Accepted Manuscript A case of recurrent acute pancreatitis in an obese child Byung Ok Kwak, M.D. Min Jung Lee, M.D. Hye Won Park, M.D. Kyo Sun Kim, M.D., PhD. Sochung Chung, M.D., PhD. PII:
S0899-9007(14)00191-9
DOI:
10.1016/j.nut.2014.04.002
Reference:
NUT 9277
To appear in:
Nutrition
Received Date: 8 October 2013 Revised Date:
10 March 2014
Accepted Date: 1 April 2014
Please cite this article as: Kwak BO, Lee MJ, Park HW, Kim KS, Chung S, A case of recurrent acute pancreatitis in an obese child, Nutrition (2014), doi: 10.1016/j.nut.2014.04.002. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 1
Case report
RI PT
A case of recurrent acute pancreatitis in an obese child Running head: recurrent pancreatitis and obesity
Byung Ok Kwak M.D., Min Jung Lee, M.D., Hye Won Park M.D., Kyo Sun Kim M.D., PhD.,
SC
Sochung Chung M.D., PhD.*
Medicine, Seoul, Korea
*Corresponding Author: Sochung Chung
M AN U
Department of Pediatrics, Konkuk University Medical Center, Konkuk University School of
TE D
Department of Pediatrics, Konkuk Medical Center, 120-1 Neungdong-ro (Hwayang-dong), Gwangjin-gu, Seoul 143-729, Korea
EP
Tel: +82 2 2030 7553
AC C
Fax: +82 2 2030 7748
E-mail address: [email protected]
BO.K., KS.K., and S.C. provided conception and design of report; BO.K., MJ.L., and HW.P. analyzed and interpreted results of research; BO.K. wrote manuscript; MJ.L., HW.P., and S.C. edited and revised manuscript; BO.K., KS.K., and S.C. approved final version of manuscript.
Word count: 1,778
ACCEPTED MANUSCRIPT 3
Abstract
Objective: To elucidate the relation between pancreatitis and obesity in children.
RI PT
Methods: We present a case of recurrent acute pancreatitis in an obese girl.
Results: A 7-year-old healthy obese girl was admitted with epigastric pain and vomiting. She
SC
had prior history of three similar episodes with epigastric pain, and diagnosed as acute pancreatitis 2 months ago. At the time of admission, her height was 128.5 cm (>95th
M AN U
percentile), weight 35.8 kg (>95th percentile), and body mass index (BMI) 21.7 kg/㎡ (>95th percentile for age). Serum amylase and lipase levels were elevated, and other laboratory findings including viral markers, autoantibodies, and genetic testing were negative. Abdominal ultrasonography and computerized tomography (CT) scan revealed acute pancreatitis with no evidence of stone or tumor. Anomalous pancreaticobiliary ductal union
TE D
(APBDU) with choledochal cyst was suspected on magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP). After the surgery with supportive care and diet, her symptoms were improved and
EP
new episode of pancreatitis was not observed for 2 years after the treatment.
AC C
Conclusions: Our experience suggests that obesity is associated with recurrence as well as severity of acute pancreatitis in children.
Keywords: Recurrent pancreatitis; Obesity; Child; Choledochal cyst; Diet
ACCEPTED MANUSCRIPT 4
Introduction Acute pancreatitis in children is uncommon, and there are limited case series or studies in pediatric population [1-8]. Recently, the prevalence of acute pancreatitis and recurrent
RI PT
pancreatitis in children has increased worldwide, and various etiologic factors such as biliary diseases, drugs, systemic diseases or gene mutations were suggested [1-4,8]. However, idiopathic cases are still high, and the relation between recurrent pancreatitis and obesity in
SC
children is unclear. Herein, we present a case of recurrent acute pancreatitis in a 7-year-old obese girl with anomalous pancreaticobiliary ductal union (APBDU) and choledochal cyst.
AC C
EP
TE D
M AN U
She was successfully treated with surgery and supportive care.
