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Multimodality endoscopic treatment of pancreatic duct disruption with stenting and pseudocyst drainage: How efficacious is it?
Digestive and Liver Disease 45 (2013) 129–133
Contents lists available at SciVerse ScienceDirect
Digestive and Liver Disease journal homepage: www.elsevier.com/locate/dld
Digestive Endoscopy
Multimodality endoscopic treatment of pancreatic duct disruption with stenting and pseudocyst drainage: How efficacious is it? Charles W. Shrode a , Patrick MacDonough a , Monica Gaidhane b , Patrick G. Northup a , Bryan Sauer a , Jennifer Ku a , Kristi Ellen a , Vanessa M. Shami a , Michel Kahaleh b,∗ a b
Digestive Health Center of Excellence, University of Virginia Health System, Charlottesville, VA, United States Weill Cornell Medical College, Division of Gastroenterology and Hepatology, Department of Medicine, New York, NY, United States
a r t i c l e
i n f o
Article history: Received 5 May 2012 Accepted 29 August 2012 Available online 1 October 2012 Keywords: Endoscopy Pancreatic duct leak Pancreatic duct disruption Pseudocyst drainage Stent
a b s t r a c t Background: Few studies have described the role of multimodality therapy and the complexity of endoscopic management of pancreatic duct disruption. Our study aim was to analyse and confirm factors associated with the resolution of pancreatic duct disruption. Methods: Over 6 years, retrospective data on patients with pancreatic duct disruption managed endoscopically were retrieved. Success was defined as resolution of the pancreatic duct disruption at 12 months. Logistic regression analysis was performed to determine factors associated with resolution. Results: 113 patients (78 male) with a mean age 51.3 year were included. Resolution of the pancreatic duct leak occurred in 80 cases (70.2%). 72 cases received transpapillary pancreatic duct stents, with 51 demonstrating resolution of pancreatic duct leak (71%) cystenterostomy was performed in 68 patients with 51 resolved (75%). In partial duct disruptions, pancreatic duct stenting combined with endoscopic drainage of fluid collections resulted in an increased rate of resolution (80%) compared to complete disruptions treated in a similar manner (57%). In complete pancreatic ductal disruptions, transpapillary pancreatic duct stenting had no additional benefit (9/17, 52.9%) compared to cystenterostomy or percutaneous drainage alone (24/34, 70.6%; P = 0.61). Conclusion: Pancreatic duct disruptions require multimodality treatment, addressing not only the integrity of the pancreatic duct but also any fluid collections associated. Partial ductal disruption should be managed by a bridging stent. © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
1. Introduction Pancreatic duct (PD) disruption results in leakage of pancreatic secretions leading to numerous complications such as pancreatic ascites, fistula, pseudocyst, abscess formation, and necrosis [1,2]. Ductal disruption is a consequence of acute or chronic pancreatitis, surgery, trauma or pancreatic malignancy [1–5]. Conservative treatment modalities include restricting oral feeds, somatostatin analogue therapies and paracentesis [6]. Conservative management of PD disruption is less likely to be successful in symptomatic fluid collections greater than 6 cm, and collections that persist greater than 6 weeks [7,8]. Less than 40% of patients with PD disruptions and associated fistulas improve with conservative therapy alone [9–14].
∗ Corresponding author at: Chief Advanced Endoscopy, Weill Cornell Medical College, Division of Gastroenterology and Hepatology, Department of Medicine, United States. Tel.: +1 646 962 4000; fax: +1 646 962 0110. E-mail address: [email protected] (M. Kahaleh).
PD disruptions and associated fluid collections can be treated by surgical, percutaneous, or endoscopic procedures. Surgical interventions include cystogastrostomy; roux loop cystoenterostomy and resection of the tail of the pancreas often combined with splenectomy [15,16]. Surgical therapies are associated with 15% morbidity, 5% mortality and 10% recurrence [15,16]. Percutaneous aspiration under radiological guidance is another therapeutic option but is associated with recurrence and external fistula [1,5,7,17–20]. Endoscopic interventions permit drainage of fluid collections. In addition, endoscopic management also allows pancreatic decompression via pancreatic sphincterotomy and, more importantly, intraductal stent placement to seal duct leakages [6,18,19,21–27]. While other studies have focused on the role of PD stenting as an adjunct to endoscopic drainage of fluid collections [28], no studies have been performed to determine whether transpapillary PD stenting alone increases the rate of resolution of PD disruption versus multimodality therapy, such as the combination of PD stenting and cystenterostomy. Our study also attempts to reinforce the role of transpapillary PD stenting in both complete and partial PD disruptions.
