Wrapping colonic anastomoses: Omentoplasty versus a carrier­ bound fibrin sealant

Wrapping colonic anastomoses: Omentoplasty versus a carrier­

bound fibrin sealant

Ayman AAlbatanonya,h,MD; Tarek M Rageha,c,MD;

MohamadA Radwand,e,MD

a) Menoufiya Faculty of Medicine, Egypt. b) Qassim College ofMedicine, KSA.

c) Al-Hayat private hospital, Jeddah, KSA.

d) Ain Shams Faculty of Medicine, Cairo, Egypt. e) King Saud hospital, Unayzah, Qassim, KSA.

Introduction: A leak from an intestinal anastomosis is the complication  most feared by the colorectal surgeon. The role of omentoplasty in securing colorectal anastomoses  shows some controversy:  being recommended  by some authors,  being  of equivocal  value to others  and to be recommend against by a third group of authors. Collagen-bound  fibrin sealant sheets have recently been used in many aspects of surgery; for example: Hernia, GI, ophthalmic, gynecologic & obstetric, renal, vascular and cardiac surgeries; and many experimental animal studies proved its efficacy in  securing  GJ anastomoses.  The  safety  and  feasibility  of using collagen-bound fibrin sealant has been proven. Its application for sealing colonic anastomosis is a new field of its application and needs to be evaluated.

Aim: To evaluate and compare the efficacy of both omentoplasty and a newly introducedfibrin sealant; TachoSil®; in decreasing the rate of anastomotic leakage in colorectal anastomoses.

Results:  97 patients were included; 48 in omentoplasty group and 49 in TachoSil® group. The rate of clinical leakage in omentoplasty group was 8.3% and in TachoSil® group was 2%. Three out of four leakages in the omentoplasty group were sever(>500 cc/day) and the only case in TachoSil® group was less sever (<500 cc/day). The average hospital stay in omentoplasty group was 9.3 days and in TachoSil® group was 7.2 days (P<0.05).

Conclusion: Omentoplasty proved no beneficial effect in sealing colonic anastomoses. There is a trend proving that TachoSil® is more effective than omentoplasty in preventing anastomotic leakage. The use of the collagen-bound fibrin sealant TachoSil® appears to be beneficial, being

better than omentoplasty  regarding the length of hospital stay and the severity of leakage, if

leakage is inevitable.

Introduction:

Aleakfrom an intestinal anastomosis is the complication most feared by the colorectal surgeon.    Reported    colonic    anastomosis leak rates range from 1.5% up to 16% with mortality rates typically quoted between 10% and 20%. 1.

Many  factors  were  proven  to  affect  the

rate of anastomosis leakage; preoperative, intra-operative       and     postoperative.      For example:  age,  sex,  general  fitness  of  the

patient, anastomotic tension, resection in an emergency setting, tumour stage, distal site, the need for postoperative blood transfusion, fecal contamination, increased blood loss during surgery, low preoperative serum albumin level, steroid use and increased duration of surgery.2-6

In  order  to  decrease   the  rate  and  the severity of anastomotic leakage and infective complications, several methods have been proposed   such   as   antibiotic   prophylaxis,

colonic  preparation with antiseptic enemas, fecal  diversion  for  protecting high-risk anastomoses, biofragmentable anastomosis ring  and  pelvic  irrigation.7  External  coating of  anastomoses  with  various   materials   has been   proposed   as  a  means   to  reduce   the leakage  rate.8

The omentum has long been used in gastro­

intestinal, cardiothoracic, neurological, gynaecological, orthopaedic, vascular, urological, plastic  and  reconstructive surgeries. 9

The role of omentoplasty in securing anastomoses  after   oesophageal   resections is well-established_10 Its role in securing colorectal anastomoses shows  some controversy: being recommended by some authors,11-13 to   be  of  equivocal  value   to others7  and to recommend against  by a third group  of authors.14

Performing an omentoplasty is not without risks. Although  uncommon, complications such  as haemorrhage, necrosis  of  omentum and attribution to an internal  herniation have been described.14

