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Alcoholic severe acute pancreatitis with positive culture of pancreatic juice treated by nasopancreatic drainage
Pancreatology 14 (2014) 151e153
Contents lists available at ScienceDirect
Pancreatology journal homepage: www.elsevier.com/locate/pan
Rapid communication
Alcoholic severe acute pancreatitis with positive culture of pancreatic juice treated by nasopancreatic drainage Masataka Kikuyama*, Kazumasa Nakamura, Takafumi Kurokami Department of Gastroenterology, Shizuoka General Hospital, Shizuoka, Japan
a r t i c l e i n f o
a b s t r a c t
Available online 27 March 2014
Background: Severe acute pancreatitis (SAP) is a serious disease associated with alcoholism and has a high mortality rate. Effective treatments have not been established. Methods: A 58-year-old man was admitted due to alcoholic SAP. Endoscopic retrograde cholangiopancreatography revealed pancreatic calculi at the pancreas head and a stricture in the pancreatic duct from the pancreas head to the body. Endoscopically, nasopancreatic drainage (NPD) was placed through the minor papilla to the pancreas tail beyond the stricture. Results: Pancreatic juice culture was positive for Streptococcus and Enterobacter. The day after NPD, upper abdominal pain was relieved. After changing NPD to a pancreatic stent, the patient was discharged on day 21 post-NPD. Conclusion: Alcoholic SAP may reflect aggravation of chronic pancreatitis. The possibility of acute bacterial inflammation should be considered in all cases of chronic alcoholic pancreatitis who present with severe features of inflammation, even in the early stages of an attack. Treatment of this subset of cases by drainage could be of great importance and NPD may be the preferred method. Copyright Ó 2014, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved.
Keywords: Alcoholic severe acute pancreatitis Nasopancreatic drainage Chronic pancreatitis Pancreatic ductitis Positive pancreatic juice culture Pancreatic stent
1. Case report A 58-year-old man was admitted to the hospital due to upper abdominal pain and fever. He had consumed more than 80 g/day of alcohol for about 30 years and had a past history of two episodes of pancreatic inflammation within 10 years. On admission, upper abdominal pain was severe with high fever (39.2 C) and tachycardia (127/min). Repeated administration of analgesics was needed. Blood examination showed an elevated white blood cell (WBC) count (16,500/mL), elevated BUN (20 mg/dL) and hypoxia (PaO2 63.2 mmHg). CT showed a swollen pancreas with slight dilatation of the main pancreatic duct (MPD) and extended inflammation reaching the pelvic cavity without gallstones or pancreatic tumors (Fig. 1). Symptoms were diagnosed as due to severe acute pancreatitis (SAP) based on the Ranson score [1] (3 points, age >55, WBC >16,000/mL, BUN increase >5 mg/dl) and APACHE II score [2] (total 13 points; temperature 39.2 C, þ3; mean arterial pressure 110, þ2; heart rate 127, þ2; PaO2 63.2 mmHg, þ2;
WBC 16,500/mm3, þ1; 58 years old, þ3). An ERCP on the day of admission showed features of chronic pancreatitis with calculi and a stricture in the main pancreatic duct. During the procedure, a NPD was placed through the minor papilla to the pancreas tail beyond the pancreatic duct stricture (Fig. 2). Culture of the pancreatic juice was positive, and Streptococcus species as well as Enterobacter cloacae were recognized. The day following the procedure, he experienced relief of upper abdominal pain and the WBC count had decreased to within normal range. However, the patient continued to complain of slight upper abdominal pain and did not wish to start meals because of anxiety about the recurrence of acute pancreatitis. Antibiotics were administered for 1 week until symptoms were relieved. Oral intake was started on hospital day 9. The patient’s NPD was changed to a pancreatic stent on hospital day 14. He was discharged on hospital day 21 after confirming that the change in pancreatic duct drainage did not induce recurrence of pancreatitis. 2. Discussion
* Corresponding author. Department of Gastroenterology, Shizuoka General Hospital, 4-27-1, Kita-ando, Aoiku, Shizuoka, Shizuoka 420-8257, Japan. Tel.: þ81 54 247 6111; fax: þ81 54 247 6140. E-mail address: [email protected] (M. Kikuyama).
