Evidence map›Paper›PMID 26171681›Full record

ArticleSurgical infections2015

GM6001 Increases Anastomotic Leakage following Colonic Obstruction Possibly by Impeding Epithelialization.

Martin Rehn, Peter-Martin Krarup, Lise H Christensen, Jakob B Seidelin, Magnus S Ågren, Ingvar Syk

Open access · greenAbstract read
In one paragraph

Article in Surgical infections, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.6field-weighted citation impact, top 31% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. The Science of Anastomotic Healing.Seminars in colon & rectal surgery · 2022
    Article
  3. Matrix Metalloproteinases: How Much Can They Do?International journal of molecular sciences · 2020
    Article
  4. Article
  5. Article
  6. Article
  7. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 2 countries.

Martin Rehn1 Department of Surgery, Skåne University Hospital , Malmö, Sweden .
Peter-Martin Krarup2 Digestive Disease Center, Bispebjerg Hospital, University of Copenhagen , Copenhagen, Denmark .
Lise H Christensen3 Department of Pathology, Bispebjerg Hospital, University of Copenhagen , Copenhagen, Denmark .
Jakob B Seidelin2 Digestive Disease Center, Bispebjerg Hospital, University of Copenhagen , Copenhagen, Denmark .
Magnus S Ågren2 Digestive Disease Center, Bispebjerg Hospital, University of Copenhagen , Copenhagen, Denmark .
Ingvar Syk1 Department of Surgery, Skåne University Hospital , Malmö, Sweden .
Bispebjerg Hospital · DKSkåne University Hospital · SEUniversity of Copenhagen · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEmergency operations performed on an obstructed colon are accompanied by an increased risk of anastomotic insufficiency. Tissue-destructive matrix metalloproteinase (MMP) activity is elevated in the obstructed colon and contributes to a loss of suture-holding submucosal collagen, which may be mediated by tumor necrosis factor (TNF)-α. Our aim was to study the effect of the non-selective MMP and TNF-α converting enzyme (TACE) inhibitor GM6001 (30 mg/kg) on anastomosis repair in obstructed left colon. GM6001 has been proved to be highly efficacious in elective anastomosis rodent models.

methodsA partial obstruction of the distal colon was induced in male Sprague-Dawley rats. After 4 d the obstructed colonic segment was resected, and an end-to-end anastomosis was constructed. Seven days later, the anastomoses were evaluated for clinical leakage. Histopathological and immunohistochemical assessments were also performed. Finally, the direct effect of GM6001 on epithelialization was studied in cultured colonic epithelial cells.

resultsUnlike the robust beneficial effect on anastomosis under uncomplicated conditions, here GM6001 had a negative impact on anastomotic wound healing following colonic obstruction and substantially (p=0.004) more rats in the GM6001 group (75%) than in the control group (11%) had developed anastomotic leakage. In the anastomotic wounds, the myofibroblast abundance and cell proliferation were similar in the two groups. Histologically, GM6001 treatment resulted in wider and minimally epithelialized wounds that were commonly necrotic on the luminal side and infiltrated with numerous granulocytes. In vitro, GM6001 also delayed (p=0.026) epithelialization of denuded intestinal epithelium grown on type I collagen.

conclusionsNon-selective MMP/TACE inhibition with GM6001 increased the anastomotic complications following colon obstruction. Inhibition of epithelialization is one possible mechanism responsible for the increased leakage following GM6001 treatment.

Indexed as

Anastomotic LeakAnimalsCaco-2 CellsColonDipeptidesDisease Models, AnimalEpithelial CellsHistocytochemistryHumansImmunohistochemistryIntestinal ObstructionMaleMatrix Metalloproteinase InhibitorsRats, Sprague-DawleyDipeptidesMatrix Metalloproteinase InhibitorsN-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide

Identifiers

PMID26171681
PMCPMC4663637
OpenAlexW1918593942

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.