Even    though     technical    modifications have    decreased   the   rate    of   leakage    in colonic  anastomosis, the  high  mortality  and severe  morbidity in patients suffering from anastomotic  leakage   justify   the   necessity for  evaluation of  additional methods for decreasing the  rate of anastomotic failure  in these  operations.15

Collagen-bound fibrin sealant  sheets  have recently been used in many aspects of surgery; for example: Hernia,16 Gastro-intestinal,17,18 ophthalmic,19    gynecologic &   obstetric,20 renal,21 vascular22 and cardiac23,24 surgeries; and many experimental animal studies proved its efficacy in securing  GI anastomoses.25-27

In   2010,   Huh   et   al.   performed a prospective study involving 223 patients  with rectal cancer who underwent laparoscopic resection. One group underwent surgery followed  by   application  of  fibrin   sealant over the stapled  anastomosis, while the other group  underwent surgery  alone.  The  clinical leakage  rate  was  5.8% for  the  fibrin  group and 10.9% for the other  group.28

De Stefano et al in 2011 conducted a study

on   63   open   resective   colorectal  surgeries and  concluded: "Our  initial  experience with TachoSil®  has  confirmed  the  safety  of  this patch and we can therefore suggest  a possible positive effect on anastomotic healing".29

In  2012,   Parker   et  ai17 concluded that

the   application  of  TachoSil®  to   reinforce the  anastomotic line  in colorectal resections appears  to  be feasible and  well  tolerated  in most circumstances.

Aim  of  the  work:  In  this  study  we  are

evaluating  and   comparing  the   efficacy   of both omentoplasty and a newly introduced fibrin  sealant;  TachoSil®;  in  decreasing the rate of anastomotic leakage  in colorectal anastomoses.

Patients and methods:

The  study   is  carried   out  between   May

2010  and April 2013  in 3 hospitals; namely: Menoufiya  University  hospital,  Shibin Alkom, Egypt, King Saud hospital, Unayzah, KSA and Al-Hayat Private hospital, Jeddah, KSA.  The study  is prospective and patients' choice will be on consecutive basis; being alternating between  both  using omentoplasty and   TachoSil®   patch   to   externally  wrap the completed anastomosis. The study is approved  by  the   appropriate  authority    in each  hospital.  The  colon  will  be  chemically and mechanically prepared,  thus patients undergoing emergency surgery  will not be included.  Patients  with known  allergy  to any of the components of collagen-bound fibrin sealants will be excluded from the study.

Surgical technique: The surgical technique

for resection anastomosis will be standardized according to  the  ASCRS  Manual  of  Colon and  Rectal  Surgery.30  Drainage   of  the abdominal cavity  will be left to the choice of each surgeon.

In  this  study   we  will   include   only  the

clinically evident  anastomotic leakage,  thus the   investigation  for  leakage   will  start  on clinical  basis  i.e.  if  the  patient  is  suffering abdominal  pain,   tenderness,  fever,   and/or leucocytosis. The occurrence of anastomotic leakage  will be evidenced  by the presence  of fecal  discharge  through the  pelvic  drain  left intra-operatively or inserted after radiological

evidences  of  leakage.  Gastrograffin  enema for  detection  of preclinical  leakage  will not be performed on routine basis.

All operations will be carried out by 3 surgeons using either hand sewn or a stapled technique without a protective stoma. After completing the anastomosis,  and testing for air tightness,31  the  patient will be  assigned to either covering the anastomosis with an omentoplasty or with a TachoSil® patch.

Omentoplasty  is defined as "A surgical procedure in which a portion of the greater omentum is used to cover or fill a defect, augment arterial or portal venous circulation, absorb effusions, or increase lymphatic drainage".32

We will follow the standard surgical techniques while performing omentoplasty, making sure that the vascular pedicle is intact, taking in consideration the valuable notes by

Topor et aP2

TachoSil® is a registered trademark  of Nycomed Pharma AS. It is a sterile, ready to­ use, absorbable surgical  patch consisting  of an equine collagen sponge coated with human fibrinogen  and  human  thrombin  measuring

9.5 x 4.8 x 0.5 em. This new carrier bound

fibrin  sealant  was  approved  by the  FDA,33 the Scottish Medicines Consortium,34 and the European Medicines Agency- Committee for

Medicinal Products for Human Use.35

While using TachoSil® patch, it will be pressed   gently  over  the   anastomotic   line for 1-3 minutes, making sure that the sheet covered  and adhered  to  at least one em on each side ofthe anastomosis.

