1. OP033 THE MANAGEMENT OF PATIENTS WITH HIGH OUTPUT ENTEROCUTANEOUS FISTULAE: A EUROPEAN SURVEY
- Author
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G. Wanten, Loris Pironi, S. W. M. Olde Damink, A Forbes, Stanislaw Klek, W.G. van Gemert, Simon M. Gabe, Jon Shaffer, Henrik Højgaard Rasmussen, Øivind Irtun, Mette Holst, and Marek Pertkiewicz
- Subjects
Cathepsin ,medicine.medical_specialty ,Nutrition and Dietetics ,business.industry ,Vastus lateralis muscle ,Medicine (miscellaneous) ,Cancer ,Esophageal cancer ,Critical Care and Intensive Care Medicine ,medicine.disease ,Gastroenterology ,Primary tumor ,Cachexia ,Internal medicine ,Medicine ,Animal studies ,Respiratory system ,business - Abstract
Rationale: Animal models have showed that ubiquitinproteasome pathway (UPP) may be the effector of muscle loss during cancer cachexia. However, evidence from clinical studies is still needed to understand mechanisms involved in cancer induced muscle catabolism in patients. Methods: Patients (n = 17, 64±6 years) diagnosed with esophageal cancer were undergoing surgery with intent of resection of the primary tumor. As a control group, weight stable patients undergoing reflux surgery (n = 10, 60±7 years) were included. Vastus lateralis muscle biopsies were taken with a Bergstrom needle. Diaphragm biopsies were obtained by open surgery (cancer group) and by laparoscopic surgery (control group). Proteasome, caspase 3, calpains and lysosomal enzymatic activities were measured by using specific fluorogenic peptide substrates. Differences between the groups were tested with a Student’s t-test. Results: Cathepsin L activity was 115% higher in the vastus lateralis of cancer patients compared to the controls (5.3±0.4 vs 2.5±0.3 pmol/min/mg; p < 0.001). Cathepsin B activity in vastus lateralis was 85% higher in the cancer group compared to the control group (2.4±0.2 vs 1.3±0.2 pmol/min/mg; p < 0.001). This latter activity was correlated to the self-reported body weight loss of cancer patients (R2 = 0.41, p = 0.03). In diaphragm, activities of both cathepsins were 60% higher in cancer patients compared to the controls (p < 0.01). Proteasome, calpain and caspase3 activities did not differ between the two groups neither in vastus lateralis nor in diaphragm. Conclusion: The finding of weight-loss related activation of cathepsins in both skeletal and respiratory muscles in patients with esophageal cancer suggest that the lysosomal pathway might be involved in the development of cancer cachexia. In contrast to animal studies, in our study, UPP seems not to be the main or exclusive system implicated in muscle loss during cachexia.
- Published
- 2012