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Medico Research Chronicles


“Superglue in GI leaks: Use of cyanoacrylate glue in GI fistulae”

ISSN No. 2394-3971

Original Research Article


SUPERGLUE IN GI LEAKS: USE OF CYANOACRYLATE GLUE IN GI FISTULAE

Atul Kumar Sood*, Atul Jha, Rahul Jain, Manish Manrai, Prerna Pallavi, Khushvinder
Sherry, Mohit Sethia

Army Hospital (Research and Referral), New Delhi – 110010, India

Submitted on: November 2018


Accepted on: November 2018
For Correspondence
Email ID:

Abstract
Background and Aims: Gastro-Intestinal Fistulae (GIF) on most occasions are iatrogenic
and come with significant morbidity and myriad of presentations from asymptomatic individuals
to severe sepsis. About a third of GIF heal but most require repeated surgeries adding to the
morbidity. We evaluated the feasibility of cyanoacrylate glue injection in the management of
non-healing GIF which had failed conservative management of nutrition, antibiotics, and
percutaneous drainage.
Methods: Seven patients of non-healing GIF were managed with CAG injection by a
sclerotherapy needle via an upper GI endoscopy. The primary endpoint was the closure of the
fistula. Feasibility of the procedure was defined as the possibility to reach the opening of the GIF
and perform the glue injection. The other parameters noted were the number of injections
required the time to achieve complete closure of the fistula and other complications
Results: Feasibility of the procedure was 100%. A median of 01 injections (Range 1-2) was
performed in the patients with 71.4% requiring only one injection. The success rate was 100%.
The average time required for GIF closure was 8.5 + 3.9 days (range 02-13 days). There were no
complications noted in the study. All the patients were followed up for 12 weeks and no
Medico Research Chronicles, 2018

mortality was recorded.


Conclusions: Endoscopic injection of CAG appears to be a safe, feasible, reliable and effective
modality which offers a minimally invasive technique as an alternative to surgical reoperation in
patients with accessible GIFs that are non-healing after standard management.
Keywords: GI Fistulae; Cyanoacrylate glue
Introduction with sepsis and may be complicated by
A Gastrointestinal fistula (GIF) is an septic shock and death 1. Studies have
abnormal communication between 2 demonstrated a mortality rate of up to 10%
2
epithelized surfaces with at least one of . On most occasions (75 – 85%) the
them pertaining to the GI tract. GIF remains etiology of the fistula is iatrogenic and
a challenging problem as they come with a follows a surgical procedure. The incidence
myriad of presentations. The manifestations of fistulae varies as per the surgery. It is
range from an asymptomatic patient to one uncommon after an esophageal surgery

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Medico Research Chronicles
“Superglue in GI leaks: Use of cyanoacrylate glue in GI fistulae”

(2.7%) and is seen frequently after a Patients consent (written) was taken after
pancreatic surgery (25%) 1. The rest (15% to detailed counseling of the patients and their
25%) are spontaneously occurring fistulae relatives. The counseling included a detailed
due to various etiologies like radiation, description of the current clinical condition
inflammatory bowel disease, diverticular of the patients, planned procedure and the
disease, appendicitis and ischemic bowel 3. potential complications of the therapy.
Almost a third of fistulae resolve Procedure: The diagnosis of GIF was
spontaneously with conservative suspected clinically in presence of persistent
4
management . In the remaining patients, the drain from the surgical site or occurrence of
options were limited. Surgery is the standard fever. The patients underwent Contrast-
management but is fraught with high Enhanced Computed Tomography (CECT)
morbidity and mortality. of the part. On detection of a collection, a
Due to the limited options in non- percutaneous drain was placed and the
healing GIFs, the last 10 years have seen in patient was managed with nutrition (through
a surge of novel techniques being developed appropriate access) and antibiotics. The
to augment the management of non-healing response to conservative therapy was
fistulae. Most of the therapeutic assessed by the decrease in the drain output
interventions that are being developed and resolution of clinical symptoms. If the
include minimally invasive approaches drain persisted for a period of a week with
which are either endoscopy based or no demonstrable decrease in the drain or the
intervention radiology based. Endoscopic collection, the diagnosis of a non-healing
interventions include placement of clips, GIF was made. The details of the seven
stents or fibrin glue 2,5,6. Interventional patients are shown in Table 1.
radiology also offers a similar management Endoscopy was done for all patients
and is usually done in patients with fistulae of non-healing GIFs. Procedures were
that can’t be approached endoscopically 7,8. performed by gastroenterologists with 5-10
Cyanoacrylate glue (CAG) is a years of experience. Upper GI endoscopy
standard feature in the armamentarium of a (Olympus, USA) was used to access the GIF
gastroenterologist and is easily available in and injection of CAG Endocrinol, Samarth,
the endoscopy theatre. The most common India) was done using sclerotherapy needle
use of CAG is an injection of fundal varies (Interject, Boston Scientific, USA).
through a sclerotherapy needle and has been On localization of the GIF, the tract
established as a safe modality of was obliterated with an injection of CAG,
management is basic precautions and composed of monomers of n-butyl-2-
protocols are followed. We present the cyanoacrylate. The glue was injected in 1 ml
result of our clinical experience with CAG aliquots. The catheter that was used for glue
injection in the management of non-healing injection was flushed with non-ionic
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GIFs after the failure of standard medical dextrose solution to prevent glue
therapy. polymerization within the catheter. The
Materials and Methods drainage catheter was left in situ to assess
Patient Population: All patients with the response to the intervention and was
a persistent non-healing GIFs were removed when the daily drain was less than
prospectively enrolled in the study during a five ml for three consecutive days. A repeat
study period of Apr 2016 to Mar 2018. CECT was done to document resolution of
Ethical clearance was taken from the the collection. Image of the fistulous
hospital ethics committee. In all cases, opening of patient no. 1 is shown in Figure
standard conservative procedures (nutrition, 1. In case of persistence of the drain, the
antibiotics and percutaneous drainage) had second session of glue injection was
failed in achieving closure of the GIF and planned if a fistulogram demonstrated the
they were diagnosed as non-healing GIFs. persistence of the fistula.

