Original Citation:
Comparison of two different barbed suture materials for end-to-end jejuno-jejunal anastomosis in pigs
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DOI:10.1186/s13028-018-0437-x Terms of use:
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anastomosis in pigs
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Full Title: Comparison of two different barbed suture materials for end-to-end jejunojejunal anastomosis in pigs
Article Type: Research Funding Information:
Abstract: Background
Hand-sewn intestinal anastomoses are a fundamental procedure in both open and laparoscopic intestinal surgery. Self-retaining barbed suture devices have been tested for a variety of surgical applications. With the exception of clinical reports and various experimental studies on enterotomy, little has been published so far on the use of barbed suture for end-to-end intestinal anastomoses. The aim of the study was to compare two different barbed suture materials for end-to-end jejuno-jejunal anastomosis in pigs. End-to-end jejuno-jejunal anastomosis were performed with unidirectional barbed (A group), bidirectional barbed (B group) or normal (C group) sutures in each animal. A comparison was then made between the groups based on adhesions scoring, suturing time, bursting pressure and histopathology.
Results
Mean construction times in the A Group (518±40 sec) and in the B group (487±45 sec) were significantly lower than in the C group (587±63 sec) but were not different between A and B group (P=0.10).
Mean bursting pressures were significantly higher in the intact intestine (197±13 mmHg) than in any other group (Group A 150±16 mmHg, Group B 145±22 mmHg, Group C 145±24 mmHg). Among anastomotic techniques, the bursting pressures were not significantly different. Histologically no difference could be detected in the grade of inflammation, collagen deposition and neovascularization at the anastomotic sites. Conclusions
Barbed sutures can be effectively used for handsewn end-to-end jejunojejunal
anastomosis in pigs. They are comparable to normal suture but could provide a shorter surgical time.
Corresponding Author: Marco Gandini
Universita degli Studi di Torino ITALY
Corresponding Author Secondary Information:
Corresponding Author's Institution: Universita degli Studi di Torino Corresponding Author's Secondary
Institution:
First Author: Gessica Giusto First Author Secondary Information:
Order of Authors: Gessica Giusto Selina Iussich Massimiliano Tursi Giovanni Perona Marco Gandini
1
Comparison of two different barbed suture materials
1for end-to-end jejuno-jejunal anastomosis in pigs
23
Gessica Giusto1, Selina Iussich1, Massimiliano Tursi1, Giovanni Perona1, Marco
4
Gandini1*
5 6
1Department of Veterinary Sciences, University of Turin, Largo P. Braccini 2-5, 7
Grugliasco (TO), Italy
8 9 *Corresponding author 10 11 Email addresses: 12 GG: gessica.giusto@unito.it 13 SI: selina.iussich@unito.it 14 MT: massimiliano.tursi@unito.it 15 GP: giovanni.perona@unito.it 16 MG: marco.gandini@unito.it 17 18 19 20 21 22 23
Abstract
24 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61Background 25
Hand-sewn intestinal anastomoses are a fundamental procedure in both open and laparoscopic
26
intestinal surgery. Self-retaining barbed suture devices have been tested for a variety of
27
surgical applications. With the exception of clinical reports and various experimental studies
28
on enterotomy, little has been published so far on the use of barbed suture for end-to-end
29
intestinal anastomoses. The aim of the study was to compare two different barbed suture
30
materials for end-to-end jejuno-jejunal anastomosis in pigs. End-to-end jejuno-jejunal
31
anastomosis were performed with unidirectional barbed (A group), bidirectional barbed (B
32
group) or normal (C group) sutures in each animal. A comparison was then made between the
33
groups based on adhesions scoring, suturing time, bursting pressure and histopathology.
34
Results 35
Mean construction times in the A Group (518±40 sec) and in the B group (487±45 sec) were
36
significantly lower than in the C group (587±63 sec) but were not different between A and B
37
group (P=0.10).