In  each patient,  we will record  the following  data  (among  others)36: Age, gender, American society of anesthesiologists score (ASA) score, body mass index (BMI), smoking, alcoholism, steroids, neo-adjuvant therapy, site of anastomosis, intra-operative blood loss, post-operative  blood transfusion, duration of surgery, use of drain, clinical leakage, severity of leakage, hospital stay, postoperative complication, postoperative mortality, anastomosis done manual or mechanical and time of evidence of GIT movement.

Each  of these  factors  will  be  compared

between both groups with two intents: testing for homogenousity of the demographic data between the two groups, as well as comparing the  outcomes.  Patients  will  be followed  up for  45  days  postoperatively  for  evidences of leakage and other surgery-related complications. The average cost ofTachoSil® patch per patient will be calculated.

Statistical analysis: The data collected were tabulated and analyzed using SPSS statistical package version 12 on IBM compatible computer. Groups  were compared  using the Chi square test for categorical  variables and Student's t-test for continuous variables. Qualitative  data  were expressed  as number and percentage (No and %) and analyzed by applying Chi-square test (X2 test). All these tests  were  used  as tests  of  significance  at p <0.05.

Results:

97 patients were included in this study, with an average of 11 patients per year for each hospital  during  the  study  period  (3  years). We excluded one patient from the study who was found to have an atrophied omentum. We encountered no patients with allergy to any of the components  of the collagen-bound fibrin sealant used in this study.

When the omentum was mobilized, it was

most often based on the left gastroepiploic artery and it was wrapped loosely around the suture line, and fixed to the colonic segments proximally  and distally  by separate  sutures. The average  cost of TachoSil® patches  per patient was 210 US Dollars. The mean postoperative  stay  in TachoSil® group  was

7.2 days, and in omentoplasty  group was 9.3 days (P<0.05).

Table (1)   represents   the  results   of  the study. A comparison between the two groups was done, taking the significance level to be at or less than 0.05%.

Discussion:

The uncomplicated healing of an intestinal anastomosis even after attentive technical performance from an experienced surgeon is still a challenge  because the healing process is   dependent   on   multiple   physiological,

Table 1: the results of the study and a comparison between the two groups.

biochemical, and morphological factors.37

Anastomotic leaks  are detected anywhere from  3 to 45 days postoperatively, and the diagnosis  is  mostly   made   between   days  6 and  9.  However,   it stands  to  a  reason  that the processes which lead to the failure start much earlier, probably in the immediate postoperative period when the wound strength is believed to be low.27

In our study, omentoplasty proved to be simple to perform and not time consuming, as evidenced  by comparing the operative time between the two groups, where no statistically proven  difference was  noticed  between the two   groups    (P   >0.05).    No   complication was  noted  due  to  the  use  of  omentoplasty in  our  study  during  the  follow   up  period. One  limitation for  the  use  of  omentoplasty is atrophy  of the omentum which may be congenital or acquired.38

Anastomotic   leakage    after    colectomy is one  of the  most  serious  complications in colorectal surgery.  Best defined as "leak  of luminal contents from a surgical join between

2   hollow    viscera,"  its   incidence  ranges from  2% to  4%  with  proximal  anastomosis, to 6% to 12% with distal extraperitoneal anastomosis, and is associated with mortality rates of 10-30%.3

When   comparing  the   two   groups regarding the  demographic data  and other factors   Table (1);  there  was  no  statistically significant difference between both groups (p>0.05), except in the length ofhospital stay and the time of evidence of GIT movement (where  p< 0.05).

