ORIGINAL ARTICLE: GASTROENTEROLOGY
Intestinal Anastomotic Ulcers in Children With Short Bowel Syndrome and Anemia Detected by Capsule Endoscopy Lee M. Bass, Jessica Zimont, Joshua Prozialeck, Riccardo Superina, and Valeria Cohran ABSTRACT Objectives: Anastomotic ulcers are a known cause of anemia in children with a history of intestinal resection. Upper endoscopy and colonoscopy can be used to diagnose these ulcers; however, the area of involvement may be difficult to visualize with standard endoscopic techniques. Capsule endoscopy (CE) offers an alternative method for visualizing the small bowel in these patients. We describe a cohort of patients with short bowel syndrome (SBS) and anemia who had anastomotic ulcers detected by CE. Methods: Retrospective chart review of patients with SBS at our institution who underwent CE for chronic gastrointestinal (GI) blood loss. Results: Four patients who underwent a total of 6 CE procedures were identified. The underlying diagnoses included necrotizing enterocolitis (n ¼ 2), gastroschisis (n ¼ 1), and jejunal atresia (n ¼ 1). All of the patients had their ileocecal valves resected during previous surgeries and had received blood transfusions within the previous several months. The median age at the time of CE was 5.5 years (range 4–14 years). Enterocolonic anastomotic ulcers were noted in the studies as wide, flat circumferential lesions with a white base. The CE results guided a change in medical management in all of the 4 patients, including surgical revision of their anastomosis. Conclusions: CE may be a helpful adjunctive tool for detecting anastomotic ulcers in patients with SBS and chronic GI blood loss. Key Words: bleeding, diagnosis, gastrointestinal, pediatric, small bowel bacterial overgrowth
(JPGN 2015;61: 215–219)
C
hildren with intestinal failure experience significant morbidity and mortality from gastrointestinal (GI) bleeding. Of the patients studied by the Pediatric Intestinal Failure Consortium, 9% died secondary to hemorrhage, with some experiencing additional bleeding because of liver failure (1). Other causes of bleeding include small bowel bacterial overgrowth (SBBO), peptic disease, and GI allergies (2). Lower GI bleeding from noninfectious colitis has also been described in patients with short bowel syndrome (SBS) and parenteral nutrition. Anastomotic ulcers are a known cause of anemia Received January 7, 2015; accepted February 26, 2015. From the Ann & Robert H. Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL. Address correspondence and reprint requests to Lee M. Bass, MD, Ann & Robert H. Lurie Children’s Hospital of Chicago, 225 E. Chicago Ave, Box No. 65, Chicago, IL 60611 (e-mail: [email protected]). This work was supported by internal research funds provided by the Ann & Robert H. Lurie Children’s Hospital of Chicago. The authors report no conflicts of interest. Copyright # 2015 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition DOI: 10.1097/MPG.0000000000000778
JPGN
Volume 61, Number 2, August 2015
What Is Known
Anastomotic ulcers are a known cause of anemia and gastrointestinal bleeding in children with short bowel syndrome. Detection of anastomotic ulcers may have implications for continuing medical and surgical management in these children. Diagnosis of anastomotic ulcers in this population provides significant challenges to the clinician.
What Is New
Capsule endoscopy can be used to diagnose anastomotic ulcers in children with short bowel syndrome with anemia and episodic gastrointestinal bleeding. Capsule endoscopy should be used as part of the diagnostic evaluation of anemia and gastrointestinal bleeding in children with short gut syndrome.
in children with a history of intestinal resection. The etiology of these ulcers may be secondary to ischemia or SBBO (3,4). Surgical resection may be required in the setting of anemia requiring multiple blood transfusions. Diagnosis of anastomotic ulcers in children with SBS presents a technical challenge. Upper and lower endoscopy can be used to diagnose these ulcers; however, in many patients with SBS, particularly following serial transverse enteroplasty (STEP) procedures, the area of involvement may be difficult to visualize with standard endoscopic techniques. Capsule endoscopy (CE), however, enables the visualization of the entire small intestinal mucosa. We describe a series of pediatric patients with SBS, anemia, and episodic GI bleeding, who had anastomotic ulcers, some within their STEP, which were undetected by conventional endoscopy but were detected by subsequent CE.
METHODS We performed a retrospective chart review of patients with SBS at our institution who underwent CE for chronic GI blood loss from September 2009 to June 2014. The study was conducted under the approval of the institutional review board at the Ann & Robert H. Lurie Children’s Hospital of Chicago. Inclusion criteria included a diagnosis of SBS and anemia with either recent transfusion requirement or supplemental iron requirement. All of the patients had prior upper and lower endoscopy and had a diagnostic upper endoscopy to the extent of the second portion of the duodenum,
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JPGN
either with or without biopsy, at the time of endoscopic capsule placement. Patients chosen for CE had a patency capsule or imaging demonstrating a lack of strictures or obstructive lesions. All of the patients received the standard preparatory protocol for CE with polyethylene glycol-3350 of 17 g given twice the day before the CE procedure. Patients were allowed clear liquids for 12 hours and nothing by mouth for 6 hours before receiving the PillCam SB2 capsule (Given Imaging, Duluth, GA). One patient swallowed the capsule endoscope in the outpatient clinic per our institutional protocol. The remaining patients had the capsule placed endoscopically. All of the procedures were performed under general endotracheal anesthesia with the patient in the left lateral decubitus position. The AdvanCE capsule delivery device (US Endoscopy, Mentor, OH) was used for deployment of the capsule endoscope in all of the patients. The device was fastened to the gastroscope according to the manufacturer’s instructions. The capsule endoscope was removed from the packaging and placed in the capsule delivery device. Recognition of the capsule was noted on the capsule device recorder. The real-time (RT) viewer was used as previously described (5). All of the patients were asked to adhere to the standard diet schedule as recommended by the manufacturer. The recording device was disconnected after 8 hours or sooner if the capsule was noted to be in the colon on the RT viewer or had been passed in the stool. Clear instructions were given to patients to observe for capsule passage, and patients were to report any adverse events including abdominal pain, nausea, vomiting, or failure to pass the capsule. The medical records of the patients were analyzed retrospectively. Information collected included age, gestational age, sex, weight, blood transfusions before CE, hemoglobin before capsule placement, patient medications, conventional endoscopic findings, CE information, and patient outcome.