1590-8658/$36.00 © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.dld.2012.08.026
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C.W. Shrode et al. / Digestive and Liver Disease 45 (2013) 129–133
2. Patients and methods Between January 2002 and July 2008, all patients referred with complicated pancreatitis and diagnosed with PD disruption on Endoscopic Retrograde Cholangiopancreatography (ERCP) were retrieved from an IRB approved endoscopy database. Data was completed by review of the medical records. All patients were consented for the procedure and the study was approved by the Investigation Review Board. A total of 113 patients were enrolled with 114 cases studied. One patient presented with a ductal disruption in the genu of the pancreas that resolved at 1 month. Seven months later, the patient presented with a new ductal disruption at the tail of the pancreas. None of these patients went to surgery as the standard of card patient management in this institution included assessment of the PD integrity by ERCP prior to any other intervention. 2.1. Material All procedures were performed under general anaesthesia. Olympus endoscopes (TJF-140 or TJF-160 or TJVF-160; Olympus America, Melville, NY) were used for all procedures. A Valley Lab electrosurgical generator (SSE2; Boulder, CO) was used for all sphincterotomies. Blended electrosurgical cutting current was used in all cases. All patients received broad spectrum antibiotic prophylaxis before intervention. 2.2. Definitions Ductal disruption was defined as extravasation of contrast from the PD on ERCP. Complete ductal disruption was defined as extravasation of contrast from the PD without opacification of the proximal PD [1]. Partial ductal disruption was defined as extravasation of contrast from the PD with opacification of the PD proximal to the disruption [29]. 2.3. Technique Dedicated pancreatico-biliary endoscopists performing more than 500 ERCP a year performed all ERCPs. Biliary sphincterotomy was routinely performed in gallstone pancreatitis. All patients with ductal disruption underwent pancreatic sphincterotomy. Every effort was made to cross the disruption. In cases where the duct proximal to the disruption was accessible with a guidewire, a 5 or 7 Fr PD stent was placed across the leak; thus sealing the leak. In cases where the guidewire was unable to cross the disruption, a transpapillary stent was placed into or abutting a pancreatic fluid collection without fully crossing the PD disruption. In all cases attempts were made to exchange transpapillary pancreatic stents every 12 weeks to assess ductal changes post treatment and prevent stent occlusion [2,30]. 2.4. Other endoscopic interventions Percutaneous endoscopic gastrostomy with jejunal feeding tubes (PEG-J) or nasojejunal feeding tubes were placed in patients requiring enteral support or bowel rest for treatment of pancreatitis. Cystenterostomy (either cystgastrostomy or cystduodenostomy) was performed when a mature and symptomatic fluid collection was identified. Inaccessible symptomatic fluid collection from the bowel, were managed percutaneously. 2.5. Classification of complications Patients who had haematemesis, melena, or bloody stools with a drop in haemoglobin level of more than 2 g/dL requiring repeat
endoscopy were considered to have clinically significant haemorrhage. Perforation was diagnosed in patients who had abdominal pain associated with intraperitoneal or retroperitoneal air on imaging. Stent migration was defined as any stent migration requiring repeat intervention. PD stenosis was characterized by a stenotic segment of the PD associated with proximal ductal dilation. 2.6. Follow-up Patients were followed with serial cross sectional imaging during clinic visits and repeat ERCPs until final outcomes. Therapeutic success was defined by resolution of the PD leak and associated complications (i.e.: pancreatic ascites, pseudocyst, pancreaticopleural fistula or poorly organized fluid collection). If the PD leak had not resolved after 12 months, the patient was considered to have failed therapy. Patients that required surgery prior to resolution were also categorized as treatment failures. 2.7. Statistical analysis Logistic regression analysis was performed on the following variables with regard to their ability to predict complete resolution within 12 months; age (<55 versus ≥55 years), gender (male versus female), aetiology (alcohol versus other), chronicity (acute versus chronic), pancreatic stenting (performed versus not), disruption type (complete versus partial), disruption location (body versus other), and enteral feeding (performed versus not). P value less than 0.05 was considered statistically significant. 3. Results One-hundred thirteen patients (113), mean age 51.25 years (range: 11–86), presented with 114 PD disruptions. Seventy-nine cases were male and 35 female. PD disruption occurred as a result of acute pancreatitis in 58 cases and chronic pancreatitis in 56 cases. Aetiologies of pancreatitis resulting in PD disruption included alcohol (32 cases) and non-alcohol related aetiologies (82 cases). Non-alcohol aetiologies of pancreatitis causing PD disruption included gallstone disease (45 cases), surgery (13), idiopathic (8), divisum (5), trauma (3), hypertriglyceridemia (3), hereditary (2), medications (2), and peritonitis due to peritoneal dialysis (1) (Fig. 1). The manifestations of PD disruption included fluid collections (104; 96 cases with pseudocysts, 8 with post-operative fluid collections), pancreatic ascites (3), and pancreatic fistula (2; one with pancreatic-cutaneous fistula and one with a pancreatic-pleural fistula). In addition, 2 cases presented with pseudocysts and ascites, 2 with pseudocyst and pancreatic-pleural fistula, and 1 case presented after a traumatic injury. In 53 cases the ductal disruption was identified in the body of the pancreas. In 3 cases a disruption occurred at multiple sites. Twenty-one patients experienced disruptions at the pancreatic head, 20 presented with disruptions at the genu, and 17 cases presented with disruption at the pancreatic tail. In 64 cases the ductal disruption was complete. Fifty (50) cases demonstrated partial disruption (Table 1). Seventy-two (72) cases received transpapillary PD stents. In 47 of these 72 cases the stent crossed the PD disruption. In the remaining 25 cases a transpapillary stent was placed at the edge of the disruption or into a pancreatic fluid collection. A total of 42 cases did not receive transpapillary stents. Of the 50 cases of partial PD disruption, 47 underwent transpapillary stenting of the PD. The 3 cases of partial disruption that did not receive a transpapillary stent were treated with cystgastrostomy only. All three of these patients resolved their PD disruption
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Fig. 1. Management of partial and complete pancreatic duct (PD) disruptions.
