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Minimally Invasive Therapy and Allied Technologies
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Effect of cyanoacrylate on closure of gastric perforation: A comparative study in
a rat model
Omer Faik Ersoy a; Namik Ozkan a; Alper Celik a; Huseyin Ayhan Kayaoglu a; Ebru Cakir b
a
Department of General Surgery, Gaziosmanpasa University Faculty of Medicine, Tokat, Turkey b
Department of Pathology, Ataturk Chest Diseases Research and Training Hospital, Ankara, Turkey
Online Publication Date: 01 January 2009
To cite this Article Ersoy, Omer Faik, Ozkan, Namik, Celik, Alper, Kayaoglu, Huseyin Ayhan and Cakir, Ebru(2009)'Effect of
cyanoacrylate on closure of gastric perforation: A comparative study in a rat model',Minimally Invasive Therapy and Allied
Technologies,18:4,225 — 231
To link to this Article: DOI: 10.1080/13645700903062387
URL: http://dx.doi.org/10.1080/13645700903062387
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Minimally Invasive Therapy. 2009; 18:4; 225–231
ORIGINAL ARTICLE
Effect of cyanoacrylate on closure of gastric perforation: A comparative
study in a rat model
Omer Faik Ersoy1, Namik Ozkan1, Alper Celik1, Huseyin Ayhan Kayaoglu1,
Ebru Cakir2
1Department
Downloaded By: [Trinity College Dublin] At: 19:13 8 November 2009
of General Surgery, Gaziosmanpasa University Faculty of Medicine, Tokat, Turkey 2Department of
Pathology, Ataturk Chest Diseases Research and Training Hospital, Ankara, Turkey
Abstract
The aim of the study was to compare suture, clip and clip combined with topical N-butyl cyanoacrylate in an experimental
model of gastric perforation. Sixty Wistar-Albino rats were divided into three groups. Midline laparotomy was performed and
a 4 mm puncture was done on the anterior surface of the stomach. Closure was performed by sutures in the first group, clip
in the second group, and clip with topical cyanoacrylate in the third group. Ten rats underwent a re-laparotomy on the 3rd
and 7th days, respectively. Intraabdominal adhesions, burst pressures, procedural time, total operation time and histological
evaluation were analyzed. In the early phase, clip with topical cyanoacrylate treatment significantly improved burst pressures
(p=0.001). In the late phase, burst pressure levels were slightly higher in the third group. Procedural period and total operation times were significantly higher in the suture-treated group and lower in the clip group. Clip with topical cyanoacrylate
treatment improved histological healing indices, with significant difference in granulation, chronic inflammation and collagenisation scores, but at the expense of a significantly increased adhesion formation (P=0.001). Our study shows that gastric
perforations can be effectively treated by the combination of clip and cyanoacrylate with shorter time and acceptable sideeffects in selected cases.
Key words: Gastric perforation, closure, suture, cyanoacrylate, clip
Introduction
Gastric perforation results from a number of diseases
(e.g. peptic ulcer) and iatrogenic causes such as
instrumental injury. There have been various attempts
to cure gastric perforations. Before the advent of
minimally invasive surgical techniques, conventional
treatment was laparotomy. However, improvements
in laparoscopic techniques and biomaterials have made
it possible to treat gastrointestinal (GI) perforations
laparoscopically (1–6).
Surgical glues have been extensively used for the
treatment of a variety of medical conditions including
variceal bleeding, embolization, and urinary, biliary,
lymphatic and anastomotic fistulas (7–14). Also glues
like fibrin, gelatin and cyanoacrylates (CA) have been
used to treat GI fistulas and perforations (15–18).
Desired properties of surgical glues include adequate
adhesive strength, gradual degradation without foreignbody response, biocompatibility and appropriate polymerization. Some of the most commonly used adhesives in clinical practice are fibrin glues, gelatin and
acrylate derivatives. Fibrin glues function by forming
a stable fibrin matrix. They are completely biodegradable and are free of toxicity (19). Gelatin glues
have a greater strength than fibrin glues, but have
cytotoxicity due to the release of formaldehyde during
degradation (20). CA have the advantages of applicability to numerous tissues and high polymerization
rate (21). Its usage for skin closure is well documented
(22–23). Also, they are stronger than fibrin glue
(24–26). These advantageous effects played the main
role in choosing CA in our study. The question to
which extent biological glues can be used to treat GI
Correspondence: Omer Faik Ersoy, Gaziosmanpasa Unıversity Faculty of Medicine, Department of General Surgery, 60100 Tokat/Turkey,
E-mail: dromerfersoy@yahoo.com
ISSN 1364-5706 print/ISSN 1365-2931 online © 2009 Informa UK Ltd
DOI: 10.1080/13645700903062387
226
O.F. Ersoy et al.
perforations remains to be proven. There is no study
comparing the safety of suturing with clip and
bioadhesives. This paper contains a unique idea of
combining CA and clip to facilitate simple closure of
a perforated stomach, which may also be used for
clinical instances such as iatrogenic injuries. Our idea
may lead to a new concept of a simple approach to
tissue approximation.