38
Mean bursting pressures were significantly higher in the intact intestine (197±13 mmHg) than
39
in any other group (Group A 150±16 mmHg, Group B 145±22 mmHg, Group C 145±24
40
mmHg). Among anastomotic techniques, the bursting pressures were not significantly
41
different. Histologically no difference could be detected in the grade of inflammation,
42
collagen deposition and neovascularization at the anastomotic sites.
43
Conclusions 44
Barbed sutures can be effectively used for handsewn end-to-end jejunojejunal anastomosis in
45
pigs. They are comparable to normal suture but could provide a shorter surgical time.
46
Keywords: barbed suture, end-to-end anastomosis, jejunojejunal , pigs 47 48
Background
49 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59Despite the introduction of mechanical staplers, the importance of hand-sewn intestinal
50
anastomoses remains uncontested in abdominal surgery, in both open and laparoscopic
51
procedures. Self-retaining (i.e. barbed) suture devices have recently come under focus for a
52
variety of surgical applications, including plastic, orthopedic, abdominal and urologic surgery
53
[1-3]. Although still considered off-label, this newer material has already been employed in
54
gastrointestinal surgery in both humans and animals [4-12]. With the exception of clinical
55
reports mostly on side-to-side anastomosis [8] and various experimental studies on
56
enterotomy [5,9-11], little has been published so far. The most interesting application of
57
barbed sutures is in plastic and laparoscopic surgery because of their handling characteristics
58
but their use has been described in in-vivo open surgery techniques in humans [9,13-17] and
59
animals [12,18-24]. Barbed sutures have proven effective in performing end-to-end
60
anastomosis ex-vivo in humans [9], dogs [25], and horses [4]; however, no experimental study
61
has evaluated the characteristics of jejuno-jejunal anastomoses in vivo to date.
62
Barbed sutures incorporate tiny barbs cut into the body of the filament, so that tissues can be
63
approximated without the need for knots. Although barbed suture materials have been
64
evaluated in clinical experience with positive results [5-6,8], concerns remain over the higher
65
risk of inflammation and/or adhesion formation [26-27] and increased susceptibility to
66
complications [27-30] especially with the use of a unidirectional barbed suture [30]. These
67
complications arise mostly from barbs that remain exposed at the suture end that can cause
68
damage to organs in the surgical field [27-30] despite having been cut flush to the surface of
69
the tissue [27]. One may hypothesize that in an intestinal end-to-end anastomosis a
purse-70
string effect could be produced as a result of intestinal contractions pushing the intestinal wall
71
along the suture while the barbed suture concurrently prevents return to its natural, designated
72 position. 73 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61
Furthermore, except for gastropexy in dogs [31], only the unidirectional glycomer-based
74
barbed suture has been described for gastrointestinal applications; differences in conformation
75
[32], handling, and postoperative complications exist between unidirectional and bidirectional
76
barbed sutures [30] that warrant further evaluation of the application of bidirectional barbed
77
suture in gastrointestinal surgery. In a recent review performed in human patients [30], the use
78
of a unidirectional barbed suture resulted in reduced operative time but increased
79
complications compared to the use of conventional sutures; the bidirectional barbed suture
80
was comparable to conventional sutures regarding operative time and complications, although
81
differences do exist in different types of surgery [30].
82
The aim of this study was to compare two different types of barbed sutures with smooth
83
suture material for end-to-end, jejuno-jejunal anastomosis in pigs, with reference to the
84
following: a) surgery time, b) complications, c) adhesion formation, d) bursting pressure, and
85
e) tissue healing.
