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Competing Interests: L. Monino is a consultant for Taewoong Medical, Fujifilm and Prion Medical, and has received speaker’s fees from Olympus Belgium and Olympus Europe. T. G. Moreels has received speaker’s fees from Olympus Belgium and Olympus Europe. L. Marique, Y. Deswysen, B. Navez, and E. Danse declare that they have no conflict of interest.

Background: Management of biliopancreatic pathology in Roux-en-Y gastric bypass (RYGB) patients is challenging despite the availability of multiple approaches like single-balloon enteroscopy-assisted ERCP (SBE-ERCP), laparoscopy-assisted ERCP (LA-ERCP), and EUS-directed transgastric intervention (EDGI). We evaluated the outcomes of the interchangeable combination of endoscopic procedures to treat biliopancreatic pathology in RYGB patients., Materials and Methods: This is a monocentric retrospective study of consecutive RYGB patients with biliopancreatic pathology between June 2014 and September 2023. Primary endpoints were technical success, adverse events (AE), and parameters of endoscopic procedures according to etiology. A clinically useful management algorithm was developed., Results: A total of 102 patients with RYGB (73 women; mean age 55 ± 10 years) were included. A total of 113 SBE-ERCP (in 90 patients), 26 EDGI (in 23 patients), and 2 LA-ERCP (in 2 patients) were performed. Technical success of SBE-ERCP was lower compared to EDGI (74.4% vs 95.1%, p = 0.002). The AE rate was lower using SBE-ERCP compared to EDGI (12.4% vs 38.5%, p = 0.003). Two sub-groups based on etiology were identified as "common bile duct stone" (CBDS) and "Other." In the CBDS group, the mean number and time of procedures were lower in SBE-ERCP as the first-line technique compared to first-line EDGI (1.1 vs 2.7, p < 0.00 and 91 ± 20.7 min vs 161 ± 61.3 min, p < 0.00)., Conclusion: A combination of endoscopic procedures can achieve high technical success in managing biliopancreatic pathology in RYGB patients with an acceptable AE rate. In the case of CBDS, SBE-ERCP appeared to be a good first-line single-step option. For other indications, EDGI should be proposed as the first line., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background & Aims: Our study aims to determine whether myostatin (MSTN) is associated with muscle mass and strength in individuals with cancer or obesity, as well as with cancer cachexia (CC) or sarcopenic obesity (SO)., Methods: The ACTICA study included individuals with CC (n = 70) or without CC (NC, n = 73). The MYDIASECRET study included individuals with obesity evaluated before (T0) and 3 months (T3) after bariatric surgery (n = 62). Body composition was assessed using bioelectrical impedance analysis (BIA). Skeletal muscle mass (SMM) and appendicular SMM (ASMM) were calculated from Janssen's and Sergi's equations, respectively, and expressed as indexes (SMMI and ASMMI). Handgrip strength (HGS) was assessed using a Jamar hand-held dynamometer. MSTN plasma levels were measured using ELISA. Spearman's coefficient was used to correlate MSTN with muscle mass and strength. Receiver operating characteristic (ROC) curve analysis was performed to identify an optimal MSTN cutoff level for the prediction of CC or SO., Results: In the ACTICA study, muscle mass and strength were lower in CC individuals than in NC individuals (SMMI: 8.0 kg/m 2 vs 9.0 kg/m 2 , p = 0.004; ASMMI: 6.2 kg/m 2 vs 7.2 kg/m 2 , p < 0.001; HGS: 28 kg vs 38 kg, p < 0.001). MSTN was also lower in CC individuals than in NC individuals (1434 pg/mL vs 2149 pg/mL, p < 0.001). Muscle mass and strength were positively correlated with MSTN (SMMI: R = 0.500, p < 0.001; ASMMI: R = 0.479, p < 0.001; HGS: R = 0.495, p < 0.001). ROC curve analysis showed a MSTN cutoff level of 1548 pg/mL (AUC 0.684, sensitivity 57%, specificity 75%, p < 0.001) for the prediction of CC. In the MYDIASECRET study, muscle mass and strength were reduced at T3 (SMMI: -8%, p < 0.001; ASMMI: -12%, p < 0.001; HGS: -6%, p = 0.005). MSTN was also reduced at T3 (1773 pg/mL vs 2582 pg/mL, p < 0.001). Muscle mass and strength were positively correlated with MSTN at T0 and T3 (SMMI-T0: R = 0.388, p = 0.002; SMMI-T3: R = 0.435, p < 0.001; HGS-T0: R = 0.337, p = 0.007; HGS-T3: R = 0.313, p = 0.013). ROC curve analysis showed a MSTN cutoff level of 4225 pg/mL (AUC 0.835, sensitivity 98%, specificity 100%, p = 0.014) for the prediction of SO at T3., Conclusions: MSTN is positively correlated with muscle mass and strength in individuals with cancer or obesity, suggesting its potential use as a biomarker of muscle mass and strength. The ROC curve analysis suggests the potential use of MSTN as a screening tool for CC and SO., Competing Interests: Conflict of interest The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Tumour progression drives profound alterations in host metabolism, such as adipose tissue depletion, an early event of cancer cachexia. As fatty acid consumption by cancer cells increases upon acidosis of the tumour microenvironment, we reasoned that fatty acids derived from distant adipose lipolysis may sustain tumour fatty acid craving, leading to the adipose tissue loss observed in cancer cachexia., Methods: To evaluate the pro-lipolytic capacities of acid-exposed cancer cells, primary mouse adipocytes from subcutaneous and visceral adipose tissue were exposed to pH-matched conditioned medium from human and murine acid-exposed cancer cells (pH 6.5), compared to naive cancer cells (pH 7.4). To further address the role of tumoral acidosis on adipose tissue loss, a pH-low insertion peptide was injected into tumour-bearing mice, and tumoral acidosis was neutralised with a sodium bicarbonate buffer. Prolipolytic mediators were identified by transcriptomic approaches and validated on murine and human adipocytes., Results: Here, we reveal that acid-exposed cancer cells promote lipolysis from subcutaneous and visceral adipocytes and that dampening acidosis in vivo inhibits adipose tissue depletion. We further found a set of well-known prolipolytic factors enhanced upon acidosis adaptation and unravelled a role for β-glucuronidase (GUSB) as a promising new actor in adipocyte lipolysis., Conclusions: Tumoral acidosis promotes the mobilization of fatty acids derived from adipocytes via the release of soluble factors by cancer cells. Our work paves the way for therapeutic approaches aimed at tackling cachexia by targeting the tumour acidic compartment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)