RESULTS Four patients who underwent a total of 6 CE studies were identified. Patient characteristics are summarized in Table 1. The underlying diagnoses included necrotizing enterocolitis (NEC) (n ¼ 2), gastroschisis (n ¼ 1), and jejunal atresia (n ¼ 1). The last surgical procedure before CE was >2 years ago for all of the patients. Patient 1 was a female who presented for CE at 14 years 10 months of age. She was born at 26-week gestation and had SBS
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secondary to NEC. The patient was on a full enteral general diet at the time of CE and was not receiving total parenteral nutrition (TPN). She did not have her ileocecal (IC) valve. The indication for CE was persistent iron deficiency anemia for which she had received several intravenous (IV) iron transfusions at our institution. An upper and lower endoscopy 1 year before presentation demonstrated a distal ileal ulcer and a positive duodenal aspirate for SBBO consisting of a quantitative culture of >10,000 CFU/mL of mixed enteric flora, which was treated with rifaximin. She received repeated IV iron transfusions over the next 12 months. Despite hemoglobin of 14 g/dL, she was noted to have hemoccult-positive stools. She had a repeat upper and lower endoscopy that was unremarkable. CE was performed to further evaluate her lower GI bleeding. The patient orally ingested the capsule endoscope. CE demonstrated a large ulcer in the distal ileum (Fig. 1A). The patient had resolution of symptoms with change in enteral antibiotics regimen to trimethoprim/sulfamethoxazole and nitazoxanide. Patient 2 initially presented at 6.5 years of age. The patient was born at 40 weeks gestation and had a history of jejunal atresia with an initial small intestinal length of 150 cm without an IC valve. She had undergone a STEP procedure at 6 months of age. She was maintained exclusively on enteral nutrition without any requirement for TPN. She presented for evaluation after multiple episodes of lower GI bleeding requiring multiple transfusions. Upper and lower endoscopies were normal and nondiagnostic. CE was performed to evaluate the small bowel source of bleeding. The patient had endoscopic placement of the capsule. A mid small bowel ulcer with a wide flat base was identified, with no visible vessel noted (Fig. 1B). At the time of CE, she had been off TPN for approximately 1 year. She had resolution of GI bleeding with a change in antibiotic regimen to nitazoxanide and rifaximin; however, her iron deficiency anemia and blood loss in the stool continued despite numerous cycles of antibiotic therapy, with hemoglobin of 7.4 g/dL before CE. A repeat CE performed at 8.25 years of age showed retrograde transit of the capsule into the stomach despite endoscopic placement in the duodenum and use of a motility agent, erythromycin. Intraoperative endoscopy was performed, and a stricture was noted within the STEP with an associated anastomotic ulcer at the stricture site. Surgical resection of the stricture was performed with resolution of symptoms and no further blood loss. Patient 3 presented at 5.25 years of age. He was an ex-25 week premature infant who had intestinal resection because of NEC. He had a small intestine length of 23 cm and did not have an IC valve. He was maintained completely on enteral feeds and had
TABLE 1. Patient characteristics at the time of capsule placement, capsule findings, treatment, and outcomes
Patient
Sex
Age, y
43.6
14
Diagnosis NEC
STEP
Completed study
Capsule findings
N
Y
Large ulcer in distal ileum with a flat, white base Mid small bowel ulcer with a wide flat base Retrograde transit into stomach Large ulcer with a wide, flat, white base and visible blood vessel Anastomotic ulcer proximal to anastomosis within the STEP Large anastomotic ulcer proximal to anastomosis within the STEP
1
F
2
F
6.5
18.6
7.9 Jejunal atresia
Y
Y
3
M
8.25 5.25
21.3 18.2
7.4 6.8 NEC
N
N Y
4
F
3.5
15.6
7.8 Gastroschisis
Y
Y
4
15.7
10.2
18.6
7.9
Median
14
Weight, Hgb, kg g/dL
Y
Resolution of symptoms
Treatment Antibiotics
Y
Antibiotics
N
Surgical revision Surgical resection
Y Y
Surgical revision
N
Antibiotics, mesalamine
Y
Hgb ¼ hemoglobin; NEC ¼ necrotizing enterocolitis; STEP ¼ serial transverse enteroplasty.
