Eastern and Western European countries is presented. The existing regulations for drinking water and bottled mineral water quality with respect to trace elements in these countries are compared to regulations of the World Health Organisation. The data obtained can be useful for further harmonisation of the respective regulations in Europe.