Table 1 Management of partial pancreatic duct disruptions. Modality
Total patients N = 50
Resolution at 12 months
Transpapillary stenting only Transpapillary stenting with cystenterostomy Cystenterostomy only
28
21
75%
19
15
78.9%
3
3
Success rate
100%
within 12 months. Twenty-five (25) complete disruptions received transpapillary PD stenting. Sixty-four cases presented with complete PD disruptions (Table 2). Eight (8) patients were treated exclusively with stenting of the PD. Exclusive therapy with cystenterostomy alone occurred in 33 cases. Fourteen patients received a cystenterostomy and PD stent. Percutaneous drainage alone was used in 2 cases. Three cases received both percutaneous drainage and a PD stent. In 4 cases, the patient did not receive a PD stent or drainage (neither percutaneously nor cystenterostomy). No patient with complete disruption received a bridging stent. A bridging stent was associated with improved outcome, but this was not statistically significant. Table 2 Management of complete pancreatic duct disruptions. Modality Transpapillary stent only Transpapillary stent and cystenterostomy Cystenterostomy only Transpapillary stent and percutaneous drain Percutaneous drain only No transpapillary stenting, cystenterostomy, or percutaneous drainage
Total patients (N = 64)
Resolution at 12 months
Success rate
8
6
75%
14
8
57%
A total of 69 cases received cystenterostomy. Five patients had percutaneous drains placed under CT-guidance or during surgery. In addition, 81 patients received nutritional support via enteral feeds with percutaneous gastrostomy with jejunal extension (78 cases) or nasojejunal tube (3 cases). 3.1. Complications Thirty patients developed complications related to ERCP and related procedures. Eight cases experienced PD stent migration. In 2 of the cases of PD stent migration, the stents were placed for PD strictures. Cystenterostomy stent migration occurred in 14 cases. Four cases required revision of the jejunal feeding extension arm (J-arm) after migration. Three episodes of perforated viscous occurred; two due to J-arm perforation of the colon and one due to complications with percutaneous gastrostomy tube placement. Wire perforation of a PD side branch occurred in 2 cases without subsequent sequelae since patients were successfully stented. Perforation of a pseudocyst occurred in 2 cases with one requiring surgical laporotomy and the other resolving with antibiotics. Five bleeding events (Hgb drop by <2 g/dL) occurred that required treatment with transfusion of packed red blood cells and EGD. In 1 case a non-ST elevation myocardial infarction occurred in the periprocedure timeframe. Six mortalities occurred during the course of the study, none of which were directly related to the procedures. Two patients died form aspiration pneumonia. A third patient died due to complications of cirrhosis. Another patient expired due to peritonitis in the setting of long-standing peritoneal dialysis. Two patients died due to sepsis, likely as sequelae of severe pancreatitis. 3.2. Clinical outcomes
33
24
72.7%
3
1
33.3%
2
2
100%
4
2
50%
Resolution of the PD disruption and associated complication was achieved in 80 patients (70.7%) within 12 months of presentation. Failure of the PD disruption to resolve or progression to surgery for treatment occurred in 20 patients (17.5%). Nine (7.9%) patients were lost to follow-up within 12 months of presentation and did not resolve prior to being lost to follow-up. Five mortalities occurred prior to resolution of PD disruption. 47/50 cases with partial PD disruption received transpapillary stents. In 28 cases of partial PD disruption, therapy consisted of transpapillary stenting without cystenterostomy; 21 of these cases resolved within 12 months (75%). A total of 19 cases of partial
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Table 3 Factors predictive of resolution. Predictive factor
Success
P value
Odds ratio
Gender (male versus female) Age (<55 versus ≥55 years) Aetiology (alcohol versus other) Chronicity (acute versus chronic) Disruption type (partial versus complete) Stent placement (performed versus not)a Disruption location (body versus other) Enteral feeding (performed versus not)
71% (56/79) versus 68.6% (24/35) 67.2% (43/64) versus 74% (37/50) 68.7% (22/32) versus 69.5% (57/82) 81.4% (44/54) versus 60% (36/60) 78% (39/50) versus 64% (41/64) 70.8% (51/72) versus 69.0% (29/42) 58 versus 70 70.3% (57/81) versus 69.7% (23/33)
0.99 0.60 0.33 0.57 0.17 0.56 0.49 0.12
1.00 1.01 1.69 1.29 2.02 0.73 1.33 0.45
95% CI 0.41–2.44 0.98–1.03 0.59–4.81 0.54–3.04 0.74–5.55 0.26–2.09 0.59–3.00 0.16–1.24
a These values reflect all patients that received transpapillary stents. Some cases received both transpapillary stents and cystenterostomy; this subgroup is included in the stent performed group.
PD disruption received multimodality therapy with transpapillary stenting and cystenterostomy, of which 15 cases resolved within 12 months (78.9%). All 3 patients with partial PD disruption treated with cystenterostomy resolved within 12 months. Sixty-four (64) cases of complete ductal disruption were identified. Transpapillary stenting was performed in 25 cases of complete PD disruption. In the 8 patients with complete disruption treated with transpapillary stenting alone, six resolved within 12 months (75%). Fourteen cases of complete PD disruption underwent transpapillary stenting with cystenterostomy, with eight resolving within 12 months (57%). Percutaneous drainage and transpapillary stenting was employed in 3 cases of complete disruption, one of which resolved within 12 months. Treatment of 35 cases of complete PD disruption consisted of cystenterostomy of percutaneous drainage only with a success rate of 68.5% (24/35). Four cases of complete disruption did not undergo transpapillary stenting, cystenterostomy, or percutaneous drainage, two of which resolved within 12 months. A total of 34 (34/114, 29.8%) treatment failures occurred during the study. Five patients required surgical intervention for debridement or partial pancreatectomy (5/34, 14.7%; overall 4/114, 4.4%). Five mortalities occurred prior to resolution of PD disruption. Ten patients eventually resolved after 12 months from presentation (10/34, 29%). At the time of study completion, 5 patients had not resolved at 12 months; and demonstrated persistent PD disruptions (5/34, 14.7%). Nine patients were lost to follow-up with failure to resolve at 12 months prior to being lost to follow-up. Logistic regression showed absence of statistically significant predictors of resolution (see Table 3). 