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Intestinal Anastomotic Ulcers in Children
FIGURE 1. Images of anastomotic ulcers as visualized by CE in patient 1 (A) and in patient 2 (B). Note the wide white base at the area of anastomosis. CE ¼ capsule endoscopy.
not been on TPN for 4.5 years at the time of presentation. The patient presented with lower GI bleeding and anemia with hemoglobin of 6.8 g/dL. He subsequently received multiple blood transfusions. Upper and lower endoscopies were unremarkable, including a duodenal aspirate that was negative for SBBO. The capsule endoscope was placed endoscopically into the duodenum. CE revealed a large ulcer with a wide flat whitish base and visible blood vessel (Fig. 2). A change in antibiotic regimen failed to improve symptoms, and he underwent resection of the ulcer along with 4 cm of bowel. He is no longer anemic and has not required any further blood transfusions. Patient 4 presented at 3.5 years of age. She was born at 35 weeks gestation with gastroschisis and had an initial intestine length of 50 cm. She did not have an IC valve. She underwent a STEP procedure and was maintained exclusively on enteral nutrition. She presented with anemia and persistent GI bleeding requiring blood transfusions for hemoglobin of 7.8 g/dL. Upper and lower endoscopy before her CE noted a small ulcer in her proximal colon without stigmata of bleeding. Quantitative bacterial culture from
FIGURE 2. Image of anastomotic ulcer as visualized by CE in patient 3. CE ¼ capsule endoscopy.
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duodenal aspirate demonstrated growth of Klebsiella oxytoca and Escherichia coli. After changes to her regimen of antibiotics for SBBO were not successful at ameliorating symptoms, CE was performed. CE revealed a larger anastomotic ulcer proximal to her anastomosis, within the STEP (this image is not shown in this article). The patient underwent surgical revision of her anastomosis with resection of the ulcer; however, the patient continued to experience GI bleeding, with hemoglobin of 10.2 g/dL. A repeat upper and lower endoscopy 6 months after the prior endoscopy at 4 years of age, noted a small white ulcer in the proximal colon. A repeat CE showed an ulcer proximal to the anastomosis. This was treated empirically with a change in both antibiotic therapy and mesalamine. The patient currently remains asymptomatic on enteral iron therapy.
DISCUSSION In this case series, we described the use of CE to detect and guide resection of anastomotic lesions in children with SBS presenting with anemia and GI bleeding. All of the patients had their last surgery at least 2 years before presentation. Each patient underwent an upper endoscopy and colonoscopy, but the source of bleeding was not readily identified. Subsequent CE led to the identification of the anastomotic lesion responsible for the symptoms. Upper endoscopy and colonoscopy have been shown to be beneficial in the evaluation of children with SBS and intestinal failure. One study looking at conventional endoscopy for evaluation of GI bleeding found allergic disease, peptic disease, and SBBO among other etiologies of anemia (6). CE may be a valuable adjunctive test for patients with chronic GI bleeding but negative upper endoscopy and colonoscopy. Our case series confirms a role for CE in evaluation of GI bleeding in pediatric patients, consistent with previous studies in adults and children. CE for evaluating GI bleeding in children was found to identify lesions with a high yield, including 1 instance of an anastomotic ulcer in 1 study (7,8). In these studies, CE also detected nonsteroidal anti-inflammatory drug enteropathy, polyps, AVM, hemangiomas, and ulcerative jejunitis. We have reported cases of CE in bleeding patients leading to specific and directed intestinal resections (9). Anastomotic ulcerations in patients with intestinal resection are a well-described phenomenon (3,10). Sondheimer et al (4) described 6 children with intestinal resection for NEC who presented with gross or occult bleeding from anastomotic ulcers that appeared to be inflammatory and only responded to surgical revision. A recent study evaluated the incidence of anastomotic ulcerations after intestinal resection in infancy. A total of 4 of 11 patients
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underwent CE for diagnosis. Charbit-Henrion et al noted the difficulty in diagnosing anastomotic ulcers and many of these patients had a long delay before diagnosis (11). Low use of CE in pediatric patients may result in an underestimation of the prevalence of this condition and possibly a delay in treatment. Turner et al (12) described anastomotic ulcers in children with rectal bleeding following small bowel transplantation. A number of mechanisms for surgical anastomosis ulceration have been proposed, including reaction to foreign body, ischemia at the anastomotic site, exposure to bile salts, exposure to excessive acid, and bacterial overgrowth. In fact, a retrospective analysis has demonstrated a high percentage of children with intestinal failure having SBBO as determined by duodenal aspirates. Parenteral nutrition was a risk factor for SBBO in that study population (13). In addition to anastomotic ulcerations, there have been reported patients with GI bleeding associated with the STEP procedure. This procedure was initially described by Kim et al (14,15) and involves the diagonal application of a gastrointestinal stapler to create a zigzag channel and thus bowel lengthening resulting in a substantial increase in small bowel absorption. Numerous studies have demonstrated the success of STEP across many centers (16) with excellent intermediate (17) and longer term outcomes in helping attain enteral autonomy (18–20). A single case of staple line ulcers was described in the group of 12 patients studied after STEP from Toronto. The involved area was resected, and although bleeding recurred within the next few years, the patient continues to do well in the reported 5-year outcomes (17,18). Gibbons et al (21) described a patient with anemia and occult blood loss with ulcerations at the surgical staple sites detected by video CE. In addition, the Boston Children’s group described 2 of the 23 of their patients who had undergone STEP and experienced GI bleeding from staple line ulcers that improved with enteral antibiotics, sulfasalazine, and bowel rest (22). In our series, patient 3 was found to have an ulceration within the STEP that was subsequently resected. Our study is the first to describe the use of CE with the goal of identifying anastomotic ulcers and potential ulcerations with the STEP to specifically guide medical treatment. CE in patients with SBS is challenging because of the history of extensive abdominal surgery and in some patients, unusual anatomy. Endoscopic capsule deployment using the AdvanCE SBS
Microcytosis/iron deficiency anemia
GI bleed
Nutritional supplementation If continued loss Patency capsule SB imaging
Upper and lower endoscopy
Capsule endoscopy
Treat
ABX enteroscopy surgery
FIGURE 3. Clinical pathway for the evaluation of GI bleeding and microcytosis/iron deficiency anemia at Lurie Children’s Hospital. A patient presenting with SBS would initially be assessed for anemia and GI bleeding. Those with active bleeding would be evaluated by upper and lower endoscopy and if negative, with CE. ABX ¼ antibiotics; CE ¼ capsule endoscopy; GI ¼ gastrointestinal; SB ¼ small bowel; SBS ¼ short bowel syndrome.