Generally, infection of the pancreas occurs in necrotic tissues about one week after SAP [3], which was considered to be caused by bacterial translocation from the intestine [4], presumed to be due to
http://dx.doi.org/10.1016/j.pan.2014.03.020 1424-3903/Copyright Ó 2014, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved.
152
M. Kikuyama et al. / Pancreatology 14 (2014) 151e153
Fig. 1. CT on admission showing a swollen pancreas with slight dilatation of the main pancreatic duct and extended inflammation.
Fig. 2. ERCP on the day of admission showing features of chronic pancreatitis with calculi and a stricture in the main pancreatic duct.
injury of the intestinal mucosal integrity [5,6]. In our case, pancreatic juice was obtained on the second day of the clinical course of SAP. Therefore, we speculated that bacterial infection of the pancreatic duct was not secondary to chronic alcoholic pancreatitis, with its associated duct abnormalities and obstruction, but primarily associated with features of acute inflammation in our patient. Alcohol abuse induces bacterial translocation due to injured mucosal integrity [7] and induces bacterial overgrowth in the intestine [8]. As a result, patients are exposed to bacteria translocated from the intestine. The present patient had disturbed pancreatic juice flow due to pancreatic duct stricture with calculi, and secondary infectious pancreatic ductitis was presumed to have occurred. Streptococcus species as well as E. cloacae were recognized on culture of the pancreatic juice in this case. Streptococcus species were reported to be identified in fecal flora although not domina [9,10], and were rarely identified in samples obtained from necrotic tissue [3]. Identification of Streptococcus species in the pancreatic
fluid may be specific to the present case. Streptococcus species are clinically important Gram-positive bacteria that are capable of causing a wide variety of diseases in humans including infection of tissues and organs. Microbial adhesion to host tissues is the initial critical event in the pathogenesis of most infections. Streptococcus species use multiple adhesins to attach to the epithelium [11]. We speculate that Streptococcus species might have been responsible for the onset of acute pancreatitis in the current patient. However, accumulation of a large number of cases is needed to confirm this hypothesis. We have reported 6 cases of acute obstructive suppurative pancreatic ductitis (AOSPD) treated with pancreatic duct drainage by NPD [12]. Causes of chronic pancreatitis were alcoholism in 5 patients and heredity in 1. All had MPD dilatation with pancreatic calculi or MPD stenosis revealed by CT on admission as well as clinical features of aggravation of chronic pancreatitis with fever. In 5 of the 6 patients, cultures of the pancreatic juice were performed, and the results were positive with Escherichia coli, Klebsiela pneumonia, Enterococcus faecalis, and Viellonella species identified in 3, 1, and 1 patient, respectively. The 5 patients with alcoholic pancreatitis had pancreatic calculi and underwent extracorporeal shock wave lithotripsy (ESWL) to remove them. In the remaining patient with hereditary pancreatitis, pancreatic stenosis was recognized and NPD was followed by stent placement. That this patient had pancreatic duct disorders, including stenosis and calculi, indicated that this case might represent aggravation of chronic pancreatitis, possibly with secondary, earlier than usual, bacterial infection. However, the demonstration of infected pancreatic juice as early as the second day of admission suggests that this patient might have had AOSPD. This case also demonstrates the possibility that some other cases of acute inflammation in the course