Surgically induced leukocytic infiltrates within the rat intestinal muscularis mediate postoperative ileus

Kalff, Jörg C.; Carlos, Timothy M.; Schraut, Wolfgang H.; Billiar, Timothy R.; Simmons, Richard L.; Bauer, Anthony J.

doi:10.1053/gast.1999.0029900378

Cited by 294 publications

(336 citation statements)

References 29 publications

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“…9,10 A characteristic of this local inflammation is the activation of the resident macrophages that lie as sentinels within the enteric muscularis. 11 This activation leads to phosphorylation of transcription factors, resulting in the subsequent induction of genes and release of cytokines, chemokines, and kinetically active substances such as nitric oxide and prostaglandins. 12 This local inflammatory milieu participates in the upregulation of adhesion molecules, which recruit degranulating leukocytes into the muscularis.…”

Section: Introductionmentioning

confidence: 99%

“…12 This local inflammatory milieu participates in the upregulation of adhesion molecules, which recruit degranulating leukocytes into the muscularis. 11,12 According to the current understanding, the inflammatory phase plays a significant role in the genesis and maintenance of gastrointestinal (GI) dysmotility after surgery, and is expected to be an important target for the future treatment of POI. However, there is still limited evidence regarding the association between inflammation and the recovery time from ileus in relation to different GI organs.…”

Section: Introductionmentioning

confidence: 99%

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Inflammation, Impaired Motility, and Permeability in a Guinea Pig Model of Postoperative Ileus

Lee

Hussain

Huh

et al. 2018

J Neurogastroenterol Motil

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Background/AimsPostoperative ileus (POI) is characterized by impaired propulsive function of the gastrointestinal tract after surgery. Although inflammation is considered to be an important pathogenesis of POI, significant data are lacking. We aim to correlate the recovery time of postoperative dysmotility with that of inflammation and mucosal permeability. MethodsAn experimental POI model of guinea pig was used. Contractile activity of the circular muscle of the stomach, jejunum, ileum, and proximal colon was measured through a tissue bath study. Inflammatory cells were counted, and the expression of calprotectin and tryptase were analyzed. The expression of protease-activated receptor 2 (PAR-2), claudin-1, and claudin-2 were analyzed with immunofluorescence. ResultsThe small bowel and colon showed decreased contractile amplitude in the POI groups compared to control. In contrast to the colon, the contractile amplitude of the small bowel significantly recovered in the POI group at 6 hours after the operation compared to the control group. Inflammation was highly significant in the POI groups compared to the control and sham groups, especially in the colon. Immunofluorescence showed increased PAR-2 expression in the POI groups compared to sham. The decreased claudin-1 expression and increased claudin-2 expression may suggest increased mucosal permeability of the small bowel and colon in the POI groups. ConclusionsIncreased inflammation and mucosal permeability may play an important role in the differential recovery stages in POI. These data may provide further insights into the pathophysiology and potential new therapeutic prospects of POI. (J Neurogastroenterol Motil 2018;24:147-158)

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inflammation, Impaired Motility, and Permeability in a Guinea Pig Model of Postoperative Ileus

Lee

Hussain

Huh

et al. 2018

J Neurogastroenterol Motil

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“…These authors described the FE in the model of IM in rodents. They examined the jejunal and colonic muscularis and discovered propagation of jejunal inflammation to the nonmanipulated colon after selective jejunal manipulation but could not provide a causal explanation (35,36,40). The functional, molecular, and cellular mechanisms determining POI are to be found within the intestinal muscularis.…”

Section: Discussionmentioning

confidence: 99%

“…Both the neuronal activation by intestinal manipulation (IM) and inflammatory cell infiltrates in the intestinal muscularis compromise gastrointestinal motility. These detrimental alterations are emphasized as major factors in the development of POI (4,8,9,15,16,[35][36][37][38][40][41][42]. We reported a time-and trauma-degree-dependent inflammatory cascade (35, 36); infiltration of leukocytes (40 -42, 72, 83), macrophages (21,22,37,87), and immunologically competent cells (35,36,40,67,69,72,81,83); and an upregulation of proinflammatory cytokines within the intestinal muscularis (36, 38 -40, 66, 68, 71, 80 -82, 84, 88).…”

mentioning

confidence: 99%

“…These detrimental alterations are emphasized as major factors in the development of POI (4, 8, 9, 15, 16, 35-38, 40 -42). We reported a time-and trauma-degree-dependent inflammatory cascade (35,36); infiltration of leukocytes (40 -42, 72, 83), macrophages (21,22,37,87), and immunologically competent cells (35,36,40,67,69,72,81,83); and an upregulation of proinflammatory cytokines within the intestinal muscularis (36, 38 -40, 66, 68, 71, 80 -82, 84, 88). The pharmacological or genetic inhibition of macrophages ameliorated the POI in rodents (87,89).…”

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confidence: 99%

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Impact of CCR7 on the gastrointestinal field effect