86
We hypothesized that bidirectional barbed sutures would be faster to use, but would withstand
87
the same bursting pressure and would not cause more complications than their unidirectional
88
counterparts for end-to-end jejuno-jejunostomies. We also postulated that no migration of the
89
intestinal wall along the suture would occur, and therefore no purse-string effect would
90 develop. 91 92 93
Methods
94The study protocol was approved by the Bioethical Committee of the University of Turin and
95
by the Italian Ministry of Health. A sample size calculation was performed using a freely
96 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59
available online sample size calculator (www.openepi.com), with alpha level of 0.05 and 80%
97
power, based on bursting pressure. We used six Large White/Landrace cross-breed female
98
pigs weighing 35±5 kg. Animals were fasted for 12 h before surgery, but had free access to
99
water. All pigs were sedated with xylazinea (2 mg/kg, intramuscularly [IM]) and anaesthesia
100
was induced with tiletamine and zolazepamb (4.4 mg/kg, IM) and maintained with isofluraneb
101
in oxygen under spontaneous ventilation. Animals were placed in dorsal recumbency and the
102
abdomen was surgically prepared. A laparotomy was performed through the linea alba to
103
expose the small intestine. Starting 30 cm distally to the suspensory ligament of the
104
duodenum, six resections were performed on the jejunum approximately 40 cm apart from
105
each other. Intestinal continuity was restored with a jejuno-jejunal, end-to-end anastomosis in
106
a continuous, appositional, extra-mucosal pattern [33-35]. Six anastomoses were created in
107
each animal as follows: two using USP 4-0, unidirectional, barbed polyglycomer 631c and a
108
26 mm, half-circle, taper-point needle (Group A); two using USP 3-0, bidirectional, barbed
109
polydioxanoned and a 26 mm half-circle taper-point, double needle (Group B); and two using
110
USP 4-0, plain glycomer 631c and a 26 mm half-circle taper-point needle (Group C). Suture
111
materials were employed in a randomly assigned order, using a random number generator
112
(www.random.org).
113
To provide consistency, all anastomoses were performed by the same surgeon (MG) after
114
having undergone training in the use of barbed sutures in end-to-end anastomoses ex-vivo.
115
Animals were treated preoperatively with a single administration of
benzylpenicillin-116
dihydrostreptomycine (20 mg/kg, intramuscularly), while post-operative analgesic therapy
117
consisted of intramuscular buprenorphinef (0.01 mg/kg SID) for 72 h post-surgery. During
118
recovery, pigs were placed under an infrared heat lamp. After recovery, access to water and
119
food was allowed after 6 and 18 h, respectively.
120 Surgical techniques 121 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61
The intestine was severed transversely with a 60° inclination on both intestinal ends to avoid a 122
stenotic anastomosis. The resulting wedge of tissue between the two ends was excised. Two
123
plain glycomer 631c stay sutures were placed on the mesenteric and antimesenteric sides.
124
Sutures were not tied; instead, their ends were held with mosquito forceps by an assistant
125
surgeon. Stay sutures were removed after completion of the procedure. Anastomoses were
126
sealed in a continuous, appositional, extramucosal pattern, which was modified according to
127
the order of bites into the tissue (Fig. 1). The suture was placed so as to initially bury the knot
128
(or the initial loop) into the submucosa and advanced with partial thickness bites, placed in a
129
diagonal direction (while transverse passages were placed extraluminally to approximate
130
edges). The suture pattern was initiated differently to suit the type of material used; however,
131
the pattern itself was identical in all cases. Differences in initiating the pattern are detailed
132
below.
133
Barbed polyglycomer 631 (Group A): This suture material is supplied with a welded loop at
134
the end opposite to the needle and has unidirectional barbs cut along its length. The first bite,
135
started from one cut edge of the intestine and catching the submucosa, exited from the serosa
136
before again entering from the serosa and exiting from the other cut edge of the intestine,
137
before feeding the needle back into the loop (Fig 1A). The suture was run for 180° in a
138
continuous, appositional, extramucosal pattern, interrupted by an overlapping loop (made by
139
backing over the suture) as previously described [4] and then continued for the remaining
140
180°. To secure the end of the suture line, two additional bites were taken once the
141
anastomosis was completed. The first bite overlapped the beginning of the suture line, while
142
the second backed over in the opposite direction Finally, the suture was cut flush with the
143
surface of the intestine.