ACCEPTED MANUSCRIPT 5
Case report
A previously healthy 7-year-old obese girl was admitted complaint of epigastric pain and
RI PT
vomiting for 2 days. She was previously healthy and had no history of trauma or gallstone. She had prior history of three similar episodes, and had diagnosed as acute pancreatitis and obesity 2 months ago. There was no family history of hyperlipidemia, pancreatitis, gall
SC
stones, or liver diseases. At the time of admission, her height was 128.5 cm (>95th
percentile), weight was 35.8kg (>95th percentile), and body mass index (BMI) was 21.7
M AN U
kg/㎡ (>95th percentile for age) (Fig. 1). Her vital signs were as follows: body temperature was 36.3℃, pulse rate 87 beats per minute, respiratory rate 22 breaths per minute, and blood pressure 101/61 mmHg. On physical examination, mild epigastric tenderness without organomegaly, masses, guarding, or rebound tenderness was noticed. She had no skin lesions or hyperpigmentation. Laboratory investigation showed hemoglobin concentration 12.4 g/dL,
TE D
white blood cell count 6,620/㎕ (60.1% neutrophils, 29.3% lymphocytes, 6.8% monocytes), platelet count 188,000/㎕, and C-reactive protein (CRP) 2.03 mg/dL. Serum electrolytes were sodium 140 mmol/L, potassium 3.8 mmol/L, chloride 105 mmol/L, and bicarbonate 21
EP
mmol/L. Serum glucose was 90 mg/dL, Hemoglobin A1c (HbA1c) 5.4%, serum insulin (AC)
AC C
4.3 uIU/mL, blood urea nitrogen (BUN) 8.5 mg/dL, serum creatinine 0.41 mg/dL, and lactate dehydrogenase (LDH) 459 mg/dL. Liver function tests showed aspartate aminotransferase (AST) 127 IU/L, alanine aminotransferase (ALT) 100 IU/L, total bilirubin 0.4 mg/dL, and alkaline phosphatase (ALP) 262 IU/L. Serum amylase and lipase levels were elevated with 1253 U/L and 3928 U/L respectively. Serum lipid profile showed total cholesterol 124 mg/dL, triglycerides (TG) 47 mg/dL, and high density lipoproteins (HDL) 23 mg/dL. Other laboratory findings including viral markers, autoantibodies, and genetic testing were performed; Cytomegalovirus (CMV) IgM antibody, Anti-nuclear antibody, anti-smooth
ACCEPTED MANUSCRIPT 6
muscle antibody, rhuematoid factor, cystic fibrosis transmembrane conductor regulator (CFTR) gene mutation were all negative. Abdominal ultrasonography and computerized tomography (CT) scan showed diffuse swelling of pancreas with peri-pancreatic fat stranding
RI PT
and fluid collection, consisted with acute pancreatitis with no evidence of stone or tumor (Fig. 2). Anomalous pancreaticobiliary ductal union (APBDU) with choledochal cyst was
suspected on magnetic resonance cholangiopancreatography (MRCP) and endoscopic
SC
retrograde cholangiopancreatography (ERCP). Excision of bile duct, cholecystectomy and
hepaticojejunostomy was performed because of recurrent symptoms, and operative findings
M AN U
showed focal dilation with mild chronic inflammation of common bile duct. After surgery, supportive care and diet control were continued, and new episode of pancreatitis was not observed. The profiles of body composition analysis were improved after 2 years of the treatment; from height 128.5 cm (>95th percentile), weight 35.8kg (>95th percentile), BMI
TE D
21.7 kg/㎡ (>95th percentile), fat mass(FM) 15.7kg, fat free mass (FFM) 20.1kg, fat mass
index (FMI) 9.5 kg/㎡, fat free mass index (FFMI) 12.2 kg/㎡, percent body fat (PBF) 44.0%
EP
to height 141.6 cm (>95th percentile), weight 42.3kg (90-95th percentile), BMI 21.1 kg/㎡
AC C
(90-95th percentile), FM 15.1kg, FFM 27.2kg, FMI 7.5 kg/㎡, FFMI 13.6 kg/㎡, PBF 35.7%.