of chronic alcoholic pancreatitis might be due primarily to bacterial infection of the pancreatic ducts. Thus there may be an important subset of patients with chronic alcoholic pancreatitis in whom AOSPD occurs and in whom treatment with NPD would be effective and important. For draining a pancreatic duct, either NPD or pancreatic stent placement can be selected. NPD has the advantage of decreasing intraductal pressure of the pancreatic duct to levels lower [13] than the duodenum while maintaining the integrity of the pancreatic duct environment to prevent infection [14,15] and avoiding reflux of duodenal juice into the injured pancreatic duct, which may contribute to repair of pancreatic duct damage and prevent worsening of inflammation. The use of NPD also allows for the evaluation of the pancreatic duct when needed [14,16]. However, a drawback of NPD is that patients must undergo transnasal placement of a drainage tube. On the other hand, a pancreatic stent also enables pancreatic fluid to flow into the duodenum and decrease the intraductal pressure of the pancreatic duct, which could lead to repair of pancreatic duct damage [17]. However, stent placement has been associated with early occlusion and infection [14,15,18] and can allow duodenal fluid reflux into the pancreatic duct. We consider that NPD should be selected as the first choice of drainage procedure in cases of chronic alcoholic pancreatitis presenting with suspected AOSPD. Then, to prevent recurrence of acute pancreatitis after resolution, stent placement following NPD would be needed because disturbance of pancreatic juice flow is considered to be a predisposing factor in AOSPD. We have described a case of acute bacterial infection complicating established chronic alcoholic pancreatitis that was successfully treated with NPD. However, to confirm the efficacy of the treatment with NPD for such cases requires a further accumulation of cases. However, one should remember that ERCP has a risk of aggravating acute pancreatitis. To make this treatment useful for
M. Kikuyama et al. / Pancreatology 14 (2014) 151e153
acute bacterial inflammation of the pancreatic ducts, selecting patients is very important. We think the possible need for duct drainage should be considered in all cases of severe exacerbation of chronic alcoholic pancreatitis. When ERCP is intended to treat acute pancreatitis with ENPD, accomplishment of the procedure should be promised. Performing ERCP for acute pancreatitis is considered to be permitted to expertized endoscopists. 3. Conclusion The possibility of acute bacterial inflammation should be considered in all cases of chronic alcoholic pancreatitis who present with severe features of inflammation, even in the early stages of an attack. Treatment of this subset of cases by drainage could be of great importance and NPD may be the preferred method. However, since cannulation of the duct system may also produce complications, the selection of patients for drainage remains a challenge. References [1] Ranson JH. Etiological and prognostic factors in human acute pancreatitis: a review. Am J Gastroenterol 1982;77:633e8. [2] Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med 1985;13:818e29. [3] Besselink MG, van Santvoort HC, Boermeester MA, Nieuwenhuijs VB, van Goor H, Dejong CHC, et al. Timing and impact of infections in acute pancreatitis. Br J Surg 2009;96:267e73. [4] Flitz S, Hackert T, Hartwiq W, Rossmanith F, Strobel O, Schneider L, et al. Bacterial translocation and infected pancreatic necrotizing pancreatitis derives from small bowel rather than from colon. Am J Surg 2010;200:111e7. [5] Flint RS, Windsor JA. The role of the intestine in the pathophysiology and management of severe acute pancreatitis. HPB 2003;5:69e85.
