CASE REPORTS

Endoscopic Therapy for Complete and the duct was cannulated with a 0.021 guidewire (Tracer Metro
Pancreatic Ductal Obstruction in a
Child With Hereditary Pancreatitis

Amy J. Virojanapa, yPunit Jhaveri,
z
Charles Dye, zAbraham Mathew,
and yChandran P. Alexander
Direct [Cook Endoscopy, Winston-Salem, NC]). Deep cannulation
was, however, not possible, and the wire could not be passed past
the stricture. The major papilla was then approached, and a papil-
lotomy was performed by a free hand needle knife technique. With
aggressive manipulation, wire access into the upstream dilated
pancreatic duct was obtained using a 0.021 guidewire (Tracer
Metro Direct [Cook Endoscopy]). The stricture was very tight
(Fig. 1A and B) and did not allow passage of a 6-Fr Soehendra
dilator or a biliary balloon dilator. At this point, a stent extractor was
adapted to gain deep access. An 8.5-Fr Soehendra stent extractor
(SSE) was placed over the wire, and its screw tip was impacted into

H ereditary pancreatitis (HP) usually presents in the first or the distal end of the stricture. Tissue was cored from the center of
Downloaded from https://journals.lww.com/jpgn by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3TDbD+Y6NAIGFWid4SH4v3Bmncl4rq3p0V/sVH8kJOCgjXe7SDm9LXQ== on 08/16/2018

second decades of life. R122H and N29I mutations are the the stricture repeatedly by rotating the SSE clockwise and retracting
most common PRSS1 mutations that cause HP by enhanced tryp- the device. As the 8.5-Fr SSE could not be advanced deeper
sinogen autoactivation (1). The complications of HP include weight (Fig. 2A and B), a 7-Fr SSE was used for establishing access by
loss, pancreatic stones, ductal obstruction and dilatation, pseudo- tissue coring in a similar manner until a 7-Fr Soehendra dilator
cyst formation, ascites, insufficiency, and adenocarcinoma. We successfully passed into the distal pancreatic duct with resultant
describe a child with HP and complete obstruction of the pancreatic
duct by a stricture that was successfully dilated using an improvised
therapeutic endoscopy method. A
A 7-year-old boy with a PRSS1 mutation at N291 presented
to our institution in February 2008 because of sequelae from his HP.
The patient was hospitalized for a large pseudocyst requiring
endoscopic cystogastrostomy and later for a post-traumatic splenic
hematoma. Since May 2011, the patient was seen repeatedly in the
emergency department every 2 months for acute pancreatitis while
on conservative medical therapy.
In April 2012, the patient had unremitting epigastric pain
causing prolonged school absence and weight loss. Ultrasonogra-
phy revealed an increase in pancreatic duct size to 6.7 mm from
1.5 mm 2 months prior. Magnetic resonance cholangiopancreato-
graphy demonstrated dilation of the pancreatic duct in the body and
tail with an abrupt cutoff in the region of the pancreatic head.
Endoscopic retrograde cholangiopancreatography (ERCP) con-
firmed complete obstruction of the pancreatic ducts within the
head of the pancreas.
The patient’s mother refused consent for his surgery because
of lack of relief from total pancreatectomy for her own HP.
Informed consent was thus obtained for endoscopic intervention.
Cannulations of both the minor and major papillae using a sphinc-
terotome and different guide wires failed. Hence, an attempt was B
made to access the pancreatic stricture by a rendezvous approach.
Under endoscopic ultrasound view, the proximal pancreatic duct
was punctured with the tip of a 19-gauge needle through which a
0.035 Jagwire (Boston Scientific) was advanced into the lumen of
the pancreatic duct, in an attempt to manipulate across the stricture
into the duodenum via the papillae. The procedure was unsuccess-
ful, and the patient was discharged home on a clear liquid diet and
parenteral nutrition.
During a repeat ERCP the following week, a free hand minor
duct sphincterotomy was performed using a traditional needle knife,

Received October 16, 2013; accepted February 21, 2014.