The overall incidence of anastomotic leakage    in   this    study    is   5.15%    (5/97), which   is  towards   the   lowest  rate  reported in  other   studies;1   this   may   be   attributed to   the   patient   selection,  as  we   excluded from this study  all emergency colectomies. Emergency  colectomy  is  well-documented to be associated with higher  incidence of anastomotic leakage.37

We excluded  the  emergency colectomies from this study due to a previous work by Chmelnik et aP9 Their experimental study in rats showed severe pre-anastomotic dilatation m additionally sealed small-diameter anastomoses when  using a fibrin-coated collagen   patch.  They  attributed this  finding to   increased  inflammation  as  a   result   of bacterial  contamination and a disproportion between   bowel   wall   and   patch   thickness. They  reported: "As  a result  of our  findings, the  application of  TachoSil®  in  small­ diameter  intestinal anastomoses cannot  be recommended. Whether  TachoSil® generally can be safely used in bacterially contaminated tissues needs to be investigated in future studies". Thus, we excluded  emergency colectomies to avoid applying  TachoSil® in a heavily  contaminated tissue.

Most of the recently  published studies40,41

suggest   that  mechanical  bowel   preparation is of no value  regarding the anastomotic integrity;  a point  that  is  in  favour  of omentoplasty and  against  TachoSil®. As already  mentioned, it is better to avoid using TachoSil® in the presence  of heavy  bacterial contamination,39 while such recommendation

is not applicable  with  omentoplasty. Colon preparation with antibiotics has recently  been proved beneficial.42

The rate ofleakage in the TachoSil® group was  2%  (1/49);   while  in  the  omentoplasty group   it  was   8.3%   (4/48),  which   implies no beneficial  effect of omentoplasty in preventing anastomotic leakage. This is in accordance with the  most  recent  publication in this field.43

When  comparing the  2 groups,  we found no statistically significant difference  between the  incidences of leakage  after  omentoplasty compared to the application of collagen-bound fibrin sealant (P>  0.05).  However,  the study showed that there  is a trend  of the  collagen­ bound fibrin sealant to be more effective than omentoplasty, because the rate was 4 cases in the  omentoplasty group  and  one  case  in the TachoSil® group.  Failure to demonstrate a statistically significant difference  may be due to the relatively small number  of the cases included in this study.

Another   finding  in  our  study  is  that:   if

leakage  is going to  occur,  it tends  to be less severe  in the  TachoSil® group  compared  to the omentoplasty group.  Three out of four leakages  in  the   omentoplasty  group   were severe   leakages   (>  500  cc  per  day),  while the   single   case   of   leakage   in  TachoSil® group  was  less  severe  (<500  cc  day).  This can be attributed to the difference  in the mechanism of action  between  omentoplasty and TachoSil® in sealing  the anastomosis.

Omentoplasty works to protect the anastomosis in many ways:

Whenplacedincontactwithananastomotic gap, an entirely viable omentum forms an effective bridge over anastomotic defects and responds  with an outgrowth of richly vascular tissue,   which   acts   as   the   major   vascular source  to the wound.  Omentoplasty provides an adherent sleeve that  plugs  or locally contains early  anastomotic leakages during the dangerous period before revascularization occurs.  The stimulated neo-angiogenesis and the richly vascularised tissue also could act as protective factors,  lowering  the  incidence of anastomotic stricture.l3

The  mechanism  of  action   of  TachoSil®

follows  the principles of physiological fibrin clot formation. Upon contact  with a bleeding or  leaking   wound   surface,   or  triggered   by the presence  of physiological saline,  the coating  of the collagen sponge  dissolves  and the  subsequent thrombin-fibrinogen reaction initiates   the   last   step   of   the   coagulation cascade:  Fibrinogen  is   converted  by  the action   of  thrombin  into   fibrin   monomers which  spontaneously polymerise to  a fibrin clot. Thrombin can also activate  endogenous factor    XIII   which    covalently   cross-links the fibrin to create a firm and stable fibrin network.35

This  stable  fibrin  clot  leads to sealing  of the  anastomosis in many  ways:   the physical barrier created by thefibrin clot,the facilitation of   tissue    approximation,   the    promotion of  tissue   healing   by  the   components,  and the   creation   of  adhesion   with  surrounding

tissues.28

These  mechanisms of action of TachoSil® are reflected in our study: both the rate and the severity ofleakage are lower in the TachoSil® group than the omentoplasty group.