4. Discussion Management of PD disruptions often involves a multidisciplinary approach [1,3–5,17–19,21–25]. Previously Barthet et al. [19] followed 30 patients who underwent ERCP with stent placement. In this study, the stents did not bridge the disruption and the majority (93%) of patients had chronic pancreatitis. The study demonstrated that 23 (76%) had resolution of their collection at mean follow-up of 15.3 months. Varadarajulu et al. [1] showed that transpapillary stenting leads to successful resolution of PD disruptions, particularly in partial disruptions and when the stent bridges the disruption. Our study represents a single centre experience of patients with PD disruptions and associated complications. After 12 months 71% of patients had complete resolution of their leakage and associated complications. Our data indicates that partial disruptions may be amenable to treatment with transpapillary stenting without systematic cystenterostomy or percutaneous drainage. Traversing the leak likely permits healing of the disruption and facilitates resorption of the fluid collection. Another important aspect of this study is the data pertaining to complete PD disruptions. We achieved good results in patients
with complete ductal disruptions treated with transpapillary stenting alone (75% resolution at 12 months). The small number of patients in this group (n = 8) precludes making conclusions as to the effectiveness of this particular mode of management at this time. However, complete PD disruptions continue to be difficult problems to manage frequently requiring multiple endoscopic, percutaneous, or surgical procedures. The argument for stenting the PD in complete PD disruption weakens with further examination of our data. In our study complete ductal disruptions receiving transpapillary stenting with concomitant peripancreatic fluid collection drainage with cystenterostomy or percutaneous therapy actually resolved at a lower rate than complete disruptions treated with cystenterostomy or percutaneous drainage alone. This suggests that complete PD disruptions should be managed with cystenterostomies when feasible. Our study was unable to demonstrate predictive values related to the location of the leak, the aetiology of the leak, and the administration of enteral feeding status. It is possible that the study is underpowered to demonstrate benefit from some of these subgroups or interventions. Our study also quotes a relatively high rate of complications. However, a large majority of the complications in our study occurred as a direct result of stent migration, either from the PD or cystenterostomy. Multiple complications also arose as a result of jejunostomy tubes and their placement (n = 6). Due to the length of time patients were followed in our study, it is reasonable to assume that we would see a higher rate of complications regarding stent and jejunostomy tube migration. In all cases, these patients were managed with endoscopic therapy. In summary, this study supports the efficacy of transpapillary stent placement in partial PD disruptions. We believe stenting across PD disruptions should be considered in patients with partial disruptions. Patients with complete PD disruptions receiving cystenterostomy likely do not benefit from placement of a transpapillary stent. Finally, our data continues to support the growing body of research suggesting that PD disruptions can be managed by endoscopic therapy. We recommend future prospective trials to further define the role of transpapillary stenting in PD disruptions. Conflict of interest statement Dr. Michel Kahaleh has received grant support from Boston Scientific, Fujinon, Emcison and MI Tech. He is a consultant for Boston Scientific and Xlumena. All other authors have no conflicts of interest to disclose. References [1] Varadarajulu S, Noone TC, Tutuian R, et al. Predictors of outcome in pancreatic duct disruption managed by endoscopic transpapillary stent placement. Gastrointestinal Endoscopy 2005;61:568–75. [2] Testoni PA. Endoscopic stenting in benign pancreatic diseases. JOP: Journal of the Pancreas [Electronic Resource] 2007;8(1 Suppl.):141–50.
C.W. Shrode et al. / Digestive and Liver Disease 45 (2013) 129–133 [3] Kozarek RA, Ball TJ, Patterson DJ, et al. Endoscopic transpapillary therapy for disrupted pancreatic duct and peripancreatic fluid collections. Gastroenterology 1991;100:1362–70. [4] Huibregtse K, Schneider B, Vrij AA, et al. Endoscopic pancreatic drainage in chronic pancreatitis. Gastrointestinal Endoscopy 1988;34:9–15. [5] Huckfeldt R, Agee C, Nichols WK, et al. Nonoperative treatment of traumatic pancreatic duct disruption using an endoscopically placed stent. Journal of Trauma-Injury Infection and Critical Care 1996;41:143–4. [6] Bracher GA, Manocha AP, DeBanto JR, et al. Endoscopic pancreatic duct stenting to treat pancreatic ascites. Gastrointestinal Endoscopy 1999;49:710–5. [7] Vitas GJ, Sarr MG. Selected management of pancreatic pseudocysts: operative versus expectant management. Surgery 1992;111:123–30. [8] Yeo CJ, Bastidas JA, Lynch-Nyhan A, et al. The natural history of pancreatic pseudocysts documented by computed tomography. Surgery, Gynecology and Obstetrics 1990;170:411–7. [9] Kellum JM, Holland GF, McNeill P. Traumatic pancreatic cutaneous fistula: comparison of enteral and parenteral feedings. Journal of Trauma-Injury Infection and Critical Care 1988;28:700–4. [10] Rosso E, Alexakis N, Ghaneh P, et al. Pancreatic pseudocyst in chronic pancreatitis: endoscopic and surgical treatment. Digestive Surgery 2003;20:397–406. [11] Eckhauser F, Raper SE, Knol JA, et al. Surgical management of pancreatic pseudocysts, pancreatic ascites, and pancreaticopleural fistulas. Pancreas 1991;6(Suppl. 1):S66–75. [12] Catalano MF, Geenen JE, Schmalz MJ, et al. Treatment of pancreatic pseudocysts with ductal communication by transpapillary pancreatic duct endoprosthesis. Gastrointestinal Endoscopy 1995;42:214–8. [13] Chebli JM, Gaburri PD, de Souza AF, et al. Internal pancreatic fistulas: proposal of a management algorithm based on a case series analysis. Journal of Clinical Gastroenterology 2004;38:795–800. [14] Feldman M, Friedman LS, Sleisenger MH, editors. Sleisenger and fordtran’s gastrointestinal and liver disease: pathophysiology/diagnosis/management. 7th ed. Philadelphia: Saunders; 2002. [15] Köhler H, Schafmayer A, Lüdtke FE, et al. Surgical treatment of pancreatic pseudocysts. British Journal of Surgery 1987;74:813–5. [16] Löhr-Happe A, Peiper M, Lankisch PG. Natural course of operated pseudocysts in chronic pancreatitis. Gut 1994;35:1479–82.