From the Department of Pediatrics, the yDivision of Pediatric Gastro-
enterology, and the zDivision of Gastroenterology, Penn State Hershey
Medical Center. Hershey, PA.
Address correspondence and reprint requests to Chandran P. Alexander,
MBBS, MD, Penn State Hershey Medical Center, 500 University Dr,
Hershey, PA 17033 (e-mail: calexander @hmc.psu.edu).
The authors report no conflicts of interest.
Copyright # 2015 by European Society for Pediatric Gastroenterology,
Hepatology, and Nutrition and North American Society for Pediatric FIGURE 1. A, Pancreatic ductal obstruction. B, Deep-wire access
Gastroenterology, Hepatology, and Nutrition contrast injection showing retrograde flow without filling of the main
DOI: 10.1097/MPG.0000000000000353 pancreatic duct.

e2 JPGN  Volume 62, Number 1, January 2016

Copyright 2015 by ESPGHAN and NASPGHAN. Unauthorized reproduction of this article is prohibited.
 JPGN  Volume 62, Number 1, January 2016
A B
FIGURE 2. A, Soehendra device at stricture. B, Passage of Soehendra device across stricture.
drainage. The 0.021 guidewire (Tracer Metro Direct [Cook Endo-
scopy]) was exchanged for a 0.035 Jagwire (Boston Scientific). The
stricture was then dilated with a 4-mm biliary dilation balloon, and a
7-Fr pancreatic stent was placed in a standard fashion to maintain
patency (Fig. 3A and B). The patient tolerated the procedure well.
The patient had dramatic improvement in abdominal pain
and gained 6.6 kg in weight and 10.6 cm in height during the next 18
months. The patient electively underwent 4 balloon dilations and
stent replacements at 4 month intervals as an outpatient, culminat-
ing in two 7 Fr stents. In May 2013, the stents were removed to
assess maintenance of ductal patency. The patient remained asymp-
tomatic until October 2013 when he was hospitalized for acute
pancreatitis. Pancreatic duct stent replacement was performed and
the patient has remained well to date. Long-term follow-up is
necessary to evaluate for sustained relief of symptoms, bearing
in mind the known complications of HP and ERCP.
DISCUSSION
The complications of therapeutic endoscopy in children
include pancreatitis, infection, bleeding, and perforation, with rates
varying from 0 to 10% (2,3).
van Someren et al (4) first reported the use of the Soehendra
device for dilating difficult malignant biliary strictures to avoid
percutaneous biliary drainage. Baron et al (5) first described the
dilation of a difficult benign pancreatic duct stricture in a 59-year-
old man with pancreas divisum using the SSE. Brand et al (6)
A B
FIGURE 3. A, Successful stent placement into dilated distal pancreatic duct. B, Adequate drainage after stent placement.
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Case Reports
evaluated the efficacy of the SSE as a dilator in 32 adults with
biliary or pancreatic duct strictures, all of whom had symptom relief
within the first week of stenting with no observed complications.
Although there is limited information on the outcomes of
endoscopic therapy in children with HP, our case testifies to its
palliative benefit in the short term. Given the refusal of consent for
surgery, multiple endoscopic attempts with various catheters and
wire configurations (including endoscopic ultrasound–guided ante-
rograde attempts) eventually allowed deep access to the upstream
obstructed pancreas. The screwing tip and the stiff nature of the SSE
device are beneficial when the stricture is tight and the angles for
pushing typical dilating devices are unfavorable. Pancreatic duct
stenting restored the quality of life in our patient. For now, the
patient has avoided surgical lateral decompression procedures that
could limit islet cell harvest when total pancreatectomy may be
indicated in the future (7).
CONCLUSIONS
We describe a child with HP and symptomatic pancreatic
duct obstruction from a recalcitrant stricture, relieved by the use of
an SSE with elective stenting over 1 year. Although originally
designed to remove stents over a wire while maintaining duct
access, the SSE has been used in adults to gain access through
strictures impassable by standard techniques. To our knowledge,
our report is the first to mention the use of this technique in children
with HP.
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 Case Reports
REFERENCES
1. Rosendahl J, Bödeker H, Mössner J, et al. Hereditary chronic pancreatitis.
Orphanet J Rare Dis 2007;2:1.
2. Halvorson L, Halsey K, Darwin P, et al. The safety and efficacy of
therapeutic ERCP in the pediatric population performed by adult gastro-
enterologists. Dig Dis Sci 2013;58:3611–9.
3. Vegting IL, Tabbers MM, Taminiau JA, et al. Is endoscopic retrograde
cholangiopancreatography valuable and safe in children of all ages?
J Pediatr Gastroenterol Nutr 2009;48:66–71.
4. van Someren RN, Benson MJ, Glynn MJ, et al. A novel technique for
dilating difficult malignant biliary strictures during therapeutic ERCP.
Gastrointest Endosc 1996;43:495–8.
5. BaronTH,MorganDE.Dilationofadifficultbenignpancreatic ductstricture