ACCEPTED MANUSCRIPT 7
Discussion
In this report, we described a healthy obese girl who presented recurrent acute pancreatitis.
analysis were improved and acute pancreatitis was not recurred.
RI PT
After supportive care and diet combined with surgery, her profiles of body composition
Recently, increasing incidence of acute pancreatitis in children was reported worldwide, and
SC
diverse etiologic factors were suggested [1-4,7,8]. In some pediatric studies, systemic and idiopathic pancreatitis were associated [1,4], and in infants and toddlers, multisystem disease
M AN U
was the most common etiology [7]. In contrast, other pediatric study reported that there was a 53% increase in pancreatitis cases, and biliary disease was the most common etiology [3]. Recurrent acute pancreatitis is observed in 10~15% of children with acute pancreatitis [3,9]. There are various etiological factors such as biliary disease or genetic mutations [8-11]. Therefore anatomic and genetic evaluation for cationic trypsinogen, serine protease 1
TE D
(PRSS1), serine protease inhibitor Kazal type 1 (SPINK1), and CFTR mutations were suggested in children with recurrent pancreatitis [9-12]. In our case, genetic testing for CFTR mutation was performed and it was negative.
EP
The increasing obesity in children has been well documented, and an association has been noted between obesity and severity of pancreatitis in adults [3,13-17]. The mechanisms which
AC C
obesity increases the severity of acute pancreatitis are unclear, and several hypotheses have been suggested: increased inflammation and accumulation of fat within the pancreas where necrosis is often located; increase in both peri- and intra-pancreatic fat and inflammatory cells; systemic inflammatory response associated with hepatic dysfunction by altering the detoxification of inflammatory mediators; increased pancreatic enzyme output associated with chronic high-fat diet which may stress the pancreas in genetically-predisposed individuals; and ventilation/perfusion mismatch associated with hypoxia and a low pancreatic
ACCEPTED MANUSCRIPT 8
flow lading to pancreatic deoxygenation and injury [1,15,18-23]. However, there is no sufficient data on the relation of obesity with acute pancreatitis in children [1,3]. Furthermore, the contribution of obesity to the frequency of pancreatitis in children has not been
RI PT
investigated. In our case, the patient had high BMI (>95th percentile for age), FM, and FMI at the time of admission. After the treatment, the profiles of body composition were improved, and no episode of recurrent pancreatitis was observed. Although the patient was treated with
SC
surgery as well, high BMI and FMI were considered as an associated factor of recurrent pancreatitis. Further studies to elucidate pathophysiology of pediatric pancreatitis considering
M AN U
the changes of body composition should be required.
In conclusion, our experience suggests that obesity is associated with recurrence as well as severity of acute pancreatitis in children. Increasing incidence of acute pancreatitis is expected with obesity epidemics, acute pancreatitis should be suspected in obese children complaint of abdominal pain. Furthermore diet control should be emphasized in these
AC C
EP
anatomical abnormalities.
TE D
patients, because recurrent pancreatitis can be induced by functional change in the absence of
ACCEPTED MANUSCRIPT 9
References [1] Nydegger A, Heine RG, Ranuh R, Gegati-Levy R, Crameri J, Oliver MR. Changing incidence of acute pancreatitis: 10-year experience at the Royal Children's Hospital, Melbourne. J Gastroenterol Hepatol 2007;22:1313-6.
RI PT
[2] Werlin SL, Kugathasan S, Frautschy BC. Pancreatitis in children. J Pediatr Gastroenterol Nutr 2003;37:591-5.
SC
[3] Park A, Latif SU, Shah AU, Tian J, Werlin S, Hsiao A, et al. Changing referral trends of acute pancreatitis in children: A 12-year single-center analysis. J Pediatr Gastroenterol Nutr 2009;49:316-22. [4] Lopez MJ. The changing incidence of acute pancreatitis in children: a single-institution perspective. J Pediatr 2002;140:622-4.
