Intestinal barrier dysfunction in clinical and experimental obstructive jaundice and its reversal by internal biliary drainage

Parks, Rowan W.; Clements, W. D. B.; Smye, Mike; Pope, C.; Rowlands, B. J.; Diamond, Tom

doi:10.1002/bjs.1800831007

Cited by 123 publications

(79 citation statements)

References 32 publications

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“…9 Humans with biliary obstruction also show evidence for enhanced susceptibility to endotoxin. [27][28][29][30][31] Possible causes for this phenomenon include alterations in circulating levels of endotoxin-binding proteins, a general activation state of neutrophils, and the fact that biliary obstruction influences the reticuloendothelial system in the liver as well as extrahepatic phagocytic cells. 27,[32][33][34] Although IL-1R Ϫ/Ϫ mice were indistinguishable from IL-1R ϩ/ϩ mice with respect to their response to bdl, they were partially protected against the effects of systemic endotoxin exposure.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-1 receptor type I gene-deficient bile duct-ligated mice are partially protected against endotoxin

et al. 2002

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Cholestatic liver injury is associated with an increased susceptibility toward endotoxininduced toxicity. To determine the role of interleukin 1 (IL-1) herein, extrahepatic cholestasis was induced by bile duct ligation (bdl) in IL-1 receptor type I gene-deficient (IL-1R ؊/؊ ) mice, which are unresponsive to IL-1␣ and IL-1␤, and normal IL-1R ؉/؉ mice. Bdl elicited increases in hepatic IL-1␣ and IL-1␤ messenger RNA (mRNA) and protein. Hepatocellular injury at 2 weeks after bdl was similar in IL-1R ؊/؊ and IL-1R ؉/؉ mice as shown by clinical chemistry and histopathology. Administration of endotoxin to cholestatic mice at 2 weeks after bdl was associated with enhanced cytokine release, more severe liver damage, and occurrence of death when compared with sham-operated mice. Endotoxin effects in shamoperated IL-1R ؊/؊ and IL-1R ؉/؉ mice were largely similar, but cholestatic IL-1R ؊/؊ mice were better protected against toxic effects of endotoxin, as reflected by lowered cytokine release, less profound liver injury, and reduced mortality. These data indicate that IL-1␣ and IL-1␤ are produced in the liver after bdl, but that these cytokines do not play a significant role in cholestatic liver damage; however, endogenous IL-1 activity is an important denominator of enhanced endotoxin sensitivity that is observed during cholestasis induced by bdl. S urgery in jaundiced patients with periampullary tumors carries an increased risk of postoperative complications. 1 Whereas in experienced centers, postoperative mortality has been reduced from 20% to 5%, morbidity remains as high as 50%. 2,3 Most complications have a septic etiology and are considered to be related with translocation of endotoxin from the intestinal lumen into the portal and systemic circulation where an inflammatory cascade is triggered. 4,5 Potential causes of translocation of endotoxin include lack of bile salts in the intestinal lumen resulting in increased bacterial translocation, 6,7 decreased function of the resident macrophages of the liver (the Kupffer cells) leading to inadequate interception of endotoxin, 6-8 and changes in plasma concentrations of lipoproteins which bind endotoxin. 9 In addition, cholestasis is associated with enhanced susceptibility toward endotoxin-induced toxicity. [9][10][11][12][13][14] Endotoxin exerts its biological effects by activating immunocompetent cells such as monocytes and macrophages. After exposure to endotoxin, these cells readily release various inflammatory mediators such as the cytokines tumor necrosis factor (TNF) and interleukin-1 (IL-1), 15 which leads to an inflammatory response. The Kupffer cells are also capable of releasing these cytokines in response to endotoxin. 16,17 IL-1␣ and IL-1␤ are pleiotropic proinflammatory cytokines that are considered to play a proximal role in initiation and regulation of the inflammatory cascade triggered in response to endotoxins or bacteremia. 15,18 Both IL-1␣ and IL-1␤ can interact with two specific cell surface receptors, the type I and type II IL-1 receptor (IL-1R), of ...

