Preoperative predictors of postsurgical adhesion formation and the Prevention of Adhesions with Plasminogen Activator (PAPA-study): results of a clinical pilot study.
OBJECTIVE
To identify predictors of postsurgical adhesion formation in peritoneal fluid and plasma, and assess efficacy and safety of reteplase (recombinant plasminogen activator [r-PA]).


METHODS
Prospective randomized study.


METHODS
University Medical Center.


METHODS
Twenty-six abdominal myomectomy patients with early second-look laparoscopy (ESL).


METHODS
Randomization to IP treatment with 1 mg reteplase in 300 mL Ringer's lactate or 300 mL Ringer's lactate only. Scoring of adhesions and collecting peritoneal fluid during both surgical procedures and collecting plasma samples at ten time points.


METHODS
Incidence, severity, and extent of adhesions at ESL. Concentrations of C-reactive protein (CRP), tissue-type plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI-1), and fibrin degradation products (FbDPs).


RESULTS
Significant correlation between the extent of uterine adhesion formation and preoperative plasma levels of CRP (r(s) = 0.558), PAI-1 (r(s) = 0.413), and the change in tPA concentration in peritoneal fluid from initial surgery to ESL (Delta+PA: r(s) = -0.636). No significant differences in adhesion scores between treatment and control groups.


CONCLUSIONS
Our finding that preoperative plasma CRP and PAI-1-levels are significantly correlated with extent of adhesion formation points to a role of chronic inflammation in the disease process. Results are highly indicative for the paradigm that adhesions are caused by an insufficiency in peritoneal fibrinolytic capacity. For successful adhesion prevention therapy relatively high amounts of r-PA are required.
Hellebrekers
Bart W J
BW
Department of Obstetrics and Gynecology, Haga Teaching Hospital, The Hague, The Netherlands. b.hellebrekers@hagaziekenhuis.nl
Trimbos-Kemper
Trudy C M
TC
Boesten
Lianne
L
Jansen
Frank Willem
FW
Kolkman
Wendela
W
Trimbos
J Baptist
JB
Press
Rogier R
RR
van Poelgeest
Mariette I E
MI
Emeis
Sjef J
SJ
Kooistra
Teake
T
D000328:Adult; D001202:Ascitic Fluid / Q000737:chemistry; D005260:Female; D013509:Gynecologic Surgical Procedures / Q000009:adverse effects; D006801:Humans; D015994:Incidence; D007247:Infertility, Female / Q000097:blood / Q000473:pathology / Q000601:surgery; D007889:Leiomyoma / Q000097:blood / Q000175:diagnosis / Q000473:pathology / Q000601:surgery*; D009215:Myometrium / Q000601:surgery; D010865:Pilot Projects; D010960:Plasminogen Activators / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000097:blood / Q000209:etiology / Q000473:pathology; D011300:Preoperative Care / Q000379:methods; D011379:Prognosis; D012307:Risk Factors; D000267:Tissue Adhesions / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D014594:Uterine Neoplasms / Q000097:blood / Q000175:diagnosis / Q000473:pathology / Q000601:surgery*; D055815:Young Adult
D010960:Plasminogen Activators