M AN U
[5] Benifla M, Weizman Z. Acute pancreatitis in childhood: analysis of literature data. J Clin Gastroenterol 2003;37:169-72. [6] Haddock G, Coupar G, Youngson GG, MacKinlay GA, Raine PA. Acute pancreatitis in children: a 15-year review. J Pediatr Surg 1994;29:719-22. [7] Kandula L, Lowe ME. Etiology and outcome of acute pancreatitis in infants and toddlers. J Pediatr 2008;152:106,10, 110.e1.
TE D
[8] Sanchez-Ramirez CA, Larrosa-Haro A, Flores-Martinez S, Sanchez-Corona J, VillaGomez A, Macias-Rosales R. Acute and recurrent pancreatitis in children: etiological factors. Acta Paediatr 2007;96:534-7. [9] Nydegger A, Couper RT, Oliver MR. Childhood pancreatitis. J Gastroenterol Hepatol 2006;21:499-509.
EP
[10] Minen F, De Cunto A, Martelossi S, Ventura A. Acute and recurrent pancreatitis in children: exploring etiological factors. Scand J Gastroenterol 2012;47:1501-4.
AC C
[11] Sultan M, Werlin S, Venkatasubramani N. Genetic prevalence and characteristics in children with recurrent pancreatitis. J Pediatr Gastroenterol Nutr 2012;54:645-50. [12] Ellis I, Lerch MM, Whitcomb DC, Consensus Committees of the European Registry of Hereditary Pancreatic Diseases, Midwest Multi-Center Pancreatic Study Group, International Association of Pancreatology. Genetic testing for hereditary pancreatitis: guidelines for indications, counselling, consent and privacy issues. Pancreatology 2001;1:405-15. [13] Bultron G, Seashore MR, Pashankar DS, Husain SZ. Recurrent acute pancreatitis associated with propionic acidemia. J Pediatr Gastroenterol Nutr 2008;47:370-1. [14] Martinez J, Sanchez-Paya J, Palazon JM, Aparicio JR, Pico A, Perez-Mateo M. Obesity: a prognostic factor of severity in acute pancreatitis. Pancreas 1999;19:15-20.
ACCEPTED MANUSCRIPT 10
[15] Papachristou GI, Papachristou DJ, Avula H, Slivka A, Whitcomb DC. Obesity increases the severity of acute pancreatitis: performance of APACHE-O score and correlation with the inflammatory response. Pancreatology 2006;6:279-85.
RI PT
[16] Martinez J, Sanchez-Paya J, Palazon JM, Suazo-Barahona J, Robles-Diaz G, PerezMateo M. Is obesity a risk factor in acute pancreatitis? A meta-analysis. Pancreatology 2004;4:42-8.
[17] Suazo-Barahona J, Carmona-Sanchez R, Robles-Diaz G, Milke-Garcia P, VargasVorackova F, Uscanga-Dominguez L, et al. Obesity: a risk factor for severe acute biliary and alcoholic pancreatitis. Am J Gastroenterol 1998;93:1324-8.
SC
[18] Frossard JL, Lescuyer P, Pastor CM. Experimental evidence of obesity as a risk factor for severe acute pancreatitis. World J Gastroenterol 2009;15:5260-5.
M AN U
[19] Abu Hilal M, Armstrong T. The impact of obesity on the course and outcome of acute pancreatitis. Obes Surg 2008;18:326-8. [20] Ghanim H, Aljada A, Hofmeyer D, Syed T, Mohanty P, Dandona P. Circulating mononuclear cells in the obese are in a proinflammatory state. Circulation 2004;110:1564-71. [21] Pitt HA. Hepato-pancreato-biliary fat: the good, the bad and the ugly. HPB (Oxford) 2007;9:92-7.
TE D
[22] Clement K, Langin D. Regulation of inflammation-related genes in human adipose tissue. J Intern Med 2007;262:422-30.
AC C
EP
[23] Lamas O, Marti A, Martinez JA. Obesity and immunocompetence. Eur J Clin Nutr 2002;56 Suppl 3:S42-5.
ACCEPTED MANUSCRIPT 11
Figure legends Fig. 1. Growth charts for height, weight, and body mass index (BMI) of the patient The arrow indicates height, weight, and BMI at the time of admission.