In  the   postoperative  period,   the  bowel

anastomosis  should   be   able   to   withstand forces  in different  directions. The bursting pressure,    which    reflects   the   capacity    of the     anastomosis   to    resist     intra-luminal forces, is a good marker to test anastomotic strength.44    Many     researchers    examined the effect of fibrin sealant on the bursting pressure  following anastomoses and  proved a beneficial  effect.45,46

It is known  that  colonic  anastomoses are most fragile  on days 3 and  4 because  of low collagen content  mediated  by high activity  of colonic  collagenase induced  by injury  to the bowel wall during the healing  phase of the anastomosis and on day 7 after  anastomosis, collagenolytic   activity    reverts    to   normal

values. 15

We should stress that collagen-bound fibrin sealants are different from the earlier fibrin glues.  Early  studies  on  using  fibrin  glues to seal colon  anastomoses were disappointing, with evidence that the glue inhibited wound healing  and  decreased  anastomotic strength, burst  strength,  and   collagen   deposition  at

treated  wound   sites.  Fibrin  glues  may  also inhibit macrophage migration and neutrophil

function.25,27

In  our  study,  when   we  compared  both groups  regarding the timing  of regaining gastrointestinal movement, we found  a statistically significant result proving  that omentoplasty, in  some  way;  delays  the recovery of gastrointestinal movement. This result   was  reported   in  a  previous   study.l4

In this aforementioned study, the authors explained that the mechanisms involved, are the presence of a pedicled  omentum in the abdominalcavitycausingarelativemechanical obstruction   and   the   devascularization of the  greater   curvature of  the  stomach, thus delaying  gastric functioning.

The   safety   of  TachoSil®  in  sealing   of

gastrointestinal anastomoses with  a collagen patch   coated   with   fibrin   components has been  proven  before  in a study  by Nordentoft et  ai.26 Their  study  revealed   equal  healing strength,  and  complication rate after  sealing with   a  collagen   patch   coated   with   fibrin glue  components  compared  with   unsealed anastomoses.  Furthermore,  they   found   no difference   in  stenoses of  the  anastomoses. Another   reported  value   of  Fibrin   sealants is  decreasing  intra-abdominal  adhesions. 47

Furthermore,  one   study   proved   TachoSil®

has no negative  physiological or histological side effects.26 Also, the feasibility of the application ofTachoSil®for sealing colorectal anastomosis was proven.l7

A  shorter   mean   postoperative  stay   of

7.2 days was observed  for patients  where TachoSil®   was   applied    compared  to   9.3 days for patients of no- TachoSil®. This difference was mainly related to anastomotic insufficiencies recorded in the no- TachoSil® group.  This was in accordance with  a recent study from Italy.29

Another     point     against     TachoSil®    1s the   possibility    of   transmission  of   blood­ born   diseases.    There   is   a   potential   risk of      transmission       of      micro-organisms from   the  blood   samples   that   are  used   to produce   TachoSil®,   even   if,  according to the manufacturer, blood  comes  only from selected  donors  and  all the  active  measures

against enveloped viruses  are used.48

In a comprehensive review  of External coating of colonic anastomoses, Pommergaard et al8 concluded that the only beneficial effect of all the fibrin sealants was that of using TachoSil®.

In our study, the average  coast per patient in the TachoSil® group  was 210 USD, which could  be  an  argument against   its  use.  This extra-coast could be compensated for, at least in part,  by the  shorter  hospital  stay.  In  our study, the TachoSil® group patients stayed for a shorter  time  in hospital  and the  difference from the omentoplasty group is statistically significant     (P <0.05).     This    finding    was reported  before.49

One  more  argument  against  TachoSil® is its being  a source  of fibrin,  thus  it may  lead to increase  in the incidence of thrombotic complications postoperatively. In  our  study, there   is  a  slight   increase   in  the  incidence of  DVT  in  the  TachoSil®  group  compared to the omentoplasty group,  but it was not statistically significant (P <0.05).  The  main effect  of TachoSil® is the  local  activation of the  coagulation cascade  leading  to the  local deposition of stable fibrin network.35 Whether or   not  this   activation  of  the   coagulation cascade   can  reach  the  systemic  circulation needs further study.

