Institutions 1 Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium 2 Department of Gastroenterology and Hepatology, Amsterdam UMC, Vrije Universiteit Amsterdam, AGEM Institute, Amsterdam, The Netherlands 3 Department of Gastroenterology and Hepatology, Imelda General Hospital, Bonheiden, Belgium 4 Department of Gastroenterology and Hepatology, Leeds Teaching Hospital NHS Trust, Leeds, UK 5 Department of Medical Gastroenterology, Asian Institute of Gastroenterology Hospitals, Gachibowli, Hyderabad, India 6 Gastroenterology Department, Colentina Clinical Hospital, Bucharest, Romania 7 Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic 8 Department of Surgery, Department of Gastroenterology and Hepatology, and Department of Advanced Interventional Endoscopy, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium 9 Department of Gastroenterology and Hepatology, Université catholique de Louvain, CHU UCL Namur, Yvoir, Belgium 10 Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA 11 Pancreatobiliary Endoscopy and Endosonography Division, IRCCS San Raffaele Scientific Institute, Milan, Italy 12 Digestive Endoscopy Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, and Center for Endoscopic Research Therapeutics and Training (CERTT), Catholic University, Rome, Italy 13 Paoli-Calmettes Institute, Department of Gastrointestinal Disease, Marseille, France 14 Division of Gastroenterology and Hepatology, Johns Hopkins Hospital, Baltimore, Maryland, USA 15 Interventional Endoscopy Services, California Pacific Medical Center, San Francisco, California, USA 16 Department of Gastroenterology, Aix-Marseille Université, APHM, Hôpital Nord, Marseille, France 17 Gastroenterology Department, Hospital Universitario Rio Hortega, Valladolid, Spain 18 Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands

Therapeutic endoscopic ultrasound: European Society of Gastrointestinal Endoscopy (ESGE) Guideline

Given the fact that tumor-associated macrophage-derived extracellular vesicles (EVs) are attributable to tumor aggressiveness, this research intends to decode the mechanism of M2 macrophage-derived EVs in the differentiation and activities of pancreatic cancer (PaCa) stem cells via delivering microRNA (miR)-21-5p. Polarized M2 macrophages were induced, from which EVs were collected and identified. miR-21-5p expression in M2 macrophage-derived EVs was tested. After cell sorting, CD24+CD44+EpCAM+ stem cells were co-cultured with M2 macrophages, in which miR-21-5p was upregulated or downregulated. The effects of M2 macrophage-derived EVs and miR-21-5p on Nanog/octamer-binding transcription factor 4 (Oct4) expression, sphere formation, colony formation, invasion and migration capacities, apoptosis, and in vivo tumorigenic ability were examined. Kruppel-like factor 3 (KLF3) expression and its interaction with miR-21-5p were determined. M2 macrophage-derived EVs promoted PaCa stem cell differentiation and activities. miR-21a-5p was upregulated in M2 macrophage-derived EVs. miR-21a-5p downregulation in M2 macrophage-derived EVs inhibited Nanog/Oct4 expression and impaired sphere-forming, colony-forming, invasion, migration, and anti-apoptosis abilities of PaCa stem cells in vitro and tumorigenic ability in vivo. miR-21-5p targeted KLF3 to mediate the differentiation and activities of PaCa stem cells, and KLF3 was downregulated in PaCa stem cells. This work explains that M2 macrophage-derived exosomal miR-21a-5p stimulates differentiation and activity of PaCa stem cells via targeting KLF3, paving a novel way for attenuating PaCa stemness.

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microRNA-21-5p from M2 macrophage-derived extracellular vesicles promotes the differentiation and activity of pancreatic cancer stem cells by mediating KLF3

CircRNAs, covalently closed noncoding RNAs, are widely expressed in a wide range of species ranging from viruses to plants to mammals. CircRNAs were enriched in the Wnt pathway. Aberrant Wnt pathway activation is involved in the development of various types of cancers. Accumulating evidence indicates that the circRNA/Wnt axis modulates the expression of cancer-associated genes and then regulates cancer progression. Wnt pathway-related circRNA expression is obviously associated with many clinical characteristics. CircRNAs could regulate cell biological functions by interacting with the Wnt pathway. Moreover, Wnt pathway-related circRNAs are promising potential biomarkers for cancer diagnosis, prognosis evaluation, and treatment. In our review, we summarized the recent research progress on the role and clinical application of Wnt pathway-related circRNAs in tumorigenesis and progression. 