RI PT
Fig. 2. Abdominal computerized tomography (CT) scan shows diffuse swelling of pancreas
AC C
EP
TE D
M AN U
SC
with peri-pancreatic fat stranding and fluid collection
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
S0899-9007(14)00191-9
DOI:
10.1016/j.nut.2014.04.002
Reference:
NUT 9277
To appear in:
Nutrition
Received Date: 8 October 2013 Revised Date:
10 March 2014
Accepted Date: 1 April 2014
Please cite this article as: Kwak BO, Lee MJ, Park HW, Kim KS, Chung S, A case of recurrent acute pancreatitis in an obese child, Nutrition (2014), doi: 10.1016/j.nut.2014.04.002. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 1
Case report
RI PT
A case of recurrent acute pancreatitis in an obese child Running head: recurrent pancreatitis and obesity
Byung Ok Kwak M.D., Min Jung Lee, M.D., Hye Won Park M.D., Kyo Sun Kim M.D., PhD.,
SC
Sochung Chung M.D., PhD.*
Medicine, Seoul, Korea
*Corresponding Author: Sochung Chung
M AN U
Department of Pediatrics, Konkuk University Medical Center, Konkuk University School of
TE D
Department of Pediatrics, Konkuk Medical Center, 120-1 Neungdong-ro (Hwayang-dong), Gwangjin-gu, Seoul 143-729, Korea
EP
Tel: +82 2 2030 7553
AC C
Fax: +82 2 2030 7748
E-mail address: [email protected]
BO.K., KS.K., and S.C. provided conception and design of report; BO.K., MJ.L., and HW.P. analyzed and interpreted results of research; BO.K. wrote manuscript; MJ.L., HW.P., and S.C. edited and revised manuscript; BO.K., KS.K., and S.C. approved final version of manuscript.
Word count: 1,778
ACCEPTED MANUSCRIPT 3
Abstract
Objective: To elucidate the relation between pancreatitis and obesity in children.
RI PT
Methods: We present a case of recurrent acute pancreatitis in an obese girl.
Results: A 7-year-old healthy obese girl was admitted with epigastric pain and vomiting. She
SC
had prior history of three similar episodes with epigastric pain, and diagnosed as acute pancreatitis 2 months ago. At the time of admission, her height was 128.5 cm (>95th
M AN U
percentile), weight 35.8 kg (>95th percentile), and body mass index (BMI) 21.7 kg/㎡ (>95th percentile for age). Serum amylase and lipase levels were elevated, and other laboratory findings including viral markers, autoantibodies, and genetic testing were negative. Abdominal ultrasonography and computerized tomography (CT) scan revealed acute pancreatitis with no evidence of stone or tumor. Anomalous pancreaticobiliary ductal union
TE D
(APBDU) with choledochal cyst was suspected on magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP). After the surgery with supportive care and diet, her symptoms were improved and
EP
new episode of pancreatitis was not observed for 2 years after the treatment.
AC C
Conclusions: Our experience suggests that obesity is associated with recurrence as well as severity of acute pancreatitis in children.
Keywords: Recurrent pancreatitis; Obesity; Child; Choledochal cyst; Diet
ACCEPTED MANUSCRIPT 4
Introduction Acute pancreatitis in children is uncommon, and there are limited case series or studies in pediatric population [1-8]. Recently, the prevalence of acute pancreatitis and recurrent
RI PT
pancreatitis in children has increased worldwide, and various etiologic factors such as biliary diseases, drugs, systemic diseases or gene mutations were suggested [1-4,8]. However, idiopathic cases are still high, and the relation between recurrent pancreatitis and obesity in
SC
children is unclear. Herein, we present a case of recurrent acute pancreatitis in a 7-year-old obese girl with anomalous pancreaticobiliary ductal union (APBDU) and choledochal cyst.
AC C
EP
TE D
M AN U
She was successfully treated with surgery and supportive care.