using the Soehendra stent extractor. Gastrointest Endosc 1997;46:178–80.
6. Brand B, Thonke F, Obytz S, et al. Stent retriever for dilation of
pancreatic and bile duct strictures. Endoscopy 1999;31:142–5.
7. Sutherland DE, Radosevich DM, Bellin MD, et al. Total pancreatectomy
and islet autotransplantation for chronic pancreatitis. J Am Coll Surg
2012;214:409–24.
Massive Hematemesis as Presentation
of Congenital Aortic Coarctation With
Superinfected Aneurysm and
Aortoesophageal Fistula
Melissa A. Sheiko and Edward J. Hoffenberg
A ortoesophageal fistula (AEF) is extremely rare in children
and usually results from an esophageal foreign body or
esophageal surgery (1,2). There are 2 reported cases of AEF from
superinfected aortic aneurysms in conjunction with undiagnosed
aortic coarctations: an 11-year-old boy and a 14-year-old boy (3,4).
Superinfected aortic aneurysms leading to AEF are more common
in adults (5,6). We report the third and oldest patient with an AEF
from an undiagnosed aortic coarctation. This case has recently been
published in the cardiology literature (7); here we focus on the
initial presentation, endoscopic features, and decision making
before the diagnosis of AEF.
A 15-year-old boy was transferred to our hospital for acute
hematemesis and anemia. Three weeks before admission, the
patient developed daily fevers for which the patient took ibuprofen
and naproxen. One week before admission, the patient developed
Received October 8, 2013; accepted March 3, 2014.
From the Digestive Health Institute, Department of Pediatrics, Children’s
Hospital Colorado, University of Colorado Denver School of Medicine,
Aurora, CO.
Address correspondence and reprint requests to Melissa A. Sheiko, MD,
Children’s Hospital Colorado, Digestive Health Institute, 13123 E. 16th
Ave B290, Aurora, CO 80045 (e-mail: Melissa.Sheiko@childrens
colorado.org).
Supplemental digital content is available for the present article. Direct URL
citations appear in the printed text, and links to the digital files are
provided in the HTML text of the present article on the journal’s Web site
(www.jpgn.org).
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.0000000000000370
e4
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JPGN  Volume 62, Number 1, January 2016
increasing fatigue, a 4-kg weight loss, diffuse back pain worse in the
right scapular area, and nonbloody, nonbilious emesis. The morning
of admission, the patient vomited 3 to 4 cups of bright red blood.
The patient presented to a local emergency department, where the
patient’s hemoglobin was 9 g/dL. The patient was transferred to our
hospital, and on arrival, the patient’s blood pressure was 148/89 and
pulse was 126. A 2/6 vibratory systolic murmur was heard best at
the left lower sternal border that radiated upward. The patient had
no back or abdominal tenderness, rash, telangiectasias, splinter
hemorrhages, or hepatosplenomegaly. The patient’s medical history
was negative, including no history of hypertension. Surgical and
family histories were noncontributory.
At admission, the patient’s white blood cell count was
12,000 cells per microliter with 82% neutrophils, and hemoglobin
was 7.9 g/dL. INR was 1.4, and PTT and fibrinogen were normal.
Erythrocyte sedimentation rate was 111 mm/hour, and C-reactive
protein was 10.1 mg/dL. Blood cultures were sent. Differential
considerations for the patient’s hematemesis were NSAID-induced
ulcers or a Mallory-Weiss tear, although these did not explain the
fever or elevated inflammatory markers. Overnight, the patient
received acid suppression, but hematemesis continued and the
patient received 2 U of packed red blood cells. Esophagogastro-
duodenoscopy was performed and showed the stomach filled with
blood, but after extensive lavage, no source of bleeding was
identified. The mucosa of the esophagus, stomach, and duodenum
appeared normal. On removal of the endoscope, the patient vomited
blood and went into hypotensive shock with a blood pressure of
50/30. The massive transfusion protocol was activated. Repeat
endoscopy again did not identify a bleeding source; a video was
obtained while withdrawing the endoscope (viewable at http://
links.lww.com/MPG/A315). A purple mass was briefly seen during
withdrawal of the endoscope, but on continued visualization it was
not seen again and was believed to be a passing blood clot (Fig. 1).
Otolaryngologic evaluation did not identify a source of bleeding.
An angiogram of the celiac, gastroduodenal, left gastric, and
superior mesenteric arteries was unremarkable. CT angiogram of
the abdomen was also normal.
Angiography was repeated, and when the thoracic aorta was
visualized, a coarctation of the aorta just past the subclavian artery
was noted. There was a small pseudoaneurysm that had a jet
medially, consistent with an AEF (Fig. 2). An aortic stent was
placed to cover the pseudoaneurysm and fistula. This was unsuc-
cessful and required subsequent aortic graft placement. In post-case