153
[6] Capurso G, Zerboni G, Signoretti M, Valente R, Stiqliano S, Piciucchi M, et al. Role of the gut barrier in acute pancreatitis. J Clin Gastroenterol 2012;46:S46e 51. [7] Yan AW, Schnabl B. Bacterial translocation and changes in the intestinal microbiome associated with alcoholic liver disease. World J Hepatol 2012;27: 110e8. [8] Bode JC, Bode C, Heidelbach R, Dürr HK, Martini GA. Jejunal microflora in patients with chronic alcohol abuse. Hepatogastroenterology 1984;31:30e4. [9] Salminen S, Bouley C, Bouton-Ruault MC, Cummings JH, Franck A, Gibson GR, et al. Functional food science and gastrointestinal physiology and function. Br J Nutr 1998;80:S147e71. [10] Guraner F, Malagelada JR. Gut flora in health and disease. Lancet 2003;361: 512e9. [11] Moschioni M, Pansegrau W, Barocchi M. Adhesion determinants of the Streptococcus species. Microbial Biotechnol 2010;3:370e88. [12] Ota Y, Kurokami T, Shigetomo M, Matsumura K, Kodama Y, Chiba T, et al. Acute obstructive suppurative pancreatic ductitis: experiences of six cases. Pancreatology 2013;13:S28. [13] Cicek B, Pariak E, Oguz E, Disibeyaz S, Koksal AS, Sahin B. Endoscopic treatment of pancreatic fistula. Surg Endosc 2006;20:1706e12. [14] Costamanga G, Mutgnani M, Ingrosso M, Vamvakousis V, Alevras P, Manta R. Endoscopic treatment of postsurgical external pancreatic fistulas. Endoscopy 2001;33:317e22. [15] Bhasin DK, Rana SS, Nanda M, Chandail VS, Bupta R, Kang M, et al. Comparative evaluation of transpapillary drainage with nasopancreatic drain and stent in patients with large pseudocysts located near tail of pancreas. J Gastrointest Surg 2011;15:772e6. [16] Miyachi A, Kikuyama M, Matsubayashi Y, Kageyama F, Sumiyoshi S, Kobayashi Y. Successful treatment of pancreatopleural fistula by nasopancreatic drainage and endoscopic removal of pancreatic calculi: a case report. Gastrointest Endosc 2004;59:454e7. [17] Kozarek RA, Ball TJ, Patterson DJ, Raltz SL, Traverso LW, Ryan JA. Transpapillary stenting for pancreaticocutaneous fistulas. J Gastrointest Surg 1997;1:357e61. [18] Kozarek RA, Dall RJ, Patterson DJ, Freeney PC, Ryan JA, Traverso LW. Endoscopic transpapillary therapy for disrupted pancreatic duct and peripancreatic fluid collection. Gastroenterology 1991;100:1362e70.
Contents lists available at ScienceDirect
Pancreatology journal homepage: www.elsevier.com/locate/pan
Rapid communication
Alcoholic severe acute pancreatitis with positive culture of pancreatic juice treated by nasopancreatic drainage Masataka Kikuyama*, Kazumasa Nakamura, Takafumi Kurokami Department of Gastroenterology, Shizuoka General Hospital, Shizuoka, Japan
a r t i c l e i n f o
a b s t r a c t
Available online 27 March 2014
Background: Severe acute pancreatitis (SAP) is a serious disease associated with alcoholism and has a high mortality rate. Effective treatments have not been established. Methods: A 58-year-old man was admitted due to alcoholic SAP. Endoscopic retrograde cholangiopancreatography revealed pancreatic calculi at the pancreas head and a stricture in the pancreatic duct from the pancreas head to the body. Endoscopically, nasopancreatic drainage (NPD) was placed through the minor papilla to the pancreas tail beyond the stricture. Results: Pancreatic juice culture was positive for Streptococcus and Enterobacter. The day after NPD, upper abdominal pain was relieved. After changing NPD to a pancreatic stent, the patient was discharged on day 21 post-NPD. Conclusion: Alcoholic SAP may reflect aggravation of chronic pancreatitis. The possibility of acute bacterial inflammation should be considered in all cases of chronic alcoholic pancreatitis who present with severe features of inflammation, even in the early stages of an attack. Treatment of this subset of cases by drainage could be of great importance and NPD may be the preferred method. Copyright Ó 2014, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved.