Conclusion :

Within the limitation of the patient number included   in  this   study,   we   conclude  that omentoplasty proved  no  beneficial  effect  in sealing colonic anastomoses. There is a trend proving   that   TachoSil®   is   more   effective than omentoplasty in preventing anastomotic leakage. The use ofthe collagen-bound fibrin sealant  TachoSil®  appears   to  be  beneficial, being   better   than   omentoplasty  regarding the  length   of  hospital   stay,  the  timing  of GIT  movement and the  severity  of leakage, if   leakage    is   inevitable.  We   agree   with

Konstantinos et al42 who  reported:  "the field

of tissue adhesives  is gaining ground  in GI surgery.  Despite  years  of research, the  ideal tissue  adhesive is yet to be found; however, the benefits of using  adhesives are becoming more apparent".

The   authors  declare  that   they   have   no conflict of interests.

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13-  Tocchi A,  Mazzoni  G,  Lepre  L,  Costa  G, Liotta G, Agostini N, Miccini M: Prospective evaluation of omentoplasty in preventing leakage of colorectal anastomosis. Dis Colon Rectum 2000; 43(7): 951-955.

14- Klaver  YL, Nienhuijs  SW, Nieuwenhuijzen GA, Rutten HJ, de Hingh IH: Omentoplasty in rectal cancer surgery prolongs post­ operative  ileus.  Jnt J Colorectal  Dis  2008;

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15- Hoeppner  J, Wassmuth B, Marjanovic G, Timme S, Hopt UT, Keck T: Anastomotic sealing by extracellular matrices (ecm) improves healing of colonic anastomoses  in the critical early phase. J Gastrointest  Surg

2010; 14: 977-986.

16-  Arslani  N,  Gajzer  B,  Papes  D,  Rajkovic Z,   Altarac   S,  Zore   Z,   Filipovic-Zore   I: A new approach for transversalis fascia reinforcement   in  Lichtenstein's  inguinal hernia repair. Surg Today 2013; 43: 211-214.

17- Parker MC, Pohlen U, Borel Rinkes IHM, Delvin  T: The application  of TachoSil® for sealing colorectal  anastomosis:  A feasibility study. Colorectal Dis 2013; 15(2): 252-257.

18- Montorsi M, Zerbi A,  Bassi C , Capussotti

L, Coppola R, Sacchi M: Efficacy of an absorbable fibrin sealant patch (TachoSil®) after distal pancreatectomy: A multicenter, randomized, controlled trial. Ann Surg 2012;

256(5): 853-860.

19-  Grau, Arturo E & Duran, Juan A:Treatment of a large corneal perforation with a multilayer of  amniotic  membrane  and  TachoSil®. Cornea 2012; 31(1): 98-100.

20-  Santulli P, Marcellin L, Touboul C, Ballester

M, Darai E, Rouzier R: Experience with TachoSil® in obstetric and gynecologic surgery.  Jnt  J  Gyn   Obst   2011;   113(2):

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21-  De Rosa P, Valeriani G, Barbato G, Cerbone V,  Ciccone  M,  Russo   E,  Vicedomini   D: Renal postexplant residual cavity hemostasis with  a TachoSil® patch. Transplantation Proceedings 2011; 43(4): 1069-1071.

22-  Dregelid  E,  Ramne:fjell MP,  Erichsen  CC, Bjarn   J,  Rawal   R:   Effective   hemostasis in severe mesenteric vein laceration with TachoSil®, using a low- or non-thrombogenic patch         to      prevent      TachoSil®-induced thrombosis. Eur J Trauma Emerg Surg 2008;

34(2): 177-180.

23-  Kuschel TA, Gruszka A, Hermanns-Sachweh B, Elyakoubib  J, Sachweh JS, Vazquez­ Jimenez  JF,  Schnoering  H:  Prevention   of

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24-  Pocar M, Passolunghi D, Bregasi A, Donatelli F: TachoSil® for postinfarction  ventricular free  wall  rupture.  lnt   CardiaVasc  Tharac Surg 2012; 14: 866-868.