review of the endoscopic video, the purple mass in the mid-
esophagus was the aneurysm pushing into the lumen (Fig. 1, video
[http://links.lww.com/MPG/A315]).
During the patient’s initial 48 hours in the hospital, the
patient required transfusion of 25 L of blood products. Blood
cultures grew Streptococcus pneumoniae. Sequelae of the patient’s
hospital course included a mild stroke in the left parietal area, which
slowed the patient’s processing speed slightly. The patient devel-
oped severe gastroparesis, believed to be from vagal nerve tran-
section during aortic graft placement. After several months on
parenteral nutrition, the patient underwent a pyloroplasty, after
which the patient tolerated enteral feeds.
DISCUSSION
In a previously healthy adolescent with no risk factors, AEF
is exceedingly rare. Several key features of this case merit further
discussion. First, the initial unexplained hypertension was a clue to
the coarctation, but because of ongoing hemodynamic instability
and recurrent hypovolemic shock, further investigation was not
performed. Second, the endoscopic appearance of a pseudoaneur-
ysm had not been previously described; the lesion was not
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 JPGN  Volume 62, Number 1, January 2016
FIGURE 1. Review of the endoscopic video (http://links.lww.com/MPG/A315) showed a nonpulsatile purple mass protrude briefly into the
esophagus, likely the aneurysm. The left image was distal to the mass in the esophagus. The middle image shows the beginning of the mass. The
image on the right shows the purple mass in the mid-esophagus.
FIGURE 2. Angiography of the thoracic vessels. The red arrow ident-
ifies the coarctation; the yellow arrow marks the site of extravasation.
pulsatile, was not bleeding, and was not easily observed. Third, the
awareness of the rapid massive bleeding and hypotension should
have led to earlier consideration of an arterial source of bleeding.
When radiologic visualization of the abdominal aortic vessels did
not identify a cause, imaging the thoracic vessels should have been
considered. A bleeding scan was also not considered, and in a brisk
bleed of this etiology, it may have been effective. Fourth, survival
depends on massive cardiovascular support, rapid diagnosis, and
availability of cardiothoracic intervention. Implementation of a
massive transfusion protocol with the use of the Belmont Rapid
Infuser (Belmont Instrument Corporation, Billerica, MA) to
rapidly administer large volumes of blood products was lifesaving.
A massive transfusion protocol was essential to deliver sufficient
blood products for survival; the use of crystalloid has been shown
to worsen outcomes in the setting of massive blood loss (8).
Following intubation with ongoing bleeding, placement of an
esophageal compression tube could have been used to slow the
bleeding in our opinion. Despite a delay in diagnosis of approxi-
mately 27 hours after arrival to our hospital, the patient survived
with minimal neurologic injury.
In summary, this patient had an undiagnosed congenital
aortic coarctation, which created turbulence leading to the devel-
opment of a pseudoaneurysm. This area of disrupted blood flow
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Case Reports
became superinfected with S pneumoniae causing back pain and
fever. The infected aneurysm then eroded into the esophagus
creating an AEF. AEF has a high mortality; of the 2 previously
reported cases from aortic coarctation, 1 survived and 1 died (3,4).
The pediatric gastroenterologist should consider AEF in context
of massive hematemesis. Recognition of the endoscopic findings
of AEF, as reported in this case, may be essential for patient
survival.
REFERENCES
1. Chang S, Cheng BC, Huang J, et al. Classification and surgical treatment
of intrathoracic esophageal injury caused by foreign body. Zhonghua Wai
Ke Za Zhi 2006;44:409–11.
2. Sigalet DL, Laberge JM, DiLorenzo M, et al. Aortoesophageal fistula:
congenital and acquired causes. J Pediatr Surg 1994;29:1212–4.
3. Burns BJ, Newey A, Numa A. Beware the starboard nasogastric tube.
Pediatr Emerg Care 2008;24:307–9.
4. McKell WM. Coarctation of the aorta presenting as massive hematem-
esis. J Miss State Med Assoc 1968;9:273–7.
5. Van Doorn RC, Reekers J, de Mol BA, et al. Aortoesophageal fistula
secondary to mycotic thoracic aortic aneurysm: endovascular repair and
transhiatal esophagectomy. J Endovasc Ther 2002;9:212–7.
6. Huang SC, Lin TC, Tsan YT, et al. Catastrophic gastrointestinal bleeding
caused by aortoesophageal fistula secondary to mycotic thoracic aortic
aneurysm. BMJ Case Rep 2009;2009.
7. Krieves MA, Merritt GR, Nichols CS, et al. Aortoesophageal fistula and
coarctation of the aorta in a 15-year-old child. Semin Cardiothorac Vasc
Anesth 2013;17:294–7.
8. Duchesne JC, Heaney J, Guidry C, et al. Diluting the benefits of
hemostatic resuscitation: a multi-institutional analysis. J Trauma Acute
Care Surg 2013;75:76–82.
Endoscopic Submucosal Dissection of a
Large Hamartoma in a Young Child