Keywords: Alcoholic severe acute pancreatitis Nasopancreatic drainage Chronic pancreatitis Pancreatic ductitis Positive pancreatic juice culture Pancreatic stent
1. Case report A 58-year-old man was admitted to the hospital due to upper abdominal pain and fever. He had consumed more than 80 g/day of alcohol for about 30 years and had a past history of two episodes of pancreatic inflammation within 10 years. On admission, upper abdominal pain was severe with high fever (39.2 C) and tachycardia (127/min). Repeated administration of analgesics was needed. Blood examination showed an elevated white blood cell (WBC) count (16,500/mL), elevated BUN (20 mg/dL) and hypoxia (PaO2 63.2 mmHg). CT showed a swollen pancreas with slight dilatation of the main pancreatic duct (MPD) and extended inflammation reaching the pelvic cavity without gallstones or pancreatic tumors (Fig. 1). Symptoms were diagnosed as due to severe acute pancreatitis (SAP) based on the Ranson score [1] (3 points, age >55, WBC >16,000/mL, BUN increase >5 mg/dl) and APACHE II score [2] (total 13 points; temperature 39.2 C, þ3; mean arterial pressure 110, þ2; heart rate 127, þ2; PaO2 63.2 mmHg, þ2;
WBC 16,500/mm3, þ1; 58 years old, þ3). An ERCP on the day of admission showed features of chronic pancreatitis with calculi and a stricture in the main pancreatic duct. During the procedure, a NPD was placed through the minor papilla to the pancreas tail beyond the pancreatic duct stricture (Fig. 2). Culture of the pancreatic juice was positive, and Streptococcus species as well as Enterobacter cloacae were recognized. The day following the procedure, he experienced relief of upper abdominal pain and the WBC count had decreased to within normal range. However, the patient continued to complain of slight upper abdominal pain and did not wish to start meals because of anxiety about the recurrence of acute pancreatitis. Antibiotics were administered for 1 week until symptoms were relieved. Oral intake was started on hospital day 9. The patient’s NPD was changed to a pancreatic stent on hospital day 14. He was discharged on hospital day 21 after confirming that the change in pancreatic duct drainage did not induce recurrence of pancreatitis. 2. Discussion
* Corresponding author. Department of Gastroenterology, Shizuoka General Hospital, 4-27-1, Kita-ando, Aoiku, Shizuoka, Shizuoka 420-8257, Japan. Tel.: þ81 54 247 6111; fax: þ81 54 247 6140. E-mail address: [email protected] (M. Kikuyama).
Generally, infection of the pancreas occurs in necrotic tissues about one week after SAP [3], which was considered to be caused by bacterial translocation from the intestine [4], presumed to be due to
http://dx.doi.org/10.1016/j.pan.2014.03.020 1424-3903/Copyright Ó 2014, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved.
152
M. Kikuyama et al. / Pancreatology 14 (2014) 151e153
Fig. 1. CT on admission showing a swollen pancreas with slight dilatation of the main pancreatic duct and extended inflammation.
Fig. 2. ERCP on the day of admission showing features of chronic pancreatitis with calculi and a stricture in the main pancreatic duct.