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[17] vanSonnenberg E, Wittich GR, Casola G, et al. Percutaneous drainage of infected and noninfected pancreatic pseudocysts: experience in 101 cases. Radiology 1989;170:757–61. [18] Kozarek RA, Jiranek GC, Traverso LW. Endoscopic treatment of pancreatic ascites. American Journal of Surgery 1994;168:223–6. [19] Barthet M, Sahel J, Bodiou-Bertei C, et al. Endoscopic transpapillary drainage of pancreatic pseudocysts. Gastrointestinal Endoscopy 1995;42:208–13. [20] Adams DB, Anderson MC. Percutaneous catheter drainage compared with internal drainage in the management of pancreatic pseudocyst. Annals of Surgery 1992;215:571–6 [discussion 576–8]. [21] Devière J, Bueso H, Baize M, et al. Complete disruption of the main pancreatic duct: endoscopic management. Gastrointestinal Endoscopy 1995;42: 445–51. [22] Kozarek RA. Endoscopic therapy of complete and partial pancreatic duct disruptions. Gastrointestinal Endoscopy Clinics of North America 1998;8:39–53. [23] Telford JJ, Farrell JJ, Saltzman JR, et al. Pancreatic stent placement for duct disruption. Gastrointestinal Endoscopy 2002;56:18–24. [24] Saeed ZA, Ramirez FC, Hepps KS. Endoscopic stent placement for internal and external pancreatic fistulas. Gastroenterology 1993;105:1213–7. [25] Cotton PB, Lehman G, Vennes J, et al. Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointestinal Endoscopy 1991;37:383–93. [26] Neoptolemos JP, London NJ, Carr-Locke DL. Assessment of main pancreatic duct integrity by endoscopic retrograde pancreatography in patients with acute pancreatitis. British Journal of Surgery 1993;80:94–9. [27] Bhasin DK, Rana SS, Udawat HP, et al. Management of multiple and large pancreatic pseudocysts by endoscopic transpapillary nasopancreatic drainage alone. American Journal of Gastroenterology 2006;101:1780–6. [28] Trevino JM, Tamhane A, Varadarajulu S. Successful stenting in ductal disruption favorably impacts treatment outcomes in patients undergoing transmural drainage of peripancreatic fluid collections. Journal of Gastroenterology and Hepatology 2010;25:526–31. [29] Devière J, Antaki F. Disconnected pancreatic tail syndrome: a plea for multidisciplinarity. Gastrointestinal Endoscopy 2008;67:680–2. [30] Kozarek RA. Pancreatic stents can induce ductal changes consistent with chronic pancreatitis. Gastrointestinal Endoscopy 1990;36:93–5.
Contents lists available at SciVerse ScienceDirect
Digestive and Liver Disease journal homepage: www.elsevier.com/locate/dld
Digestive Endoscopy
Multimodality endoscopic treatment of pancreatic duct disruption with stenting and pseudocyst drainage: How efficacious is it? Charles W. Shrode a , Patrick MacDonough a , Monica Gaidhane b , Patrick G. Northup a , Bryan Sauer a , Jennifer Ku a , Kristi Ellen a , Vanessa M. Shami a , Michel Kahaleh b,∗ a b
Digestive Health Center of Excellence, University of Virginia Health System, Charlottesville, VA, United States Weill Cornell Medical College, Division of Gastroenterology and Hepatology, Department of Medicine, New York, NY, United States
a r t i c l e
i n f o
Article history: Received 5 May 2012 Accepted 29 August 2012 Available online 1 October 2012 Keywords: Endoscopy Pancreatic duct leak Pancreatic duct disruption Pseudocyst drainage Stent
a b s t r a c t Background: Few studies have described the role of multimodality therapy and the complexity of endoscopic management of pancreatic duct disruption. Our study aim was to analyse and confirm factors associated with the resolution of pancreatic duct disruption. Methods: Over 6 years, retrospective data on patients with pancreatic duct disruption managed endoscopically were retrieved. Success was defined as resolution of the pancreatic duct disruption at 12 months. Logistic regression analysis was performed to determine factors associated with resolution. Results: 113 patients (78 male) with a mean age 51.3 year were included. Resolution of the pancreatic duct leak occurred in 80 cases (70.2%). 72 cases received transpapillary pancreatic duct stents, with 51 demonstrating resolution of pancreatic duct leak (71%) cystenterostomy was performed in 68 patients with 51 resolved (75%). In partial duct disruptions, pancreatic duct stenting combined with endoscopic drainage of fluid collections resulted in an increased rate of resolution (80%) compared to complete disruptions treated in a similar manner (57%). In complete pancreatic ductal disruptions, transpapillary pancreatic duct stenting had no additional benefit (9/17, 52.9%) compared to cystenterostomy or percutaneous drainage alone (24/34, 70.6%; P = 0.61). Conclusion: Pancreatic duct disruptions require multimodality treatment, addressing not only the integrity of the pancreatic duct but also any fluid collections associated. Partial ductal disruption should be managed by a bridging stent. © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
1. Introduction Pancreatic duct (PD) disruption results in leakage of pancreatic secretions leading to numerous complications such as pancreatic ascites, fistula, pseudocyst, abscess formation, and necrosis [1,2]. Ductal disruption is a consequence of acute or chronic pancreatitis, surgery, trauma or pancreatic malignancy [1–5]. Conservative treatment modalities include restricting oral feeds, somatostatin analogue therapies and paracentesis [6]. Conservative management of PD disruption is less likely to be successful in symptomatic fluid collections greater than 6 cm, and collections that persist greater than 6 weeks [7,8]. Less than 40% of patients with PD disruptions and associated fistulas improve with conservative therapy alone [9–14].
