Postoperative Ileus and Postoperative Gastrointestinal Tract Dysfunction: Pathogenic Mechanisms and Novel Treatment Strategies Beyond Colorectal Enhanced Recovery After Surgery Protocols.
Postoperative Ileus and Postoperative Gastrointestinal Tract Dysfunction: Pathogenic Mechanisms and Novel Treatment Strategies Beyond Colorectal Enhanced Recovery After Surgery Protocols.
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DOI：
10.3389/fphar.2020.583422
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发表时间：
2020
影响因子：
5.6
通讯作者：
Christofi FL
中科院分区：
文献类型：
--
作者：
Mazzotta E;Villalobos-Hernandez EC;Fiorda-Diaz J;Harzman A;Christofi FL
术后肠梗阻（POI）和术后胃肠道功能障碍（POGD）是影响肠道手术患者的常见并发症。胃肠道症状包括恶心、呕吐、疼痛、腹胀、腹胀和便秘。这些医源性疾病与住院时间延长、发病率增加和数十亿美元的医疗保健费用相关，目前的治疗策略有限。这是一个叙述性的审查，重点是最近的概念，在发病机制的POI和POGD，管道药物或治疗方法。发病机制中涉及的机制、细胞靶标和途径包括肠道手术操作和手术创伤、神经炎症、反应性肠神经胶质细胞、巨噬细胞、肥大细胞、单核细胞、中性粒细胞和ICC。免疫、炎症、神经和神经胶质细胞之间的精确相互作用还不清楚。反应性肠神经胶质细胞是一种新兴的治疗靶点，正在对肠神经病、GI动力障碍和POI进行深入研究。我们的综述强调了当前的治疗策略，从实施结直肠术后增强恢复方案开始，以防止POI和POGD。然而，尽管结直肠手术后恢复增强，它仍然是一个重大的医疗问题和医疗保健系统的负担。在Clin.Trials. gov中列出了超过100种管道药物或治疗方法，其中包括5 HT 4 R激动剂（普卢卡必利和TAK 954）、迷走神经刺激ENS-巨噬细胞nAChR胆碱能通路、针灸、草药、外周作用阿片类拮抗剂（Alvimopen，Methlnaltexone，Naldemedine），抗腹胀/胀气药物（Simethiocone），一种胃饥饿激素促动力激动剂（Ulimovelin），喝咖啡和尼古丁口香糖。在我们能够制定更好的预防和治疗策略之前，更好地了解短期和长期结果的致病机制是必要的。
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 5HT4R 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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影响因子：
3.7
作者：
Deng G;Wong WD;Guillem J;Chan Y;Affuso T;Yeung KS;Coleton M;Sjoberg D;Vickers A;Cassileth B
通讯作者：
Cassileth B
影响因子：
3.1
作者：
Cox, Charles S., Jr.;Radhakrishnan, Ravi;Laine, Glen A.
通讯作者：
Laine, Glen A.
DOI：
10.1152/ajpgi.00384.2016
发表时间：
2017-02-01
影响因子：
4.5
作者：
Chow, Aaron K.;Gulbransen, Brian D.
通讯作者：
Gulbransen, Brian D.
影响因子：
29.4
作者：
Christofi, FL;Kim, M;Cooke, HJ
通讯作者：
Cooke, HJ
影响因子：
3.5
作者：
Chu J;Miller CT;Kislitsyna K;Laine GA;Stewart RH;Cox CS;Uray KS
通讯作者：
Uray KS