Adhesion reformation and the limited translational value of experiments with adhesion barriers: A systematic review and meta-analysis of animal models

Abstract

Today, 40-66% of elective procedures in general surgery are reoperations. During reoperations, the need for adhesiolysis results in increased operative time and a more complicated convalescence. In pre-clinical evaluation, adhesion barriers are tested for their efficacy in preventing 'de novo' adhesion formation, However, it is unknown to which extent barriers are tested for prevention of adhesion reformation. The aim of this systematic review and meta-analysis is to assess the efficacy of commercially available adhesion barriers and laparoscopic adhesiolysis in preventing adhesion reformation in animal models. Pubmed and EMBASE were searched for studies which assessed peritoneal adhesion reformation after a standardized peritoneal injury (in the absence of an intra-peritoneal mesh), and reported the incidence of adhesions, or an adhesion score as outcome. Ninety-three studies were included. No study met the criteria for low risk of bias. None of the commercially available adhesion barriers significantly reduced the incidence of adhesion reformation. Three commercially available adhesion barriers reduced the adhesion score of reformed adhesions, namely Seprafilm (SMD 1.38[95% CI]; p < 0.01), PEG (SMD 2.08[95% CI]; p < 0.01) and Icodextrin (SMD 1.85[95% CI]; p < 0.01). There was no difference between laparoscopic or open adhesiolysis with regard to the incidence of adhesion reformation (RR 1.14[95% CI]; p ≥ 0.05) or the adhesion score (SMD 0.92[95% CI]; p ≥ 0.05). Neither currently commercially available adhesion barriers, nor laparoscopic adhesiolysis without using an adhesion barrier, reduces the incidence of adhesion reformation in animal models. The methodological quality of animal studies is poor.

Figure 1

Flow-chart.

Figure 2

General characteristics of the studies included in the systematic review. Animal species: 1 rabbit, 2 rat, 3 other, 4 not applicable (NA), 5 NA; Sex: 1 male, 2 female, 3 mixed, 4 unknown, 5 NA; Type of experimental model: 1 cecal abrasion, 2 uterine horn, 3 other, 4 NA, 5 NA; Type of control group: 1 external control, 2 internal control, 3 NA, 4 NA, 5 NA; Intervention used in control group: 1 no intervention, 2 saline, 3 placebo, 4 multiple control groups, 5 other adhesion barrier; Time interval between 2nd operation and sacrifice: 1 7 days, 2 14 days, 3 21 days, 4 other, 5 unknown; Repeated peritoneal injury at second laparotomy; 1 Yes, 2 No, 3 Unknown, 4 NA, 5 NA; Method of adhesiolysis: 1 blunt/sharp, 2 coagulation, 3 unknown, 4 NA, 5 NA; Perioperative antibiotics, fluid resuscitation or analgesia: 1 Yes, 2 No, 3 Unknown, 4 NA, 5 NA; Type of scoring system: 1 tenacity, 2 extent, 3 morphology, 4 combined, 5 other.

Figure 3

Risk of bias for the studies included in the systematic review. showing the proportion of studies scoring with low risk of bias (yes), high risk of bias (no) or that did not specify (NS) the key methodological variables.

Figure 4

Funnel plot showing the incidence of adhesion reformation as a percentage of the total number of animals in the control group.

Figure 5

Forest plot showing the efficacy of commercially available adhesion barriers in reducing the incidence of adhesion reformation.

Figure 6

Forest plot showing the efficacy of commercially available adhesion barriers in reducing the adhesion score of reformed adhesions.

Figure 7

Forest plot showing the efficacy of laparoscopic versus open adhesiolysis in reducing the incidence of adhesion reformation.