144
Barbed polydioxanone (Group B): This suture material is supplied with two needles, using
145
one at each end. The filament is divided into two half-portions with barbs arrayed in opposite
146 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59
directions (bidirectional) from the midpoint. To create an anastomosis, we began by placing
147
two stay sutures, one on the mesenteric and one on the antimesenteric side. Then one needle
148
was inserted in an extramucosal pattern from the cut edge of the intestine on each jejunal
149
stump without completely pulling the suture out, but leading to the formation of a loop. Then,
150
both needles were fed into the loop thus formed at the middle of the suture (Fig 1B). At this
151
point, each side of the anastomosis was sealed in a continuous, modified, extramucosal
152
pattern, using one needle for each side. As above, two additional bites were taken to lock the
153
suture in place at the point the half-circumference was completed.
154
Unbarbed glycomer (group C): After placing the two stay sutures, the anastomosis was 155
completed in a modified, continuous, appositional extramucosal pattern, starting on the
156
mesenteric side and burying the initial knot submucosally. The suture was tied at the
157
antimesenteric side and continued until completion of the circumference.
158
The abdomen was lavaged with warm Ringer’s solution and closed in two layers.
159
On postoperative day 7, animals were again anaesthetized as described above and euthanized
160
by intracardiac injection of embutramide, mebenzonium iodide, and tetracaine hydrochloride
161
solutiong. Necropsy was performed by an operator who was blinded to the suture materials 162
used. The following necropsy findings were recorded: a) adhesions at the site, and distant
163
from the site, of anastomosis; b) intestinal stenosis (defined as the presence of a dilated
164
portion of the intestine proximal to the anastomosis [36]; c) leakage (defined as the leaking of
165
intestinal content at the anastomotic sites after gentle pressure is applied proximally); and d)
166
presence of abscesses or granulomas at the anastomotic sites.
167
Adhesions were scored using the method implemented by Demyttenaere [5] (Table 1). Those
168
that could be separated by applying gentle traction were released. Bursting pressure of the
169
anastomosis was measured using an inflation tank test as previously described [37] (Fig 2).
170
Briefly, the intestine was severed 10 cm proximally and 10 cm distally to the anastomotic site.
171 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61
Next, the two ends were closed with plastic tie-wraps. A 20 G needle attached to a column
172
manometer was tunneled through the intestinal wall at one end. At the opposite end, another
173
20 G needle attached to an air compressor was inserted in the same fashion. The entire
174
specimen was held underwater as the air compressor began inflating at a rate of 0.5 L/min.
175
The entire procedure was digitally filmed. Anastomotic leakage and bursting were indicated
176
by air bubbles in the water tank and by a sudden pressure drop as measured by the
177
manometer. The exact peak pressure was reported with the help of videography. The bursting
178
pressures of 12 intact intestinal samples harvested from the same animals were also recorded
179
as controls.
180
For histopathology, samples were taken from the antimesenteric site of the anastomosis,
181
stained with haematoxylin and eosin, and examined by a blinded pathologist for inflammation
182
and neovascularization. Sample slices were also stained with Masson's trichrome to assess
183
collagen content [5]. Histologic parameters scored on a scale from Hope et al. [38], included
184
inflammation, collagen deposition and vascularity (Table 2).
185
Statistical analysis
186
The distribution of data was evaluated using the Shapiro-Wilk test. We used the Repeated
187
Measures ANOVA test for comparison of anastomosis times and bursting pressures (for
188
normally distributed data), and a Friedman test to compare adhesions and histopathology
189
scores (for data not normally distributed). All statistical analysis was performed using
190
commercially available softwareh with the significance set at P<0.05. 191
Results
192All six pigs started eating 18 h after surgery and survived until euthanized. No postoperative
193
complications were encountered. A total of thirty-six anastomoses (twelve for each group [A,
194
B, and C]) were performed for the study.
195 Suturing time 196 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59
Mean construction times were 518±40 sec for the A group, 487±45 sec for the B group, and
197
587±63 sec for the C group. Overall, anastomoses in the A group and B group were
198
significantly faster to construct than in the C group (P=0.0012). No difference was detected in
199
construction time between the A and B groups.