injury of the intestinal mucosal integrity [5,6]. In our case, pancreatic juice was obtained on the second day of the clinical course of SAP. Therefore, we speculated that bacterial infection of the pancreatic duct was not secondary to chronic alcoholic pancreatitis, with its associated duct abnormalities and obstruction, but primarily associated with features of acute inflammation in our patient. Alcohol abuse induces bacterial translocation due to injured mucosal integrity [7] and induces bacterial overgrowth in the intestine [8]. As a result, patients are exposed to bacteria translocated from the intestine. The present patient had disturbed pancreatic juice flow due to pancreatic duct stricture with calculi, and secondary infectious pancreatic ductitis was presumed to have occurred. Streptococcus species as well as E. cloacae were recognized on culture of the pancreatic juice in this case. Streptococcus species were reported to be identified in fecal flora although not domina [9,10], and were rarely identified in samples obtained from necrotic tissue [3]. Identification of Streptococcus species in the pancreatic
fluid may be specific to the present case. Streptococcus species are clinically important Gram-positive bacteria that are capable of causing a wide variety of diseases in humans including infection of tissues and organs. Microbial adhesion to host tissues is the initial critical event in the pathogenesis of most infections. Streptococcus species use multiple adhesins to attach to the epithelium [11]. We speculate that Streptococcus species might have been responsible for the onset of acute pancreatitis in the current patient. However, accumulation of a large number of cases is needed to confirm this hypothesis. We have reported 6 cases of acute obstructive suppurative pancreatic ductitis (AOSPD) treated with pancreatic duct drainage by NPD [12]. Causes of chronic pancreatitis were alcoholism in 5 patients and heredity in 1. All had MPD dilatation with pancreatic calculi or MPD stenosis revealed by CT on admission as well as clinical features of aggravation of chronic pancreatitis with fever. In 5 of the 6 patients, cultures of the pancreatic juice were performed, and the results were positive with Escherichia coli, Klebsiela pneumonia, Enterococcus faecalis, and Viellonella species identified in 3, 1, and 1 patient, respectively. The 5 patients with alcoholic pancreatitis had pancreatic calculi and underwent extracorporeal shock wave lithotripsy (ESWL) to remove them. In the remaining patient with hereditary pancreatitis, pancreatic stenosis was recognized and NPD was followed by stent placement. That this patient had pancreatic duct disorders, including stenosis and calculi, indicated that this case might represent aggravation of chronic pancreatitis, possibly with secondary, earlier than usual, bacterial infection. However, the demonstration of infected pancreatic juice as early as the second day of admission suggests that this patient might have had AOSPD. This case also demonstrates the possibility that some other cases of acute inflammation in the course of chronic alcoholic pancreatitis might be due primarily to bacterial infection of the pancreatic ducts. Thus there may be an important subset of patients with chronic alcoholic pancreatitis in whom AOSPD occurs and in whom treatment with NPD would be effective and important. For draining a pancreatic duct, either NPD or pancreatic stent placement can be selected. NPD has the advantage of decreasing intraductal pressure of the pancreatic duct to levels lower [13] than the duodenum while maintaining the integrity of the pancreatic duct environment to prevent infection [14,15] and avoiding reflux of duodenal juice into the injured pancreatic duct, which may contribute to repair of pancreatic duct damage and prevent worsening of inflammation. The use of NPD also allows for the evaluation of the pancreatic duct when needed [14,16]. However, a drawback of NPD is that patients must undergo transnasal placement of a drainage tube. On the other hand, a pancreatic stent also enables pancreatic fluid to flow into the duodenum and decrease the intraductal pressure of the pancreatic duct, which could lead to repair of pancreatic duct damage [17]. However, stent placement has been associated with early occlusion and infection [14,15,18] and can allow duodenal fluid reflux into the pancreatic duct. We consider that NPD should be selected as the first choice of drainage procedure in cases of chronic alcoholic pancreatitis presenting with suspected AOSPD. Then, to prevent recurrence of acute pancreatitis after resolution, stent placement following NPD would be needed because disturbance of pancreatic juice flow is considered to be a predisposing factor in AOSPD. We have described a case of acute bacterial infection complicating established chronic alcoholic pancreatitis that was successfully treated with NPD. However, to confirm the efficacy of the treatment with NPD for such cases requires a further accumulation of cases. However, one should remember that ERCP has a risk of aggravating acute pancreatitis. To make this treatment useful for
M. Kikuyama et al. / Pancreatology 14 (2014) 151e153
acute bacterial inflammation of the pancreatic ducts, selecting patients is very important. We think the possible need for duct drainage should be considered in all cases of severe exacerbation of chronic alcoholic pancreatitis. When ERCP is intended to treat acute pancreatitis with ENPD, accomplishment of the procedure should be promised. Performing ERCP for acute pancreatitis is considered to be permitted to expertized endoscopists. 3. Conclusion The possibility of acute bacterial inflammation should be considered in all cases of chronic alcoholic pancreatitis who present with severe features of inflammation, even in the early stages of an attack. Treatment of this subset of cases by drainage could be of great importance and NPD may be the preferred method. However, since cannulation of the duct system may also produce complications, the selection of patients for drainage remains a challenge. References [1] Ranson JH. Etiological and prognostic factors in human acute pancreatitis: a review. Am J Gastroenterol 1982;77:633e8. [2] Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med 1985;13:818e29. [3] Besselink MG, van Santvoort HC, Boermeester MA, Nieuwenhuijs VB, van Goor H, Dejong CHC, et al. Timing and impact of infections in acute pancreatitis. Br J Surg 2009;96:267e73. [4] Flitz S, Hackert T, Hartwiq W, Rossmanith F, Strobel O, Schneider L, et al. Bacterial translocation and infected pancreatic necrotizing pancreatitis derives from small bowel rather than from colon. Am J Surg 2010;200:111e7. [5] Flint RS, Windsor JA. The role of the intestine in the pathophysiology and management of severe acute pancreatitis. HPB 2003;5:69e85.