Koscielny

Engel

Maurer

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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.2010.-Standardized intestinal manipulation (IM) leads to local bowel wall inflammation subsequently spreading over the entire gastrointestinal tract. Previously, we demonstrated that this so-called gastrointestinal field effect (FE) is immune mediated. This study aimed to investigate the role of CCR7 in IM-induced FE. Since CCR7 is expressed on activated dendritic cells and T cells and is well known to control their migration, we hypothesized that lack of CCR7 reduces or abolishes FE. Small bowel muscularis and colonic muscularis from CCR7Ϫ/Ϫ and wild-type (WT) mice were obtained after IM of the jejunum or sham operation. FE was analyzed by measuring gastrointestinal transit time of orally given fluorescent dextran (geometric center), colonic transit time, infiltration of MPO-positive cells, and circular smooth muscle contractility. Furthermore, mRNA levels of the inflammatory cytokine IL-6 were determined by RT-PCR. The number of dendritic cells and CD3ϩCD25ϩ T cells separately isolated from jejunum and colon was determined in mice after IM and sham operation. There was no significant difference in IL-6 mRNA upregulation in colonic muscularis between sham-operated WT and CCR7 Ϫ/Ϫ mice after IM. Contractility of circular muscularis strips of the colon was significantly improved in CCR7 Ϫ/Ϫ animals following IM and did not vary significantly from sham-operated animals. Additionally, inflammation of the colon determined by the number of MPO-positive cells and colonic transit time was significantly reduced in CCR7 Ϫ/Ϫ mice. In contrast, jejunal contractility and jejunal inflammation of transgenic mice did not differ significantly from WT mice after IM. These data are supported by a significant increase of CD3ϩCD25ϩ T cells in the colonic muscularis of WT mice after IM, which could not be observed in CCR7Ϫ/Ϫ mice. These data demonstrate that CCR7 is required for FE and postoperative ileus. CCR7 indirectly affects FE by inhibiting migration of activated dendritic cells and of T cells from the jejunum to the colon. These findings support the critical role of the adaptive immune system in FE. postoperative ileus; chemokine receptor 7 POSTOPERATIVE ILEUS (POI) is an inevitable sequela of abdominal surgery or trauma with a variably gradual manifestation. It leads to postoperative discomfort, prolonged hospitalization, and increased patient morbidity and has a high impact on socioeconomic costs (27,43,49,63). The pathophysiology of POI and postoperative gastrointestinal dysmotility, respectively, has been elucidated in recent years. POI is marked by a neurogenic phase and a clinically relevant prolonged inflammatory phase. Both the neuronal activation by intestinal manipulation (IM) and inflammatory cell infiltrates in the intestinal muscularis compromise gastrointestinal motility. These detrimental alterations are emphasized as major factors in the development of POI (4,8,9,15,16,[35][36][37][38][40][41][42]. We reported a time-and trauma-degree-dependent inflammatory cascade (35, 36); infiltration of leukocytes (40 -42...

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Combined Surgery and Extensive Intraoperative Peritoneal Lavage vs Surgery Alone for Treatment of Locally Advanced Gastric Cancer

Guo

Sun

et al. 2019

JAMA Surg

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IMPORTANCE Peritoneal metastasis is the most frequent pattern of postoperative recurrence in patients with gastric cancer. Extensive intraoperative peritoneal lavage (EIPL) is a new prophylactic strategy for treatment of peritoneal metastasis of locally advanced gastric cancer; however, the safety and efficacy of EIPL is currently unknown.OBJECTIVE To evaluate short-term outcomes of patients with advanced gastric cancer who received combined surgery and EIPL or surgery alone. DESIGN, SETTING, AND PARTICIPANTS From March 2016 to November 2017, 662 patients with advanced gastric cancer receiving D2 gastrectomy were enrolled in a large, multicenter, randomized clinical trial from 11 centers across China. In total, 329 patients were randomly assigned to receive surgery alone, and 333 patients were randomly assigned to receive surgery plus EIPL. Clinical characteristics, operative findings, and postoperative short-term outcomes were compared between the 2 groups in the intent-to-treat population.MAIN OUTCOMES AND MEASURES Short-term postoperative complications and mortality. RESULTSThe present analysis included data from 550 patients, 390 men and 160 women, with a mean (SD) age of 60.8 (10.7) years in the surgery alone group and 60.6 (10.8) in the surgery plus EIPL group. Patients assigned to the surgery plus EIPL group exhibited reduced mortality (0 of 279 patients) compared with those assigned to surgery alone (5 of 271 patients [1.9%]) (difference, 1.9%; 95% CI, 0.3%-3.4%; P = .02). A significant difference in the overall postoperative complication rate was observed between patients receiving surgery alone (46 patients [17.0%]) and those receiving surgery plus EIPL (31 patients [11.1%]) (difference, 5.9%; 95% CI, 0.1%-11.6%; P = .04). Postoperative pain occurred more often following surgery alone (48 patients [17.7%]) than following surgery plus EIPL (30 patients [10.8%]) (difference, 7.0%; 95% CI, 0.8%-13.1%; P = .02).CONCLUSIONS AND RELEVANCE Inclusion of EIPL can increase the safety of D2 gastrectomy and decrease postoperative short-term complications and wound pain. As a new, safe, and simple procedure, EIPL therapy is easily performed anywhere and does not require any special devices or techniques. Our study suggests that patients with advanced gastric cancer appear to be candidates for the EIPL approach.

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Surgically induced leukocytic infiltrates within the rat intestinal muscularis mediate postoperative ileus

Cited by 294 publications

References 29 publications

Inflammation, Impaired Motility, and Permeability in a Guinea Pig Model of Postoperative Ileus

Inflammation, Impaired Motility, and Permeability in a Guinea Pig Model of Postoperative Ileus

Impact of CCR7 on the gastrointestinal field effect

Combined Surgery and Extensive Intraoperative Peritoneal Lavage vs Surgery Alone for Treatment of Locally Advanced Gastric Cancer

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