200
Necropsy findings
201
The omentum was adhered to the abdominal incision in four out of six animals. There was no
202
evidence of stenosis, leakage or granuloma/abscess at the anastomotic sites. Adhesions
203
between the anastomosis site and other portions of the small intestine, which were not
204
involved in the anastomosis procedures were found in 3/12 anastomoses in the A group, 4/12
205
in the B group, and 3/12 in the C group. The median adhesion score was 1.5 in the A and B
206
group, and 1 in the C group, but difference between these values was not significant (P=0.81).
207
Busting pressure
208
Bursting occurred at the mesenteric site in 12/12 intact intestinal samples and in 28/36
209
anastomoses (8/12 in group A, 10/12 in group B, and 10/12 in group C). Other sites where
210
bursting occurred were the antimesenteric site (n=4, two each in the A and C groups) and, in
211
four cases, midway between the two (2/12 both in the A and B group). No suture and/or knot
212
failure was detected, whereas tissue failure was a regular occurrence. Mean bursting pressures
213
were significantly higher (P<0.0001) in the intact intestine (198±13 mmHg) than in any other
214
group (Group A, 150±16 mmHg; Group B, 145±22 mmHg; Group C, 145±24). The bursting
215
pressures were not significantly different between anastomotic techniques.
216
Histology No significant differences were found in any of the histological parameters (Table
217
3 – median and range), but there was a non-statistically significant trend for lower values of
218
neovascularization and inflammation in groups A and B (barbed suture), while collagen
219
content was lower in group C (non-barbed suture).
220 221 222 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61
Discussion
223Both tested barbed sutures proved to be safe and effective for one-layer, extramucosal,
end-to-224
end, jejuno-jejunal anastomoses. In this regard, our results confirm experimentally the
225
findings empirically reported in clinical settings.
226
Adverse effects mostly caused by exposed barbs, such as adhesions with other organs and
227
intestinal obstruction, have been reported with the clinical use of barbed suture [27-30].
228
In our study, adhesions at the anastomotic site were encountered with both barbed suture
229
materials although they did not occur in a significantly different percentage compared to
230
unbarbed suture. This could be due to the suture pattern used or the fact that we tested these
231
sutures in healthy animals. Using different suture patterns or operating in a clinical setting
232
may lead to different results. Further, longer follow-up periods might have highlighted
233
different complications.
234
Regarding both barbed sutures, extra care must be taken to position the needle accurately
235
before each bite because the suture cannot be retrieved once in place [31]. Good tension
236
control of each bite is essential for the same reason. An easy way to achieve this is by evenly
237
applying tension on the stay sutures at the mesenteric site and the antimesenteric border of the
238
anastomosis. In our case, two stay sutures were sufficient to avoid a purse-string effect, with
239
no need for an additional suture as hypothesized in a previous study [31].
240
Overall, we found the main advantages with barbed sutures to be suturing time and handling,
241
in accordance with previous studies [30]. In fact, since they are a knotless material,
242
construction times were significantly shorter using the barbed sutures compared to the
243
traditional suture. Even more advantageously, the barbs are specifically designed to
self-244
engage into the tissue as the suture line proceeds. Not only did this result in a further
245
reduction of surgical time, it also facilitated a more ergonomic suture technique, as it removed
246
the need to apply tension on the suture while placing the following bites of the continuous
247 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59
pattern [4]. On the whole, the bidirectional device was easier to handle and appeared to
248
provide less tissue drag, factors that may contribute to the reduction in surgical time recorded
249
with this suture material. These characteristics are possibly due to its lower barb number and
250
longer spacing between barbs compared to the unidirectional barbed suture[32] or owing to
251
the different material (polydioxanone vs. glycomer 631).
252
Although statistically significant, reduction in surgical time in the laparotomy model studied 253
here was minimal; but while this could be of little clinical relevance, we should not
254
underestimate their usefulness, especially during difficult procedures. For these reasons,
255
barbed sutures may be indicated in anastomoses performed in poorly accessible sites, or with
256
extensive resections where time may be a determinant for a successful outcome.
257
Our study is not without limitations, the most obvious being related to the type of suture used
258
as a control. We chose glycomer 631 because, out of all the options available, it is the most
259
similar to the suture material used in Group A, which has already been employed for
260
gastrointestinal anastomosis. Other types of sutures might have caused a milder inflammatory
261
response or yielded different results.