∗ Corresponding author at: Chief Advanced Endoscopy, Weill Cornell Medical College, Division of Gastroenterology and Hepatology, Department of Medicine, United States. Tel.: +1 646 962 4000; fax: +1 646 962 0110. E-mail address: [email protected] (M. Kahaleh).
PD disruptions and associated fluid collections can be treated by surgical, percutaneous, or endoscopic procedures. Surgical interventions include cystogastrostomy; roux loop cystoenterostomy and resection of the tail of the pancreas often combined with splenectomy [15,16]. Surgical therapies are associated with 15% morbidity, 5% mortality and 10% recurrence [15,16]. Percutaneous aspiration under radiological guidance is another therapeutic option but is associated with recurrence and external fistula [1,5,7,17–20]. Endoscopic interventions permit drainage of fluid collections. In addition, endoscopic management also allows pancreatic decompression via pancreatic sphincterotomy and, more importantly, intraductal stent placement to seal duct leakages [6,18,19,21–27]. While other studies have focused on the role of PD stenting as an adjunct to endoscopic drainage of fluid collections [28], no studies have been performed to determine whether transpapillary PD stenting alone increases the rate of resolution of PD disruption versus multimodality therapy, such as the combination of PD stenting and cystenterostomy. Our study also attempts to reinforce the role of transpapillary PD stenting in both complete and partial PD disruptions.
1590-8658/$36.00 © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.dld.2012.08.026
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2. Patients and methods Between January 2002 and July 2008, all patients referred with complicated pancreatitis and diagnosed with PD disruption on Endoscopic Retrograde Cholangiopancreatography (ERCP) were retrieved from an IRB approved endoscopy database. Data was completed by review of the medical records. All patients were consented for the procedure and the study was approved by the Investigation Review Board. A total of 113 patients were enrolled with 114 cases studied. One patient presented with a ductal disruption in the genu of the pancreas that resolved at 1 month. Seven months later, the patient presented with a new ductal disruption at the tail of the pancreas. None of these patients went to surgery as the standard of card patient management in this institution included assessment of the PD integrity by ERCP prior to any other intervention. 2.1. Material All procedures were performed under general anaesthesia. Olympus endoscopes (TJF-140 or TJF-160 or TJVF-160; Olympus America, Melville, NY) were used for all procedures. A Valley Lab electrosurgical generator (SSE2; Boulder, CO) was used for all sphincterotomies. Blended electrosurgical cutting current was used in all cases. All patients received broad spectrum antibiotic prophylaxis before intervention. 2.2. Definitions Ductal disruption was defined as extravasation of contrast from the PD on ERCP. Complete ductal disruption was defined as extravasation of contrast from the PD without opacification of the proximal PD [1]. Partial ductal disruption was defined as extravasation of contrast from the PD with opacification of the PD proximal to the disruption [29]. 2.3. Technique Dedicated pancreatico-biliary endoscopists performing more than 500 ERCP a year performed all ERCPs. Biliary sphincterotomy was routinely performed in gallstone pancreatitis. All patients with ductal disruption underwent pancreatic sphincterotomy. Every effort was made to cross the disruption. In cases where the duct proximal to the disruption was accessible with a guidewire, a 5 or 7 Fr PD stent was placed across the leak; thus sealing the leak. In cases where the guidewire was unable to cross the disruption, a transpapillary stent was placed into or abutting a pancreatic fluid collection without fully crossing the PD disruption. In all cases attempts were made to exchange transpapillary pancreatic stents every 12 weeks to assess ductal changes post treatment and prevent stent occlusion [2,30]. 2.4. Other endoscopic interventions Percutaneous endoscopic gastrostomy with jejunal feeding tubes (PEG-J) or nasojejunal feeding tubes were placed in patients requiring enteral support or bowel rest for treatment of pancreatitis. Cystenterostomy (either cystgastrostomy or cystduodenostomy) was performed when a mature and symptomatic fluid collection was identified. Inaccessible symptomatic fluid collection from the bowel, were managed percutaneously. 2.5. Classification of complications Patients who had haematemesis, melena, or bloody stools with a drop in haemoglobin level of more than 2 g/dL requiring repeat
endoscopy were considered to have clinically significant haemorrhage. Perforation was diagnosed in patients who had abdominal pain associated with intraperitoneal or retroperitoneal air on imaging. Stent migration was defined as any stent migration requiring repeat intervention. PD stenosis was characterized by a stenotic segment of the PD associated with proximal ductal dilation. 2.6. Follow-up Patients were followed with serial cross sectional imaging during clinic visits and repeat ERCPs until final outcomes. Therapeutic success was defined by resolution of the PD leak and associated complications (i.e.: pancreatic ascites, pseudocyst, pancreaticopleural fistula or poorly organized fluid collection). If the PD leak had not resolved after 12 months, the patient was considered to have failed therapy. Patients that required surgery prior to resolution were also categorized as treatment failures. 2.7. Statistical analysis Logistic regression analysis was performed on the following variables with regard to their ability to predict complete resolution within 12 months; age (<55 versus ≥55 years), gender (male versus female), aetiology (alcohol versus other), chronicity (acute versus chronic), pancreatic stenting (performed versus not), disruption type (complete versus partial), disruption location (body versus other), and enteral feeding (performed versus not). P value less than 0.05 was considered statistically significant. 