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DOI No. 10.26838/MEDRECH.2018.5.6.452
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Medico Research Chronicles
“Superglue in GI leaks: Use of cyanoacrylate glue in GI fistulae”

Data Analysis: The primary endpoint was the closure of the was defined as the possibility to reach the opening of the GIF and
fistula. Healing/closure of the GIF was defined by a stoppage of the perform the glue injection. The other parameters that were noted
persistent drain followed by imaging of the part which had to were the number of injections required the time to achieve complete
document the absence of a collection. Feasibility of the procedure closure of the fistula and other complications.

Table 1: Patient characteristics


The total
Site of Size of No of Healing Follow
Age Sex Disease Management dose of
Fistula fistula Injections time up
CAG
Duodenal 12
1. 32 Male Omental patch Duodenum 1.5 cm 01 08 days 2 ml
Perforation weeks
Choledocholithiasis
12
2. 55 Male Post ERCP duodenal Conservative Duodenum 1.5 cm 01 09 days 2.5 ml
weeks
perforation
Necrosectomy
Necro-
Severe Acute followed by 12 1 ml + 1
3. 45 Male cutaneous 1 cm 02 12 days
Pancreatitis ERCP and MPD weeks ml
fistula
stenting
Foreign Body (Coin) Endoscopy – 12

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4. 05 Male Esophagus 2.5 cms 01 10 days 1 ml
Esophagus Hemoclip weeks
Necrosectomy
Necro-
Moderate Severe followed by 12 1 ml + 1
5. 36 Male cutaneous 1.5 cms 02 13 days
Pancreatitis ERCP and MPD weeks ml
fistula
stenting
Perforating
Gastrojejunosto 12
6. 28 Male duodenal ulcer with Duodenum 1.5 cms 01 02 days 2 ml
my weeks
GOO
Removal of PEG
12
7. 58 Male Fistula at PEG site tube and Stomach 1 cm 01 05 days 1 ml
weeks
antibiotics
Abbreviations
PEG: Percutaneous Endoscopic Gastrostomy
ERCP: Endoscopic Retrograde Cholangiopancreatography
MPD: Main Pancreatic Duct
GOO: Gastric outlet obstruction
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“Superglue in GI leaks: Use of cyanoacrylate glue in GI fistulae”