262
Another limitation lies in the use of different suture materials within the same animal. Our
263
selection aimed to avoid potential biases caused by individual reactions to the surgical
264
procedure. This may, nevertheless, have taken a toll on the accuracy of the results and led to
265
deceptively uniform inflammation scores. Furthermore, this may not reflect the effective
266
degree of inflammatory reaction to a given suture material.
267
As reported in previous work [1,31], the choice of suture size had to take into account
268
labeling differences. While unidirectional sutures are rated equal to traditional sutures in
269
tensile strength, bidirectional sutures are rated one USP size smaller [1,31]. This did not affect
270
our findings, however, as knot or suture failure did not occur. Based on our experience, we
271
recommend USP 4-0 as the smallest size of smooth, non-barbed suture employable for
end-to-272 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61
end jejuno-jejunostomies in pigs with an average weight of 35 kg. Finally, none of the suture
273
materials cut through the tissues at any time during the procedures; nevertheless, sutures of
274
varying sizes might have behaved differently.
275
In addition, we used an extramucosal appositional suture pattern for all procedures. A
276
different pattern might have yielded different results, but, to date, no studies have compared
277
the effects of suture pattern with barbed suture either in the intestine or in other tissues.
278
To the best of our knowledge, this is the first report on the in-vivo use of barbed suture
279
materials for an end-to-end anastomosis in animals. Bidirectional barbed sutures proved just
280
as effective as unidirectional barbed sutures and both were comparable to traditional,
non-281
barbed sutures, but gave a statistically significant reduction in surgical time. This could pave
282
the way to a wider use of barbed suture materials in open, as well as in laparoscopic, surgery.
283
Unfortunately, barbed sutures are more expensive than smooth sutures of the same materials
284
and this may limit their use in clinical practice.
285
Conclusions
286Both unidirectional and bidirectional barbed sutures can be safely and effectively used for
287
appositional, extramucosal anastomosis in pigs. Barbed suture devices are comparable to
non-288
barbed glycomer 631 in terms of anastomotic healing and suture-holding capacity, but barbed
289
sutures are associated with reduced surgical time.
290
Declarations
291Ethics approval
292All procedures were approved by the Bioethical Committee of the University of Turin and by
293
the Italian Ministry of Health.
294
Consent to publish
295 Not applicable 296 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59Availability of data and material
297The data and materials used and/or analysed during the current study are available from the 298
corresponding author on reasonable request. 299
Competing interests
300The authors declare that they have no competing interests
301 302
Prior publication
303An abstract of this work was accepted for poster presentation at the 49th Congress of the
304
European Society for Surgical Research, Budapest, Hungary, 21-24 May 2014.
305 306
Funding
307This study was not externally funded.
308 309
Author’s contributions
310GG and MG designed and performed the study, acquired, analyzed and interpreted the data,
311
wrote and reviewed the paper. GP performed the study, acquired and analyzed the data and
312
reviewed the paper. SI and MT performed the histological analysis, interpreted the data and
313
reviewed the paper. All authors have read and approved the final version of the manuscript.
314
Endnotes
315a. Bayer Animal Health, Milano, Italy
316
b. Virbac, Milano, Italy
317
c. Covidien, Segrate, Italy
318 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61
d. Quill SRSSurgical Specialties Corporation, Wyomissing, PA, USA
319
e. Fatro SpA, Bologna, Italy
320
f. Schering-Plug, Milano, Italy
321
g. MSD Animal Health srl, Milano, Italy
322
h. GraphPad Software Inc, La Jolla, CA, USA
323
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Figure legends
444Fig 1: Diagram demonstrating step by step procedure for the continuous modified
445
extramucosal pattern used in the present study
446
Fig 2: Diagram demonstrating the system used for bursting pressure measurements of the
447
anastomoses
448
Fig 3: Photomicrograph of granulation tissue between submucosa and muscle layers at the
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anastomotic site for each group (A, Byosin unbarbed suture, B, unidirectional barbed suture,
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C, bi-directional barbed suture). A) foreign material – suture (red arrow) surrounded by a
451
large amount of inflammatory cells (lymphocytes and giant cells (*); B and C) a large hole
452
indicates the area of suture material, surrounded by a large number of inflammatory cells (*)
453
and abundant fibrous tissue with a lot of collagen fibres. (black arrow). Hematoxylin-Eosin; 454 Bar: 100 µm. 455 456
Table legends
457Table 1: Scale used for scoring adhesions present at necropsy in each group
458
Table 2: Scale used for histological evaluation of the anastomotic healing: value from 1 to 4
459
for the inflammation and 1 to 3 for vascularization and collagen content.