3. Results One-hundred thirteen patients (113), mean age 51.25 years (range: 11–86), presented with 114 PD disruptions. Seventy-nine cases were male and 35 female. PD disruption occurred as a result of acute pancreatitis in 58 cases and chronic pancreatitis in 56 cases. Aetiologies of pancreatitis resulting in PD disruption included alcohol (32 cases) and non-alcohol related aetiologies (82 cases). Non-alcohol aetiologies of pancreatitis causing PD disruption included gallstone disease (45 cases), surgery (13), idiopathic (8), divisum (5), trauma (3), hypertriglyceridemia (3), hereditary (2), medications (2), and peritonitis due to peritoneal dialysis (1) (Fig. 1). The manifestations of PD disruption included fluid collections (104; 96 cases with pseudocysts, 8 with post-operative fluid collections), pancreatic ascites (3), and pancreatic fistula (2; one with pancreatic-cutaneous fistula and one with a pancreatic-pleural fistula). In addition, 2 cases presented with pseudocysts and ascites, 2 with pseudocyst and pancreatic-pleural fistula, and 1 case presented after a traumatic injury. In 53 cases the ductal disruption was identified in the body of the pancreas. In 3 cases a disruption occurred at multiple sites. Twenty-one patients experienced disruptions at the pancreatic head, 20 presented with disruptions at the genu, and 17 cases presented with disruption at the pancreatic tail. In 64 cases the ductal disruption was complete. Fifty (50) cases demonstrated partial disruption (Table 1). Seventy-two (72) cases received transpapillary PD stents. In 47 of these 72 cases the stent crossed the PD disruption. In the remaining 25 cases a transpapillary stent was placed at the edge of the disruption or into a pancreatic fluid collection. A total of 42 cases did not receive transpapillary stents. Of the 50 cases of partial PD disruption, 47 underwent transpapillary stenting of the PD. The 3 cases of partial disruption that did not receive a transpapillary stent were treated with cystgastrostomy only. All three of these patients resolved their PD disruption
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Fig. 1. Management of partial and complete pancreatic duct (PD) disruptions.
Table 1 Management of partial pancreatic duct disruptions. Modality
Total patients N = 50
Resolution at 12 months
Transpapillary stenting only Transpapillary stenting with cystenterostomy Cystenterostomy only
28
21
75%
19
15
78.9%
3
3
Success rate
100%
within 12 months. Twenty-five (25) complete disruptions received transpapillary PD stenting. Sixty-four cases presented with complete PD disruptions (Table 2). Eight (8) patients were treated exclusively with stenting of the PD. Exclusive therapy with cystenterostomy alone occurred in 33 cases. Fourteen patients received a cystenterostomy and PD stent. Percutaneous drainage alone was used in 2 cases. Three cases received both percutaneous drainage and a PD stent. In 4 cases, the patient did not receive a PD stent or drainage (neither percutaneously nor cystenterostomy). No patient with complete disruption received a bridging stent. A bridging stent was associated with improved outcome, but this was not statistically significant. Table 2 Management of complete pancreatic duct disruptions. Modality Transpapillary stent only Transpapillary stent and cystenterostomy Cystenterostomy only Transpapillary stent and percutaneous drain Percutaneous drain only No transpapillary stenting, cystenterostomy, or percutaneous drainage
Total patients (N = 64)
Resolution at 12 months
Success rate
8
6
75%
14
8
57%
A total of 69 cases received cystenterostomy. Five patients had percutaneous drains placed under CT-guidance or during surgery. In addition, 81 patients received nutritional support via enteral feeds with percutaneous gastrostomy with jejunal extension (78 cases) or nasojejunal tube (3 cases). 3.1. Complications Thirty patients developed complications related to ERCP and related procedures. Eight cases experienced PD stent migration. In 2 of the cases of PD stent migration, the stents were placed for PD strictures. Cystenterostomy stent migration occurred in 14 cases. Four cases required revision of the jejunal feeding extension arm (J-arm) after migration. Three episodes of perforated viscous occurred; two due to J-arm perforation of the colon and one due to complications with percutaneous gastrostomy tube placement. Wire perforation of a PD side branch occurred in 2 cases without subsequent sequelae since patients were successfully stented. Perforation of a pseudocyst occurred in 2 cases with one requiring surgical laporotomy and the other resolving with antibiotics. Five bleeding events (Hgb drop by <2 g/dL) occurred that required treatment with transfusion of packed red blood cells and EGD. In 1 case a non-ST elevation myocardial infarction occurred in the periprocedure timeframe. Six mortalities occurred during the course of the study, none of which were directly related to the procedures. Two patients died form aspiration pneumonia. A third patient died due to complications of cirrhosis. Another patient expired due to peritonitis in the setting of long-standing peritoneal dialysis. Two patients died due to sepsis, likely as sequelae of severe pancreatitis. 3.2. Clinical outcomes
33
24
72.7%
3
1
33.3%
2
2
100%
4
2
50%
Resolution of the PD disruption and associated complication was achieved in 80 patients (70.7%) within 12 months of presentation. Failure of the PD disruption to resolve or progression to surgery for treatment occurred in 20 patients (17.5%). Nine (7.9%) patients were lost to follow-up within 12 months of presentation and did not resolve prior to being lost to follow-up. Five mortalities occurred prior to resolution of PD disruption. 47/50 cases with partial PD disruption received transpapillary stents. In 28 cases of partial PD disruption, therapy consisted of transpapillary stenting without cystenterostomy; 21 of these cases resolved within 12 months (75%). A total of 19 cases of partial
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Table 3 Factors predictive of resolution. Predictive factor
Success
P value
Odds ratio
Gender (male versus female) Age (<55 versus ≥55 years) Aetiology (alcohol versus other) Chronicity (acute versus chronic) Disruption type (partial versus complete) Stent placement (performed versus not)a Disruption location (body versus other) Enteral feeding (performed versus not)
71% (56/79) versus 68.6% (24/35) 67.2% (43/64) versus 74% (37/50) 68.7% (22/32) versus 69.5% (57/82) 81.4% (44/54) versus 60% (36/60) 78% (39/50) versus 64% (41/64) 70.8% (51/72) versus 69.0% (29/42) 58 versus 70 70.3% (57/81) versus 69.7% (23/33)
0.99 0.60 0.33 0.57 0.17 0.56 0.49 0.12
1.00 1.01 1.69 1.29 2.02 0.73 1.33 0.45
95% CI 0.41–2.44 0.98–1.03 0.59–4.81 0.54–3.04 0.74–5.55 0.26–2.09 0.59–3.00 0.16–1.24
a These values reflect all patients that received transpapillary stents. Some cases received both transpapillary stents and cystenterostomy; this subgroup is included in the stent performed group.