25-  Vuocolo T, Haddad R, Edwards  GA, Lyons RE, Liyou  NE, Werkmeister  JA, Ramshaw JA, Elvin CM: A highly elastic and adhesive gelatin tissue sealant for gastrointestinal surgery and colon anastomosis.]Gastraintest Surg 2012; 16: 744--752.

26-  Nordentoft T, R.0mer J, S0rensen M: Sealing of gastrointestinal  anastomoses with a fibrin glue-coated  collagen patch: A safety study. J Invest Surg 2007; 20: 363-369.

27-  Der Vijver RJ, Laarhoven  CJ, de Man BM, Lomme RM, Hendriks T: The effect of fibrin glue on the early healing phase of intestinal anastomoses  in the rat. lnt  J Calarectal Dis

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28-  Huh  JW, Kim  HR,  Kim  YJ:  Anastomotic leakage after laparoscopic resection of rectal cancer: the impact of fibrin glue. Am J Surg

2010; 199(4): 435--441.

29-  De Stefano A, Bettarini F, DiMare G, Neri A: Enteric anastomosis and TachoSil®. Minerva Chir 2011; 66(3): 183-188.

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34-  Scottish  Medicines  Consortium.  TachoSil®

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35-  Scientific  Discussion:  This  module  reflects

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8.  EMEA   2005.http://www.ema.europa.eu/

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36-  Dekker   JWT,  Liefers   GJ,   Otterloo   JCD, Putter H, Rob AEM. Tollenaar RAM: Predicting  the  risk  of  anastomotic  leakage in left-sided colorectal surgery using a colon leakage score. J Surg Res 2011; 166: 27-34.

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38- Ali SD, Sheeraz-ur-Rahman S: Common presentation uncommon diagnosis primary omental  torsion.  J  Pak  Med  Assac  2013;

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39- Chmelnik M, Lasch L, Weih S, Wink E, Romero P, Holland-Cunz  S: Anastomotic sealing  with  a fibrin-coated  collagen  patch in small-diameter  bowel. Langenbecks  Arch Surg 2011; 396: 685-691.

40-  Kolovrat  M,  Busic  Z,  Lovric  Z,  Arnie  F, Cavka  V,  Boras  Z,  S  Drazen,  Lemac   D, Busic   N:   Mechanical   bowel   preparation in  colorectal  surgery.  Call  Antrapal  2012;

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42- Toneva GD, Deierhoi RJ, Morris M, Richman J, Cannon JA, Altom KL, Hawn MT: Oral antibiotic  bowel preparation  reduces  length of stay and readmissions after colorectal surgery.  J  Am   Call   Surg   2013;   216(4):

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43- Moloo   H,   Etzioni   DA:   Intraoperative adjuncts  in  colorectal  surgery. Surg Clin  N Am 2013; 93; 33--43.

44- Subhas G, Bhullar JS, Cook  J, Shah A, Silberberg  B, Andrus  L, Decker  M,  Mittal VK:  Topical  gentamicin  does  not  provide any additional anastomotic strength when combined  with fibrin glue. Am J Surg 2011;

201: 339-343.

45- Vakalopoulos   KA,   Daams   F,   Wu  Z, Timmermans  L, Jeekel JJ, Kleinrensink  GJ, van der Ham A, Lange JF: Tissue adhesives in gastrointestinal anastomosis: A systematic review. J Surg Res 2013; 180(2): 290-300.

46- Verhage   RJ,    Ruiz    A,    Verheem   A, Goldschmeding     R,    Rinkes    IHB,    van Hillegersberg R: Fibrin-thrombin coated sealant increases strength of esophagogastric anastomoses in a rat model. J Surg Res 2012;

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49-  Anegga  U,  Rychlikb  R,  Smolle-Juattnera F: Do the benefits of shorter hospital stay associated with the use of fleece-bound sealing outweigh the cost of the materials?lnt CardiaVase Thorac Surg 2008; 7: 292-296.