James Wall, Micaela Esquivel, Matias Bruzoni,

Robert Wright, yWilliam Berquist, and Craig Albanese
E ndoscopic submucosal dissection (ESD) is an evolving tech-
nique for the intraluminal resection of intestinal tumors. The
technique uses commercially available endoscopic instruments to
elevate the mucosa off of the submucosa, incise the mucosa, and
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 Case Reports JPGN  Volume 62, Number 1, January 2016

dissect along the submucosal plane (1,2). It differs from standard

endoscopic mucosal resection (EMR), which includes various
techniques for lifting and snaring mucosal lesions without formal
dissection of the submucosal plane. ESD enables en bloc resection
of large and broad-based mucosal lesions that would otherwise
require surgical resection. ESD has been applied extensively in
Japan for the resection of early stage gastric malignancies. Although
generally taking longer than EMR, it improves en bloc resection and
allows precise pathologic analysis particularly in tumors greater
than 2 cm in size (3). The risk of bleeding appears similar between
ESD and EMR in a large meta-analysis; however, perforation rates
are higher with ESD independent of the exact devices used (4). This
may be a result of ESD being used to resect larger tumors with
potentially larger vascular networks (5). Fortunately, perforation
has not been linked to significant mortality and can typically be
managed with a combination of endoscopic closure techniques
and observation.
Gastric hamartoma is rare in the pediatric population (6).
Surgical resection is recommended for large, broad based, or
anatomically inaccessible tumors that are not amenable to standard
EMR techniques. There has been 1 report of ESD in a 21-month-old
with gastric outlet obstruction from a polyp (7).

METHODS
A 5-year-old girl was found to have melanotic lesions of the
perioral and buccal mucosa that prompted a workup for Peutz-
Jeghers syndrome. An upper gastrointestinal series with small
bowel follow-through revealed a distal polyp on the lesser curvature
near the gastric outlet (Fig. 1). She was asymptomatic and without
weight loss. Endoscopy confirmed a large broad-based polyp at the
incisura in the distal stomach along the lesser curvature (Fig. 2A).
Endoscopic biopsy revealed hyperplasia but was not diagnostic of
hamartoma. The patient was transferred to our institution for
consideration of surgical resection after 2 pediatric gastroenterol-
ogy groups deemed the lesion not to be amenable to standard ESR
techniques. The parents were offered the option of laparoscopic
surgical resection or ESD with en bloc endoscopic removal of the
tumor and elected to proceed with ESD.
ESD was performed by a pediatric surgeon in the presence of
a multidisciplinary team. An Olympus GIFQ 180 upper endoscope
(Olympus, Tokyo, Japan) with an 8.8-mm diameter and a 2.8-mm
working channel was used. A solution of normal saline and meth-
ylene blue was injected into the submucosa (Fig. 2B) using a 25-G
endoscopic needle (Boston Scientific, Natick, MA). This was
performed circumferentially around the broad base of the tumor
to create a larger working space in the submucosal plane. A needle
knife (Boston Scientific) was used to make a mucosal incision,
exposing the submucosal plane (Fig. 2C). Multiple tools including a
triangle tip knife (Olympus), needle knife and forceps (Olympus)
were then used with a combination of electrosurgical current and
blunt dissection to dissect into the submucosal plane (Fig. 2D). The
Received February 13, 2014; accepted March 20, 2014.
From the Division of Pediatric Surgery, and the yDivision of Pediatric
Gastroenterology, Lucile Packard Children’s Hospital at Stanford Uni-
versity, Palo Alto, CA.
Address correspondence and reprint requests to James Wall, MD, 777 Welch
Rd, Stanford, CA 94305 (e-mail: jkwall@stanford.edu).
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.0000000000000376
FIGURE 1. Upper gastrointestinal series showing large gastric polyp
along the lesser curvature.
tumor was elevated onto a small stalk with circumferential
dissection and the stalk was divided with a standard polypectomy
snare. The resection left a mucosal defect of approximately 2 cm
 2 cm where hemostasis was achieved using forceps electro-
cautery.
RESULTS
The procedure took 136 minutes under general anesthesia.
The patient was placed on intravenous proton pump inhibitor (PPI)
and transitioned to oral PPI in the postoperative period. A regular
diet was tolerated on postoperative day 1. No narcotics were
required after discharge from the recovery room. Pathologic exam-
ination revealed a 16  14  10 mm hamartoma consistent with
Peutz-Jeghers syndrome. She underwent surveillance endoscopy at
3 months that showed fully healed gastric mucosa without gastritis,
ulceration, or tumor recurrence.
DISCUSSION
ESD was successfully applied to a case of a large broad-
based hamartoma in a 5-year-old girl with Peutz-Jeghers syndrome.
Large and broad-based gastrointestinal tumors are relatively rare in
the pediatric population, but are typically referred for surgery.
Although ESD is generally applied to malignant tumors in the
adult population, a large benign lesion that was not amenable to
ESR seemed appropriate for the early application of ESD in the
pediatric population in order to prove feasibility.
This case was successfully performed in the limited working
space of a 5-year-old patient of with a standard 8.8 mm diameter
gastroscope using existing ESD equipment through a 2.8-mm
diameter working channel. No endoscopic cap was available at
the time the case was performed for an 8.9-mm scope, which could
have improved visualization. Even larger therapeutic endoscopes