PD disruption received multimodality therapy with transpapillary stenting and cystenterostomy, of which 15 cases resolved within 12 months (78.9%). All 3 patients with partial PD disruption treated with cystenterostomy resolved within 12 months. Sixty-four (64) cases of complete ductal disruption were identified. Transpapillary stenting was performed in 25 cases of complete PD disruption. In the 8 patients with complete disruption treated with transpapillary stenting alone, six resolved within 12 months (75%). Fourteen cases of complete PD disruption underwent transpapillary stenting with cystenterostomy, with eight resolving within 12 months (57%). Percutaneous drainage and transpapillary stenting was employed in 3 cases of complete disruption, one of which resolved within 12 months. Treatment of 35 cases of complete PD disruption consisted of cystenterostomy of percutaneous drainage only with a success rate of 68.5% (24/35). Four cases of complete disruption did not undergo transpapillary stenting, cystenterostomy, or percutaneous drainage, two of which resolved within 12 months. A total of 34 (34/114, 29.8%) treatment failures occurred during the study. Five patients required surgical intervention for debridement or partial pancreatectomy (5/34, 14.7%; overall 4/114, 4.4%). Five mortalities occurred prior to resolution of PD disruption. Ten patients eventually resolved after 12 months from presentation (10/34, 29%). At the time of study completion, 5 patients had not resolved at 12 months; and demonstrated persistent PD disruptions (5/34, 14.7%). Nine patients were lost to follow-up with failure to resolve at 12 months prior to being lost to follow-up. Logistic regression showed absence of statistically significant predictors of resolution (see Table 3). 4. Discussion Management of PD disruptions often involves a multidisciplinary approach [1,3–5,17–19,21–25]. Previously Barthet et al. [19] followed 30 patients who underwent ERCP with stent placement. In this study, the stents did not bridge the disruption and the majority (93%) of patients had chronic pancreatitis. The study demonstrated that 23 (76%) had resolution of their collection at mean follow-up of 15.3 months. Varadarajulu et al. [1] showed that transpapillary stenting leads to successful resolution of PD disruptions, particularly in partial disruptions and when the stent bridges the disruption. Our study represents a single centre experience of patients with PD disruptions and associated complications. After 12 months 71% of patients had complete resolution of their leakage and associated complications. Our data indicates that partial disruptions may be amenable to treatment with transpapillary stenting without systematic cystenterostomy or percutaneous drainage. Traversing the leak likely permits healing of the disruption and facilitates resorption of the fluid collection. Another important aspect of this study is the data pertaining to complete PD disruptions. We achieved good results in patients
with complete ductal disruptions treated with transpapillary stenting alone (75% resolution at 12 months). The small number of patients in this group (n = 8) precludes making conclusions as to the effectiveness of this particular mode of management at this time. However, complete PD disruptions continue to be difficult problems to manage frequently requiring multiple endoscopic, percutaneous, or surgical procedures. The argument for stenting the PD in complete PD disruption weakens with further examination of our data. In our study complete ductal disruptions receiving transpapillary stenting with concomitant peripancreatic fluid collection drainage with cystenterostomy or percutaneous therapy actually resolved at a lower rate than complete disruptions treated with cystenterostomy or percutaneous drainage alone. This suggests that complete PD disruptions should be managed with cystenterostomies when feasible. Our study was unable to demonstrate predictive values related to the location of the leak, the aetiology of the leak, and the administration of enteral feeding status. It is possible that the study is underpowered to demonstrate benefit from some of these subgroups or interventions. Our study also quotes a relatively high rate of complications. However, a large majority of the complications in our study occurred as a direct result of stent migration, either from the PD or cystenterostomy. Multiple complications also arose as a result of jejunostomy tubes and their placement (n = 6). Due to the length of time patients were followed in our study, it is reasonable to assume that we would see a higher rate of complications regarding stent and jejunostomy tube migration. In all cases, these patients were managed with endoscopic therapy. In summary, this study supports the efficacy of transpapillary stent placement in partial PD disruptions. We believe stenting across PD disruptions should be considered in patients with partial disruptions. Patients with complete PD disruptions receiving cystenterostomy likely do not benefit from placement of a transpapillary stent. Finally, our data continues to support the growing body of research suggesting that PD disruptions can be managed by endoscopic therapy. We recommend future prospective trials to further define the role of transpapillary stenting in PD disruptions. Conflict of interest statement Dr. Michel Kahaleh has received grant support from Boston Scientific, Fujinon, Emcison and MI Tech. He is a consultant for Boston Scientific and Xlumena. All other authors have no conflicts of interest to disclose. References [1] Varadarajulu S, Noone TC, Tutuian R, et al. Predictors of outcome in pancreatic duct disruption managed by endoscopic transpapillary stent placement. Gastrointestinal Endoscopy 2005;61:568–75. [2] Testoni PA. Endoscopic stenting in benign pancreatic diseases. JOP: Journal of the Pancreas [Electronic Resource] 2007;8(1 Suppl.):141–50.
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