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The functional roles of the circRNA/Wnt axis in cancer

Cancer cachexia is a multifactorial syndrome that is characterised by a loss of skeletal muscle mass, is commonly associated with adipose tissue wasting and malaise, and responds poorly to therapeutic interventions. Although cachexia can affect patients who are severely ill with various malignant or non-malignant conditions, it is particularly common among patients with pancreatic cancer. Pancreatic cancer often leads to the development of cachexia through a combination of distinct factors, which, together, explain its high prevalence and clinical importance in this disease: systemic factors, including metabolic changes and pathogenic signals related to the tumour biology of pancreatic adenocarcinoma; factors resulting from the disruption of the digestive and endocrine functions of the pancreas; and factors related to the close anatomical and functional connection of the pancreas with the gut. In this review, we conceptualise the various insights into the mechanisms underlying pancreatic cancer cachexia according to these three dimensions to expose its particular complexity and the challenges that face clinicians in trying to devise therapeutic interventions.

Pancreatic cancer cachexia: three dimensions of a complex syndrome.

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BackgroundPancreatic cancer is the fourth leading cause of cancer mortality. Most patients are diagnosed with advanced pancreatic cancer, either at locally advanced or metastatic stages, and have a...

Pancreatic exocrine insufficiency and pancreatic enzyme replacement therapy in patients with advanced pancreatic cancer: A systematic review and meta-analysis:

Background: Malnutrition and cachexia are common in patients with advanced pancreatic ductal adenocarcinoma (PDAC) and have a significant influence on the tolerance and response to treatments. If timely identified, malnourished PDAC patients could be treated to increase their capacity to complete the planned treatments and, therefore, possibly, improve their efficacy. Aims: The aim of this study is to assess the impact of nutritional status, pancreatic exocrine insufficiency (PEI), and other clinical factors on patient outcomes in patients with advanced PDAC. Methods: PAncreatic Cancer MAlnutrition and Pancreatic Exocrine INsufficiency in the Course of Chemotherapy in Unresectable Pancreatic Cancer (PAC-MAIN) is an international multicenter prospective observational cohort study. The nutritional status will be determined by means of Mini-Nutritional Assessment score and laboratory blood tests. PEI will be defined by reduced fecal elastase levels. Main outcome adherence to planned chemotherapy in the first 12 weeks following the diagnosis, according to patients' baseline nutritional status and quantified and reported as "percent of standard chemotherapy dose delivered." Secondary outcomes rate of chemotherapy-related toxicity, progression-free survival, survival at 6 months, overall survival, quality of life, and the number of hospitalizations. Analysis chemotherapy dosing over the first 12 weeks of therapy (i.e., percent of chemotherapy received in the first 12 weeks, as defined above) will be compared between well-nourished and malnourished patients. Sample size based on an expected percentage of chemotherapy delivered of 70% in well-nourished patients, with a type I error of 0.05 and a type II error of 0.20, a sample size of 93 patients per group will be required in case of a percentage difference of chemotherapy delivered of 20% between well-nourished and malnourished patients, 163 patients per group in case of a difference of 15% between the groups, and 356 patients per group in case of a 10% difference. Centers from Russia, Romania, Turkey, Spain, Serbia, and Italy will participate in the study upon Local Ethics Committee approval. Discussion: PAC-MAIN will provide insights into the role of malnutrition and PEI in the outcomes of PDAC. The study protocol was registered at clinicaltrials.gov as NCT04112836.

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Maryana Bozhychko

Papers

Pancreatic exocrine insufficiency and pancreatic enzyme replacement therapy in patients with advanced pancreatic cancer: A systematic review and meta-analysis:

Pancreatic Cancer Malnutrition and Pancreatic Exocrine Insufficiency in the Course of Chemotherapy in Unresectable Pancreatic Cancer.

Dietary fat patterns and outcomes in acute pancreatitis