153
[6] Capurso G, Zerboni G, Signoretti M, Valente R, Stiqliano S, Piciucchi M, et al. Role of the gut barrier in acute pancreatitis. J Clin Gastroenterol 2012;46:S46e 51. [7] Yan AW, Schnabl B. Bacterial translocation and changes in the intestinal microbiome associated with alcoholic liver disease. World J Hepatol 2012;27: 110e8. [8] Bode JC, Bode C, Heidelbach R, Dürr HK, Martini GA. Jejunal microflora in patients with chronic alcohol abuse. Hepatogastroenterology 1984;31:30e4. [9] Salminen S, Bouley C, Bouton-Ruault MC, Cummings JH, Franck A, Gibson GR, et al. Functional food science and gastrointestinal physiology and function. Br J Nutr 1998;80:S147e71. [10] Guraner F, Malagelada JR. Gut flora in health and disease. Lancet 2003;361: 512e9. [11] Moschioni M, Pansegrau W, Barocchi M. Adhesion determinants of the Streptococcus species. Microbial Biotechnol 2010;3:370e88. [12] Ota Y, Kurokami T, Shigetomo M, Matsumura K, Kodama Y, Chiba T, et al. Acute obstructive suppurative pancreatic ductitis: experiences of six cases. Pancreatology 2013;13:S28. [13] Cicek B, Pariak E, Oguz E, Disibeyaz S, Koksal AS, Sahin B. Endoscopic treatment of pancreatic fistula. Surg Endosc 2006;20:1706e12. [14] Costamanga G, Mutgnani M, Ingrosso M, Vamvakousis V, Alevras P, Manta R. Endoscopic treatment of postsurgical external pancreatic fistulas. Endoscopy 2001;33:317e22. [15] Bhasin DK, Rana SS, Nanda M, Chandail VS, Bupta R, Kang M, et al. Comparative evaluation of transpapillary drainage with nasopancreatic drain and stent in patients with large pseudocysts located near tail of pancreas. J Gastrointest Surg 2011;15:772e6. [16] Miyachi A, Kikuyama M, Matsubayashi Y, Kageyama F, Sumiyoshi S, Kobayashi Y. Successful treatment of pancreatopleural fistula by nasopancreatic drainage and endoscopic removal of pancreatic calculi: a case report. Gastrointest Endosc 2004;59:454e7. [17] Kozarek RA, Ball TJ, Patterson DJ, Raltz SL, Traverso LW, Ryan JA. Transpapillary stenting for pancreaticocutaneous fistulas. J Gastrointest Surg 1997;1:357e61. [18] Kozarek RA, Dall RJ, Patterson DJ, Freeney PC, Ryan JA, Traverso LW. Endoscopic transpapillary therapy for disrupted pancreatic duct and peripancreatic fluid collection. Gastroenterology 1991;100:1362e70.