460
Table 3: Histology results for the jejuno-jejunal anastomosis groups using different suture
461
materials: total scores derived summarizing the values described in material and methods
462
section (1 to 4 for the inflammation, 1 to 3 for vascularization and collagen content).
463 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61
Table 1: Scale used for scoring adhesions present at necropsy in each group
Adhesion scoring 0 No adhesions
1 Solitary adhesion to/from omentum; fibrinous and avascular; adhesion easily released with gentle digital traction
2 Omental adhesions or solitary adhesion to adjacent viscera or body wall; fibrinous/unorganized and avascular; adhesions easily released with gentle digital traction
3 Same as (2) but adhesions are organized, dense, and vascularized; required blunt dissection to free 4 Adhesions (omental, visceral, body wall); well
organized dense, vascularized; required sharp dissection to separate
5 Extensive organized adhesions requiring sharp adhesiolysis
Table 2: Scale used for histological evaluation of the anastomotic healing
Score Inflammation: (number amount of gGiant cCells –( GC) and
lymphocytes –( L) Collagen deposition (layers) Blood vessels in mucosa at anastomosis 1 GC, L <5 Thickness 1-3 layers <5 2 GC, L 5-10 Thickness 4-10 layers 6-10 3 GC, L 11-15 Thickness >10 layers >10 4 GC, L >15 - -
Table 3: Histology results for the jejunojejunal anastomosis groups using different suture materials
Collagen content Neovascularization Inflammation sScore
Group A 3.5 (2-4) 1 (1-3) 1.5 (1-2)
Group B 3 (2-4) 1 (1-3) 2 (1-3)
Group C 2 (1-4) 2 (1-3) 2.5 (1-3)
We would like to thank the Editor and Reviewer for theri comments. We addressed every single comment as detailed below.
Nevertheless some doubts remain regarding comment #3 of reviewer #2, on which we would like to have the Editor’s opinion
Reviewer #1: Thank you for an interesting and well performed study. I have a few comments:
1)Rows 27-32 in the abstract and 52-59 of the introduction are identical. The abstract should not repeat what is already stated in the text, so please rephrase either one or the other.
1) lines in the abstract have been changed
2)Row 32: The aim of this study 2)changed, see text
3)Row 35: A comparison was then made between the groups (is that what you mean here?) 3) changed, see text
4)Row 36: what do you mean by adhesions type? If you mean adhesion score, which is the term you have used in the text, better to use that term consistently.
4) changed, see text
5)Row 42: If no particular reason to keep the order you propose, Group A should probably go first 5) changed, see text
6)Row 49; jejuno-jejunal : you use both this form and jejunojejunal in the text, keep it consistent 6) changed, see text
7)Row 59: "The main use of barbed sutures will be in laparoscopic surgery"; what do you mean by that, is that a subjective author prediction, is it the intention of the manufacturer, or if it is currently the main area of use of the barbed sutures, rephrase.
7) changed, see text
8)Row 59: reference nr 12 is not on enterotomy 8)changed, see text
9)Row 67: "concerns" suffices, doubts and hesitations can be omitted. 9)changed, see text
10)Row 69: susceptibility to complications 10) changed, see text
12)Row 97: Please explain how the power calculations were performed? 12) inserted in text
13)Rows 115-6: benzylpenicillin- dihydrostreptomycin 13) changed, see text
14)Row 140: Rephrase please; "To secure the end of the suture line, two addtional bites were placed once the anastomosis was complete."