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capsule device and the RT viewer is useful for negotiating unusual anatomy such as that seen after extensive small bowel surgery as in these patients (5). This technique was used in all of the patients with endoscopic placement of capsule in the study. Previous small bowel surgery has been shown to be a risk factor for incomplete CE and possible capsule retention (23). At our institution, the decision to perform CE is made in conjunction with medical and surgical teams so that, although every effort is made to avoid a situation that may result in a retained capsule, both parents and care teams are prepared to properly deal with capsule retention if it occurs. Thus, in children with short gut who have iron deficiency anemia or overt GI bleeding, CE can be an important adjunctive tool for diagnosis of treatable anastomotic ulcers. At our institution, we follow a clinical pathway incorporating CE in the evaluation of children with SBS and anemia or GI bleeding (Fig. 3), which may be a guide for future studies of CE in these patients. Although other studies have reported anastomotic ulcers on CE, ours is the first case series to evaluate CE as a guide toward treatment. All of the patients had a change in management as a result of findings on CE. We recommend the use of CE in patients with SBS and recurrent anemia or GI blood loss. A prospective study of CE in these patients may be useful for demonstrating shorter time to accurate diagnosis of anastomotic ulcers. Acknowledgments: The authors thank Michael Miller, MD, and Stacey C. Tobin, PhD, for article review and editorial support.
REFERENCES 1. Squires RH, Duggan C, Teitelbaum DH, et al. Natural history of pediatric intestinal failure: initial report from the Pediatric Intestinal Failure Consortium. J Pediatr 2012;161:723–728.e2. 2. Goulet O, Ruemmele F. Causes and management of intestinal failure in children. Gastroenterology 2006;130 (2 suppl 1):S16–28. 3. Hamilton AH, Beck JM, Wilson GM, et al. Severe anaemia and ileocolic anastomotic ulceration. Arch Dis Child 1992;67:1385–6. 4. Sondheimer JM, Sokol RJ, Narkewicz MR, et al. Anastomotic ulceration: a late complication of ileocolonic anastomosis. J Pediatr 1995; 127:225–30. 5. Bass LM, Misiewicz L. Use of a real-time viewer for endoscopic deployment of capsule endoscope in the pediatric population. J Pediatr Gastroenterol Nutr 2012;55:552–5. 6. Ching YA, Modi BP, Jaksic T, et al. High diagnostic yield of gastrointestinal endoscopy in children with intestinal failure. J Pediatr Surg 2008;43:906–10. 7. Thomson M, Fritscher-Ravens A, Mylonaki M, et al. Wireless capsule endoscopy in children: a study to assess diagnostic yield in small bowel disease in paediatric patients. J Pediatr Gastroenterol Nutr 2007; 44:192–7. 8. Fritscher-Ravens A, Scherbakov P, Bufler P, et al. The feasibility of wireless capsule endoscopy in detecting small intestinal pathology in children under the age of 8 years: a multicentre European study. Gut 2009;58:1467–72. 9. Naiditch JA, Bass L, Parsons WG, et al. Capsule endoscopy guided bowel resection for obscure gastrointestinal hemorrhage. Eur J Pediatr Surg 2012;22:332–4. 10. Bhargava SA, Putnam PE, Kocoshis SA. Gastrointestinal bleeding due to delayed perianastomotic ulceration in children. Am J Gastroenterol 1995;90:807–9. 11. Charbit-Henrion F, Chardot C, Ruemmele F, et al. Anastomotic ulcerations after intestinal resection in infancy. J Pediatr Gastroenterol Nutr 2014;59:531–6. 12. Turner D, Martin S, Ngan BY, et al. Anastomotic ulceration following small bowel transplantation. Am J Transplant 2006;6:236–40. 13. Gutierrez IM, Kang KH, Calvert CE, et al. Risk factors for small bowel bacterial overgrowth and diagnostic yield of duodenal aspirates in children with intestinal failure: a retrospective review. J Pediatr Surg 2012;47:1150–4.
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14. Kim HB, Fauza D, Garza J, et al. Serial transverse enteroplasty (STEP): a novel bowel lengthening procedure. J Pediatr Surg 2003;38:425–9. 15. Kim HB, Lee PW, Garza J, et al. Serial transverse enteroplasty for short bowel syndrome: a case report. J Pediatr Surg 2003;38:881–5. 16. Modi BP, Javid PJ, Jaksic T, et al. First report of the international serial transverse enteroplasty data registry: indications, efficacy, and complications. J Am Coll Surg 2007;204:365–71. 17. Wales PW, de Silva N, Langer JC, et al. Intermediate outcomes after serial transverse enteroplasty in children with short bowel syndrome. J Pediatr Surg 2007;42:1804–10. 18. Oliveira C, de Silva N, Wales PW. Five-year outcomes after serial transverse enteroplasty in children with short bowel syndrome. J Pediatr Surg 2012;47:931–7.
