Complications of Double Balloon Enteroscopy

Definition of Complication 

In general, a complication of an endoscopic procedure is defined as any event that changes the health status of a patient in a negative way, mostly within 30 days after the procedure. It is common to subcategorize complications in minor (requiring upto 3 days of hospitalization), moderate (requiring 3-10 days of hospitalization), and major (requiring >10 days of hospitalization, and/or endoscopic, radiological, or surgical intervention, and/or contributing to the death of the patient).

Until now, no standards or definitions for complications during or after DBE have been established. Potential complications during or after DBE might be: perforation, bleeding, balloon dislocation, and sedation-related. Recently, post-DBE pancreatitis has been recognized as a complication.

Reports of Complications in Literature 

In the initial series on DBE, no complications during or after DBE were reported.2, 3 Three reports with larger series of procedures, mentioned explicitly no complications in series of 147, 70, and 89 DBE procedures.5, 6, 7 Subsequent series of DBE procedures published until now report the absence of complications or a paucity of unplanned events.4, 8, 9, 10, 11 The first major complications were reported in 2 smaller series of procedures: one distal colonic perforation during rectal insertion and one perforation after contact diathermy.12, 13 These were followed by publication of a peristomal perforation in a larger series of procedures.14 Two reports concerning polypectomy by DBE procedures in Peutz–Jeghers syndrome patients were published as an abstract.15, 16 In one abstract, 4 intervention-related complications were reported from a series of 34 polypectomies: 2 bleedings, 1 perforation, and 1 sedation-related complication.15 A case report on intestinal necrosis as a complication after epinephrine injection therapy was reported by Yen and coworkers.17 Furthermore, 4 cases of DBE-related acute pancreatitis were reported, all 4 after perorally performed, diagnostic DBE procedures.18, 19, 20, 21, 22

Analysis of Complications Associated with DBE 

In a recent international survey on complications during or after DBE led by our own group, a total of 40 complications in 2362 DBE procedures were reported for an overall complication rate of 1.7%. Complication rates were compared between diagnostic and therapeutic interventions, leading to complication rates of 0.8% and 4.3%, respectively. The incidence of acute pancreatitis after diagnostic DBE was 0.3%. No mortality was reported in this survey.22 From the National German DBE register, a recent report showed an overall complication rate of 1.2% in a large series of 3894 DBE procedures. The incidence of acute pancreatitis was also 0.3% in this study. The perforation rate was 3.4%, and 6 major bleedings were reported (4 after polypectomy and 2 after biopsies). In this study, 2 lethal cases were reported: 1 patient after acute pancreatitis and 1 patient after a perforation.23 A recent publication by May and coworkers confined to therapeutic DBE procedures reported an overall complication rate of 3.4%.24

Perforation 

The first reports of perforation as complication during or after DBE procedures were a rectosigmoid perforation during retrograde insertion and a small bowel perforation after APC therapy in an active bleeding arteriovenous malformation.12, 13 May and coworkers reported 3 (6.5%) cases of perforation after 46 polypectomy procedures; all 3 required surgical intervention, and no mortality was reported. All perforations in this study occurred after polypectomy of polyps with a diameter larger than 3 cm.24 In another patient with Peutz—Jeghers, a transmural perforation occurred, distal to the site of polypectomy, likely as the result of shear forces induced by the push-and-pull maneuvers during DBE procedure in this patient with bowel adhesions.25 The international complication survey reported 6 (0.3%) perforations: 1 (0.1%) after diagnostic and 5 (0.8%) after therapeutic DBE procedures. Of the 5 therapeutic DBE procedures complicated by perforation, 3 (1.2%) resulted from APC treatment of arteriovenous malformations (of 253 procedures where APC was used) and 2 (2.9%) were after dilation therapy of small bowel tumors. Also no mortality was reported after perforations in this study.22

As compared with therapeutic procedures in the upper and lower gastrointestinal tract, the perforation rate of therapeutic DBE procedures is higher, respectively 0.4-2.0% and 4.3-6.5%.22, 24, 26, 27, 28, 29, 30 An explanation for this difference might be the relatively thin wall of the small bowel, as compared with the thicker wall of the upper and lower gastrointestinal tract. In the study of May and coworkers, all perforations after polypectomy occurred in polyps greater than 3 cm, after standard submucosal injection with diluted epinephrine–saline solution (1:100,000).24 These data suggest that polypectomy of larger polyps should be performed with extra care. To decrease the risk of clinically significant perforations, preventive placement of hemoclips can be considered. The latter management technique already proved worthwhile in gastric and colonic endoscopic submucosal dissections of neoplasms.31, 32

Perforation after the use of APC, especially for treatment of arteriovenous malformations, has been reported after 1% of procedures.22, 24 The energy levels used in APC treatment might be of significant importance in combination with the diameter of the APC probe. A standard catheter diameter of 1.5 mm (4.5 French) in combination with energy levels of 30 to 40 W (APC 300/Erbotom ICC 200) or 15 to 25 W and pulse 2 mode (Vio APC 2; both Erbe Elektromedizin, Tübingen, Germany) seems safe.24

The rate of perforation after dilation therapy using DBE, varies from 0% to 2.9% in present literature.22, 24 Dilation therapy is mainly performed in patients with stenosis due to Crohn’s disease or malignant obstruction. In case of Crohn’s disease patients, the risk of perforation depends on the presence of, and activity of, ulcerated mucosa. In general, it is advised not to perform dilation therapy in stenosis with active ulcerated mucosal disease. Also the length of the stenosis has to be taken into consideration: dilation therapy of a longer stenosis carries a higher risk of perforation. The common practice is to optimize medical treatment in patients with stenosis due to active Crohn’s disease. The patients with persisting clinical symptoms, despite intensified medical therapy, might be candidates for repeated DBE, to re-evaluate the possibility of endoscopic treatment.