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Section: Discussionmentioning

confidence: 99%

Interleukin-1 receptor type I gene-deficient bile duct-ligated mice are partially protected against endotoxin

et al. 2002

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“…(Grade 2, evidence level C) Statement: In humans, it is well known that the increased intestinal permeability caused by obstructive jaundice is recovered after internal biliary drainage by EBS [94,95]. A recent study also showed that bile replacement by oral intake during external drainage helps restore intestinal barrier function in patients with biliary obstruction [96].…”

Section: Cq13: Is Bile Replacement Useful For Patients With External mentioning

confidence: 99%

Clinical practice guidelines for the management of biliary tract cancers 2015: the 2^nd English edition

Miyazaki

Yoshitomi

Miyakawa³

et al. 2015

J Hepato Biliary Pancreat

237

165

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Background The Japanese Society of Hepato-Biliary-Pancreatic Surgery launched the clinical practice guidelines for the management of biliary tract and ampullary carcinomas in 2008. Novel treatment modalities and handling of clinical issues have been proposed after the publication. New approaches for editing clinical guidelines, such as the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, also have been introduced for better and clearer grading of recommendations. Methods Clinical questions (CQs) were proposed in seven topics. Recommendation, grade of recommendation and statement for each CQ were discussed and finalized by evidencebased approach. Recommendation was graded to grade 1 (strong) and 2 (weak) according to the concept of GRADE system. Results The 29 CQs covered seven topics: (1) prophylactic treatment, (2) diagnosis, (3) biliary drainage, (4) surgical treatment, (5) chemotherapy, (6) radiation therapy, and (7) pathology. In 27 CQs, 19 recommendations were rated strong and 11 recommendations weak. Each CQ included the statement of how the recommendation was graded. Conclusions This guideline provides recommendation for important clinical aspects based on evidence. Future collaboration with cancer registry will be a key for assessment of the guidelines and establishment of new evidence. Free full-text articles and a mobile application of this guideline are available via

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“…[10][11][12] The endotoxin concentration in the portal circulation is increased, as a result of lack of bile salts in the gut lumen with, consequently, an unbalanced bacterial intestinal microflora and increased permeability of the intestinal mucosal barrier, promoting translocation of bacteria. 13,14 Inadequate clearance of endotoxins in obstructive jaundice has been attributed to an altered reticuloendothelial system (RES) function of Kuppfer cells in the liver. 14,15 Recently, it has been demonstrated that, in isolated liver Kuppfer cells from cholestatic mice, increased numbers of viable intracellular bacteria after infection were present, suggesting an impaired intracellular bacterial killing.…”

Section: Experimental Studiesmentioning

confidence: 99%

Preoperative Biliary Drainage in Patients with Obstructive Jaundice: History and Current Status

Gaag

Kloek

Castro

et al. 2009

Journal of Gastrointestinal Surgery

159

114

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Rationale Preoperative biliary drainage (PBD) has been introduced to improve outcome after surgery in patients suffering from obstructive jaundice due to a potentially resectable proximal or distal bile duct/pancreatic head lesion. In experimental models, PBD is almost exclusively associated with beneficial results: improved liver function and nutritional status; reduction of systemic endotoxemia; cytokine release; and, as a result, an improved immune response. Mortality was significantly reduced in these animal models. Human studies show conflicting results. Findings For distal obstruction, currently the "best-evidence" available clearly shows that routine PBD does not yield the appreciated improvement in postoperative morbidity and mortality in patients undergoing resection. Moreover, PBD harbors its own complications. However, most of the available data are outdated or suffer from methodological deficits. Conclusion The highest level of evidence for PBD to be performed in proximal obstruction, as well as over the preferred mode, is lacking but, nevertheless, assimilated in the treatment algorithm for many centers. Logistics and waiting lists, although sometimes inevitable, could be factors that might influence the decision to opt for PBD, as well as an extended diagnostic workup with laparoscopy (on indication) or scheduled preoperative chemotherapy.

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Intestinal barrier dysfunction in clinical and experimental obstructive jaundice and its reversal by internal biliary drainage

Cited by 123 publications

References 32 publications

Interleukin-1 receptor type I gene-deficient bile duct-ligated mice are partially protected against endotoxin

Interleukin-1 receptor type I gene-deficient bile duct-ligated mice are partially protected against endotoxin

Clinical practice guidelines for the management of biliary tract cancers 2015: the 2^nd English edition

Preoperative Biliary Drainage in Patients with Obstructive Jaundice: History and Current Status

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Intestinal barrier dysfunction in clinical and experimental obstructive jaundice and its reversal by internal biliary drainage

Cited by 123 publications

References 32 publications

Interleukin-1 receptor type I gene-deficient bile duct-ligated mice are partially protected against endotoxin

Interleukin-1 receptor type I gene-deficient bile duct-ligated mice are partially protected against endotoxin

Clinical practice guidelines for the management of biliary tract cancers 2015: the 2nd English edition

Preoperative Biliary Drainage in Patients with Obstructive Jaundice: History and Current Status

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Clinical practice guidelines for the management of biliary tract cancers 2015: the 2^nd English edition