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Intestinal Anastomotic Ulcers in Children
19. Mercer DF, Hobson BD, Gerhardt BK, et al. Serial transverse enteroplasty allows children with short bowel to wean from parenteral nutrition. J Pediatr 2014;164:93–8. 20. Ching YA, Fitzgibbons S, Valim C, et al. Long-term nutritional and clinical outcomes after serial transverse enteroplasty at a single institution. J Pediatr Surg 2009;44:939–43. 21. Gibbons TE, Casteel HB, Vaughan JF, et al. Staple line ulcers: a cause of chronic GI bleeding following STEP procedure. J Pediatr Surg 2013; 48:E1–3. 22. Fisher JG, Stamm DA, Modi BP, et al. Gastrointestinal bleeding as a complication of serial transverse enteroplasty. J Pediatr Surg 2014;49: 745–749. 23. Westerhof J, Weersma RK, Koornstra JJ. Risk factors for incomplete small-bowel capsule endoscopy. Gastrointest Endosc 2009;69:74–80.
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Intestinal Anastomotic Ulcers in Children With Short Bowel Syndrome and Anemia Detected by Capsule Endoscopy Lee M. Bass, Jessica Zimont, Joshua Prozialeck, Riccardo Superina, and Valeria Cohran ABSTRACT Objectives: Anastomotic ulcers are a known cause of anemia in children with a history of intestinal resection. Upper endoscopy and colonoscopy can be used to diagnose these ulcers; however, the area of involvement may be difficult to visualize with standard endoscopic techniques. Capsule endoscopy (CE) offers an alternative method for visualizing the small bowel in these patients. We describe a cohort of patients with short bowel syndrome (SBS) and anemia who had anastomotic ulcers detected by CE. Methods: Retrospective chart review of patients with SBS at our institution who underwent CE for chronic gastrointestinal (GI) blood loss. Results: Four patients who underwent a total of 6 CE procedures were identified. The underlying diagnoses included necrotizing enterocolitis (n ¼ 2), gastroschisis (n ¼ 1), and jejunal atresia (n ¼ 1). All of the patients had their ileocecal valves resected during previous surgeries and had received blood transfusions within the previous several months. The median age at the time of CE was 5.5 years (range 4–14 years). Enterocolonic anastomotic ulcers were noted in the studies as wide, flat circumferential lesions with a white base. The CE results guided a change in medical management in all of the 4 patients, including surgical revision of their anastomosis. Conclusions: CE may be a helpful adjunctive tool for detecting anastomotic ulcers in patients with SBS and chronic GI blood loss. Key Words: bleeding, diagnosis, gastrointestinal, pediatric, small bowel bacterial overgrowth
(JPGN 2015;61: 215–219)
C
hildren with intestinal failure experience significant morbidity and mortality from gastrointestinal (GI) bleeding. Of the patients studied by the Pediatric Intestinal Failure Consortium, 9% died secondary to hemorrhage, with some experiencing additional bleeding because of liver failure (1). Other causes of bleeding include small bowel bacterial overgrowth (SBBO), peptic disease, and GI allergies (2). Lower GI bleeding from noninfectious colitis has also been described in patients with short bowel syndrome (SBS) and parenteral nutrition. Anastomotic ulcers are a known cause of anemia Received January 7, 2015; accepted February 26, 2015. From the Ann & Robert H. Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL. Address correspondence and reprint requests to Lee M. Bass, MD, Ann & Robert H. Lurie Children’s Hospital of Chicago, 225 E. Chicago Ave, Box No. 65, Chicago, IL 60611 (e-mail: [email protected]). This work was supported by internal research funds provided by the Ann & Robert H. Lurie Children’s Hospital of Chicago. The authors report no conflicts of interest. Copyright # 2015 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition DOI: 10.1097/MPG.0000000000000778
JPGN
Volume 61, Number 2, August 2015
What Is Known
Anastomotic ulcers are a known cause of anemia and gastrointestinal bleeding in children with short bowel syndrome. Detection of anastomotic ulcers may have implications for continuing medical and surgical management in these children. Diagnosis of anastomotic ulcers in this population provides significant challenges to the clinician.
What Is New
Capsule endoscopy can be used to diagnose anastomotic ulcers in children with short bowel syndrome with anemia and episodic gastrointestinal bleeding. Capsule endoscopy should be used as part of the diagnostic evaluation of anemia and gastrointestinal bleeding in children with short gut syndrome.
in children with a history of intestinal resection. The etiology of these ulcers may be secondary to ischemia or SBBO (3,4). Surgical resection may be required in the setting of anemia requiring multiple blood transfusions. Diagnosis of anastomotic ulcers in children with SBS presents a technical challenge. Upper and lower endoscopy can be used to diagnose these ulcers; however, in many patients with SBS, particularly following serial transverse enteroplasty (STEP) procedures, the area of involvement may be difficult to visualize with standard endoscopic techniques. Capsule endoscopy (CE), however, enables the visualization of the entire small intestinal mucosa. We describe a series of pediatric patients with SBS, anemia, and episodic GI bleeding, who had anastomotic ulcers, some within their STEP, which were undetected by conventional endoscopy but were detected by subsequent CE.