ACCEPTED MANUSCRIPT 5
Case report
A previously healthy 7-year-old obese girl was admitted complaint of epigastric pain and
RI PT
vomiting for 2 days. She was previously healthy and had no history of trauma or gallstone. She had prior history of three similar episodes, and had diagnosed as acute pancreatitis and obesity 2 months ago. There was no family history of hyperlipidemia, pancreatitis, gall
SC
stones, or liver diseases. At the time of admission, her height was 128.5 cm (>95th
percentile), weight was 35.8kg (>95th percentile), and body mass index (BMI) was 21.7
M AN U
kg/㎡ (>95th percentile for age) (Fig. 1). Her vital signs were as follows: body temperature was 36.3℃, pulse rate 87 beats per minute, respiratory rate 22 breaths per minute, and blood pressure 101/61 mmHg. On physical examination, mild epigastric tenderness without organomegaly, masses, guarding, or rebound tenderness was noticed. She had no skin lesions or hyperpigmentation. Laboratory investigation showed hemoglobin concentration 12.4 g/dL,
TE D
white blood cell count 6,620/㎕ (60.1% neutrophils, 29.3% lymphocytes, 6.8% monocytes), platelet count 188,000/㎕, and C-reactive protein (CRP) 2.03 mg/dL. Serum electrolytes were sodium 140 mmol/L, potassium 3.8 mmol/L, chloride 105 mmol/L, and bicarbonate 21
EP
mmol/L. Serum glucose was 90 mg/dL, Hemoglobin A1c (HbA1c) 5.4%, serum insulin (AC)
AC C
4.3 uIU/mL, blood urea nitrogen (BUN) 8.5 mg/dL, serum creatinine 0.41 mg/dL, and lactate dehydrogenase (LDH) 459 mg/dL. Liver function tests showed aspartate aminotransferase (AST) 127 IU/L, alanine aminotransferase (ALT) 100 IU/L, total bilirubin 0.4 mg/dL, and alkaline phosphatase (ALP) 262 IU/L. Serum amylase and lipase levels were elevated with 1253 U/L and 3928 U/L respectively. Serum lipid profile showed total cholesterol 124 mg/dL, triglycerides (TG) 47 mg/dL, and high density lipoproteins (HDL) 23 mg/dL. Other laboratory findings including viral markers, autoantibodies, and genetic testing were performed; Cytomegalovirus (CMV) IgM antibody, Anti-nuclear antibody, anti-smooth
ACCEPTED MANUSCRIPT 6
muscle antibody, rhuematoid factor, cystic fibrosis transmembrane conductor regulator (CFTR) gene mutation were all negative. Abdominal ultrasonography and computerized tomography (CT) scan showed diffuse swelling of pancreas with peri-pancreatic fat stranding
RI PT
and fluid collection, consisted with acute pancreatitis with no evidence of stone or tumor (Fig. 2). Anomalous pancreaticobiliary ductal union (APBDU) with choledochal cyst was
suspected on magnetic resonance cholangiopancreatography (MRCP) and endoscopic
SC
retrograde cholangiopancreatography (ERCP). Excision of bile duct, cholecystectomy and
hepaticojejunostomy was performed because of recurrent symptoms, and operative findings
M AN U
showed focal dilation with mild chronic inflammation of common bile duct. After surgery, supportive care and diet control were continued, and new episode of pancreatitis was not observed. The profiles of body composition analysis were improved after 2 years of the treatment; from height 128.5 cm (>95th percentile), weight 35.8kg (>95th percentile), BMI
TE D
21.7 kg/㎡ (>95th percentile), fat mass(FM) 15.7kg, fat free mass (FFM) 20.1kg, fat mass
index (FMI) 9.5 kg/㎡, fat free mass index (FFMI) 12.2 kg/㎡, percent body fat (PBF) 44.0%
EP
to height 141.6 cm (>95th percentile), weight 42.3kg (90-95th percentile), BMI 21.1 kg/㎡
AC C
(90-95th percentile), FM 15.1kg, FFM 27.2kg, FMI 7.5 kg/㎡, FFMI 13.6 kg/㎡, PBF 35.7%.