14) changed, see text
15)Row 145-151: this is difficult to understand, please rephrase and explain, use the terms mesenteric and antimesenteric where they apply to more clearly illustrate.
15) changed, see text
16)Row 168: Do you mean that the adhesions were released? Bursting pressure 16) changed, see text
17)Row 183-186; you dont have to specify the different scores in the text, they are presented in Table 2. It is sufficient to state the parameters i.e inflammation, collagen deposition and
vascularity, and preferably in the same order as they are presented at Table 2. 17) changed, see text
18)Row 192: s after softwareh 18) changed, see text
19)Under the Results / Necropsy findings paragraph, please report presence/abscence of abscesses or granulomas at the anastomotic sites.
19) inserted, see text
20)Row 204: "no evidence of obstruction" by obstruction do you mean stenosis? If so please use stenosis, otherwise please define obstruction in your objectives
20) changed, see text
21)Row 218 stating p value here is redundant, omit. 21) changed, see text
22)Row 219-222: .., but there was a non-statistically significant trend with lower values…. collagen content was lower in…
22) changed, see text
23)Rows 231-233 rephrase please 23) changed, see text
24)Row 247 result in a further reduction 24) changed, see text
25)Row 249: removed 25) changed, see text
26) changed, see text
27)Row 255: reference on different handling properties of polydioxanone compared to glycomer 631
27) reference #32
28)Rows 256-259: this sentence is hard to understand, please explain/rephrase. Do you mean that the reduction of surgical time would be greater in a laparoscopic setting compared to open
surgery? Or that the same reduction in surgical time would be more significant in laparoscopic surgery? If so why is that?
28)changed, see text
29)Row 272-273: Rephrase, what do you mean 29) changed, see text
30)Figure 1A: the loop described in the text is not visible in the figure. More detail showing the loop would be valuable for the understanding of how this suture is secured.
Figure 1B: Also not as detailed as required to illustrate the text description. Maybe if both needles are depicted, and the course of the thread through the formed loop is better illustrated.
30) the entire figure 1 has been designed again
Reviewer #2: This paper is certainly of interest and in general well written and easy to follow. However there are a few major concerns mostly in regards to study design that should be addressed.
Major concerns:
1) The wording of the paragraph (P4/L88) hypothesis suggests that this is a non-inferiority study with regards to effectiveness, it is however not possible to assess on which prerequisites the sample site was calculated in part because effectiveness is not defined. From the conclusion it seems that it is a conclusion based on the collective outcome of end-points. Details on the samplesize calculation prerequisites should be given.
1) The reviewer is right. The Hypothesis was poorly written. We rephrased it.
2) Sample size calculation was performed using Bursting pressure as a prerequisite. It is specified in materials and methods
2) Testing the 3 suture groups against intact intestine seems not logical in particular not when the initial hypothesis is consulted. This test should be omitted from analysis
2)We inserted the intact intestine as a comparison for two reason: first , healing of an anastomosis should lead the tissue to be as strong as the intact intestine. In such a way intact intestine is our positive control. Second, it is also a control for the procedure. We would like to have the Editor opinion wether to remove this control from the analysis or not
supported by the statistical results. Testing of suture groups should be redesigned as a non-inferiority test.
3)see comment#2
4) The statically significant reduction in suture time seems without clinical importance - the difference between shortest and longest mean suture time is less than 2 min.
4) true, this has been addressed in the discussion
5) Details of experimental animal management should be reported - preferably in accordance with the ARRIVE guideline and in particular: 1) How was intraoperative nociception adressed and 2) How often was buprenorphin given post operatively.
5) details have been inserted in the text: 1) line 105: tiletamine+ xylazine + isofluorane 2) line 122
Recommendation:
These observations seem of interest to the gastrointestinal surgeon and to experimental surgeons. Why not rewrite this paper with an exploratory aim to establish well supported hypotheses that may be tested.
We thank the reviewer for this recommendation, but we would like to have the Editor opinion on this matter