METHODS We performed a retrospective chart review of patients with SBS at our institution who underwent CE for chronic GI blood loss from September 2009 to June 2014. The study was conducted under the approval of the institutional review board at the Ann & Robert H. Lurie Children’s Hospital of Chicago. Inclusion criteria included a diagnosis of SBS and anemia with either recent transfusion requirement or supplemental iron requirement. All of the patients had prior upper and lower endoscopy and had a diagnostic upper endoscopy to the extent of the second portion of the duodenum,
215
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Bass et al
JPGN
either with or without biopsy, at the time of endoscopic capsule placement. Patients chosen for CE had a patency capsule or imaging demonstrating a lack of strictures or obstructive lesions. All of the patients received the standard preparatory protocol for CE with polyethylene glycol-3350 of 17 g given twice the day before the CE procedure. Patients were allowed clear liquids for 12 hours and nothing by mouth for 6 hours before receiving the PillCam SB2 capsule (Given Imaging, Duluth, GA). One patient swallowed the capsule endoscope in the outpatient clinic per our institutional protocol. The remaining patients had the capsule placed endoscopically. All of the procedures were performed under general endotracheal anesthesia with the patient in the left lateral decubitus position. The AdvanCE capsule delivery device (US Endoscopy, Mentor, OH) was used for deployment of the capsule endoscope in all of the patients. The device was fastened to the gastroscope according to the manufacturer’s instructions. The capsule endoscope was removed from the packaging and placed in the capsule delivery device. Recognition of the capsule was noted on the capsule device recorder. The real-time (RT) viewer was used as previously described (5). All of the patients were asked to adhere to the standard diet schedule as recommended by the manufacturer. The recording device was disconnected after 8 hours or sooner if the capsule was noted to be in the colon on the RT viewer or had been passed in the stool. Clear instructions were given to patients to observe for capsule passage, and patients were to report any adverse events including abdominal pain, nausea, vomiting, or failure to pass the capsule. The medical records of the patients were analyzed retrospectively. Information collected included age, gestational age, sex, weight, blood transfusions before CE, hemoglobin before capsule placement, patient medications, conventional endoscopic findings, CE information, and patient outcome.
RESULTS Four patients who underwent a total of 6 CE studies were identified. Patient characteristics are summarized in Table 1. The underlying diagnoses included necrotizing enterocolitis (NEC) (n ¼ 2), gastroschisis (n ¼ 1), and jejunal atresia (n ¼ 1). The last surgical procedure before CE was >2 years ago for all of the patients. Patient 1 was a female who presented for CE at 14 years 10 months of age. She was born at 26-week gestation and had SBS
Volume 61, Number 2, August 2015
secondary to NEC. The patient was on a full enteral general diet at the time of CE and was not receiving total parenteral nutrition (TPN). She did not have her ileocecal (IC) valve. The indication for CE was persistent iron deficiency anemia for which she had received several intravenous (IV) iron transfusions at our institution. An upper and lower endoscopy 1 year before presentation demonstrated a distal ileal ulcer and a positive duodenal aspirate for SBBO consisting of a quantitative culture of >10,000 CFU/mL of mixed enteric flora, which was treated with rifaximin. She received repeated IV iron transfusions over the next 12 months. Despite hemoglobin of 14 g/dL, she was noted to have hemoccult-positive stools. She had a repeat upper and lower endoscopy that was unremarkable. CE was performed to further evaluate her lower GI bleeding. The patient orally ingested the capsule endoscope. CE demonstrated a large ulcer in the distal ileum (Fig. 1A). The patient had resolution of symptoms with change in enteral antibiotics regimen to trimethoprim/sulfamethoxazole and nitazoxanide. Patient 2 initially presented at 6.5 years of age. The patient was born at 40 weeks gestation and had a history of jejunal atresia with an initial small intestinal length of 150 cm without an IC valve. She had undergone a STEP procedure at 6 months of age. She was maintained exclusively on enteral nutrition without any requirement for TPN. She presented for evaluation after multiple episodes of lower GI bleeding requiring multiple transfusions. Upper and lower endoscopies were normal and nondiagnostic. CE was performed to evaluate the small bowel source of bleeding. The patient had endoscopic placement of the capsule. A mid small bowel ulcer with a wide flat base was identified, with no visible vessel noted (Fig. 1B). At the time of CE, she had been off TPN for approximately 1 year. She had resolution of GI bleeding with a change in antibiotic regimen to nitazoxanide and rifaximin; however, her iron deficiency anemia and blood loss in the stool continued despite numerous cycles of antibiotic therapy, with hemoglobin of 7.4 g/dL before CE. A repeat CE performed at 8.25 years of age showed retrograde transit of the capsule into the stomach despite endoscopic placement in the duodenum and use of a motility agent, erythromycin. Intraoperative endoscopy was performed, and a stricture was noted within the STEP with an associated anastomotic ulcer at the stricture site. Surgical resection of the stricture was performed with resolution of symptoms and no further blood loss. Patient 3 presented at 5.25 years of age. He was an ex-25 week premature infant who had intestinal resection because of NEC. He had a small intestine length of 23 cm and did not have an IC valve. He was maintained completely on enteral feeds and had
TABLE 1. Patient characteristics at the time of capsule placement, capsule findings, treatment, and outcomes
Patient
Sex
Age, y
43.6
14
Diagnosis NEC
STEP
Completed study
Capsule findings
N
Y
Large ulcer in distal ileum with a flat, white base Mid small bowel ulcer with a wide flat base Retrograde transit into stomach Large ulcer with a wide, flat, white base and visible blood vessel Anastomotic ulcer proximal to anastomosis within the STEP Large anastomotic ulcer proximal to anastomosis within the STEP
1
F
2
F
6.5
18.6
7.9 Jejunal atresia
Y
Y
3
M
8.25 5.25
21.3 18.2
7.4 6.8 NEC
N
N Y
4
F
3.5
15.6
7.8 Gastroschisis
Y
Y
4
15.7
10.2
18.6
7.9
Median
14
Weight, Hgb, kg g/dL
Y
Resolution of symptoms
Treatment Antibiotics
Y
Antibiotics
N
Surgical revision Surgical resection
Y Y
Surgical revision
N
Antibiotics, mesalamine
Y
Hgb ¼ hemoglobin; NEC ¼ necrotizing enterocolitis; STEP ¼ serial transverse enteroplasty.