ACCEPTED MANUSCRIPT 7
Discussion
In this report, we described a healthy obese girl who presented recurrent acute pancreatitis.
analysis were improved and acute pancreatitis was not recurred.
RI PT
After supportive care and diet combined with surgery, her profiles of body composition
Recently, increasing incidence of acute pancreatitis in children was reported worldwide, and
SC
diverse etiologic factors were suggested [1-4,7,8]. In some pediatric studies, systemic and idiopathic pancreatitis were associated [1,4], and in infants and toddlers, multisystem disease
M AN U
was the most common etiology [7]. In contrast, other pediatric study reported that there was a 53% increase in pancreatitis cases, and biliary disease was the most common etiology [3]. Recurrent acute pancreatitis is observed in 10~15% of children with acute pancreatitis [3,9]. There are various etiological factors such as biliary disease or genetic mutations [8-11]. Therefore anatomic and genetic evaluation for cationic trypsinogen, serine protease 1
TE D
(PRSS1), serine protease inhibitor Kazal type 1 (SPINK1), and CFTR mutations were suggested in children with recurrent pancreatitis [9-12]. In our case, genetic testing for CFTR mutation was performed and it was negative.
EP
The increasing obesity in children has been well documented, and an association has been noted between obesity and severity of pancreatitis in adults [3,13-17]. The mechanisms which
AC C
obesity increases the severity of acute pancreatitis are unclear, and several hypotheses have been suggested: increased inflammation and accumulation of fat within the pancreas where necrosis is often located; increase in both peri- and intra-pancreatic fat and inflammatory cells; systemic inflammatory response associated with hepatic dysfunction by altering the detoxification of inflammatory mediators; increased pancreatic enzyme output associated with chronic high-fat diet which may stress the pancreas in genetically-predisposed individuals; and ventilation/perfusion mismatch associated with hypoxia and a low pancreatic
ACCEPTED MANUSCRIPT 8
flow lading to pancreatic deoxygenation and injury [1,15,18-23]. However, there is no sufficient data on the relation of obesity with acute pancreatitis in children [1,3]. Furthermore, the contribution of obesity to the frequency of pancreatitis in children has not been
RI PT
investigated. In our case, the patient had high BMI (>95th percentile for age), FM, and FMI at the time of admission. After the treatment, the profiles of body composition were improved, and no episode of recurrent pancreatitis was observed. Although the patient was treated with
SC
surgery as well, high BMI and FMI were considered as an associated factor of recurrent pancreatitis. Further studies to elucidate pathophysiology of pediatric pancreatitis considering
M AN U
the changes of body composition should be required.
In conclusion, our experience suggests that obesity is associated with recurrence as well as severity of acute pancreatitis in children. Increasing incidence of acute pancreatitis is expected with obesity epidemics, acute pancreatitis should be suspected in obese children complaint of abdominal pain. Furthermore diet control should be emphasized in these
AC C
EP
anatomical abnormalities.
TE D
patients, because recurrent pancreatitis can be induced by functional change in the absence of
ACCEPTED MANUSCRIPT 9
References [1] Nydegger A, Heine RG, Ranuh R, Gegati-Levy R, Crameri J, Oliver MR. Changing incidence of acute pancreatitis: 10-year experience at the Royal Children's Hospital, Melbourne. J Gastroenterol Hepatol 2007;22:1313-6.
RI PT
[2] Werlin SL, Kugathasan S, Frautschy BC. Pancreatitis in children. J Pediatr Gastroenterol Nutr 2003;37:591-5.
SC
[3] Park A, Latif SU, Shah AU, Tian J, Werlin S, Hsiao A, et al. Changing referral trends of acute pancreatitis in children: A 12-year single-center analysis. J Pediatr Gastroenterol Nutr 2009;49:316-22. [4] Lopez MJ. The changing incidence of acute pancreatitis in children: a single-institution perspective. J Pediatr 2002;140:622-4.