Material and methods
Downloaded By: [Trinity College Dublin] At: 19:13 8 November 2009
Experimental protocol
This study was approved by the institutional ethical
committee. Sixty Wistar-albino rats, weighing 250–350 g
were randomly allocated to three groups (n=20,
per group). All operative processes and follow-up
were performed at Gaziosmanpasa University Animal
Studies Research Center. Two to three rats of the
same sex were housed in separate wire cages with free
access to food and water under standard laboratory
conditions (room temperature 23°C, 12 h light-dark
cycles). Rats were fasted 12 h before surgery, but had
free access to water. On the operative day rats were
weighed before surgery, anesthesia was conducted by
intraperitoneal injection of ketamin hydrochloride
(75 mg/kg) and xylazin (10 mg/kg). Under anesthesia,
a midline laparotomy (1.5 cm) was made and a standard 4 mm gastric perforation was performed on the
ventral side at a fixed point on the anterior aspect of
the gastric corpus, at the midline between each
curvatures. In the first group (S group) closure of the
gastric perforation was performed by a single suture
using 4/0 coated braided lactomer (Autosuture,
Norwalk, CT, USA), in the second group (C group)
by a single 4 mm clip (Versatack, Autosuture, Tyco
Healthcare, Norwalk, CT, USA), and in the third
group (CCA group) by a clip together with cyanoacrylate (Glubran®, General Enterprise Marketing,
Viareggio, Italy). A clip was applied on the perforation
in a perpendicular manner. Two drops (40 μl) of CA
were applied. The stomach was returned to the abdomen and the incision was closed. Liquid resuscitation
was achieved by subcutaneous application of sterile
saline solution (5 ml/100 g body weight) in the back
site at the end of the operation. All animals were
deprived of food, but had free access to water for
12 h after the operative process. After 12 h, rats were
fed ad libitum. Randomly selected ten rats in each
group were anesthetized, and sacrificed by decapitation
on postoperative day (POD) 3, and the remaining ten
rats in each group were sacrificed on POD 7. We
measured all procedure periods, and total operation
period by chronometer. Procedure period was defined
as the time from gastric incision to the end of gastric
closure. Total operation time was defined as the time
from the beginning of the skin incision to the completion
of the last skin suture.
Adhesion score
Immediate relaparotomy was performed after sacrifice;
presence and severity of adhesions were scored as
suggested by Knightly as follows; 0: No adhesions;
1: Filmy adhesions; 2: Definite localized adhesions;
3: Dense multiple visceral adhesions; 4: Dense adhesions
extending to abdominal wall (27).
Burst pressure (BP)
After the evaluation of intraabdominal adhesions, all
rats underwent total gastrectomy. The esophagus was
transected 1-1,5 cm from gastric cardia and double
suture ligated. The pyloric end was attached to a
polyurethane tube and securely tied in order to prevent
air leakage. The other end of the tube was connected
to an air infusion pump and a mercury manometer
by a Y type connector. Gastrectomy material was further submerged into a water-filled container and air
was pumped at a regular rate of 2 ml/min. The pressure at which the pressure suddenly decreased or
bubbles were seen was accepted as BP. Maximum
pressure available with this manometer was 300
mmHg. For this reason, pressures exceeding this level
were recorded as 300 mmHg.
Histopathological assessment
After the measurement of burst pressures, suture
materials or clip were gently removed from the
perforation area, and gastrectomy materials were
separately kept in formalin-filled containers. All histological analysis was done by the same blinded
pathologist. Pathological assessment was done by the
following scale: Presence or absence of superficial
exudates, fibroblastic proliferation, presence and severity
of granulation tissue, acute and chronic inflammation
and collagen deposition. By this scale, the status of
wound healing was evaluated in a quantitative manner
for evaluation of early and late term healing. Granulation tissue, acute and chronic inflammation and
collagen deposition were quantitatively evaluated
[0: absent; 1: mild; 2: moderate, 3: severe].
Statistical analysis
Categorical variables were analyzed using Chi-square
test. Numerical variables were assessed by One
Cyanoacrylate on perforation
227
Table I. Demonstration of burst pressure and histological healing indices. (* = p