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Intestinal Anastomotic Ulcers in Children
FIGURE 1. Images of anastomotic ulcers as visualized by CE in patient 1 (A) and in patient 2 (B). Note the wide white base at the area of anastomosis. CE ¼ capsule endoscopy.
not been on TPN for 4.5 years at the time of presentation. The patient presented with lower GI bleeding and anemia with hemoglobin of 6.8 g/dL. He subsequently received multiple blood transfusions. Upper and lower endoscopies were unremarkable, including a duodenal aspirate that was negative for SBBO. The capsule endoscope was placed endoscopically into the duodenum. CE revealed a large ulcer with a wide flat whitish base and visible blood vessel (Fig. 2). A change in antibiotic regimen failed to improve symptoms, and he underwent resection of the ulcer along with 4 cm of bowel. He is no longer anemic and has not required any further blood transfusions. Patient 4 presented at 3.5 years of age. She was born at 35 weeks gestation with gastroschisis and had an initial intestine length of 50 cm. She did not have an IC valve. She underwent a STEP procedure and was maintained exclusively on enteral nutrition. She presented with anemia and persistent GI bleeding requiring blood transfusions for hemoglobin of 7.8 g/dL. Upper and lower endoscopy before her CE noted a small ulcer in her proximal colon without stigmata of bleeding. Quantitative bacterial culture from
FIGURE 2. Image of anastomotic ulcer as visualized by CE in patient 3. CE ¼ capsule endoscopy.
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duodenal aspirate demonstrated growth of Klebsiella oxytoca and Escherichia coli. After changes to her regimen of antibiotics for SBBO were not successful at ameliorating symptoms, CE was performed. CE revealed a larger anastomotic ulcer proximal to her anastomosis, within the STEP (this image is not shown in this article). The patient underwent surgical revision of her anastomosis with resection of the ulcer; however, the patient continued to experience GI bleeding, with hemoglobin of 10.2 g/dL. A repeat upper and lower endoscopy 6 months after the prior endoscopy at 4 years of age, noted a small white ulcer in the proximal colon. A repeat CE showed an ulcer proximal to the anastomosis. This was treated empirically with a change in both antibiotic therapy and mesalamine. The patient currently remains asymptomatic on enteral iron therapy.
DISCUSSION In this case series, we described the use of CE to detect and guide resection of anastomotic lesions in children with SBS presenting with anemia and GI bleeding. All of the patients had their last surgery at least 2 years before presentation. Each patient underwent an upper endoscopy and colonoscopy, but the source of bleeding was not readily identified. Subsequent CE led to the identification of the anastomotic lesion responsible for the symptoms. Upper endoscopy and colonoscopy have been shown to be beneficial in the evaluation of children with SBS and intestinal failure. One study looking at conventional endoscopy for evaluation of GI bleeding found allergic disease, peptic disease, and SBBO among other etiologies of anemia (6). CE may be a valuable adjunctive test for patients with chronic GI bleeding but negative upper endoscopy and colonoscopy. Our case series confirms a role for CE in evaluation of GI bleeding in pediatric patients, consistent with previous studies in adults and children. CE for evaluating GI bleeding in children was found to identify lesions with a high yield, including 1 instance of an anastomotic ulcer in 1 study (7,8). In these studies, CE also detected nonsteroidal anti-inflammatory drug enteropathy, polyps, AVM, hemangiomas, and ulcerative jejunitis. We have reported cases of CE in bleeding patients leading to specific and directed intestinal resections (9). Anastomotic ulcerations in patients with intestinal resection are a well-described phenomenon (3,10). Sondheimer et al (4) described 6 children with intestinal resection for NEC who presented with gross or occult bleeding from anastomotic ulcers that appeared to be inflammatory and only responded to surgical revision. A recent study evaluated the incidence of anastomotic ulcerations after intestinal resection in infancy. A total of 4 of 11 patients
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underwent CE for diagnosis. Charbit-Henrion et al noted the difficulty in diagnosing anastomotic ulcers and many of these patients had a long delay before diagnosis (11). Low use of CE in pediatric patients may result in an underestimation of the prevalence of this condition and possibly a delay in treatment. Turner et al (12) described anastomotic ulcers in children with rectal bleeding following small bowel transplantation. A number of mechanisms for surgical anastomosis ulceration have been proposed, including reaction to foreign body, ischemia at the anastomotic site, exposure to bile salts, exposure to excessive acid, and bacterial overgrowth. In fact, a retrospective analysis has demonstrated a high percentage of children with intestinal failure having SBBO as determined by duodenal aspirates. Parenteral nutrition was a risk factor for SBBO in that study population (13). In addition to anastomotic ulcerations, there have been reported patients with GI bleeding associated with the STEP procedure. This procedure was initially described by Kim et al (14,15) and involves the diagonal application of