| 1. |
- Azhar, Najia, et al.
(författare)
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Laparoscopic Lavage vs Primary Resection for Acute Perforated Diverticulitis: Long-term Outcomes From the Scandinavian Diverticulitis (SCANDIV) Randomized Clinical Trial
- 2021
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Ingår i: JAMA Surgery. - Chicago, IL, United States : American Medical Association. - 2168-6254 .- 2168-6262. ; 156:2, s. 121-127
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Perforated colonic diverticulitis usually requires surgical resection, with significant morbidity. Short-term results from randomized clinical trials have indicated that laparoscopic lavage is a feasible alternative to resection. However, it appears that no long-term results are available.OBJECTIVE To compare long-term (5-year) outcomes of laparoscopic peritoneal lavage and primary resection as treatments of perforated purulent diverticulitis.DESIGN, SETTING, AND PARTICIPANTS This international multicenter randomized clinical trial was conducted in 21 hospitals in Sweden and Norway, which enrolled patients between February 2010 and June 2014. Long-term follow-upwas conducted between March 2018 and November 2019. Patients with symptoms of left-sided acute perforated diverticulitis, indicating urgent surgical need and computed tomography-verified free air, were eligible. Those available for trial intervention (Hinchey stagesINTERVENTIONS Patients were assigned to undergo laparoscopic peritoneal lavage or colon resection based on computer-generated, center-stratified block randomization.MAIN OUTCOMES AND MEASURES The primary outcome was severe complications within 5 years. Secondary outcomes included mortality, secondary operations, recurrences, stomas, functional outcomes, and quality of life.RESULTS Of 199 randomized patients, 101were assigned to undergo laparoscopic peritoneal lavage and 98were assigned to colon resection. At the time of surgery, perforated purulent diverticulitiswas confirmed in 145 patients randomized to lavage (n = 74) and resection (n = 71). The median follow-upwas 59 (interquartile range, 51-78; full range, 0-110) months, and 3 patientswere lost to follow-up, leaving a final analysis of 73 patients who had had laparoscopic lavage (mean [SD] age, 66.4 [13] years; 39 men [53%]) and 69 who had received a resection (mean [SD] age, 63.5 [14] years; 36 men [52%]). Severe complications occurred in 36%(n = 26) in the laparoscopic lavage group and 35%(n = 24) in the resection group (P = .92). Overall mortalitywas 32%(n = 23) in the laparoscopic lavage group and 25%(n = 17) in the resection group (P = .36). The stoma prevalencewas 8%(n = 4) in the laparoscopic lavage group vs 33% (n = 17; P =.002) in the resection group among patients who remained alive, and secondary operations, including stoma reversal, were performed in 36%(n = 26) vs 35%(n = 24; P = .92), respectively. Recurrence of diverticulitiswas higher following laparoscopic lavage (21% [n = 15] vs 4%[n = 3]; P = .004). In the laparoscopic lavage group, 30%(n = 21) underwent a sigmoid resection. Therewere no significant differences in the EuroQoL-5Dquestionnaire or Cleveland Global Quality of Life scores between the groups.CONCLUSIONS AND RELEVANCE Long-term follow-up showed no differences in severe complications. Recurrence of diverticulitis after laparoscopic lavage was more common, often leading to sigmoid resection. This must be weighed against the lower stoma prevalence in this group. Shared decision-making considering both short-term and long-term consequences is encouraged.
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| 2. |
- Münch, Andreas, 1970-, et al.
(författare)
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Dynamics of mucosal permeability and inflammation in collagenous colitis before, during, and after loop ileostomy
- 2005
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 54:8, s. 1126-1128
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Tidskriftsartikel (refereegranskat)abstract
- Collagenous colitis has become a more frequent diagnosis but the aetiology of this disease is still unknown. We describe a female patient with intractable collagenous colitis who was treated with a temporary loop ileostomy. She was followed clinically, histopathologically, and functionally by measuring mucosal permeability before surgery, after ileostomy, and after bowel reconstruction. In our case report, active collagenous colitis was combined with increased transcellular and paracellular mucosal permeability. Diversion of the faecal stream decreased inflammation of the mucosa and normalised epithelial degeneration and mucosal permeability. After restoration of bowel continuity, mucosal permeability was altered prior to the appearance of a collagenous layer.