Fig 1: The Fistulous opening of Patient No 1


Results the GIF results in increased morbidity and
Seven cases of non-healing GIF mortality. Secondly, it increases the
were managed with CAG injection over the financial burden of healthcare as it implies
study period. Feasibility of the procedure an increase in hospital stay and the need for
was 100% and the fistula was localized in multidisciplinary management both of
all cases. A median of 01 injections (Range which increase the cost of the treatment.
1-2) was performed in the patients with Surgical management of non-healing
most (71.4%, 5/7) requiring only one GIFs is a challenge on its own and the
injection. The CAG injection data is shown resultant surgery comes with significant
in Table 1. morbidity. The acceptance for a second
The success rate of the procedure surgery by the patient is usually difficult as
was 100% and all the patients with GIF had most of the GIFs are iatrogenic and the
complete closure of the fistula after the patient already has a severe illness. Hence
CAG injection. The average time required over the last decade, multiple new
for GIF closure was 8.5 + 3.9 days (range approaches have been devised to treat these
02-13 days). Two patients (33%) required a GIFs. These approaches include clips
repeat injection and both the patients had (Hemoclips and OTSC), Loops
been a case of severe acute pancreatitis (Endoloops), Sutures (ENDOCLINCH),
requiring necrosectomy leading to a Stents (ALIMAX) and tissue sealants
persistent GIF despite ERCP and pancreatic (including fibrin sealant and glue injection)
duct stenting. All other patients had closure [4]. Series have also been published
with a single injection only. Possibly the indicating the feasibility of intervention
inflammation of the pancreatic head played radiology using CAG for management of
a role in the decreased response to the fistula 9.
intervention. Tissue sealants are substances that
There were no complications noted polymerize and stick together epithelial
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in the study. All the patients were followed surfaces following contact with tissue fluid
up for 12 weeks and no mortality was or water. Polymerization is followed by
recorded. There was no recurrence of the epithelisation which results in fistula
GIF during the follow-up. closure. Fibrin glue is a type of tissue
Discussion sealant that has been used more extensively
GIFs mark an important event in the in the management of GIF. Rabago et al
management of patients of gastrointestinal used fibrin glue for effective treatment of
catastrophe. The manifestation of GIFs can postoperative fistulas resistant to
10
be diverse and the spectrum includes conservative treatment . Various studies
patients who range from asymptomatic have proven the safety and the benefit of
individuals to patients with sepsis. fibrin sealant in the management of entero-
Nonhealing GIF can pose an even important cutaneous fistulas 11.
challenge due to multiple reasons. Firstly

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“Superglue in GI leaks: Use of cyanoacrylate glue in GI fistulae”

Chemical glue without fibrin is recommending CAG in the management of


another option for management of GIF. non-healing GIFs. But with non-healing
CAG is a readily available sealant in a GIFs being a rare entity, it might not be
standard endoscopy theatre and thus is feasible to have a large study. Secondly, the
easily available to most gastroenterologists. amount of CAG to be injected has not been
Cyanoacrylate was the first super glue used standardized. It was given in aliquots of 1
for the purpose. Cyanoacrylate use resulted ml. Thus this study cannot recommend any
in severe local inflammation and thus was definite amount of CAG. Thirdly, there was
not used in humans. Subsequent studies in no standard duration after the onset of
animals showed that N-butyl cyanoacrylate fistula that CAG was offered. The attempts
and N-octyl cyanoacrylate cause less were made after failure of conservative
inflammation when N-butyl cyanoacrylate therapy at varying intervals from the onset
was used in the closure of cystostomy in of fistula.
dogs 12. CAG is also bacteriostatic in nature. Conclusion
Hence, CAG has been utilized in humans Endoscopic injection of CAG
for management of numerous fistulas like appears to be a safe, feasible, reliable and
vesicovaginal fistula 13. effective modality which offers a minimally
CAG has been used in numerous invasive technique as an alternative to
studies by interventional radiologists in the surgical reoperation in patients with
management of non-healing GI fistulas. Bae accessible GIFs that are non-healing after
et al described 11 patients of enteric or standard management.
biliary fistulae who were managed with Conflict of Interest: None
percutaneous CAG injection with a high References
success rate 14. Mauri et al also used CAG, 1. Girard E, Messager M, Sauvanet A,
albeit a different material, for management Benoist S, Piessen G, Mabrut JY et al.
of non-healing GIFs with a success rate of Anastomotic leakage after
88.9% 9. The authors argued that Glubran-2 gastrointestinal surgery: diagnosis and
has a different chemical structure which management. J ViscSurg 2014;151:441–
produces a more stable polymer leading to 450
less inflammation. Glubran-2 can be easily 2. Joyce MR, Dietz DW. Management of
identified under fluoroscopy and has been complex gastrointestinal fistula. Curr
shown to have antibacterial properties 15. Probl Surg 2009;46:384–430
We used CAG for management of 3. González-Pinto I, González EM.
non-healing GIFs with a high success rate Optimizing the treatment of upper
and no complications. CAG injection in the gastrointestinal fistulae. Gut.
management of GIF, however, has been 2001;49(suppl 4):iv22–iv31
reported only as case reports and series 4. Kumar N, Larsen MC, Thompson CC.
Medico Research Chronicles, 2018
16,17,18,19
. In our knowledge, this is the Endoscopic Management of
largest study of endoscopic injection of Gastrointestinal Fistulae. Gastroenterol
CAG for management of non-healing GIFs. Hepatol. 2014; 10(8): 495–452.
The fact that CAG is easily available in 5. Jacobsen HJ, Nergard BJ, Leifsson BG,
endoscopy theatres and has a high success Frederiksen SG, Agajahni E, Ekelund M
rate for accessible fistulae with low et al. Management of suspected
complication rate makes it an interesting anastomotic leaks after bariatric
and useful option in the management of laparoscopic Roux-en-y gastric
non-healing GIFs. bypass.Br J Surg 2014;101:417–423
Some limitations of this study have 6. Kumar N, Thompson CC. Endoscopic
to be taken into account. Firstly this is a therapy for post-operative leaks and
study with a limited sample size and larger fistulae. Gastrointest Endosc Clin N Am
studies have to be conducted before 2013;238:123–136