a gastrointestinal stapler to create a zigzag channel and thus bowel lengthening resulting in a substantial increase in small bowel absorption. Numerous studies have demonstrated the success of STEP across many centers (16) with excellent intermediate (17) and longer term outcomes in helping attain enteral autonomy (18–20). A single case of staple line ulcers was described in the group of 12 patients studied after STEP from Toronto. The involved area was resected, and although bleeding recurred within the next few years, the patient continues to do well in the reported 5-year outcomes (17,18). Gibbons et al (21) described a patient with anemia and occult blood loss with ulcerations at the surgical staple sites detected by video CE. In addition, the Boston Children’s group described 2 of the 23 of their patients who had undergone STEP and experienced GI bleeding from staple line ulcers that improved with enteral antibiotics, sulfasalazine, and bowel rest (22). In our series, patient 3 was found to have an ulceration within the STEP that was subsequently resected. Our study is the first to describe the use of CE with the goal of identifying anastomotic ulcers and potential ulcerations with the STEP to specifically guide medical treatment. CE in patients with SBS is challenging because of the history of extensive abdominal surgery and in some patients, unusual anatomy. Endoscopic capsule deployment using the AdvanCE SBS
Microcytosis/iron deficiency anemia
GI bleed
Nutritional supplementation If continued loss Patency capsule SB imaging
Upper and lower endoscopy
Capsule endoscopy
Treat
ABX enteroscopy surgery
FIGURE 3. Clinical pathway for the evaluation of GI bleeding and microcytosis/iron deficiency anemia at Lurie Children’s Hospital. A patient presenting with SBS would initially be assessed for anemia and GI bleeding. Those with active bleeding would be evaluated by upper and lower endoscopy and if negative, with CE. ABX ¼ antibiotics; CE ¼ capsule endoscopy; GI ¼ gastrointestinal; SB ¼ small bowel; SBS ¼ short bowel syndrome.
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capsule device and the RT viewer is useful for negotiating unusual anatomy such as that seen after extensive small bowel surgery as in these patients (5). This technique was used in all of the patients with endoscopic placement of capsule in the study. Previous small bowel surgery has been shown to be a risk factor for incomplete CE and possible capsule retention (23). At our institution, the decision to perform CE is made in conjunction with medical and surgical teams so that, although every effort is made to avoid a situation that may result in a retained capsule, both parents and care teams are prepared to properly deal with capsule retention if it occurs. Thus, in children with short gut who have iron deficiency anemia or overt GI bleeding, CE can be an important adjunctive tool for diagnosis of treatable anastomotic ulcers. At our institution, we follow a clinical pathway incorporating CE in the evaluation of children with SBS and anemia or GI bleeding (Fig. 3), which may be a guide for future studies of CE in these patients. Although other studies have reported anastomotic ulcers on CE, ours is the first case series to evaluate CE as a guide toward treatment. All of the patients had a change in management as a result of findings on CE. We recommend the use of CE in patients with SBS and recurrent anemia or GI blood loss. A prospective study of CE in these patients may be useful for demonstrating shorter time to accurate diagnosis of anastomotic ulcers. Acknowledgments: The authors thank Michael Miller, MD, and Stacey C. Tobin, PhD, for article review and editorial support.
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14. Kim HB, Fauza D, Garza J, et al. Serial transverse enteroplasty (STEP): a novel bowel lengthening procedure. J Pediatr Surg 2003;38:425–9. 15. Kim HB, Lee PW, Garza J, et al. Serial transverse enteroplasty for short bowel syndrome: a case report. J Pediatr Surg 2003;38:881–5. 16. Modi BP, Javid PJ, Jaksic T, et al. First report of the international serial transverse enteroplasty data registry: indications, efficacy, and complications. J Am Coll Surg 2007;204:365–71. 17. Wales PW, de Silva N, Langer JC, et al. Intermediate outcomes after serial transverse enteroplasty in children with short bowel syndrome. J Pediatr Surg 2007;42:1804–10. 18. Oliveira C, de Silva N, Wales PW. Five-year outcomes after serial transverse enteroplasty in children with short bowel syndrome. J Pediatr Surg 2012;47:931–7.
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19. Mercer DF, Hobson BD, Gerhardt BK, et al. Serial transverse enteroplasty allows children with short bowel to wean from parenteral nutrition. J Pediatr 2014;164:93–8. 20. Ching YA, Fitzgibbons S, Valim C, et al. Long-term nutritional and clinical outcomes after serial transverse enteroplasty at a single institution. J Pediatr Surg 2009;44:939–43. 21. Gibbons TE, Casteel HB, Vaughan JF, et al. Staple line ulcers: a cause of chronic GI bleeding following STEP procedure. J Pediatr Surg 2013; 48:E1–3. 22. Fisher JG, Stamm DA, Modi BP, et al. Gastrointestinal bleeding as a complication of serial transverse enteroplasty. J Pediatr Surg 2014;49: 745–749. 23. Westerhof J, Weersma RK, Koornstra JJ. Risk factors for incomplete small-bowel capsule endoscopy. Gastrointest Endosc 2009;69:74–80.
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