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 JPGN  Volume 62, Number 1, January 2016
FIGURE 2. Endoscopic submucosal dissection of a broad based gastric hamartoma.
are tolerated by children more than 10 to 15 kg and offer additional
working channels with improved visualization. Currently, 2.8 mm
channels are not available on smaller diameter endoscopes. With
advances in optics and tools, endoscopes less than 5 mm in diameter
could, however, be devised to enable interventional endoscopic
techniques in smaller children.
These techniques bring significant clinical benefit, but also
offer higher risks including perforation and bleeding that could
require prompt surgical intervention. The submucosa is rich in
blood supply and may be at risk for bleeding with postoperative
exposure to gastric contents. A PPI is indicated in the postresec-
tion period to protect the resection bed and promote re-epithe-
lialization. Experience with these techniques further opens the
door to hybrid approaches for the pediatric endoscopist using a
combination of endoscopic and minimally invasive surgical
techniques.
CONCLUSIONS
ESD is a technique that enables en bloc resection of large and
broad-based mucosal tumors of the intestine. It is technically
feasible in pediatric mucosal tumors not amenable to standard
endoscopic resection techniques. Although this case presented a
rare situation, general proficiency with advanced endoscopy will
enable pediatric specialists to take part in an increasing number of
cases where endoscopic intervention may take the place of surgical
intervention.
REFERENCES
1. Kakushima N, Fujishiro M. Endoscopic submucosal dissection
for gastrointestinal neoplasms. World J Gastroenterol 2008;14:
2962–7.
2. Yamamoto H. Technology insight: endoscopic submucosal dissection of
gastrointestinal neoplasms. Nat Clin Pract Gastroenterol Hepatol
2007;4:511–20.
3. Cao Y, Liao C, Tan A, et al. Meta-analysis of endoscopic submucosal
dissection versus endoscopic mucosal resection for tumors of the gastro-
intestinal tract. Endoscopy 2009;41:751–7.
4. Lian J, Chen S, Zhang Y, et al. A meta-analysis of endoscopic submucosal
dissection and EMR for early gastric cancer. Gastrointest Endosc
2012;76:763–70.
5. Lu ZS, Yang YS, Feng D, et al. Predictive factors of endoscopic
submucosal dissection procedure time for gastric superficial neoplasia.
World J Gastroenterol 2012;18:7009–14.
6. Curtis JL, Burns RC, Wang L, et al. Primary gastric tumors of infancy and
childhood: 54-year experience at a single institution. J Pediatr Surg
2008;43:1487–93.
7. Jung EY, Choi SO, Cho KB, et al. Successful endoscopic submucosal
dissection of a giant polyp in a 21-month-old female. World J Gastro-
enterol 2014;20:323–5.
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Case Reports
Dengue Hemorrhagic Fever in a Child
With Early-Onset Fistulizing Crohn
Disease Under Infliximab and
Azathioprine Treatment
Mary A. Carvalho, Juliana T. Dias,
Debora A.P. Satrapa, Renato G.S.C. Silva,
and Nilton C. Machado
T he dengue virus infection is a major mosquito-borne disease in
the tropical/subtropical areas of the world (1). Endemic in
many countries, dengue has experienced global reemergence (2),
reaching epidemic proportions in Brazil. Travelers or persons living
in these regions are at risk for the infection. Therefore, the associ-
ation between dengue and unusual diseases is to be expected. Here,
we report a case of dengue hemorrhagic fever (DHF) in a child with
Crohn disease (CD) undergoing regular treatment with infliximab
and azathioprine. To the best of our knowledge, there is no previous
report of dengue infection in an immunosuppressed patient with
CD. An informed consent from the guardians of the child
was obtained.
A 7-year-old girl was diagnosed as having early-onset
fistulizing CD when she was 15 months old, through the detection
of a noncaseating granuloma during a colon histopathology (Fig. 1).
Her medical history with CD comprised a febrile, inflammatory
diarrhea; oral lesions; fecal–vaginal discharge (rectovaginal fistu-
lae) associated with anemia; and malnutrition. She was asympto-
matic at a checkup 1 month before the onset of the dengue
symptoms, with a normal laboratory panel (Table 1). At that time,
she was taking azathioprine (1.5 mg  kg1  day1), oral mesalazine
Received September 22, 2013; accepted March 20, 2014.
From the Division of Pediatric Gastroenterology, Hepatology and
Nutrition, Department of Pediatrics, Botucatu Medical School, UNESP,
Sao Paulo State University, Botucatu, SP, Brazil.
Address correspondence and reprint requests to Mary Assis Carvalho,
Department of Pediatrics, Botucatu Medical School, UNESP, Sao Paulo
State University, Botucatu, SP Brazil, CEP 18618-970 (e-mail:
maryped@fmb.unesp.br).
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.0000000000000377
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 Case Reports JPGN  Volume 62, Number 1, January 2016