Bleeding 

Postprocedural bleeding has been described as a complication of diagnostic DBE procedures in up to 15% of procedures.4, 6, 22 In most cases, these are self-limiting mucosal bleedings, possibly due to friction of the overtube balloon on the small bowel mucosa. After therapeutic DBE procedures, more severe bleeding complications have been reported. May and coworkers reported 2 bleeding complications after 46 (4.3%) polypectomy procedures (only 1 bleeding episode requiring blood transfusion).24 The collected data of the international survey reported 12 (3.3%) bleeding complications after 364 polypectomies. These bleedings were reported as minor in 5 (1.4%), moderate in 7 (1.9%) cases, and no major bleeding episodes were reported. Also, 1 (0.4%) moderate bleeding was reported after 253 DBE procedures using argon plasma coagulation (APC) for treatment of 1 or more arteriovenous malformations.22 There was no need for surgical or radiological intervention, and no mortality was reported in both reports. The National German DBE register group reported 6 major bleeding complications: 4 after polypectomy and 2 after biopsy sampling. None of these bleedings required surgical or angiographical intervention, all could be managed endoscopically, and no mortality occurred.23

Post-DBE Pancreatitis 

The first case reports on acute pancreatitis after DBE were reported by the Rotterdam group.18 Honda and coworkers followed by presenting a case of acute pancreatitis after peroral DBE.19 Subsequently, the latter group reported a high frequency of hyperamylasemia within 24 hours post-DBE and a correlation with the development of an acute pancreatitis after perorally performed DBE procedures.21

From both the international survey and the Germany register, it emerged that acute pancreatitis was the most common (0.3%) complication after diagnostic DBE procedures. Also, one pancreatitis (0.2%) was reported after therapeutic DBE procedures, in this case after an ERCP procedure in a patient with a Roux-en-Y reconstruction. The majority of patients with pancreatitis (6 of 7) presented with abdominal pain within 24 hours after the procedure.22, 23

Controversy exists about the pathophysiologic cause of acute pancreatitis after (peroral) DBE procedures. To date, two theories about the cause of acute pancreatitis have been stated. One theory is based on the principle of overpressure in the intestinal compartment between the two inflated balloons, causing reflux of duodenal contents into the pancreatic duct.18 The theory of duodenal overpressure leading to reflux in the pancreatic duct was first described in the 1950s and has been supported by experimental (animal) studies.33, 34 The other theory is based on the shortening of the duodenum and the proximal jejunum by the push-and-pull technique used by DBE. This might lead to severe strain to the papilla of Vater and increased intraluminal pressure in the duodenum, which may disturb the secretion of pancreatic juice.20, 34 Our group decided, after the first cases of acute pancreatitis, to inflate both balloons not only after two insertions (being at least 50 cm distal from the papilla of Vater), while performing a peroral DBE. In the following 180 perorally performed DBE procedures, no post-DBE pancreatitis was encountered.

Summary 

The overall complication rate of DBE procedures is 1.2-1.7%.22, 23 Diagnostic DBE seems a relative safe procedure, with an overall complication rate of 0.8%.22 This complication rate is higher compared with the complication rate of diagnostic gastroduodenoscopy (0.01-0.1%), but comparable with the complication rate of diagnostic colonoscopy (0.02-2.4%).24, 25, 26, 27, 28, 29, 30, 35, 36, 37 The most common complication after diagnostic DBE procedures is acute pancreatitis, occurring in 0.3% of procedures.22, 23 In patients with persistent or worsened abdominal complaints after a DBE procedure, an acute pancreatitis has to be considered. Theoretically, delayed inflation of both balloons, while performing a peroral procedure, might prevent the development of acute pancreatitis. However, the latter theory is not supported by (experimental or clinical) data, so far.

The complication rate of therapeutic DBE is 3.4-4.3% and considerably higher compared with therapeutic gastroduodenoscopy (0.02-0.2%) and therapeutic colonoscopy (1.2-2.0%).24, 25, 26, 27, 28, 29 This might be related to the relative thin small bowel wall, compared with the stomach and the (distal) colon. Additive measures to prevent hemorrhage and perforation after therapeutic DBE interventions, like submucosal injection of saline (with or without epinephrine) and placement of (hemo-) clips, might decrease the risks of these complications. The effect of these measurements after therapeutic interventions has to be evaluated in future studies. As more and more therapeutic procedures are performed during DBE procedures, prospective studies on complications are needed in the future.