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Postoperative Ileus and Postoperative Gastrointestinal Tract Dysfunction: Pathogenic Mechanisms and Novel Treatment Strategies Beyond Colorectal Enhanced Recovery After Surgery Protocols

Postoperative ileus (POI) and postoperative gastrointestinal tract dysfunction (POGD) are well-known complications affecting patients undergoing intestinal surgery. GI symptoms include nausea, vomiting, pain, abdominal distention, bloating, and constipation. These iatrogenic disorders are associated...

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Autores principales: Mazzotta, Elvio, Villalobos-Hernandez, Egina Criseida, Fiorda-Diaz, Juan, Harzman, Alan, Christofi, Fievos L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774512/
https://www.ncbi.nlm.nih.gov/pubmed/33390950
http://dx.doi.org/10.3389/fphar.2020.583422
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author Mazzotta, Elvio
Villalobos-Hernandez, Egina Criseida
Fiorda-Diaz, Juan
Harzman, Alan
Christofi, Fievos L.
author_facet Mazzotta, Elvio
Villalobos-Hernandez, Egina Criseida
Fiorda-Diaz, Juan
Harzman, Alan
Christofi, Fievos L.
author_sort Mazzotta, Elvio
collection PubMed
description Postoperative ileus (POI) and postoperative gastrointestinal tract dysfunction (POGD) are well-known complications affecting patients undergoing intestinal surgery. GI symptoms include nausea, vomiting, pain, abdominal distention, bloating, and constipation. These iatrogenic disorders are associated with extended hospitalizations, increased morbidity, and health care costs into the billions and current therapeutic strategies are limited. This is a narrative review focused on recent concepts in the pathogenesis of POI and POGD, pipeline drugs or approaches to treatment. Mechanisms, cellular targets and pathways implicated in the pathogenesis include gut surgical manipulation and surgical trauma, neuroinflammation, reactive enteric glia, macrophages, mast cells, monocytes, neutrophils and ICC’s. The precise interactions between immune, inflammatory, neural and glial cells are not well understood. Reactive enteric glial cells are an emerging therapeutic target that is under intense investigation for enteric neuropathies, GI dysmotility and POI. Our review emphasizes current therapeutic strategies, starting with the implementation of colorectal enhanced recovery after surgery protocols to protect against POI and POGD. However, despite colorectal enhanced recovery after surgery, it remains a significant medical problem and burden on the healthcare system. Over 100 pipeline drugs or treatments are listed in Clin.Trials.gov. These include 5HT(4)R agonists (Prucalopride and TAK 954), vagus nerve stimulation of the ENS—macrophage nAChR cholinergic pathway, acupuncture, herbal medications, peripheral acting opioid antagonists (Alvimopen, Methlnaltexone, Naldemedine), anti-bloating/flatulence drugs (Simethiocone), a ghreline prokinetic agonist (Ulimovelin), drinking coffee, and nicotine chewing gum. A better understanding of the pathogenic mechanisms for short and long-term outcomes is necessary before we can develop better prophylactic and treatment strategies.
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spelling pubmed-77745122021-01-01 Postoperative Ileus and Postoperative Gastrointestinal Tract Dysfunction: Pathogenic Mechanisms and Novel Treatment Strategies Beyond Colorectal Enhanced Recovery After Surgery Protocols Mazzotta, Elvio Villalobos-Hernandez, Egina Criseida Fiorda-Diaz, Juan Harzman, Alan Christofi, Fievos L. Front Pharmacol Pharmacology Postoperative ileus (POI) and postoperative gastrointestinal tract dysfunction (POGD) are well-known complications affecting patients undergoing intestinal surgery. GI symptoms include nausea, vomiting, pain, abdominal distention, bloating, and constipation. These iatrogenic disorders are associated with extended hospitalizations, increased morbidity, and health care costs into the billions and current therapeutic strategies are limited. This is a narrative review focused on recent concepts in the pathogenesis of POI and POGD, pipeline drugs or approaches to treatment. Mechanisms, cellular targets and pathways implicated in the pathogenesis include gut surgical manipulation and surgical trauma, neuroinflammation, reactive enteric glia, macrophages, mast cells, monocytes, neutrophils and ICC’s. The precise interactions between immune, inflammatory, neural and glial cells are not well understood. Reactive enteric glial cells are an emerging therapeutic target that is under intense investigation for enteric neuropathies, GI dysmotility and POI. Our review emphasizes current therapeutic strategies, starting with the implementation of colorectal enhanced recovery after surgery protocols to protect against POI and POGD. However, despite colorectal enhanced recovery after surgery, it remains a significant medical problem and burden on the healthcare system. Over 100 pipeline drugs or treatments are listed in Clin.Trials.gov. These include 5HT(4)R agonists (Prucalopride and TAK 954), vagus nerve stimulation of the ENS—macrophage nAChR cholinergic pathway, acupuncture, herbal medications, peripheral acting opioid antagonists (Alvimopen, Methlnaltexone, Naldemedine), anti-bloating/flatulence drugs (Simethiocone), a ghreline prokinetic agonist (Ulimovelin), drinking coffee, and nicotine chewing gum. A better understanding of the pathogenic mechanisms for short and long-term outcomes is necessary before we can develop better prophylactic and treatment strategies. Frontiers Media S.A. 2020-11-24 /pmc/articles/PMC7774512/ /pubmed/33390950 http://dx.doi.org/10.3389/fphar.2020.583422 Text en Copyright © 2020 Mazzotta, Villalobos-Hernandez, FIORDA-DIAZ, Harzman and Christofi http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Mazzotta, Elvio
Villalobos-Hernandez, Egina Criseida
Fiorda-Diaz, Juan
Harzman, Alan
Christofi, Fievos L.
Postoperative Ileus and Postoperative Gastrointestinal Tract Dysfunction: Pathogenic Mechanisms and Novel Treatment Strategies Beyond Colorectal Enhanced Recovery After Surgery Protocols
title Postoperative Ileus and Postoperative Gastrointestinal Tract Dysfunction: Pathogenic Mechanisms and Novel Treatment Strategies Beyond Colorectal Enhanced Recovery After Surgery Protocols
title_full Postoperative Ileus and Postoperative Gastrointestinal Tract Dysfunction: Pathogenic Mechanisms and Novel Treatment Strategies Beyond Colorectal Enhanced Recovery After Surgery Protocols
title_fullStr Postoperative Ileus and Postoperative Gastrointestinal Tract Dysfunction: Pathogenic Mechanisms and Novel Treatment Strategies Beyond Colorectal Enhanced Recovery After Surgery Protocols
title_full_unstemmed Postoperative Ileus and Postoperative Gastrointestinal Tract Dysfunction: Pathogenic Mechanisms and Novel Treatment Strategies Beyond Colorectal Enhanced Recovery After Surgery Protocols
title_short Postoperative Ileus and Postoperative Gastrointestinal Tract Dysfunction: Pathogenic Mechanisms and Novel Treatment Strategies Beyond Colorectal Enhanced Recovery After Surgery Protocols
title_sort postoperative ileus and postoperative gastrointestinal tract dysfunction: pathogenic mechanisms and novel treatment strategies beyond colorectal enhanced recovery after surgery protocols
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774512/
https://www.ncbi.nlm.nih.gov/pubmed/33390950
http://dx.doi.org/10.3389/fphar.2020.583422
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