manifestations. There were normal respiratory sounds, epigastric

FIGURE 1. Epithelioid cell granuloma at initial colonoscopy biopsy
specimens (hematoxylin & eosin stain, panoramic original
magnification100, and on detail original magnification400).
(60 mg  kg1  day1), and infliximab intravenous infusion
(5 mg  kg1  infusion1), every 2 months (the last infusion
was 1 month earlier).
At admission, on day 3 of disease onset, she presented with a
history of fever, myalgia, and abdominal pain. There was neither
active bleeding nor neurological manifestations. Admission
coincided with a dengue epidemic in her living area, and stepfather
being recently confirmed with dengue infection.
Physical examination revealed an alert, hydrated girl, with
fever (38.48C), tachycardia (120 beats/min), eupnea (24 breaths/
min), and blood pressure of 95/50 mmHg (50th percentile). There
was no postural decline in blood pressure or a narrowed pulse
pressure to indicate intravascular volume depletion, or hemorrhagic
discomfort, with tender mild hepatomegaly, and no splenomegaly
or signs of ascites. On anthropometry weight was found to be
20.7 kg (0.88 z score), height 111 cm (2.37 z score), and body
mass index 16.8 (0.64 z score).
Laboratory results are presented in Table 1. At admission,
there was no evidence of hemoconcentration or hypoalbuminemia,
but leukopenia (neutropenia and lymphopenia with no atypical
lymphocytes) and thrombocytopenia. There was a mild elevation
of aspartate aminotransferase liver enzyme and activated partial
thromboplastin time. Serological tests were negative for HIV, anti-
hepatitis A virus, hepatitis B surface antigen, anti-hepatitis C virus,
Epstein–Barr virus immunoglobulin (Ig) M (IgM), cytomegalo-
virus IgM, toxoplasmosis IgM, and syphilis (venereal disease
research laboratory). Epstein–Barr virus IgG and anti-hepatitis B
surface antibodies (anti-Hbs) were positive. Blood and urine cul-
tures were negative. Dengue viral expressed soluble nonstructural
protein 1 was detected by the lateral-flow rapid test.
Her condition was managed with intravenous fluids and
antipyretics, and the azathioprine and mesalazine administrations
were withdrawn. On day 5 after disease onset, her fever subsided,
but she developed nostril bleeding, abdominal petechiae, and
hemorrhagic blebs reaching a maximum size of 2  2 m at vene-
puncture sites. Also, she had a cough with rales, diminution of
respiratory sounds, and dullness on the right chest. The platelet
count dropped to 18,000/mm (3), and she presented hypoalbumi-
nemia. The tourniquet test, a screening method to evaluate capillary
fragility, turned to positive. The dengue-specific IgM was assessed
by enzyme-linked immunosorbent assay and was positive at 16.27
(negative <9 and positive >11). Dengue virus IgG and genotype by
PCR were not available. The chest radiograph was normal on
admission (Fig. 2A), but a moderate right pleural effusion was
observed on day 5 (Fig. 2B). Ultrasonography of the thorax and
abdomen showed bilateral pleural effusion, mild ascites volume,

