BACKGROUND: Severe acute pancreatitis (AP) often leads to distant organ dysfunction with a high morbidity and mortality rate. The most common and earliest organ to fail is the lungs, but the exact pathophysiological mechanisms underlying the disease are still unclear. No successful targeted therapy exists, and treatment is limited to organ supportive care. It is believed that the gut is involved in the development of distant organ failure, as severe AP is associated with changes in the microcirculation, gut permeability/motility, bacterial translocation, and activation of the gut-associated lymphoid tissue (GALT). Experimental evidence implicates the mesenteric lymph as a primary route for these toxic factors to gain access to the systemic circulation. This literature overview was made to survey these mechanisms and the potential of surgical interventions on the thoracic duct as a means of therapy. METHODS: Review of the pertinent English-language literature. RESULTS: In experimental studies, interruption of mesenteric lymphatic flow has preventive qualities for acute lung injury (ALI) in the setting of critical illness with various etiologies. Experimentally, diversion of mesenteric lymph is able to prevent ALI if done before its development, whereas a later intervention partially reduces the lung damage. Few studies have investigated surgical approaches to the thoracic duct in human beings under these circumstances, and the ones that have been performed are of low quality and have conflicting results. It seems likely that the intervention would need to be performed prior to the development of ALI to obtain maximum benefits, which complicates its application clinically, because prediction of ALI cannot today be done with high precision. CONCLUSION: Studies are ongoing to identify the factors carried in mesenteric lymph that may cause end-organ failure (e.g., ALI) and, once recognized, might allow the development of novel targeted agents that would modify the disease course.
BACKGROUND: Severe acute pancreatitis (AP) often leads to distant organ dysfunction with a high morbidity and mortality rate. The most common and earliest organ to fail is the lungs, but the exact pathophysiological mechanisms underlying the disease are still unclear. No successful targeted therapy exists, and treatment is limited to organ supportive care. It is believed that the gut is involved in the development of distant organ failure, as severe AP is associated with changes in the microcirculation, gut permeability/motility, bacterial translocation, and activation of the gut-associated lymphoid tissue (GALT). Experimental evidence implicates the mesenteric lymph as a primary route for these toxic factors to gain access to the systemic circulation. This literature overview was made to survey these mechanisms and the potential of surgical interventions on the thoracic duct as a means of therapy. METHODS: Review of the pertinent English-language literature. RESULTS: In experimental studies, interruption of mesenteric lymphatic flow has preventive qualities for acute lung injury (ALI) in the setting of critical illness with various etiologies. Experimentally, diversion of mesenteric lymph is able to prevent ALI if done before its development, whereas a later intervention partially reduces the lung damage. Few studies have investigated surgical approaches to the thoracic duct in human beings under these circumstances, and the ones that have been performed are of low quality and have conflicting results. It seems likely that the intervention would need to be performed prior to the development of ALI to obtain maximum benefits, which complicates its application clinically, because prediction of ALI cannot today be done with high precision. CONCLUSION: Studies are ongoing to identify the factors carried in mesenteric lymph that may cause end-organ failure (e.g., ALI) and, once recognized, might allow the development of novel targeted agents that would modify the disease course.
Authors: Nicole L Komara; Pedram Paragomi; Phil J Greer; Anette S Wilson; Cameron Breze; Georgios I Papachristou; David C Whitcomb Journal: Am J Physiol Gastrointest Liver Physiol Date: 2020-09-02 Impact factor: 4.052