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| 3. |
- Wallon, Conny, 1966-
(författare)
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Neuro-immune regulation of macromolecular permeability in the normal human colon and in ulcerative colitis
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background and aim: Persistent stress and life events affect the course of ulcerative colitis (UC) by largely unknown mechanisms. Regulation of epithelial permeability to antigens is crucial for the balance between inflammation and immuno-surveillance, and increased intestinal permeability has been shown in patients with ulcerative colitis. Corticotropin releasing hormone (CRH) has been implicated as an important mediator of stress-induced abnormalities in intestinal mucosal function in animal models. Further cholinergic signalling during stresshas been reported to increase bowel ion secretion in humans and uptake of HRP in rodents via activation of mast cells.The overall aim of this thesis was to examine the role of CRH-mediated and cholinergic signalling, and their interaction with mast cells and eosinophils, in the regulation of the mucosal barrier function in the normal human colon and in UC. In vivo studies or the use of surgical specimens for such studies have major shortcomings. Therefore a method with endoscopic biopsies in Ussing chambers was established for studies of protein antigen uptake and electrophysiology in human colonic biopsies, and used in subsequent investigations.Materials and methods: In the four studies a total of 91 healthy volunteers, 3 patients with rectal cancer, and 15 UC patients were included. Biopsies from the sigmoid colon were assessed for macromolecular permeability (Horseradish peroxidase (HRP), and 51Cr-EDTA), and electrophysiology during challenge with sodium caprate (C10), CRH or carbachol. Experiments were repeated with CRH receptor antagonists, carbachol receptor antagonists, mast cell stabilizers and nerve conductance blockers in Ussing chambers. The biopsies were examined by electron and light microscopy for endocytosis of HRP, morphological changes and receptor expression. Moreover, the human mast cell line, HMC-1; was used in studying expression of CRH receptors on mast cells.Results: Endoscopic biopsies of human colon were viable in Ussing chambers, and the technique was shown to be a reliable tool for studies of mucosal permeability to HRP. CRH stimulates transcellular uptake of HRP in human colon via CRH receptor subtypes R1 and R2 on subepithelial mast cells. Further, carbachol acts on muscarinic receptors, located on subepithelial eosinophils. Activated muscarinic M2 and M3 receptors on increased numbers of CRHproducing eosinophils in UC, lead to activation of mast cells and increased macromolecular uptake across the colonic mucosa. This signalling cascade is previously unrecognized, and may be involved in the inflammatory process in UC.Conclusions: In conclusion, we have demonstrated a chain of events leading to increased permeability to the protein antigen HRP in biopsies from healthy volunteers and patients with UC. The important steps begin with a cholinergic signal to muscarinic receptors on the CRH containing eosinophils. The next step includes activation of CRH receptors on mast cells leading to degranulation and increased macromolecular uptake across the epithelium. This explanatory model will have implications for understanding of the pathogenesis of UC and future treatment of the disease.
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| 4. |
- Yakymenko, Olena, 1988-, et al.
(författare)
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Infliximab restores colonic barrier to adherent-invasive E. coli in Crohn's disease via effects on epithelial lipid rafts
- 2018
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Ingår i: Scandinavian Journal of Gastroenterology. - Oxfordshire, United Kingdom : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 53:6, s. 677-684
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Infliximab is important in the therapeutic arsenal of Crohn’s disease (CD). However, its effect on mucosal barrier function is not fully understood. Adherent-invasive Escherichia coli (AIEC) are important in CD pathophysiology, but the transmucosal uptake routes are partly unknown. We investigated effects of infliximab on uptake of colon-specific AIEC HM427 across CD colonic mucosa.Materials and methods: Endoscopic biopsies from non-inflamed colon of seven patients with CD, before and after two infliximab infusions, and eight non-inflammation controls, were mounted in Ussing chambers. Paracellular permeability (51Cr-EDTA) and transmucosal passage of GFP-expressing HM427 were studied. Mechanisms of HM427 transepithelial transport were investigated in Caco-2 monolayers treated with TNF, in the presence of infliximab and/or endocytosis inhibitors.Results: Before infliximab treatment, colonic passage of HM427 [CD: 2475 CFU (450–3000); controls 1163(225–1950)] and 51Cr-EDTA permeability were increased in CD (p < .05), but were restored to control levels by infliximab (CD: 150 (18.8–1069)). In TNF-exposed Caco-2 monolayers HM427 transport and lipid rafts/HM427 co-localization was decreased by infliximab. The lipid raft inhibitor methyl-β-cyclodextrin decreased HM427 transport.Conclusion: Infliximab restored the colonic barrier to AIEC in CD; an effect partially mediated by blocking lipid rafts in epithelial cells. This ability likely contributes to infliximab’s clinical efficacy in colonic CD.
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