TABLE 1. Laboratory findings pre- and post-DHF diagnosis

Days after disease onset

1 month Day 3 Day 9 7 days after

Tests before (admission) Day 5 Day 6 Day 7 (discharge) discharge

Hemoglobin, g/dL 12.9 11.9 12.8 10.3 — 11.3 12.6

Hematocrit, % 36.5 37.0 37.4 28.3 — 31.6 36.7
Platelet count, cells/mm3 390,000 40,000 18,000 42,000 — 106,000 519,000
Total leucocyte, cells/mm3 6500 1660 1840 2790 — 4290 5000
Neutrophils, cells/mm3 2021 1062 552 711 — 1123 1400
Lymphocytes, cells/mm3 4075 465 700 1328 — 2273 2700
C-reactive protein, mg/dL 0.5 1.4 1.0 — — — 0.5
INR — 1.16 — — — — —
APTT ratio — 1.69 1.62 — — — —
Aspartate aminotransferase, U/L 35 102 174 — — 154 39
Alanine aminotransferase, U/L 27 45 61 — — 73 19
Alkaline phosphatase, U/L 153 135 99 — — 109 131
g-Glutamyltransferase, U/L 31 31 36 — — 52 46
Total bilirubin, mg/dL — 0.6 — — — — —
Direct bilirubin, mg/dL — 0.3 — — — — —
Total protein (albumin), g/dL — 6.8 (4.1) 5.2 (2.9) — 7.0 (3.8) 8.4 (4.8) 8.5 (4.9)
Serum creatinine, mg/dL 0.5 0.4 0.6 — — — —
Serum urea, mg/dL 43 23 15 — — — —
Serum sodium, mmol/L — 142 — — — — —
Serum potassium, mmol/L — 4.0 — — — — —

C-reactive protein reference value <1 mg/dL. APTT ¼ activated partial thromboplastin time; DHF ¼ dengue hemorrhagic fever; INR ¼ international
normalized ratio.

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 JPGN  Volume 62, Number 1, January 2016
A B
D
FIGURE 2. A, Normal chest radiograph taken 3 days after the onset of fever. B, At 5 days with a moderate right pleural effusion as the major
finding.
and hepatomegaly, indicating the onset of plasma leakage and the
start of critical/leakage phase. She was given platelet transfusion
and managed expectantly for the pleural effusion. Thereafter, the
hemorrhagic manifestations and respiratory symptoms improved
gradually. In parallel, the platelet and white blood cell counts
improved until day 9, and the chest radiograph revealed no signs
of pleural effusion. She was discharged after 7 days of hospitaliz-
ation. One week later, in the outpatient clinic visit, she was free of
symptoms and maintaining clinical remission of the CD. The
immunosuppressive and anti-inflammatory medications were rein-
troduced, and an infliximab infusion was scheduled. At 9 months of
follow-up she has had no CD relapse, and the course of the CD was
not altered by DHF.
DISCUSSION
We reported a case of severe dengue infection and CD. The
patient met the 4 criteria for defining DHF, according to WHO
guidelines (3) (acute fever lasting <7 days with myalgia; skin and
mucosal hemorrhagic manifestations; thrombocytopenia <100,000
cells/mm3; pleural effusion, ascites, and hypoproteinemia compa-
tible with plasma leakage). Both the laboratory identification of
dengue virus nonstructural protein 1 antigen performed in the first
4 days of disease and the IgM serology afterward confirmed the
diagnoses. On day 5, she developed the typical massive leakage, the
hallmark of DHF, with the gradual recovery of thrombocytopenia
and no worsening of the CD.
DHF typically occurs in individuals who have been infected
with the dengue virus and are presently infected with a different
dengue virus serotype. In this case, the dengue-specific IgG that
would substantiate this pattern was not available, and secondary
dengue infection was not confirmed. DHF occurrence and
severity are also influenced by certain genetic polymorphisms
involving cytokine genes, cytokine concentration, and viral sero-
type. It was reported that dengue virus-infected monocytes and
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Case Reports
D
endothelial cells produce multiple cytokines, especially tumor
necrosis factors (TNF)-a. This cytokine has a well-known activity
in inducing plasma leakage (4). CD is commonly treated with
immunosuppressive drugs, including anti-TNFs, which predisposes
individuals to various infections (5); however, the majority of
dengue reports in immunosuppressed patients are in renal transplant
recipients. Renaud et al (6) and Azevedo et al (7) suggest that these
patients are less likely to develop the more severe form of dengue
infections, but Prasad et al (8) demonstrated the contrary. Given the
information available, in this case, the DHF cannot be definitively
stated to stem from prior infection with a different serotype or from
immunosuppression/TNF inhibition. Additional research is needed
to elucidate the immunopathological interactions between dengue,
CD, and anti-TNF treatment.
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