Sood A. K., Med. Res. Chron., 2018, 5 (6), 448-453 452


DOI No. 10.26838/MEDRECH.2018.5.6.452
Downloaded from
Medico Research Chronicles
“Superglue in GI leaks: Use of cyanoacrylate glue in GI fistulae”

7. Mauri G, Mattiuz C, Sconfienza LM, G, Rivera-Cruz JM. Comparison of n-


Pedicini V, Poretti D, Mel-chiorre F et butyl-2-cyanoacrylate tissue adhesive in
al. Role of interventional radiology in bladder perforation closure with double-
the management of complications after layer suture in a dog model. Rev Mex
pancreatic surgery: a pictorial Urol 2010;70:103-10
review.Insights Imaging 2014;6:231– 13. Sawant AS, Kasat GV, Kumar V.
239 Cyanoacrylate injection in the
8. Pedicini V, Poretti D, Mauri G, Trimboli management of recurrent vesicovaginal
M, Brambilla G, Sconfienza LM et al. fistula: Our experience. Indian J Urol
Management of post-surgical biliary 2016;32:323-5
leakage with percutaneous transhepatic 14. Bae JH, Kim GC, Ryeom HK, Jang YJ.
biliary drainage (PTBD) and occlusion Percutaneous embolization of persistent
balloon (OB) in patients without biliary and enteric fistulas with
dilatation of the biliary tree: preliminary Histoacryl. J Vasc Interv Radiol
results. Eur Radiol 2010;20:1061–1068 2011;22:879–883
9. Mauri G, Pescatori LC, Mattiuz C, 15. Rogalski P, Daniluk J, Baniukiewicz A,
Poretti D, Pedicini V, Melchiorre F et al. Wroblewski E, Dabrowski A.
Non-healing post-surgical fistulae: Endoscopic management of
treatment with an image-guided gastrointestinal perforations, leaks and
percutaneous injection of cyanoacrylic fistulas. World J Gastroenterol
glue. Radiol Med. 2017;122(2):88-94. 2015;21:10542–10552
10. Rábago LR, Ventosa N, Castro JL, 16. Seewald S, Brand B, Groth S.
Marco J, Herrera N, Gea F. Endoscopic Endoscopic sealing of pancreatic fistula
treatment of postoperative fistulas by using N-butyl-2-cyanoacrylate.
resistant to conservative management Gastrointest Endosc 2004;59:463–470
using biological fibrin glue. Endoscopy 17. Rotondano G, Viola M, Orsini L.
2002; 34(8):632-8 Uncommon cause of early postoperative
11. Jorge Avalos-González, Eliseo Portilla- colonic fistula successfully treated with
deBuen, Caridad Aurea Leal-Cortés, endoscopic acrylate glue injection.
Abel Orozco-Mosqueda, María del Gastrointest Endosc 2008;67:183–186
Carmen Estrada-Aguilar et al. Reduction 18. Billi P, Alberani A, Baroncini D.
of the closure time of postoperative Management of gastrointestinal fistulas
enterocutaneous fistulas with fibrin with n-2-butyl-cyanoacrylate.
sealant World J Gastroenterol. 2010; Endoscopy 1998;30: S69
16(22): 2793–2800. 19. Ojima Toshiyasu. Alpha-cyanoacrylate
12. Davila-Serapio F, Villicana-Benítez JJ, injection for esophageal fistulas.
Montejo-Velazquez C, Martínez-Olivera Endoscopy 2014; 46: E62–E63
Medico Research Chronicles, 2018

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