M AN U
[5] Benifla M, Weizman Z. Acute pancreatitis in childhood: analysis of literature data. J Clin Gastroenterol 2003;37:169-72. [6] Haddock G, Coupar G, Youngson GG, MacKinlay GA, Raine PA. Acute pancreatitis in children: a 15-year review. J Pediatr Surg 1994;29:719-22. [7] Kandula L, Lowe ME. Etiology and outcome of acute pancreatitis in infants and toddlers. J Pediatr 2008;152:106,10, 110.e1.
TE D
[8] Sanchez-Ramirez CA, Larrosa-Haro A, Flores-Martinez S, Sanchez-Corona J, VillaGomez A, Macias-Rosales R. Acute and recurrent pancreatitis in children: etiological factors. Acta Paediatr 2007;96:534-7. [9] Nydegger A, Couper RT, Oliver MR. Childhood pancreatitis. J Gastroenterol Hepatol 2006;21:499-509.
EP
[10] Minen F, De Cunto A, Martelossi S, Ventura A. Acute and recurrent pancreatitis in children: exploring etiological factors. Scand J Gastroenterol 2012;47:1501-4.
AC C
[11] Sultan M, Werlin S, Venkatasubramani N. Genetic prevalence and characteristics in children with recurrent pancreatitis. J Pediatr Gastroenterol Nutr 2012;54:645-50. [12] Ellis I, Lerch MM, Whitcomb DC, Consensus Committees of the European Registry of Hereditary Pancreatic Diseases, Midwest Multi-Center Pancreatic Study Group, International Association of Pancreatology. Genetic testing for hereditary pancreatitis: guidelines for indications, counselling, consent and privacy issues. Pancreatology 2001;1:405-15. [13] Bultron G, Seashore MR, Pashankar DS, Husain SZ. Recurrent acute pancreatitis associated with propionic acidemia. J Pediatr Gastroenterol Nutr 2008;47:370-1. [14] Martinez J, Sanchez-Paya J, Palazon JM, Aparicio JR, Pico A, Perez-Mateo M. Obesity: a prognostic factor of severity in acute pancreatitis. Pancreas 1999;19:15-20.
ACCEPTED MANUSCRIPT 10
[15] Papachristou GI, Papachristou DJ, Avula H, Slivka A, Whitcomb DC. Obesity increases the severity of acute pancreatitis: performance of APACHE-O score and correlation with the inflammatory response. Pancreatology 2006;6:279-85.
RI PT
[16] Martinez J, Sanchez-Paya J, Palazon JM, Suazo-Barahona J, Robles-Diaz G, PerezMateo M. Is obesity a risk factor in acute pancreatitis? A meta-analysis. Pancreatology 2004;4:42-8.
[17] Suazo-Barahona J, Carmona-Sanchez R, Robles-Diaz G, Milke-Garcia P, VargasVorackova F, Uscanga-Dominguez L, et al. Obesity: a risk factor for severe acute biliary and alcoholic pancreatitis. Am J Gastroenterol 1998;93:1324-8.
SC
[18] Frossard JL, Lescuyer P, Pastor CM. Experimental evidence of obesity as a risk factor for severe acute pancreatitis. World J Gastroenterol 2009;15:5260-5.
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[19] Abu Hilal M, Armstrong T. The impact of obesity on the course and outcome of acute pancreatitis. Obes Surg 2008;18:326-8. [20] Ghanim H, Aljada A, Hofmeyer D, Syed T, Mohanty P, Dandona P. Circulating mononuclear cells in the obese are in a proinflammatory state. Circulation 2004;110:1564-71. [21] Pitt HA. Hepato-pancreato-biliary fat: the good, the bad and the ugly. HPB (Oxford) 2007;9:92-7.
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[22] Clement K, Langin D. Regulation of inflammation-related genes in human adipose tissue. J Intern Med 2007;262:422-30.
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Figure legends Fig. 1. Growth charts for height, weight, and body mass index (BMI) of the patient The arrow indicates height, weight, and BMI at the time of admission.
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Fig. 2. Abdominal computerized tomography (CT) scan shows diffuse swelling of pancreas
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with peri-pancreatic fat stranding and fluid collection
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